[Mechanism of total saponins of Panax japonicus against liver injury induced by acetaminophen in mice based on ERK/NF-κB/COX-2 signaling pathway].

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.

Voltage-gated sodium channel gene mutation and P450 gene expression are associated with the resistance of Aphis spiraecola Patch (Hemiptera: Aphididae) to lambda-cyhalothrin.

Aphis spiraecola Patch is one of the most economically important tree fruit pests worldwide. The pyrethroid insecticide lambda-cyhalothrin is commonly used to control A. spiraecola. In this 2-year study, we quantified the resistance level of A. spiraecola to lambda-cyhalothrin in different regions of the Shaanxi province, China. The results showed that A. spiraecola had reached extremely high resistance levels with a 174-fold resistance ratio (RR) found in the Xunyi region. In addition, we compared the enzymatic activity and expression level of P450 genes among eight A. spiraecola populations. The P450 activity of A. spiraecola was significantly increased in five regions (Xunyi, Liquan, Fengxiang, Luochuan, and Xinping) compared to susceptible strain (SS). The expression levels of CYP6CY7, CYP6CY14, CYP6CY22, P4504C1-like, P4506a13, CYP4CZ1, CYP380C47, and CYP4CJ2 genes were significantly increased under lambda-cyhalothrin treatment and in the resistant field populations. A L1014F mutation in the sodium channel gene was found and the mutation rate was positively correlated with the LC50 of lambda-cyhalothrin. In conclusion, the levels of lambda-cyhalothrin resistance of A. spiraecola field populations were associated with P450s and L1014F mutations. Our combined findings provide evidence on the resistance mechanism of A. spiraecola to lambda-cyhalothrin and give a theoretical basis for rational and effective control of this pest species.

Urolithin B Attenuates Cerebral Ischemia-reperfusion Injury by Modulating Nrf2-regulated Anti-oxidation in Rats.

Ischemia-reperfusion (IR) induces a wide range of irreversible injuries. Cerebral IR injury (IRI) refers to additional brain tissue damage that occurs after blood flow is restored following cerebral ischemia. Currently, no established methods exist for treating IRI. Oxidative stress is recognized as a primary mechanism initiating IRI and a crucial focal target for its treatment. Urolithin B, a metabolite derived from ellagitannins, antioxidant polyphenols, has demonstrated protective effects against oxidative stress in various disease conditions. However, the precise mechanism underlying UB's effect on IRI remains unclear. In our current investigation, we assessed UB's ability to mitigate neurological functional impairment induced by IR using a neurological deficit score. Additionally, we examined cerebral infarction following UB administration through TTC staining and neuron Nissl staining. UB's inhibition of neuronal apoptosis was demonstrated through the TUNEL assay and Caspase-3 measurement. Additionally, we examined UB's effect on oxidative stress levels by analyzing malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, and immunohistochemistry analysis of inducible nitric oxide synthase (iNOS) and 8-hydroxyl-2'-deoxyguanosine (8-OHdG). Notably, UB demonstrated a reduction in oxidative stress levels. Mechanistically, UB was found to stimulate the Nrf2/HO-1 signaling pathway, as evidenced by the significant reduction in UB's neuroprotective effects upon administration of ATRA, an Nrf2 inhibitor. In summary, UB effectively inhibits oxidative stress induced by IR through the activation of the Nrf2/HO-1 signaling pathway. These findings suggest that UB holds promise as a therapeutic agent for the treatment of IRI.

Overexpression of the Chemosensory Protein CSP7 Gene Contributed to Lambda-Cyhalothrin Resistance in the Bird Cherry-Oat Aphid Rhopalosiphum padi.

Lambda-cyhalothrin is one of the most important pyrethroids used for controlling wheat aphids. Extensive spraying of lambda-cyhalothrin has led to the development of high resistance to this pyrethroid inRhopalosiphum padi. The mechanisms of resistance are complex and not fully understood. In this study, we found that a laboratory-selected strain of R. padi showed extremely high resistance to lambda-cyhalothrin and cross-resistance to bifenthrin and deltamethrin. The expression level of RpCSP7 was significantly elevated in the resistant strain compared to that in the susceptible strain. Knockdown of RpCSP7 increased the susceptibility of R. padi to lambda-cyhalothrin, whereas the susceptibility to bifenthrin and deltamethrin was not significantly changed. The recombinant RpCSP7 displayed a high affinity for lambda-cyhalothrin but no affinities to bifenthrin and deltamethrin. These findings suggest that the overexpression of RpCSP7 contributes to the resistance of R. padi to lambda-cyhalothrin. This study provides valuable insights into CSP-mediated insecticide resistance in insects.

Efficacy and safety of electroacupuncture combined with Suanzaoren decoction for insomnia following stroke: study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is a common but frequently overlooked sleep disorder after stroke, and there are limited effective therapies for insomnia following stroke. Traditional Chinese medicine (TCM), including acupuncture and the Chinese herbal medication (CHM) Suanzaoren decoction (SZRD), has been reported as an alternative option for insomnia relief after stroke in China for thousands of years. Here, this study aims to investigate the efficacy and safety of electroacupuncture (EA) in combination with SZRD in the treatment of insomnia following stroke. METHODS: A total of 240 patients with post-stroke insomnia will be included and randomized into four groups: the EA group, SZRD group, EA & SZRD group, and sham group. The same acupoints (GV20, GV24, HT7, and SP6) will be used in the EA group, EA & SZRD group, and sham group, and these patients will receive the EA treatment or sham manipulation every other day for 4 consecutive weeks. SZRD treatments will be given to participants in the SZRD group and EA & SZRD group twice a day for 4 consecutive weeks. The primary outcome measures include Pittsburgh Sleep Quality Index scores and polysomnography. Secondary outcome measures include the Insomnia Severity Index, the National Institutes of Health Stroke Scale, the Hospital Anxiety and Depression Scale, brain magnetic resonance imaging, functional magnetic resonance imaging, and nocturnal melatonin concentrations. The primary and secondary outcomes will be assessed at baseline (before treatment), during the 2nd and 4th weeks of the intervention, and at the 8th and 12th weeks of follow-up. Safety assessments will be evaluated at baseline and during the 4th week of the intervention. DISCUSSION: This study will contribute to assessing whether the combination of these two therapies is more beneficial for post-stroke insomnia than their independent use, and the results of this clinical trial will improve our understanding of the possible mechanisms underlying the effects of combination therapies. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2000031413 . Registered on March 30, 2020.

[Protective effect of total triterpenoids from Chaenomeles speciosa against Helicobacter pylori-induced gastritis in mice].

This study investigated the protective effect of total triterpenoids from Chaenomeles speciosa against Helicobacter pylori(Hp)-induced gastritis in mice and explored its possible mechanism. The chronic atrophic gastritis(CAG) model mice were randomly divided into four groups of model, total triterpenoids from C. speciosa(50 and 100 mg·kg~(-1)) and triple therapy, with C57 BL/6 J mice without Hp infection taken as the normal group. Mice in the treatment groups were given corresponding drugs once a day for 4 weeks. Then the following indexes were detected: the contents of reactive oxygen species(ROS), monocyte chemotactic protein 1(MCP-1), keratinocyte chemokines(KC), TNF-α, IL-1ß, IL-6, IL-18, IL-4 and IL-10 in blood and gastric tissue, the activities and contents of LDH, MPO, SOD, GSH-Px, CAT and MDA in gastric tissue and the activities of ß-glucuronidase, ß-galactosidase, cathepsins B and D in blood, gastric tissue and lysosome. Besides, the mRNA expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), Bcl-2, Bcl-xl, Bax and Bad in gastric tissue were determined by quantitative real-time PCR. Western blot was employed to detect the protein expression levels of TLR4, MyD88, p-IKKß, p-IκBα, NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein(ASC), pro-caspase-1, caspase-1, thioredoxin-interacting protein(TXNIP), pro-IL-1ß, pro-IL-18, Bcl-2, Bcl-xl, Bax, Bad, cytochrome C, apoptotic protease-activating factor-1(Apaf-1), pro-caspase-9, pro-caspase-3, cleaved-caspase-9, cleaved-caspase-3, poly(ADP-ribose) polymerase 1(PARP-1), cleaved-PARP-1 and cytosol and nucleus NF-κB p65 in gastric tissue. The results indicated that the total triterpenoids from C. speciosa significantly suppressed Hp proliferation, alleviated the damage to gastric mucosa and improved lymphocyte infiltration and gland atrophy. They were also effective in reducing the activities of ß-glucuronidase, ß-galactosidase, cathepsins B and D in blood and gastric tissue, elevating the activities of ß-glucuronidase and cathepsin D in lysosomal organelles, decreasing the contents of ROS, MCP-1, KC, TNF-α, IL-1ß, IL-6, IL-18 in blood, MDA content and MPO and LDH activities in gastric tissue and increasing the contents of IL-4 and IL-10 in blood and activities of SOD, CAT and GSH-Px in gastric tissue. Other phenomena were also observed after the treatment with total triterpenoids from C. speciosa, including the down-regulation of the mRNA and protein expression levels of TLR4, MyD88, Bax and Bad, the protein expression levels of p-IKKß, p-IκBα, NLRP3, ASC, pro-caspase-1, caspase-1, TXNIP, pro-IL-1ß, pro-IL-18, cytochrome C, Apaf-1, cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 and nuclear NF-κB p65, reduction of p-IKKß/IKKß and p-IκBα/IκBα ratios and up-regulation of the mRNA and protein expression levels of Bcl-2 and Bcl-xl, up-regulation of pro-caspase-9, pro-caspace-3, cytosol NF-κB p65 protein expression levels and Bcl-2/Bax and Bcl-xl/Bad ratios in gastric tissue. These aforementioned results suggest that the total triterpenoids from C. speciosa have significant protective effects against CAG induced by Hp, and its mechanism may be related to enhancing the function of endogenous antioxidant system, suppressing the oxidative stress and inflammatory reaction induced by Hp, correcting lysosomal dysfunction and inflammatory activation of TLR4/NF-κB/NLRP3 inflammasome signaling pathway and thus inhibiting mitochondria-mediated apoptosis.

Pyrethroid Resistance and Fitness Cost Conferred by the super-kdr Mutation M918L in Rhopalosiphum padi (Hemiptera: Aphididae).

Pyrethroid insecticides have been widely utilized for insect pest control. Target-site resistance is one of the major mechanisms explaining pest resistance to pyrethroids. This study quantified pyrethroid resistance and fitness cost conferred by the voltage-gated sodium channel (VGSC) M918L mutation in Rhopalosiphum padi. Six s-kdr-SS and six s-kdr-RS parthenogenetic lineages were established from the same field population and were reared in the laboratory without exposure to pesticides for more than one year. Enzyme activity analysis demonstrated that metabolic resistance had no impact on these lineages. Bioassays showed that the M918L mutation strongly affected pyrethroid efficiency, conferring moderate resistance to bifenthrin (type I) (39.0-fold) and high resistance to lambda-cyhalothrin (type II) (194.7-fold). Compared with the life table of s-kdr-SS lineages, s-kdr-RS lineages exhibited a relative fitness cost with significant decreases in longevity and fecundity. Meanwhile, competitive fitness was measured by blending various ratios of s-kdr-SS and s-kdr-SS aphids. The results indicated that M918L-mediated resistance showed a significant fitness cost in the presence of wild aphids without insecticide pressure. The fitness cost strongly correlated with the initial resistance allele frequency. This work characterized the novel s-kdr M918L mutation in R. padi, defined its function in resistance to different types of pyrethroids, and documented that the M918L-mediated resistance has a significant fitness cost.

LncRNA PCGEM1 contributes to malignant behaviors of glioma by regulating miR-539-5p/CDK6 axis.

BACKGROUND: Glioma, one of the most prevalent and aggressive cancers, is regulated by long noncoding RNAs (lncRNAs). This study aims to research the functional mechanism of lncRNA PCGEM1 involved in glioma progression. METHODS: Expression levels of PCGEM1, miR-539-5p and CDK6 were analyzed by qRT-PCR in NHA, U251, U87, and LN229 cells or glioma tissues. shRNAs were used to knock down PCGEM1 in U251 and LN229 cells. Kaplan-Meier curve and log rank test were utilized to examine survival rate. CCK8 (Cell Counting Kit-8) assay, colony formation assay and EdU staining were conducted to detect cell proliferation. Transwell assay was performed to evaluate cell migration and invasion. Luciferase reporter assay was conducted to assess RNA interaction between PCGEM1 and miR-539-5p. Nude mice were used for tumor xenograft assay. RESULTS: LncRNA PCGEM1 was upregulated in glioma tissues and tumor cell lines. PCGEM1 upregulation predicted unsatisfactory prognosis. PCGEM1 knockdown inhibited proliferation, colony formation, migration and invasion. PCGEM1 knockdown delayed tumor growth in vivo. PCGEM1 played as a competing endogenous RNA (ceRNA) for miR-539-5p to promote CDK6 expression. MiR-539-5p mimics repressed glioma progression while CDK6 overexpression reversed the roles of PCGEM1 knockdown. CONCLUSION: PCGEM1 knockdown suppressed glioma progression through sponging miR-539-5p and regulating CDK6 expression, implying PCGEM1 as a potential therapeutic target.

Genetic factors involved in delayed methotrexate elimination in children with acute lymphoblastic leukemia.

BACKGROUND: Delayed excretion of methotrexate can lead to life-threatening toxicity that may result in treatment cessation, irreversible organ damage, and death. Various factors have been demonstrated to influence the pharmacokinetic process of methotrexate, including genetic and nongenetic factors. METHODS: We investigated the genetic factors primarily related to the metabolic pathway of methotrexate in children with acute lymphoblastic leukemia with delayed elimination, defined as C44-48h ≥ 1.0µmol/L in this study. A total of 196 patients (delayed excretion group: 98; normal excretion group: 98) who received CCCG-ALL-2015 protocol after propensity score-matched analysis were included in the study. Twenty-eight target single-nucleotide polymorphisms (SNPs) were analyzed by multiplex polymerase chain reaction and sequencing, and 25 SNPs were finally included in the study. RESULTS: The genotype distribution of SLCO1B1 rs2306283 SNP was different between the delayed and normal excretion groups. SLCO1B1 rs2306283 AA carriers had a significantly lower methotrexate C44-48h /D ratio than GG carriers in both groups. Furthermore, compared with the normal excretion group, SLCO1B1 rs2306283 AG and GG were risk factors for developing oral mucositis (odds ratio [OR]: 2.13; 95% confidence interval [CI]: 1.11-4.08; P < .001), hepatotoxicity (OR: 2.12; 95% CI: 1.26-3.56; P < .001), and myelosuppression (OR: 1.21; 95% CI: 1.04-1.41; P = .005) in delayed excretion group. CONCLUSIONS: The results from this study indicate the potential role of SLCO1B1 rs2306283 as a pharmacogenomic marker to guide and optimize methotrexate treatment for delayed elimination in children with acute lymphoblastic leukemia.

Involvement of chemosensory proteins in host plant searching in the bird cherry-oat aphid.

Chemosensory systems are considered to play an important role in host plant selection in herbivorous insects. However, few studies have focused on chemosensory proteins (CSPs) for aphid host-location mechanisms. The roles of CSPs in searching for different Poaceae species (wheat, barley, triticale, maize and sorghum) were tested in Rhopalosiphum padi, an important cereal pest. The olfactometer assays showed that R. padi responds to plant odors. Seven R. padi CSP genes were identified. Influence of aphid morph, tissue and starvation state on expression patterns of CSPs was evaluated. Expression levels of CSP1, CSP4, CSP5 and CSP6 in winged aphids were significantly higher than those in wingless ones. Transcription levels of four genes (CSP1, CSP4, CSP5 and CSP6) were relatively higher in the head with antennae, and the four genes tended to be upregulated following starvation. Silencing of three CSPs (CSP4, CSP5 and CSP6) altered aphid host-location behavior in response to the five different host plants tested. Three volatile compounds of host plants (octanal, [E]-2-hexenol and linalool) have significant attraction to winged R. padi according to the four-arm olfactometer tests. Molecular docking predicted hydrogen bonding sites which played key roles in the binding of CSP4, CSP5 and CSP6 with volatile compounds. Knockdown of CSP4 or CSP5 significantly decreased the staying time of R. padi in the arms with octanal. However, knockdown of CSP6 could not affect the response of R. padi to octanal. These results bring evidence for the involvement of three CSPs in R. padi host-location behavior.

Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 as a biomarker of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) greatly contributes to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. Expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was substantially raised in the basilar arterial wall of SAH rabbits. We attempted to ascertain the relationship between serum soluble LOX-1 (sLOX-1) levels and the occurrence of DCI after aSAH. MATERIALS AND METHODS: We enrolled 125 aSAH patients and 125 healthy controls. Serum sLOX-1 levels were quantified using commercial enzyme-linked immunosorbent assay kit. The relationship between sLOX-1 levels and DCI was analyzed utilizing the multivariate logistic regression analysis. RESULTS: Serum sLOX-1 levels were significantly higher in stroke patients than in controls (median: 1,450.2 vs. 445.7 pg/ml, p < .001). Serum sLOX-1 levels were highly correlated with World Federation of Neurological Surgeons (WFNS) scores, Hunt-Hess scores, and modified Fisher scores (r = .574, .625, and .569, respectively). Forty-two patients (33.6%) experienced DCI. Serum sLOX-1 > 1,450.2 pg/ml, WFNS scores and modified Fisher scores were the independent predictors of DCI. Under receiver operating characteristic curve, serum sLOX-1 levels exhibited a significant discriminatory capability (area under curve 0.825, 95% confidence interval 0.747-0.887). The predictive power of serum sLOX-1 levels was similar to those of WFNS scores and modified Fisher grade (both p > .05). Moreover, serum sLOX-1 levels significantly improved their predictive capability (both p < .05). CONCLUSIONS: Serum soluble LOX-1, in positive association with hemorrhagic severity, appears to have the potential to become a promising predictor of DCI after aSAH.

Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 concentrations and prognosis of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) and its receptor, lectin-like ox-LDL receptor-1 (LOX-1) are involved in the pathogenesis of atherosclerosis. Expression of LOX-1 was substantially raised in the basilar arterial wall of subarachnoid hemorrhage (SAH) rabbits. We ascertained the relationship between serum soluble LOX-1 concentrations and functional outcome after human aneurysmal SAH. METHODS: We enrolled 94 aneurysmal SAH patients and 94 healthy controls. Serum soluble TOX-1 concentrations were quantified using commercial enzyme-linked immunosorbent assay kit. A poor outcome was defined as Glasgow outcome scale score of 1-3. RESULTS: Median values of serum soluble LOX-1 in stroke patients were significantly higher than those in controls (1.5 vs. 0.4 ng/ml, P < 0.001). Thirty patients (31.9%) had a poor outcome at 6 months after stroke. Serum soluble LOX-1 was a strong predictor of poor outcome (OR 5.20, 95% CI 1.25-22.04). Serum soluble LOX-1 concentrations exhibited a significant discriminatory capability (area under curve 0.811, 95% confidence interval 0.717-0.884). The predictive powers of World Federation of Neurological Surgeons grade, Hunt-Hess grade, modified Fisher grade, and serum soluble LOX-1 concentrations were comparable (all P > 0.05). CONCLUSIONS: Serum soluble LOX-1 appears to have the potential to become a promising prognostic predictor after human aneurysmal SAH.

Macrophage migration inhibitory factor levels in serum from patients with acute intracerebral hemorrhage: Potential contribution to prognosis.

BACKGROUND: Intracerebral hemorrhage (ICH) pathophysiology involves inflammation. Macrophage migration inhibition factor (MIF), a pro-inflammatory cytokine, is related to prognosis of ischemic stroke. The aim of this study was to investigate whether serum MIF levels are associated with severity and outcomes in patients with acute ICH. METHODS: We enrolled a total of 120 consecutive ICH patients and 120 healthy controls and sampled blood on admission and at study entry respectively. Enzyme-linked immunosorbent assay was used to quantify serum MIF levels. RESULTS: Serum MIF levels were higher in patients compared with controls and correlated with hematoma volume, National Institutes of Health Stroke Scale (NIHSS) scores and plasma C-reactive protein levels. After adjusting for other significant outcome predictors, MIF in serum was an independent predictor of 6-month overall survival and unfavorable outcome (modified Rankin Scale score >2). Areas under receiver-operating characteristic curve (ROC) of serum MIF levels, hematoma volume and NIHSS scores were similar for 6-month unfavorable outcome. Moreover, serum MIF levels significantly improved areas under ROC of hematoma volume and NIHSS scores. CONCLUSIONS: MIF in serum might be a potential biomarker for reflecting inflammation, severity and prognosis of ICH patients.

Folate-conjugated and pH-responsive polymeric micelles for target-cell-specific anticancer drug delivery.

In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. In this system, FA was attached to the terminal of the hydrophilic segment of poly(lactic acid)-poly(L-lysine) (PLA-PLL), and PLL was modified by a citric acid group. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency. STATEMENT OF SIGNIFICANCE: Negatively charged nano-carriers prolonged anti-cancer drugs' blood circulation. However it is difficult to be internalised. Therefore, a negative-to-positive charged micelle surface could improve selectivity for tumour cells and increase uptake chance. In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency.

Geographical Variations in the Life Histories of Rhopalosiphum padi (Hemiptera: Aphididae) in China.

Population dynamics of an insect can be affected by its life-history traits. Understanding of the life-history variations among geographical populations of an insect pest is important for developing the corresponding control strategies in different regions. Rhopalosiphum padi is a cosmopolitan cereal pest, and life-history traits identification of R. padi from different geographical regions is rare. Here, we experimentally evaluated variations in the life histories and life-table parameters of R. padi populations from six widely ranging geographical regions, including Baoding (HB), Xianyang (SX), Nanyang (HN), Wuhan (HW), Beibei (CB), and Guiyang (GG), in China. Total longevity was similar for HB, CB, and GG populations and generally shorter than that of the SX, HN, and HW populations. The age at first reproduction of HB and HW populations was significantly different from that of the other four populations. Mean fecundity of the SX population was significantly higher than that of the other five populations, and the mean fecundity of the GG population was the lowest. Principal component analysis (PCA) also showed that the life-history and life-table parameters of R. padi differed among the six geographical populations. According to PCA results, the HW population was in one cluster; the GG population was in another cluster; the SX, HN, and CB populations were in one cluster; and the HB population differed from the above three clusters. The complexity of local genetic adaptation in aphids was discussed. The current results will likely be of importance to management practices and population dynamics forecasting of R. padi.

Diagnostic and prognostic value of serum vitronectin levels in human glioma.

OBJECTIVE: Vitronectin is an extracellular matrix protein, the synthesis of which by glioma cells correlates with tumor grade. The current study was designed to investigate the relationship between serum vitronectin levels and clinicopathological characteristics, diagnosis and prognosis in glioma patients. METHODS: In a prospective observatory study, a total of 98 glioma patients, 98 healthy controls, 98 other non-glioma brain tumors, and 98 other non-tumor neurological diseases were recruited. Following univariate analyses, multivariate analyses were performed to explore the associations of serum vitronectin levels with survival and clinicopathological parameters. Receiver operating characteristic curve analysis was done to assess its diagnostic and prognostic predictive value. RESULTS: Serum vitronectin levels were significantly elevated in glioma patients as compared with other groups. High Wealth Health Organization grade was independently associated with high vitronectin levels. Serum vitronectin levels could significantly distinguish glioma patients from other groups and discriminate high-grade glioma from low-grade glioma. Vitronectin levels markedly predicted 5-year progression and 5-year mortality. Moreover, serum vitronectin was identified as an independent predictor for 5-year overall survival and 5-year progression-free survival as well as 5-year mortality and 5-year progression. CONCLUSION: Serum vitronectin may be a promising diagnostic and prognostic biomarker that can be detected in the peripheral blood of patients with glioma.

MOLECULAR CLONING, EXPRESSION PATTERN OF MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 1 (MRP1, ABCC1) GENE, AND THE SYNERGISTIC EFFECTS OF VERAPAMIL ON TOXICITY OF TWO INSECTICIDES IN THE BIRD CHERRY-OAT APHID.

The ATP-binding cassette (ABC) transporters are important transmembrane proteins encoded by a supergene family. The majority of ABC proteins are primary active transporters that bind and hydrolyze ATP to mediate the efflux of a diverse range of substrates across lipid membranes. In this study, we cloned and characterized a putative multidrug resistance associated protein 1 (MRP1) from Rhopalosiphum padi encoded by ABCC1. Structural analysis showed that this protein has structural features typical of the ABC transporter family. Phylogenetic analysis indicated that the amino acid sequence was highly similar that of the corresponding protein from Acyrthosiphon pisum. Real-time quantitative polymerase chain reaction (PCR) analysis showed that ABCC1 was expressed throughout all R. padi developmental stages, with the highest level of expression in the fourth larval instar. We also examined ABCC1 expression in four different tissue types and found that it was most highly expressed in the midgut. Exposing R. padi to imidacloprid and chlorpyrifos increased ABCC1 expression. Furthermore, ABCC1 expression was higher in the imidacloprid-resistant (IR) and chlorpyrifos-resistant (CR) strains than in an insecticide-susceptible strain (SS) of R. padi. Exposing R. padi to verapamil in combination with insecticides significantly increased the toxicity of the insecticides. The respective synergy factor of CR and IR R. padi strain was 1.33 and 1.26, which was lower than that (2.72 and 1.64, respectively) of the SS. Our results clarify the biological function of ABCC1 in R. padi, particularly its role in insecticide resistance, and suggest novel strategies for pest management that use ABC transporter inhibitors to increase the effectiveness of insecticides.

The prognostic value of plasma soluble CD40 ligand levels following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Increased circulating soluble CD40 ligand (sCD40L) levels have been reported to be associated with severity and mortality of severe traumatic brain injury. The current study tested the hypothesis that elevated plasma sCD40L levels are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Plasma sCD40L concentrations of 120 aSAH patients and 120 healthy volunteers were measured using enzyme-linked immunosorbent assay. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. RESULTS: Plasma sCD40L levels were significantly elevated in aSAH patients compared with healthy controls; plasma sCD40L levels were highly associated with clinical severity reflected by World Federation of Neurological Surgeons (WFNS) score and Fisher score; sCD40L emerged as an independent predictor of 6-month mortality and unfavorable outcome and 6-month overall survival; although a combined logistic-regression model did not demonstrate the additive benefit of sCD40L to WFNS score and Fisher score, sCD40L possessed similar predictive value to WFNS score and Fisher score based on receiver operating characteristic curves. CONCLUSIONS: Higher plasma sCD40L levels on presentation are associated with clinical severity and have potential to be a good prognostic biomarker of aSAH.

Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery.

Copeptin can reflect individual's stress state and are correlated with poor outcome of critical illness. The occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD) is associated with worse outcome after coronary artery bypass graft (CABG) surgery. The present study aimed to investigate the ability of postoperative plasma copeptin level to predict POD and POCD in patients undergoing CABG surgery. Postoperative plasma copeptin levels of 108 patients were measured by an enzyme-linked immunosorbent assay. It was demonstrated that plasma copeptin levels were substantially higher in patients with POD than without POD (1.8±0.6 ng/mL vs. 1.1±0.3 ng/mL; P<0.001) and in patients with POCD than without POCD (1.9±0.6 ng/mL vs. 1.1±0.4 ng/mL; P<0.001). Plasma copeptin level and age were identified as independent predictors for POD [odds ratio (OR), 67.386; 95% confidence interval (CI), 12.031-377.426; P<0.001 and OR, 1.202; 95% CI, 1.075-1.345; P=0.001] and POCD (OR, 28.814; 95% CI, 7.131-116.425; P<0.001 and OR, 1.151; 95% CI, 1.030-1.285; P=0.003) using a multivariate analysis. For prediction of POD, the area under receiver operating characteristic curve (AUC) of the copeptin concentration (AUC, 0.883; 95% CI, 0.807-0.937) was markedly higher than that of age (AUC, 0.746; 95% CI, 0.653-0.825; P=0.020). For prediction of POCD, the AUC of the copeptin concentration (AUC, 0.870; 95% CI, 0.792-0.927) was markedly higher than that of age (AUC, 0.735; 95% CI, 0.641-0.815; P=0.043). Thus, postoperative plasma copeptin level may be a useful, complementary tool to predict POD and POCD in patients undergoing CABG surgery.

Identification of plasma adrenomedullin as a possible prognostic biomarker for aneurysmal subarachnoid hemorrhage.

Increased plasma adrenomedullin levels have been reported in critically ill patients. This study tested the hypothesis that plasma adrenomedullin levels are significantly increased in patients with acute spontaneous aneurysmal subarachnoid hemorrhage, and are predictive of clinical outcomes. Plasma adrenomedullin levels from 120 adult patients with spontaneous aneurysmal subarachnoid hemorrhage and 120 healthy volunteers during the study period were evaluated. Mortality and poor long-term outcome (Glasgow Outcome Scale score of 1-3) at 6 months were recorded. Data showed that circulating plasma adrenomedullin levels significantly increased in patients on admission compared with the volunteers. In patients who died or had poor outcome at 6 months, plasma adrenomedullin levels were significantly higher compared with survivors and patients with good outcome. Plasma adrenomedullin levels on presentation were highly associated with clinical severity assessed using World Federation of Neurological Surgeons score and Fisher score, emerged as the independent risk factor of 6-month mortality and poor outcome, and possessed similar predictive value to World Federation of Neurological Surgeons score and Fisher score based on receiver operating characteristic curves. A combined logistic-regression model did not demonstrate the additive benefit of adrenomedullin to World Federation of Neurological Surgeons score and Fisher score. Thus, higher plasma adrenomedullin levels on presentation are associated with clinical severity and worse outcomes in patients with acute spontaneous aneurysmal subarachnoid hemorrhage.