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Background: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive., Methods: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis., Results: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure., Conclusions: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

By experimental methods, 26 specimens were designed to conduct elastic and elastic-plastic buckling tests on cylindrical shells containing cracks. This study discusses the influence of factors such as the length-diameter ratio, the diameter-thickness ratio, the crack length, the inclination of the crack, etc., on the buckling load. Additionally, finite element models were established to compare with experimental results. For the PMMA cylindrical shell, the results showed that as the length-diameter ratio of the cylindrical shell increased, the buckling load first decreased and then increased. For the 6063 aluminum alloy cylindrical shell, with increasing length-diameter ratio, diameter-thickness ratio, and crack length of the cylindrical shell, the buckling load decreased accordingly. However, concerning the crack inclination, as the crack inclination increased, the buckling load increased accordingly. This indicates that the larger the crack inclination, the higher the load capacity of the cylindrical shell containing cracks. Through finite element simulations of cylindrical shells with cracks, it was found that through compressive mechanical properties, both elastic and elastic-plastic buckling loads yielded results that are closer to the experimental results. Additionally, the inclusion of contact effects in numerical simulations further improved the agreement with the experimental results, and the variation trend of the buckling load in the finite element simulation was consistent with the experimental results. The research findings provide valuable references for the assessment of load capacity in structures containing cracks.

Based on fracture mechanics theory, a finite element method was used to determine the stress intensity factors of the inclined crack on the inner surface of the pipe under axial compression load and external pressure. The effects of different influencing factors on the stress intensity factor along the crack front considering crack closure were systematically explored, which were different to those under internal pressure. The effects of high aspect ratio on K II , the crack inclination asymmetry caused by curvature and the effects of the friction coefficient on the stress intensity factors of the pipe with an inclined inner surface crack under axial compression load and external pressure were explored in this paper. To be fit for defect assessment, the solutions for stress intensity factors K II and K III were derived, and new correction factors f θ and f μ were proposed in the empirical solutions to accommodate the crack inclination asymmetry and the friction coefficient, respectively.

Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca 2+ ([Ca 2+ ] i ) and the third component of complement (C3) were increased in 4-AP-induced mice and astrocytes. Perturbations in the immune microenvironment in the brain were balanced by TRPV4 inhibition or the manipulation of [Ca 2+ ] i  in astrocytes. Knocking down YAP with siRNA significantly inhibited 4-AP-induced pathological changes in astrocytes. Our study demonstrated that astrocytic TRPV4 activation promoted neuroinflammation through the TRPV4/Ca 2+ /YAP/STAT3 signaling pathway in mice with seizures. Astrocyte TRPV4 inhibition attenuated neuroinflammation, reduced neuronal injury, and improved neurobehavioral function. Targeting astrocytic TRPV4 activation may provide a promising therapeutic approach for managing epilepsy., (© 2022. The American Society for Experimental NeuroTherapeutics, Inc.)

Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma (NKTL) treatment. However, these chemotherapy regimens inevitably cause relatively high incidence of treatment-related adverse events (TRAEs). Herein we retrospectively evaluated the efficacy and safety of the combined regimen of anti-PD-1 antibody, anlotinib and pegaspargase "sandwich" with radiotherapy in localized NKTL. Anti-PD-1 antibody and pegaspargase at 2500 U/m 2 were administered on day 1, while anlotinib (12 mg once a day) was orally administered on days 1-14. The treatment was repeated every 3 weeks. All the eight patients included received 3 cycles of the regimen followed by radiotherapy and an additional 3 cycles. The overall response rate was 100%, and the complete response rate was 87.5%. With a median follow-up time of 35.5 months (range, 34.03-40.90 months), median PFS and OS times were not reached. The 3-year PFS and OS rates were 100% and 100%, respectively. All patients were alive at the last follow-up. No treatment-related death and no grade 4 TRAE was reported. No grade 3/4 hematological toxicity was detected, and half of the patients didn't report any hematological toxicity. This study indicates that anti-PD-1 antibody combined with anlotinib and pegaspargase is a promising chemoradiotherapy regimen for localized NTKL, with mild toxicity and good tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Wang, Yang, Chen, Nie, Sun, He, Huang, Huang and Li.)

Background: For foamy virus, the transactivator of spumaretrovirus (Tas) could bind directly to target DNA sequences termed as Tas responsive elements and trigger the viral internal promoter (IP) and long terminal repeat (LTR) promoters. The cellular endogenous factors also play an important role in viral gene expressions. We hypothesized that except the viral transcription factor Tas, the cellular endogenous factors also affect the viral gene expression., Methods: The full length of the prototype foamy virus (PFV) genome (U21247) was used to predict the potential binding sites of the transcription factors by online software JASPAR (http://jaspar.genereg.net) and Softberry (http://linux1.softberry.com/berry.phtml?topic=index&group=programs&subgroup=promoter). The Dual-Luciferase® Reporter Assay System (Promega, USA) was used to confirm the relative luciferase activities of the test groups. The different representative activating agents or inhibitors of each canonical signal pathway were used to identify the impact of these pathways on PFV 5'LTR and IP promoters., Results: The results showed different cellular endogenous factors might have respective effects on PFV 5'LTR and IP. It is worth mentioning that activator protein-1 and BCL2-associated athanogene 3, 2 kinds of vital proteins associated with NF-κB and PKC pathways, could activate the basal activity of 5'LTR and IP promoters but inhibit the Tas-regulated activity of both promoters. Furthermore, PFV Tas was identified to trigger the transcription of the NF-κB promoter., Conclusion: NF-κB had a negative effect on PFV 5'LTR and IP promoter activities, the PKC pathway might upregulate 5'LTR and IP promoter activities, and the JNK and NF-AT signal pathway could increase the Tas-regulated promoter activity of PFV 5'LTR. This study sheds light on the interaction between PFV and the host cell and may help utilize the viral promoters in retroviral vectors designed for gene transfer experiments., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders., (© 2021. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

The morphology and ultrastructure of the compound eye of the predatory bug, Montandoniola moraguesi (Puton, 1986) was investigated using scanning and transmission electron microscopy. Its compound eyes, which contain ∼195 ommatidia per eye, have the following characteristics: each ommatidium possesses a laminated corneal lens measuring ∼9 μm in diameter and ∼7 μm in thickness, a tetrapartite eucone crystalline cone, which is approximately 5.5 μm long, like a dumbbell with the distal end larger than the proximal end, eight clustered retinula cells ∼25.6 μm in length, two primary pigment cells and eight secondary primary pigment cells. The rhabdomeres of the eight retinula cells form a circular, tiered rhabdom of two elongated and six peripheral retinula cells. The rhabdomeres of cells R7 and R8 are distributed along the basolateral surface of the cone and form a centrally-fused rhabdom that spans nearly the full length of the ommatidium. The microvilli of the peripheral rhabdom (R1-R6) are radially arranged and form a bilobed, V-like shape in the central rhabdom. Based on the similarity of the compound eye of M. moraguesi to the eyes of other predatory insect species, the evolution and function of eyes in predators are briefly discussed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Diffuse large B cell lymphoma (DLBCL) with MYC rearrangement or double expression of MYC and BCL-2 (DE DLBCL) has a relatively poor prognosis and does not respond well to standard R-CHOP. In the current study, we aimed to investigate the efficacy and safety of R-split-EPOCH plus high dose methotrexate (HD-MTX) in the particular patient population. Methods: A total of 28 patients diagnosed with DE DLBCL or DLBCL with MYC rearrangement between January 2015 and December 2018 were included and retrospectively analyzed. All the participants underwent R-split-EPOCH plus HD-MTX as introduction therapy, with split infusion of etoposide, doxorubicin, and vincristine for 48 hours on D1-2 and D10-11, respectively. Results: The overall objective response (ORR) rate was 100%, with 24 (85.7%) complete response (CR) and 4 (14.3%) partial response (PR). The CR rate was 76.9% and 93.3% for DLBCL patients with MYC rearrangement and DE DLBCL patients, respectively. The 1- and 3-year PFS rate was 100% and 74.9%, respectively. The 1- and 3-year OS rate was 100% and 92.9%, respectively. Grade 3/4 non-hematological toxicity and grade 3/4 hematological toxicity occurred in 50% and 85.7% of patients, respectively. No treatment-related death was reported. Conclusions: R-split-EPOCH plus HD-MTX regimen is an effective and feasible treatment option for DE DLBCL and DLBCL with MYC rearrangement., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus model through QPCR analysis. Astrocytes polarizing toward neurotoxic A1 phenotype and neurons loss were observed after status epilepticus. Through injecting circIgf1r siRNA into the lateral ventricle, it was found that knocking down circIgf1r in vivo would induce the polarization of astrocytes to phenotype A2 and reduce neuronal loss. The results in vitro further confirmed that inhibiting the expression of circIgf1r in astrocytes could protect neurons by converting reactive astrocytes from A1 to the protective A2. In addition, knocking down circIgf1r in astrocytes could functionally promote astrocyte autophagy and relieve the destruction of 4-AP-induced autophagy flux. In terms of mechanism, circIgf1r promoted the polarization of astrocytes to phenotype A1 by inhibiting autophagy. Taken together, our results reveal circIgf1r may serve as a potential target for the prevention and treatment of neuron damage after epilepsy., (© 2021 Federation of American Societies for Experimental Biology.)

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

[Purpose] This study aimed to explore whether trunk kinesiology taping (KT) can improve trunk function, mobility, and balance in post-stroke patients with hemiparesis. [Participants and Methods] We conducted a single-group pre-post design pilot feasibility study. Thirteen individuals with post-stroke hemiplegia were recruited for this study. All patients received therapeutic trunk KT on the skin, representing the direction of fibres of the trunk muscles underneath. We used the Trunk Impairment Scale (TIS) and Trunk Control Test (TCT) to measure trunk function, Fugl-Meyer assessment (FMA) for balance, limits of stability (LOS) to evaluate balance, and the modified Rivermead mobility index (MRMI) to assess mobility in post-stroke patients. All measures were assessed before and immediately after the intervention. [Results] No adverse effects were found and all patients completed the trial. Compared to the baseline, TIS scores were significantly increased after KT, whereas no changes in TCT score were detected. The directional control of LOS was significantly improved, while no significant changes were seen in the other parameters of LOS, FMA-balance, and MRMI scores. [Conclusion] The results of this investigation show that trunk KT has immediate effects that improve certain trunk functional and balance parameters in stroke patients., Competing Interests: We declare that we have no conflicts of interest in this work., (2020©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication with severe long-term sequelae such as cerebral palsy, epilepsy and cognitive disabilities. Na + -K + -2Cl - cotransporters 1 (NKCC1) is dramatically upregulated after hypoxia-ischemia (HI), which aggravates brain edema and brain damage. Clinically, an NKCC1-specific inhibitor, bumetanide, is used to treat diseases related to aberrant NKCC1 expression, but the underlying mechanism of aberrant NKCC1 expression has rarely been studied in HIE. In this study, the cooperative effect of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor of activated T cells 5 (NFAT5) on NKCC1 expression was explored in hippocampal neurons under hypoxic conditions. HI increased HIF-1α nuclear localization and transcriptional activity, and pharmacological inhibition of the HIF-1α transcription activity or mutation of hypoxia responsive element (HRE) motifs recovered the hypoxia-induced aberrant expression and promoter activity of NKCC1. In contrast, oxygen-glucose deprivation (OGD)-induced downregulation of NFAT5 expression was reversed by treating with hypertonic saline, which ameliorated aberrant NKCC1 expression. More importantly, knocking down NFAT5 or mutation of the tonicity enhancer element (TonE) stimulated NKCC1 expression and promoter activity under normal physiological conditions. The positive regulation of NKCC1 by HIF-1α and the negative regulation of NKCC1 by NFAT5 may serve to maintain NKCC1 expression levels, which may shed light on the transcription regulation of NKCC1 in hippocampal neurons after hypoxia., (Copyright © 2019 Yang, Zeng, Shao, Jiang, Cheng, Chen, Han, Yin, Liu, He and Peng.)

Background: Neonatal hypoxic-ischemic brain damage (HIBD), a leading cause of neonatal mortality, has intractable sequela such as epilepsy that seriously affected the life quality of HIBD survivors. We have previously shown that ion channel dysfunction in the central nervous system played an important role in the process of HIBD-induced epilepsy. Therefore, we continued to validate the underlying mechanisms of TRPV1 as a potential target for epilepsy., Methods: Neonatal hypoxic ischemia and oxygen-glucose deprivation (OGD) were used to simulate HIBD in vivo and in vitro. Primarily cultured astrocytes were used to assess the expression of TRPV1, glial fibrillary acidic protein (GFAP), cytoskeletal rearrangement, and inflammatory cytokines by using Western blot, q-PCR, and immunofluorescence. Furthermore, brain electrical activity in freely moving mice was recorded by electroencephalography (EEG). TRPV1 current and neuronal excitability were detected by whole-cell patch clamp., Results: Astrocytic TRPV1 translocated to the membrane after OGD. Mechanistically, astrocytic TRPV1 activation increased the inflow of Ca 2+ , which promoted G-actin polymerized to F-actin, thus promoted astrocyte migration after OGD. Moreover, astrocytic TRPV1 deficiency decreased the production and release of pro-inflammatory cytokines (TNF, IL-6, IL-1β, and iNOS) after OGD. It could also dramatically attenuate neuronal excitability after OGD and brain electrical activity in HIBD mice. Behavioral testing for seizures after HIBD revealed that TRPV1 knockout mice demonstrated prolonged onset latency, shortened duration, and decreased seizure severity when compared with wild-type mice., Conclusions: Collectively, TRPV1 promoted astrocyte migration thus helped the infiltration of pro-inflammatory cytokines (TNF, IL-1β, IL-6, and iNOS) from astrocytes into the vicinity of neurons to promote epilepsy. Our study provides a strong rationale for astrocytic TRPV1 to be a therapeutic target for anti-epileptogenesis after HIBD.

Background: Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication with high incidence in both advanced and developing countries. Children surviving from HIE often have severe long-term sequela including cerebral palsy, epilepsy, and cognitive disabilities. The severity of HIE in infants is tightly associated with increased IL-1β expression and astrocyte activation which was regulated by transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel in the TRP family., Methods: Neonatal hypoxic ischemia (HI) and oxygen-glucose deprivation (OGD) were used to simulate HIE in vivo and in vitro. Primarily cultured astrocytes were used for investigating the expression of glial fibrillary acidic protein (GFAP), IL-1β, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and activation of the nucleotide-binding, oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome by using Western blot, q-PCR, and immunofluorescence. Brain atrophy, infarct size, and neurobehavioral disorders were evaluated by Nissl staining, 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining and neurobehavioral tests (geotaxis reflex, cliff aversion reaction, and grip test) individually., Results: Astrocytes were overactivated after neonatal HI and OGD challenge. The number of activated astrocytes, the expression level of IL-1β, brain atrophy, and shrinking infarct size were all downregulated in TRPV1 KO mice. TRPV1 deficiency in astrocytes attenuated the expression of GFAP and IL-1β by reducing phosphorylation of JAK2 and STAT3. Meanwhile, IL-1β release was significantly reduced in TRPV1 deficiency astrocytes by inhibiting activation of NLRP3 inflammasome. Additionally, neonatal HI-induced neurobehavioral disorders were significantly improved in the TRPV1 KO mice., Conclusions: TRPV1 promotes activation of astrocytes and release of astrocyte-derived IL-1β mainly via JAK2-STAT3 signaling and activation of the NLRP3 inflammasome. Our findings provide mechanistic insights into TRPV1-mediated brain damage and neurobehavioral disorders caused by neonatal HI and potentially identify astrocytic TRPV1 as a novel therapeutic target for treating HIE in the subacute stages (24 h).

Aim: Multiple sclerosis (MS) is a neurological autoimmune disorder characterized by mistaken attacks of inflammatory cells against the central nervous system (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can inhibit T-cell activation and have been designed for MS therapy. However, little is known about the effects of Kv1.3 blockers on protecting myelin sheaths/axons in MS. This study aimed at investigating the neuroprotection efficacy of a selective Kv1.3 channel blocker ImKTx88 (ImK) in MS animal model., Methods: Experimental autoimmune encephalomyelitis (EAE) rat model was established. The neuroprotective effect of ImK was assessed by immunohistochemistry and transmission electron microscopy (TEM). In addition, the antiinflammatory effect of ImK by suppressing T-cell activation was assessed by flow cytometry and ELISA in vitro., Results: Our results demonstrated that ImK administration ameliorated EAE clinical severity. Moreover, ImK increased oligodendrocytes survival, preserved axons, and myelin integrity and reduced the infiltration of activated T cells into the CNS. This protective effect of the peptide may be related to its suppression of autoantigen-specific T-cell activation via calcium influx inhibition., Conclusion: ImK prevents neurological damage by suppressing T-cell activation, suggesting the applicability of this peptide in MS therapy., (© 2018 John Wiley & Sons Ltd.)

Background: Neonatal hypoxic-ischemic brain damage, characterized by tissue loss and neurologic dysfunction, is a leading cause of mortality and a devastating disease of the central nervous system. We have previously shown that vitexin has been attributed various medicinal properties and has been demonstrated to have neuroprotective roles in neonatal brain injury models. In the present study, we continued to reinforce and validate the basic understanding of vitexin (45 mg/kg) as a potential treatment for epilepsy and explored its possible underlying mechanisms., Methods: P7 Sprague-Dawley (SD) rats that underwent right common carotid artery ligation and rat brain microvascular endothelial cells (RBMECs) were used for the assessment of Na + -K + -Cl - co-transporter1 (NKCC1) expression, BBB permeability, cytokine expression, and neutrophil infiltration by western blot, q-PCR, flow cytometry (FCM), and immunofluorescence respectively. Furthermore, brain electrical activity in freely moving rats was recorded by electroencephalography (EEG)., Results: Our data showed that NKCC1 expression was attenuated in vitexin-treated rats compared to the expression in the HI group in vivo. Oxygen glucose deprivation/reoxygenation (OGD) was performed on RBMECs to explore the role of NKCC1 and F-actin in cytoskeleton formation with confocal microscopy, N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide, and FCM. Concomitantly, treatment with vitexin effectively alleviated OGD-induced NKCC1 expression, which downregulated F-actin expression in RBMECs. In addition, vitexin significantly ameliorated BBB leakage and rescued the expression of tight junction-related protein ZO-1. Furthermore, inflammatory cytokine and neutrophil infiltration were concurrently and progressively downregulated with decreasing BBB permeability in rats. Vitexin also significantly suppressed brain electrical activity in neonatal rats., Conclusions: Taken together, these results confirmed that vitexin effectively alleviates epilepsy susceptibility through inhibition of inflammation along with improved BBB integrity. Our study provides a strong rationale for the further development of vitexin as a promising therapeutic candidate treatment for epilepsy in the immature brain.

Neonatal hypoxic-ischemic is a major cause of death and disability in neonates. In this study, we suggest for the first time that pretreatment with vitexin may suppress a pro-apoptotic signaling pathway in hypoxic-ischemic neuronal injury in neonates by inhibition of the phosphorylation of Ca2+/Calmodulin-dependent protein kinase II. Here we found that vitexin pretreatment reduced brain infarct volume in a dose-dependent manner. In addition, vitexin decreased the number of TUNEL-positive cells and brain atrophy. Furthermore, vitexin improved neurobehavioral outcomes. Vitexin also reduced oxygen glucose deprivation-induced neuronal injury and calcium entry. Vitexin pretreatment increased the Bcl-2/Bax protein ratio and decreased phosphorylation of Ca2+/Calmodulin-dependent protein kinase II and NF-κB, cleaved caspase-3 protein expression 24 hours after injury. Our data indicate that pretreatment with vitexin protects against neonatal hypoxic-ischemic brain injury and thus has potential as a treatment for hypoxic-ischemic brain injury.

Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na + -K + -Cl - -co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR. Brain electrical activity in freely rats was monitored by electroencephalography (EEG) recordings. HI-induced neurogenesis was detected by immunofluorescence staining. Neurobehavioral test was to investigate the neuro-protective role of bumetanide, an inhibitor of NKCC1, on neonatal rats after HI. The results showed that bumetanide treatment significantly reduced brain electrical activity and the seizure stage of epilepsy induced by pentylenetetrazol (PTZ) in vivo after HI. In addition, bumetanide restored aberrant hippocampal neurogenesis and associated cognitive function. Our data demonstrated that bumetanide reduces the susceptibility of epilepsy induced by PTZ in rats suffering from HI injury during neonatal period via restoring the ectopic newborn neurons in dentate gyrus (DG) and cognitive function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Vitexin and isovitexin are active components of many traditional Chinese medicines, and were found in various medicinal plants. Vitexin (apigenin-8-C-glucoside) has recently received increased attention due to its wide range of pharmacological effects, including but not limited to anti-oxidant, anti-cancer, anti-inflammatory, anti-hyperalgesic, and neuroprotective effects. Isovitexin (apigenin-6-C-glucoside), an isomer of vitexin, generally purified together with vitexin, also exhibits diverse biological activities. Latest research has suggested that vitexin and isovitexin could be potential substitute medicines for diversity diseases, and may be adjuvants for stubborn diseases or health products. This review summarized recent findings on various pharmacological activities and associative signalling pathways of vitexin and isovitexin to provide a reference for future research and clinical applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Previous studies have demonstrated that the early suppression of HIF-1α after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1α inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood-brain barrier (BBB) integrity, brain edema, HIF-1α and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1α by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1α and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1α inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To observe the effect of acupuncture stimulation of acupoints of the Conception Vessel, Kidney Meridian, Spleen Meridian, and Bladder Meridian on menstrual cycles and duration, and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estrogen 2 (E(2)) levels in patients with diminished ovarian reserve (DOR)., Methods: A total of 96 patients with DOR of both yin and yang deficiency were randomly divided into medication group and acupuncture group (n = 48 cases in each group). Patients of the medication group were treated by Estradiol Valerate tablets, 2 mg/d on the first 10 days, and Estradiol Cyproterone, 3 mg/d from day 11 to 21, followed by 5 -7 days' rest, and the next therapeutic course, continuously for 6 months. For patients of the acupuncture group, filiform acupuncture needles were separately inserted into every 5 points of the Conceptional Vessel, Kidney, Spleen and Bladder Meridians, manipulated with uniform reinforcing and reducing methods till Deqi, and retained for 40 min. The treatment was conducted once daily for consecutive 10 days in one menstrual cycle, beginning from the 10(th) day on after menstruation, which was repeated for 6 months. The integrative scores (normal = 0, mild=2, moderate=4 and severe=6 points) of menstrual cycle, menstrual duration, amount, color, quality [blood blot or ame- nia, symptoms of traditional Chinese medicine (TCM)] were assessed according to "Guiding Principles for Clinical Trials of New Drugs of Chinese Materia Medica". Serum FSH, LH and E(2) contents were detected by Roche's electrochemical luminescence method., Results: After the treatment, of the two 48 cases in the medication and acupuncture groups, 12 (25.0%) and 20 (4.7) were cured, 11 (22.9 %) and 12 (25.0 %) experienced marked improvement in their symptoms, 20 (41.7%) and 10 (20.8%) were effective, and 5 (10.4%) and 6 (12.5%) failed, with the effective rate being 89.6% and 87.5%, respectively. The integral score of TOM symptoms, menstrual cycle, serum FSH, LH and E2 contents were considerably diminished in both groups after 6 months of treatment (P<0.05), and the TOM symptom score, menstrual cycle, and serum FSH, LH and E2 levels were significantly lower in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05), while the menstrual duration in each cycle was notably longer in both groups after the treatment, and evidently longer in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05). No significant differences were found between the two groups in the effective rate, score of TOM symptoms, menstrual cycle and duration, and serum FSH, LH and E(2) contents following the treatment (P>0.05)., Conclusion: Acupuncture stimulation of acupoints of the Conception Vessel, Kidney, Spleen, and Bladder Meridians is effective in improving clinical symptoms of DOR patients with deficiency of both yin and yang, and has a longer effect, which may be closely associated with its functions in lowering serum FSH, LH and E(2) levels through regulating the hypothalamic-pituitary-ovarian axis.

Background: Existing literature has shown that patients with coronary artery disease (CAD) can benefit greatly from the strength training; therefore, the strength training should play a more important role in cardiac rehabilitation. However, the medical community may still have conservation to apply the strength training owing to no comprehensive study so far to compare the effectiveness of the strength training to the other trainings, such as aerobic training., Objective: To evaluate the effect of strength training on motor function in patients with CAD., Methods: Published articles from the earliest date available to July 2015 were identified using electronic searches. Two reviewers selected independently relevant randomized controlled trials (RCTs) investigating exercise program with strength training versus control interventions (exercise without strength training, including aerobic training and no exercise group) for the treatment of CAD patients. We examined effects of exercise with strength training versus control interventions on peak oxygen uptake (VO2peak), duration of exercise test and muscle strength. Two reviewers extracted data independently., Results: Twenty seven trials that represented 1151 participants passed the selection criteria and were evaluated for the effects of strength training in CAD patients. For improving VO2peak [SMD (95%CI) = 0.58 (0.11, 1.06)] and muscle strength [upper limb, SMD (95% CI) =0.44 (0.34, 0.55); lower limb, SMD (95% CI) =0.33 (0.16, 0.50)], exercise program with strength training were significantly more effective than one without it. But there is no significantly difference on duration of exercise test [SMD (95%CI) = 0.17 (-0.04, 0.39)] in strength training group than in control group., Conclusions: We conclude strength training is effective in improving muscle strength and VO2peak, in CAD patients, when compared to patients with control group. Furthermore, our evaluations suggest that strength training does not compromise clinical trial completion or safety.

Febrile seizure (FS) is the most common seizure disorder in children, and children with FS are regarded as a high risk for the eventual development of epilepsy. Brain inflammation may be implicated in the mechanism of FS. Transient receptor potential vanilloid 1 (TRPV1) is believed to act as a monitor and regulator of body temperature. The role of inflammation in synaptic plasticity mediation indicates that TRPV1 is relevant to several nervous system diseases, such as epilepsy. Here, we report a critical role for TRPV1 in a febrile seizure mouse model and reveal increased levels of pro-inflammatory factors in the immature brain. Animals were subjected to hyperthermia for 30 min, which generates seizures lasting approximately 20 min, and then were used for experiments. To invoke frequently repetitive febrile seizures, mice are exposed to hyperthermia for three times daily at an interval of 4h between every time induced seizure, and a total of 4 days to induce. Behavioral testing for febrile seizures revealed that a TRPV1 knock-out mouse model demonstrated a prolonged onset latency and a shortened duration and seizure grade of febrile seizure when compared with wild type (WT) mice. The expression levels of both TRPV1 mRNA and protein increased after a hyperthermia-induced febrile seizure in WT mice. Notably, TRPV1 activation resulted in a significant elevation in the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and HMGB1) in the hippocampus and cortex. These data indicate that the reduction of TRPV1 expression parallels a decreased susceptibility to febrile seizures. Thus, preventative strategies might be developed for use during febrile seizures., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both development and function of the brain. Down-regulation of GABAergic inhibition may result in the generation of epileptiform activity. Loss, axonal sprouting, and dysfunction of interneurons are regarded as mechanisms involved in epileptogenesis. Recent evidence suggests that network connectivity and the properties of interneurons are responsible for excitatory-inhibitory neuronal circuits. The balance between excitation and inhibition in CA1 neuronal circuitry is considerably altered during epileptic changes. This review discusses interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the possibility of using GABAergic neuronal progenitors for the treatment of epilepsy.

Gene therapy has promised to be a highly effective antitumor treatment by introducing a tumor suppressor gene or the abrogation of an oncogene. Among the potential therapeutic transgenes, the tumor suppressor gene p53 serves as an attractive target. Restoration of wild-type p53 function in tumors can be achieved by introduction of an intact complementary deoxyribonucleic acid copy of the p53 gene using a suitable viral vector, in most cases an adenoviral vector (Adp53). Preclinical in vitro and in vivo studies have shown that Adp53 triggers a dramatic tumor regression response in various cancers. These viruses are engineered to lack certain early proteins and are thus replication defective, including Gendicine, SCH-58500, and Advexin. Several types of tumor-specific p53-expressing conditionally replicating adenovirus vectors (known as replication-competent CRAdp53 vectors) have been developed, such as ONYX 015, AdDelta24-p53, SG600-p53, OBP-702, and H101. Various clinical trials have been conducted to investigate the safety and efficiency of these adenoviral vectors. In this review we will talk about the biological mechanisms, clinical utility, and therapeutic potentials of the replication-deficient Adp53-based and replication-competent CRAdp53-based gene therapy.

We previously observed that A-type potassium currents were decreased and membrane excitability increased in hippocampal dentate granule cells after neonatal global hypoxia associated with seizures. Here, we studied the effects of hypoxia on the function and expression of Kv4.2 and Kv4.3 α subunit channels, which encode rapidly inactivating A-type K currents, in transfected HEK-293 cells to determine if hypoxia alone could regulate IA in vitro. Global hypoxia in neonatal rat pups resulted in early decreased hippocampal expression of Kv4.2 mRNA and protein with 6 or 12 h post-hypoxia. Whole-cell voltage-clamp recordings revealed that similar times after hypoxia (1%) in vitro decreased peak currents mediated by recombinant Kv4.2 but not Kv4.3 channels. Hypoxia had no significant effect on the voltage-dependencies of activation and inactivation of Kv4.2 channels, but increased the time constant of activation. The same result was observed when Kv4.2 and Kv4.3 channels were co-expressed in a 1:1 ratio. These data suggested that hypoxia directly modulates A-type potassium channels of the subfamily typically expressed in principal hippocampal neurons, and does so in a manner to decrease function. Given the role of IA to slow action potential firing, these data are consistent with a direct effect of hypoxia to decrease IA as a mechanism of increased neuronal excitability and promotion of seizures.

This study examined whether a novel imidazoline I₂ receptor ligand CR4056 could serve as a discriminative stimulus and whether it shares similar discriminative stimulus effects with other reported I₂ receptor ligands. Eight male Sprague-Dawley rats were trained to discriminate 10.0 mg/kg CR4056 (i.p.) from vehicle in a two-lever food-reinforced drug discrimination procedure. Once rats acquired the discrimination, substitution and combination studies were conducted to elucidate the underlying receptor mechanisms. All rats acquired CR4056 discrimination after an average of 26 training sessions. Several I₂ receptor ligands (phenyzoline, tracizoline, RS45041, and idazoxan, 3.2-75 mg/kg, i.p.) all occasioned > 80% CR4056-associated lever responding. Other drugs that occasioned partial or no CR4056-associated lever responding included methamphetamine, ketamine, the endogenous imidazoline ligand agmatine, the monoamine oxidase (MAO) inhibitor harmane, the α₂-adrenoceptor agonist clonidine, the μ-opioid receptor agonists morphine and methadone, and the selective I₂ receptor ligands BU224 and 2-BFI. The α₁ adrenoceptor antagonist WB4101, α₂ adrenoceptor antagonist yohimbine and μ-opioid receptor antagonist naltrexone failed to alter the stimulus effects of CR4056. Together, these results show that CR4056 can serve as a discriminative stimulus in rats, which demonstrates high pharmacological specificity and appears to be mediated by imidazoline I₂ receptors.

Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Transient receptor potential vanilloid 1 (TRPV1) channel has been found to be expressed in a variety of tissues over the last few years, including the central nervous system (CNS). However, the distribution of TRPV1 in the CNS remains a controversial question. Here, we reveal that the expression of TRPV1 can be detected in the C57BL/6 mouse hippocampus and cortex using real-time PCR and western blot. Beyond that, mRNA and protein expression levels of TRPV1 show dynamic changes during brain development. Compared with the earliest timepoint examined at 2 weeks, the expression levels of mRNA progressively increased at 4 and 8 weeks, peaking at the later timepoint, then declined at 16 weeks but remained elevated. However, compared with 2-week-old mice, the expression levels of the other three groups (4-, 8-, and 16-week-old mice) increased overall. These results indicate that TRPV1 channel expression is detectable in the CNS and it varies during postnatal development.

This study was designed to investigate the role of experimental febrile seizures in the induction of generalized clonic seizures and the involvement of heat-sensitive channel TRPV1. Pentylenetetrazol-induced clonic seizure was used as the seizure model, and Trpv1 gene knock-out and wild-type C57/BL6 mice were used as experimental subjects. Electroencephalograph and seizure behavior were recorded for the evaluation of the severity of seizures. Increased frequency of the experimental febrile seizures facilitated PTZ-induced generalized clonic seizures. Trpv1 gene deficiency decreased the properties of generalized clonic seizure. The intensity of experimental febrile seizures reduced the threshold to generalized clonic seizure, and Trpv1 gene deficiency decreased the susceptibility to PTZ-induced seizures following early-life hyperthermia challenges in mice., (© 2013.)

The transient receptor potential vanilloid 1(TRPV1) channels are members of the transient receptor potential (TRP) superfamily. Members of this family are expressed in primary sensory neurons and are best known for their role in nociception and sensory transmission. Multiple painful stimuli can activate these channels. In this review, we discussed the mechanisms of different types of venoms that target TRPV1, such as scorpion venom, botulinum neurotoxin, spider toxin, ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning (NSP). Some of these toxins activate TRPV1; however, some do not. Regardless of TRPV1 inhibition or activation, they occur through different pathways. For example, BoNT/A decreases TRPV1 expression levels by blocking TRPV1 trafficking to the plasma membrane, although the exact mechanism is still under debate. Vanillotoxins from tarantula (Psalmopoeus cambridgei) are proposed to activate TRPV1 via interaction with a region of TRPV1 that is homologous to voltage-dependent ion channels. Here, we offer a description of the present state of knowledge for this complex subject., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: Cerebral hypoxia is a major cause of neonatal seizures, and can lead to epilepsy. Pathologic anatomic and physiologic changes in the dentate gyrus have been associated with epileptogenesis in many experimental models, as this region is widely believed to gate the propagation of limbic seizures. However, the consequences of hypoxia-induced seizures for the immature dentate gyrus have not been extensively examined., Methods: Seizures were induced by global hypoxia (5-7% O2 for 15 min) in rat pups on postnatal day 10. Whole-cell voltage-clamp recordings were used to examine A-type potassium currents (IA ) in dentate granule cells in hippocampal slices obtained 1-17 days after hypoxia treatment., Key Findings: Seizure-inducing hypoxia resulted in decreased maximum IA amplitude in dentate granule cells recorded within the first week but not at later times after hypoxia treatment. The decreased IA amplitude was not associated with changes in the voltage-dependence of activation or inactivation removal, or in sensitivity to inhibition by 4-aminopyridine (4-AP). However, consistent with the role of IA in shaping firing patterns, we observed in the hypoxia group a significantly decreased latency to first spike with depolarizing current injection from hyperpolarized potentials. These differences were not associated with changes in resting membrane potential or input resistance, and were eliminated by application of 10 m 4-AP., Significance: Given the role of IA to slow action potential firing, decreased IA could contribute to long-term hippocampal pathology after neonatal seizure-inducing hypoxia by increasing dentate granule cell excitability during a critical window of activity-dependent hippocampal maturation., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

To determine the immune function of Taishan Robinia pseudoacacia Polysaccharide (TRPPS) on chickens, 240 chickens were selected as experimental animals and treated with various doses of TRPPS by hypodermic injection before immunized NDV inactivated vaccine. The results indicated that any dose of TRPPS could significantly promote the development of the immune organs, increase the quantity of leukocyte and the ratio of lymphocyte, and improve the antibody titers against Newcastle disease. Meanwhile, it also increased the magnitude of SIgA in duodenum. However, the dose of 200 mg/ml showed to be the most effective. Therefore, in terms of improving immunologic function and production performance, TRPPS could be used as a vaccine immunopotentiator for immune responses., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

The voltage-gated Kv1.3 K(+) channel in effector memory T cells serves as a new therapeutic target for multiple sclerosis. In our previous studies, the novel peptide ADWX-1 was designed and synthesized as a specific Kv1.3 blocker. However, it is unclear if and how ADWX-1 alleviates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. In this study, the administration of ADWX-1 significantly ameliorated the rat experimental autoimmune encephalomyelitis model by selectively inhibiting CD4(+)CCR7(-) phenotype effector memory T cell activation. In contrast, the Kv1.3-specific peptide had little effect on CD4(+)CCR7(+) cells, thereby limiting side effects. Furthermore, we determined that ADWX-1 is involved in the regulation of NF-κB signaling through upstream protein kinase C-θ (PKCθ) in the IL-2 pathway of CD4(+)CCR7(-) cells. The elevated expression of Kv1.3 mRNA and protein in activated CD4(+)CCR7(-) cells was reduced by ADWX-1 engagement; however, an apparent alteration in CD4(+)CCR7(+) cells was not observed. Moreover, the selective regulation of the Kv1.3 channel gene expression pattern by ADWX-1 provided a further and sustained inhibition of the CD4(+)CCR7(-) phenotype, which depends on the activity of Kv1.3 to modulate its activation signal. In addition, ADWX-1 mediated the activation of differentiated Th17 cells through the CCR7(-) phenotype. The efficacy of ADWX-1 is supported by multiple functions, which are based on a Kv1.3(high) CD4(+)CCR7(-) T cell selectivity through two different pathways, including the classic channel activity-associated IL-2 pathway and the new Kv1.3 channel gene expression pathway.

Febrile seizures (FSs) are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β (IL-1β) is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs.

Foamy virus can establish lifelong persistent infection in mammal hosts without inducing diseases. Such special characteristic stimulates the interests of researchers. As reported, the accessory protein Bet of foamy virus could regulate the gene expression and infection cycle of foamy virus and take part in the generation of chronic viral infection. And also, Bet might prevent the host cellular defense factor APO-BEC3 from interfering the replication of virus and play a role in maintaining viral persistent infection. In order to elucidate the roles of Bet in the foamy virus replication and infection, this review summarized the research progress of Bet protein reported in recent years.

One of the most fascinating findings in retrovirology is the construction of viral vectors based on foamy viruses (FVs) for gene therapy. The envelope glycoprotein (Env), one of the structural proteins of FV, is an important antigen in the immunoassays, as it is highly specific. To compare the characteristics of all 15 available FV Envs, the phylogenesis, hydrophobicity, modifications, and conserved motifs were analyzed based on the Env sequences. Meanwhile, the secondary structures of transmembrane (TM) domains of FV Envs were predicted. The results of phylogenetic analyses based on Envs indicated that the foamy viruses from different hosts could form three groups. The hydrophobicity analysis revealed that FV Envs had two prominent hydrophobic regions, which was similar to other retroviruses. Though the glycosylation, ubiquitination, and the secondary structures of TM domains of FV Envs were in line with other retroviruses, the roles were distinctly different. Interestingly, the analyses of conserved motifs suggested that FV Envs possessed several specific functional motifs.

Aim: To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy., Methods: Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin (OXA) alone, or a combination of both. Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry., Results: Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose-dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells. Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompanied by increased expression of caspase-3., Conclusion: rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.

The H-current (I(H)) regulates membrane electrical activity in many excitable cells. The antiepileptic drug gabapentin (GBP) has been shown to increase I(H) in hippocampal area CA1 pyramidal neurons, and this has been proposed as an anticonvulsant mechanism of action. I(H) also regulates excitability in some types of hippocampal interneuron that provide synaptic inhibition to CA1 pyramidal neurons, suggesting that global pharmacological I(H) enhancement could have more complex effects on the local synaptic network. However, whether I(H) in CA1 interneurons is modulated by GBP has not been examined. In this study, we tested the effects of GBP on I(H) on hippocampal area CA1 stratum oriens non-pyramidal neurons, and on spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in immature rat brain slices. GBP (100μM) increased I(H) in approximately 67% of interneurons that exhibited I(H), with no apparent effect on cell types that did not exhibit I(H). GBP also increased the frequency of spontaneous (but not miniature) inhibitory postsynaptic currents in pyramidal neurons without altering amplitudes or rise and decay times. These data indicate that I(H) in a subset of CA1 interneuron types can be increased by GBP, similarly to its effect on I(H) in pyramidal neurons, and further, that indirectly increased spontaneous inhibition of pyramidal neurons could contribute to its anticonvulsant effects., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The hyperpolarization-activated cation current (I(H)) regulates the electrical activity of many excitable cells, but its precise function varies across cell types. The antiepileptic drug lamotrigine (LTG) was recently shown to enhance I(H) in hippocampal CA1 pyramidal neurons, showing a potential anticonvulsant mechanism, as I(H) can dampen dendrito-somatic propagation of excitatory postsynaptic potentials in these cells. However, I(H) is also expressed in many hippocampal interneurons that provide synaptic inhibition to CA1 pyramidal neurons, and thus, I(H) modulation may indirectly regulate the inhibitory control of principal cells by direct modulation of interneuron activity. Whether I(H) in hippocampal interneurons is sensitive to modulation by LTG, and the manner by which this may affect the synaptic inhibition of pyramidal cells has not been investigated. In this study, we examined the effects of LTG on I(H) and spontaneous firing of area CA1 stratum oriens interneurons, as well as on spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons in immature rat brain slices. LTG (100 microM) significantly increased I(H) in the majority of interneurons, and depolarized interneurons from rest, promoting spontaneous firing. LTG also caused an increase in the frequency of spontaneous (but not miniature) IPSCs in pyramidal neurons without significantly altering amplitudes or rise and decay times. These data indicate that I(H) in CA1 interneurons can be increased by LTG, similarly to I(H) in pyramidal neurons, that I(H) enhancement increases interneuron excitability, and that these effects are associated with increased basal synaptic inhibition of CA1 pyramidal neurons.

Objective: To investigate the infection of HEV in Quzhou area of Zhejiang Province., Methods: All sera from blood donors in the central blood bank of Quzhou from April 2006 to April 2007 were used. Anti-HEV IgG and anti-HEV IgM were measured by EIA. RT-PCR was also performed to the samples with positive anti-HEV IgM. Genotype and sequence homology were analyzed after sequencing., Results: The positive ratio of anti-HEV IgG was 40.60%, in which the male infection ratio was higher than the female significantly (43.09% VS 36.09%; chi2=22.6; P < 0.01). The infection ratio was increased with age. The positive ratio of anti-HEV IgM was 0.43%. The positive ratio of anti-HEV IgG and the titers of antibody were higher in the inferior clinical infectors with positive anti-HEV IgM than the negative ones (P < 0.05). Two samples were positive in HEV PCR among 21 samples with positive anti-HEV IgM. The toxemia ratio was 0.4% of all the donors. And the genotype of the two samples with toxemia were both HEV-IV., Conclusion: The HEV infection was correlation with age and sex significantly and the infection occurred in the adults mainly in Quzhou area. HEV toxemia was not infrequency in the blood donors.

Background & Objective: Accurate target localization is the essential requirement in the quality control in fractionated stereotactic radiotherapy (FSRT). This paper is to analyze the magnitude of errors in FSRT for head and neck carcinoma including the errors of CT localization, mechanical isocenter, setup of patients, and CT image., Methods: The stereotactic radiotherapy treatment planning system (SRT-TPS), target simulator and head frame were used to check the errors of target localization during each radiation procedure. Five reference points were set randomly; the CT localization error was measured using the target simulator. Seven different mechanical angles of Gantry/Table were selected; the magnitude of isocentric errors of Philips SL-18 linear accelerator were acquired with films. Setup errors were collected by portal films. The image error possibly from CT image artifact was analyzed after scanning a self-made phantom by CT., Results: The CT localization error was(1.5+/-0.4)mm. The maximal error of the mechanical isocenter was (1.0+/-0.6)mm according to the different mechanical gantry/table angles. The distance error of patient setup was (1.0+/-0.3)mm. The maximal total errors estimate was (2.1+/-0.8)mm., Conclusions: The effect of target localization of every procedure should be taken in account in FSRT, the results of the error analysis can be used to determinate the planning target volume in the treatment.

From a cDNA library of Chinese scorpion Buthus martensii Karsch, full-length cDNAs of 351 nucleotides encoding precursors (named BmKIM) that contain signal peptides of 21 amino acid residues, a mature toxin of 61 residues with four disulfide bridges, and an extra Gly-Lys-Lys tail, were isolated. The genomic sequence of BmKIM was cloned and sequenced; it consisted of two exons disrupted by an intron of 1622 bp, the largest known in scorpion toxin genomes, inserted in the region encoding the signal peptide. The cDNA was expressed in Escherichia coli. The recombinant BmKIM was toxic to both mammal and insects. This is the first report that a toxin with such high sequence homology with an insect-specific depressant toxin group exhibits toxicity to mammals. Using whole cell patch-clamp recording, it was discovered that the recombinant BmKIM inhibited the sodium current in rat dorsal root ganglion neurons and ventricular myocytes and protected against aconitine- induced cardiac arrhythmia.