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Acute liver failure (ALF) is a life-threatening disease and affects multiple organ systems. Pro-inflammatory factors derived from macrophage plays a key role in septicemia. Pinocembrin is a natural favonoid compound, which can be extracted from honey, propolis and several other plants. Recent investigations demonstrate that Pinocembrin has a variety of pharmacological activities, including anti-inflammatory and antioxidant. To investigate the effects of Pinocembrin on ALF, we explored its possible molecular mechanisms through the experiments in vivo and in vitro. Pre-treatment with Pinocembrin attenuated LPS-induced hepatocyte dysfunction and reduced levels of pro-inflammatory factors and macrophages infiltration. Pinocembrin inhibited the hepatocyte apoptosis and pro-inflammatory reaction of peritoneal macrophages by reducing reactive oxygen species (ROS) via the Sirt1/PPARα signaling pathway. Our study suggests that Pinocembrin might represent a novel therapeutic drug and offers a new method for the treatment of ALF., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. It is well known that PKM2 plays a vital role in the proliferation of tumor cells. However, PKM2 can also exert its biological functions by mediating multiple signaling pathways in neurological diseases, such as Alzheimer's disease (AD), cognitive dysfunction, ischemic stroke, post-stroke depression, cerebral small-vessel disease, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, Parkinson's disease (PD), epilepsy, neuropathic pain, and autoimmune diseases. In these diseases, PKM2 can exert various biological functions, including regulation of glycolysis, inflammatory responses, apoptosis, proliferation of cells, oxidative stress, mitochondrial dysfunction, or pathological autoimmune responses. Moreover, the complexity of PKM2's biological characteristics determines the diversity of its biological functions. However, the role of PKM2 is not entirely the same in different diseases or cells, which is related to its oligomerization, subcellular localization, and post-translational modifications. This article will focus on the biological characteristics of PKM2, the regulation of PKM2 expression, and the biological role of PKM2 in neurological diseases. With this review, we hope to have a better understanding of the molecular mechanisms of PKM2, which may help researchers develop therapeutic strategies in clinic. [ABSTRACT FROM AUTHOR]

Copyright of Traditional Chinese Drug Research & Clinical Pharmacology is the property of Traditional Chinese Drug Research & Clinical Pharmacology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ischemic stroke is a common acute cerebrovascular disease in clinical practice， which poses a severe threat to human health. In recent years， with deepening understanding of ischemic stroke， significant progress has been made in the diagnosis and treatment. However， current treatments for ischemic stroke are partially limited due to extremely complex pathological mechanisms. Studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of ischemic stroke. Therefore， modulation of mitochondrial function through mitochondrial dynamics is essential to ameliorate the damage of cerebral ischemic neuronal cells. In this article， the molecular mechanism of mitochondrial dynamics and its role in ischemic stroke were reviewed， aiming to provide useful reference for the treatment of ischemic stroke.

Background: This study investigated the contact between adult dental pulp stem cells (DPSCs) and carbamide peroxide (CP), a bleaching agent that is a popular choice for at-home whitening products, using an in vitro model. Objectives: The aim of this study was to evaluate the impact of exposure to different concentrations and timings of a commonly used peroxide-based home tooth-whitening product on DPSCs. Materials and methods: Human DPSCs obtained from impacted third molars were cultured and exposed to various concentrations of carbamide peroxide (0.1%, 0.5%, and 1%). The effects of CP on DPSC proliferation and apoptosis were investigated by MTT assay and flow cytometry. Migration was investigated by micrographs of wound healing. An enzyme-linked immunosorbent assay (IL-6 and IL-8) was used to investigate the CP-stimulated cytokine production of DPSCs. Each experiment was performed three times with independent batches of DPSCs. Statistical analysis of the collected data was performed using one-way and two-way ANOVAs with the significance threshold set at p < 0.05. Tukey's post hoc multiple comparison test was used to identify differences between groups. Results: Cell viability and adherence were lower in the CP-exposed cells compared to the non-stimulated cells, probably due to increased cell death (** p ≤ 0.01, **** p ≤ 0.0001). CP-stimulated DPSCs exhibited a dose-dependent release of IL-6 and IL-8 (**** p ≤ 0.0001). CP did not affect wound healing at any concentration tested. Conclusions: Human DPSCs were able to sense CP. Consequently, CP contributed significantly to cell apoptosis and local inflammatory responses through cytokine release. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a common acute cerebrovascular disease in clinical practice, which poses a severe threat to human health. In recent years, with deepening understanding of ischemic stroke, significant progress has been made in the diagnosis and treatment. However, current treatments for ischemic stroke are partially limited due to extremely complex pathological mechanisms. Studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of ischemic stroke. Therefore, modulation of mitochondrial function through mitochondrial dynamics is essential to ameliorate the damage of cerebral ischemic neuronal cells. In this article, the molecular mechanism of mitochondrial dynamics and its role in ischemic stroke were reviewed, aiming to provide useful reference for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is one of the leading causes of death and morbidity worldwide. As a novel form of cell death, ferroptosis is an important mechanism of ischemic stroke. Nuclear factor E2-related factor 2 (Nrf2) is the primary regulator of cellular antioxidant response. In addition to alleviating ischemic stroke nerve damage by reducing oxidative stress, Nrf2 regulates genes associated with ferroptosis, suggesting that Nrf2 may inhibit ferroptosis after ischemic stroke. However, the specific pathway of Nrf2 on ferroptosis in the field of ischemic stroke remains unclear. Therefore, this paper provides a concise overview of the mechanisms underlying ferroptosis, with a particular focus on the regulatory role of Nrf2. The discussion highlights the potential connections between Nrf2 and the mitigation of oxidative stress, regulation of iron metabolism, modulation of the interplay between ferroptosis and inflammation, as well as apoptosis. This paper focuses on the specific pathway of Nrf2 regulation of ferroptosis after ischemic stroke, providing scientific research ideas for further research on the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: This study investigated the contact between adult dental pulp stem cells (DPSCs) and carbamide peroxide (CP), a bleaching agent that is a popular choice for at-home whitening products, using an in vitro model. Objectives: The aim of this study was to evaluate the impact of exposure to different concentrations and timings of a commonly used peroxide-based home tooth-whitening product on DPSCs. Materials and methods: Human DPSCs obtained from impacted third molars were cultured and exposed to various concentrations of carbamide peroxide (0.1%, 0.5%, and 1%). The effects of CP on DPSC proliferation and apoptosis were investigated by MTT assay and flow cytometry. Migration was investigated by micrographs of wound healing. An enzyme-linked immunosorbent assay (IL-6 and IL-8) was used to investigate the CP-stimulated cytokine production of DPSCs. Each experiment was performed three times with independent batches of DPSCs. Statistical analysis of the collected data was performed using one-way and two-way ANOVAs with the significance threshold set at p < 0.05. Tukey’s post hoc multiple comparison test was used to identify differences between groups. Results: Cell viability and adherence were lower in the CP-exposed cells compared to the non-stimulated cells, probably due to increased cell death (** p ≤ 0.01, **** p ≤ 0.0001). CP-stimulated DPSCs exhibited a dose-dependent release of IL-6 and IL-8 (**** p ≤ 0.0001). CP did not affect wound healing at any concentration tested. Conclusions: Human DPSCs were able to sense CP. Consequently, CP contributed significantly to cell apoptosis and local inflammatory responses through cytokine release.

Simple Summary: Soy antigen proteins are regarded as the cause of fish enteritis, of which glycinin is one of the main soy antigen proteins. By comparing different levels of glycinin within a high-soybean-meal diet, we found that dietary high glycinin (10%) could decrease hepatic antioxidant ability, lead to microbiota dysbiosis, and change the relative abundance of some intestinal microbiota and intestinal morphology, thereby causing intestinal inflammation. The results showed that dietary high glycinin (10%) may be the potential trigger of soybean-induced enteritis of orange-spotted grouper (Epinephelus coioides). The aim of the study was to investigate whether the negative effects of dietary glycinin are linked to the structural integrity damage, apoptosis promotion and microbiota alteration in the intestine of orange-spotted grouper (Epinephelus coioides). The basal diet (FM diet) was formulated to contain 48% protein and 11% lipid. Fish meal was replaced by soybean meal (SBM) in FM diets to prepare the SBM diet. Two experimental diets were prepared, containing 4.5% and 10% glycinin in the FM diets (G-4.5 and G-10, respectively). Triplicate groups of 20 fish in each tank (initial weight: 8.01 ± 0.10 g) were fed the four diets across an 8 week growth trial period. Fish fed SBM diets had reduced growth rate, hepatosomatic index, liver total antioxidant capacity and GSH-Px activity, but elevated liver MDA content vs. FM diets. The G-4.5 exhibited maximum growth and the G-10 exhibited a comparable growth with that of the FM diet group. The SBM and G-10 diets down-regulated intestinal tight junction function genes (occludin, claudin-3 and ZO-1) and intestinal apoptosis genes (caspase-3, caspase-8, caspase-9, bcl-2 and bcl-xL), but elevated blood diamine oxidase activity, D-lactic acid and endotoxin contents related to intestinal mucosal permeability, as well as the number of intestinal apoptosis vs FM diets. The intestinal abundance of phylum Proteobacteria and genus Vibrio in SBM diets were higher than those in groups receiving other diets. As for the expression of intestinal inflammatory factor genes, in SBM and G-10 diets vs. FM diets, pro-inflammatory genes (TNF-α, IL-1β and IL-8) were up-regulated, but anti-inflammatory genes (TGF-β1 and IL-10) were down-regulated. The results indicate that dietary 10% glycinin rather than 4.5% glycinin could decrease hepatic antioxidant ability and destroy both the intestinal microbiota profile and morphological integrity through disrupting the tight junction structure of the intestine, increasing intestinal mucosal permeability and apoptosis. These results further trigger intestinal inflammatory reactions and even enteritis, ultimately leading to the poor growth of fish. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common disabling disease which has a high incidence rate in the elderly. Studies have found that many factors are involved in the pathogenesis of OA. Hypoxia-inducible factors (HIFs) are core regulators that induce hypoxia genes, repair the cellular oxygen environment, and play an important role in the treatment of OA. For example, HIF-1α can maintain the stability of the articular cartilage matrix, HIF-2α is able to cause chondrocyte apoptosis and intensify in-flammatory response, and HIF-3α may be the target gene of HIF-1α and HIF-2α, thereby playing a negative regulatory role. This review examines the mechanism of HIFs in cartilage extracellular matrix degradation, apoptosis, inflammatory reaction, autophagy and then further expounds on the roles of HIFs in OA, consequently providing theoretical support for the pathogenesis of OA and a new target for OA treatment. [ABSTRACT FROM AUTHOR]

Extensive environmental pollution by microplastics has increased the risk of human exposure to plastics. However, the biosafety of polypropylene microplastics (PP-MPs), especially of PP particles < 10 μm, in mammals has not been studied. Thus, here, we explored the mechanism of action and effect of exposure to small and large PP-MPs, via oral ingestion, on the mouse intestinal tract. Male C57BL/6 mice were administered PP suspensions (8 and 70 μm; 0.1, 1.0, and 10 mg/mL) for 28 days. PP-MP treatment resulted in inflammatory pathological damage, ultrastructural changes in intestinal epithelial cells, imbalance of the redox system, and inflammatory reactions in the colon. Additionally, we observed damage to the tight junctions of the colon and decreased intestinal mucus secretion and ion transporter expression. Further, the apoptotic rate of colonic cells significantly increased after PP-MP treatment. The expression of pro-inflammatory and pro-apoptosis proteins significantly increased in colon tissue, while the expression of anti-inflammatory and anti-apoptosis proteins significantly decreased. In summary, this study demonstrates that PP-MPs induce colonic apoptosis and intestinal barrier damage through oxidative stress and activation of the TLR4/NF-κB inflammatory signal pathway in mice, which provides new insights into the toxicity of MPs in mammals. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate whether the negative effects of dietary glycinin are linked to the structural integrity damage, apoptosis promotion and microbiota alteration in the intestine of orange-spotted grouper (Epinephelus coioides). The basal diet (FM diet) was formulated to contain 48% protein and 11% lipid. Fish meal was replaced by soybean meal (SBM) in FM diets to prepare the SBM diet. Two experimental diets were prepared, containing 4.5% and 10% glycinin in the FM diets (G-4.5 and G-10, respectively). Triplicate groups of 20 fish in each tank (initial weight: 8.01 ± 0.10 g) were fed the four diets across an 8 week growth trial period. Fish fed SBM diets had reduced growth rate, hepatosomatic index, liver total antioxidant capacity and GSH-Px activity, but elevated liver MDA content vs. FM diets. The G-4.5 exhibited maximum growth and the G-10 exhibited a comparable growth with that of the FM diet group. The SBM and G-10 diets down-regulated intestinal tight junction function genes (occludin, claudin-3 and ZO-1) and intestinal apoptosis genes (caspase-3, caspase-8, caspase-9, bcl-2 and bcl-xL), but elevated blood diamine oxidase activity, D-lactic acid and endotoxin contents related to intestinal mucosal permeability, as well as the number of intestinal apoptosis vs FM diets. The intestinal abundance of phylum Proteobacteria and genus Vibrio in SBM diets were higher than those in groups receiving other diets. As for the expression of intestinal inflammatory factor genes, in SBM and G-10 diets vs. FM diets, pro-inflammatory genes (TNF-α, IL-1β and IL-8) were up-regulated, but anti-inflammatory genes (TGF-β1 and IL-10) were down-regulated. The results indicate that dietary 10% glycinin rather than 4.5% glycinin could decrease hepatic antioxidant ability and destroy both the intestinal microbiota profile and morphological integrity through disrupting the tight junction structure of the intestine, increasing intestinal mucosal permeability and apoptosis. These results further trigger intestinal inflammatory reactions and even enteritis, ultimately leading to the poor growth of fish.

Objective To explore the effect of miR-133a-3p on the apoptosis and inflammatory response of bronchial epithelial cells infected by respiratory syncytial virus (RSV) and its regulatory effect on CD2-associated protein (CD2AP). Methods The bronchial mucosal tissue specimens from 59 children with bronchial asthma were collected as the AsP group and 59 bronchial mucosal tissue specimens from non-asthmatic children with bronchiec- tasis were selected as the NC group. RT-qPCR method was used to detect the expression of miR-133a-3p and CD2AP in the tissues. RSV infected bronchial epithelial cells (16-HBE) were used to establish a cell injury model (RSV group). miR-NC, miR-133a-3p mimics, si-NC, si-CD2AP, pcDNA-NC, pcDNA-CD2AP, miR-133a-3p mimics and pcDNA-NC, miR-133a-3p mimics and pcDNA-CD2AP were respectively transferred into 16-HBE cells infected with RSV. RT-qPCR and Western blot were used to detect the expression of miR-133a-3p and CD2AP in the cells. ELISA was used to detect the level of TNF-α, IL-6, and IL-1α. Flow cytometry was used to detect apoptosis . The dual luciferase reporter experiment was used to detect the targeting relationship between miR-133a-3p and CD2AP. Western blot method was used to detect the protein expression of cleaved-caspase-3. Results Compared with NC group, the expression of miR-133a-3p in the bronchial mucosa tissue of the AsP group was decreased (P＜0.05), and the expression of CD2AP mRNA was increased (P＜0.05). The expression of miR-133a-3p in RSV-infected 16-HBE cells was decreased (P＜0.05), and the expression level of CD2AP, TNF-α, IL-6 and IL-1α was increased (P＜0.05), the apoptosis rate and the protein level of cleaved-caspase-3 were increased(P＜0.05). Transfection of miR-133a-3p mimics or transfection of si-CD2AP into RSV-infected 16-HBE cells significantly reduced the level of TNF-α, IL-6, IL-1α, the apoptosis rate and the protein level of cleaved-caspase-3 (P＜0.05). The dual luciferase report experiment confirmed that CD2AP was the target gene of miR-133a-3p. Co-transfection of miR-133a-3p mimics and pcDNA-CD2AP significantly reversed the effects of miR-133a-3p mimics transfection on 16-HBE cell apoptosis and inflammation. Conclusions The over-expression of miR-133a-3p inhibits the inflammatory response and apoptosis of RSV-infected bronchial epithelial cells by negatively regulating the expression of CD2AP and thereby reducing cell damage.

The aim of this study was to investigate the damage caused to HaCaT cells by 60Co γ-rays at different doses and the underlying mechanism and to establish a cell model of radiation-induced skin injury. HaCaT cells were irradiated with a single dose of 60Co γ-rays (the radiation source was 3 m away from the cells, and the dose rate was 100.68 cGy/min). The cell activity was detected using the CCK-8 method, the vitality of superoxide dismutase (SOD) was measured using the water soluble tetrazolium salt staining method, the malondialdehyde (MDA) level was determined using the thiobarbituric acid method, the apoptosis rate was monitored through flow cytometry, and the expression of the apoptosis- and inflammation-related proteins was detected via western blotting. After irradiation with 60Co γ-rays at 18 Gy for 24 h, the morphology of HaCaT cells changed significantly, cell activity decreased to 57.5%, MDA level increased to 66.28 µmol/mg, inhibition rate of SOD increased to 32.12%, apoptosis rate increased to 18.05%, and expression of inflammatory factors increased. After incubation for 24 h at an absorbed dose of 18 Gy, the cellular models of radiation-induced skin injury were established. The mechanism of cell injury may be related to cell oxidative damage, apoptosis, and inflammatory reaction.

Yishen Gushu Formula (YSGSF) is composed of Epimedium, prepared Rehmannia, Drynaria, Eucommia, Dodder, ginseng, Astragalus, Ligusticum wallichii, Aucklandia and Panax notoginseng. It can improve bone mineral density by regulating bone metabolism. However, the mechanism of YSGSF in the treatment of Postmenopausal osteoporosis (PMOP) remains unclear. The compounds, targets, and molecular mechanisms of YSGSF in the treatment of PMOP were investigated using broad-spectrum target metabolomics from plants, combined with network pharmacology and animal studies, leading to a discussion on a novel approach to understanding YSGSF's action in PMOP treatment. Using ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) within a comprehensive targeted metabolomics framework, the active constituents of YSGSF were identified. This, alongside network pharmacology and molecular docking, facilitated the identification of critical signaling pathways and targets pertinent to YSGSF's therapeutic effect on PMOP. Subsequently, an animal model for PMOP was developed. Following intervention grouping, rats' weight changes were recorded; serum bone metabolic factors were assessed via ELISA; bone microstructure was examined using HE staining and Micro-CT; and key signaling pathway proteins and genes were analyzed through immunohistochemistry to validate YSGSF's potential mechanism in PMOP treatment. A total of 84 main active components of YSGSF were identified. The key signaling pathways affected by YSGSF in the treatment of PMOP were the TNF and IL-7 signaling pathways, closely related to TNF-α, IL-1β, c-jun and other protein targets. The results of animal experiments showed that YSGSF could downregulate the expression of TNF-a, IL-1β and c-Jun proinflammatory factors by regulating the TNF and IL-7 signaling pathways and regulate the inflammatory response, osteocyte differentiation and apoptosis to control the development of PMOP. YSGSF activates the TNF-α and IL-7 signaling pathways in PMOP rats, reducing TNF-α and IL-1β levels, the c-Jun inflammatory response, and osteocyte differentiation and apoptosis, thus playing a significant role in treating PMOP. [Display omitted] [ABSTRACT FROM AUTHOR]

Extensive environmental pollution by microplastics has increased the risk of human exposure to plastics. However, the biosafety of polypropylene microplastics (PP-MPs), especially of PP particles < 10 μm, in mammals has not been studied. Thus, here, we explored the mechanism of action and effect of exposure to small and large PP-MPs, via oral ingestion, on the mouse intestinal tract. Male C57BL/6 mice were administered PP suspensions (8 and 70 μm; 0.1, 1.0, and 10 mg/mL) for 28 days. PP-MP treatment resulted in inflammatory pathological damage, ultrastructural changes in intestinal epithelial cells, imbalance of the redox system, and inflammatory reactions in the colon. Additionally, we observed damage to the tight junctions of the colon and decreased intestinal mucus secretion and ion transporter expression. Further, the apoptotic rate of colonic cells significantly increased after PP-MP treatment. The expression of pro-inflammatory and pro-apoptosis proteins significantly increased in colon tissue, while the expression of anti-inflammatory and anti-apoptosis proteins significantly decreased. In summary, this study demonstrates that PP-MPs induce colonic apoptosis and intestinal barrier damage through oxidative stress and activation of the TLR4/NF-κB inflammatory signal pathway in mice, which provides new insights into the toxicity of MPs in mammals.

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (DEX) is a highly selective and potent α2-adrenoceptor (α2-AR) agonist that is widely used as a clinical anesthetic to induce anxiolytic, sedative, and analgesic effects. In recent years, a growing body of evidence has demonstrated that DEX protects against acute kidney injury (AKI) caused by sepsis, drugs, surgery, and ischemia-reperfusion (I/R) in organs or tissues, indicating its potential role in the prevention and treatment of AKI. In this review, we summarized the evidence of the renoprotective effects of DEX on different models of AKI and explored the mechanism. We found that the renoprotective effects of DEX mainly involved antisympathetic effects, reducing inflammatory reactions and oxidative stress, reducing apoptosis, increasing autophagy, reducing ferroptosis, protecting renal tubular epithelial cells (RTECs), and inhibiting renal fibrosis. Thus, the use of DEX is a promising strategy for the management and treatment of perioperative AKI. The aim of this review is to further clarify the renoprotective mechanism of DEX to provide a theoretical basis for its use in basic research in various AKI models, clinical management, and the treatment of perioperative AKI. • The renoprotective effects of dexmedetomidine are mainly involved in seven ways. • The various renoprotective mechanisms of dexmedetomidine are not completely independent but are connected to form a network. • Inhibiting oxidative stress is one of most important mechanisms of dexmedetomidine, and can reduce inflammation, apoptosis. [ABSTRACT FROM AUTHOR]

Xuezheng Fan,1 Linshen Mu2 1Department of Neurosurgery, People’s Hospital of Guangming New District, Shenzhen, Guangdong, People’s Republic of China; 2Department of Neurosurgery, Guangzhou Medical University Affiliated Brain Hospital, Guangzhou, Guangdong, People’s Republic of China Objective: To investigate the role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH).Methods: Thirty-six adult Sprague Dawley (SD) male rats were randomly divided into sham operation, ICH and zinc protoporphyrin (ZPP) group. Rats (except for the sham operation group) were given 50 µL stereotactic injection of autologous blood from the femoral artery into the caudate nucleus, to establish an ICH model. In addition, rats in the ZPP group were given 10 mg/kg intraperitoneal injection of ZPP. At day 3 postoperative, neurobehavioral changes and brain water content were evaluated, brain tissue HO-1 expression was detected with immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), brain tissue apoptosis was evaluated with TUNEL method, Caspase 3, Caspase 8 and Caspase 9 activity were detected with colorimetric method, level of TNF-α, IL-1β, IL-6 and IL-8 were measured with the enzyme-linked immunosorbent assay (ELISA), while Bcl-2, Bax, p-NF-κB p65 and p-IκBα protein expression were detected with Western blot.Results: ICH group compared to sham operation: HO-1 positive rate and mRNA expression were increased, neurological deficit score and cell apoptosis rate were increased, Caspase 3, Caspase 8 and Caspase 9 activity were increased, level of TNF-α, IL-1β, IL-6 and IL-8 were increased, Bcl-2 expression was downregulated, Bax, p-NF-κB p65 and p-IκBβ expression were upregulated. The differences were statistically significant (P

Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL) and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours) by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

Previous diffusion tensor imaging (DTI) studies regarding pediatric patients with motor dysfunction have confirmed the correlation between DTI parameters of the injured corticospinal tract and the severity of motor dysfunction. There is also evidence that DTI parameters can help predict the prognosis of motor function of patients with cerebral palsy. But few studies are reported on the DTI parameters that can reflect the motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment. In the present study, 36 pediatric patients with hemiplegic cerebral palsy were included. Before and after rehabilitation treatment, DTI was used to measure the fiber number (FN), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of bilateral corticospinal tracts. Functional Level of Hemiplegia scale (FxL) was used to assess the therapeutic effect of rehabilitative therapy on clinical hemiplegia. Correlation analysis was performed to assess the statistical interrelationship between the change amount of DTI parameters and FxL. DTI findings obtained at the initial and follow-up evaluations demonstrated that more affected corticospinal tract yielded significantly decreased FN and FA values and significantly increased ADC value compared to the less affected corticospinal tract. Correlation analysis results showed that the change amount of FxL was positively correlated to FN and FA values, and the correlation to FN was stronger than the correlation to FA. The results suggest that FN and FA values can be used to evaluate the motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment and FN is of more significance for evaluation.

Mismatch negativity is generated automatically, and is an early monitoring indicator of neuronal integrity impairment and functional abnormality in patients with brain injury, leading to decline of cognitive function. Antipsychotic medication cannot affect mismatch negativity. The present study aimed to explore the relationships of mismatch negativity with neurocognition, daily life and social functional outcomes in patients after brain injury. Twelve patients with traumatic brain injury and 12 healthy controls were recruited in this study. We examined neurocognition with the Wechsler Adult Intelligence Scale-Revised China, and daily and social functional outcomes with the Activity of Daily Living Scale and Social Disability Screening Schedule, respectively. Mismatch negativity was analyzed from electroencephalogram recording. The results showed that mismatch negativity amplitudes decreased in patients with traumatic brain injury compared with healthy controls. Mismatch negativity amplitude was negatively correlated with measurements of neurocognition and positively correlated with functional outcomes in patients after traumatic brain injury. Further, the most significant positive correlations were found between mismatch negativity in the fronto-central region and measures of functional outcomes. The most significant positive correlations were also found between mismatch negativity at the FCz electrode and daily living function. Mismatch negativity amplitudes were extremely positively associated with Social Disability Screening Schedule scores at the Fz electrode in brain injury patients. These experimental findings suggest that mismatch negativity might efficiently reflect functional outcomes in patients after traumatic brain injury.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study investigated serum level of matrix metalloproteinase 9 as a predictor of restenosis after 40 patients underwent cervical and/or intracranial angioplasty and stenting. Results showed that restenosis occurred in 30% (3/10) of patients when the serum level of matrix metalloproteinase 9 at 3 days after surgery was 2.5 times higher than preoperative level. No restenosis occurred when the serum level of matrix metalloproteinase 9 at 3 days after surgery was not 2.5 times higher than preoperative level. Restenosis occurred in 12% (2/17) of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for more than 30 days after surgery, but only occurred in 4% (1/23) of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for less than 30 days after surgery. However, the differences observed were not statistically significant (P > 0.05). Experimental findings indicate that when the serum level of matrix metalloproteinase 9 is 2.5 times higher than preoperative level at 3 days after cervical and intracranial angioplasty and stenting, it may serve as a predictor of in-stent restenosis.

OBJECTIVE: To assess the efficacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA RETRIVAL: We searched the main databases for eligible trials including Medline (from 1966 to June 2014), Embase (from 1980 to June 2014), Cochrane Library (Issue 6, 2014), Chinese National Knowledge Infrastructure (from 1995 to June 2014), Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org). All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the English words: "cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke." No restrictions were put on publications or publication language. SELECTION CRITERIA: Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspirin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria described in Cochrane Reviewer′s Handbook 5.0.1. RevMan 5.2 software was used for data analysis. MAIN OUTCOME MEASURES: Clinical efficacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnetic resonance angiography and transcranial Doppler. RESULTS: Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis (OR = 0.21, 95%CI: 0.09-0.47, P < 0.01), it had no beneficial effect on symptom regression (OR = 1.42, 95%CI: 0.80-2.51, P = 0.24). During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients. CONCLUSION: Cilostazol may prevent the progression of symptomatic intracranial artery stenosis, which could reduce the incidence of ischemic stroke.

Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we established a unilateral corticospinal tract injury model in rats by pyramidotomy, and used a single pellet reaching task and horizontal ladder walking task as exercise interventions postoperatively. Functional recovery of forelimbs and forepaws in the rat models was noticeably enhanced after the exercises. Furthermore, TUNEL staining revealed significantly fewer apoptotic cells in the spinal cord of exercised rats, and western blot analysis showed that spinal cord expression of the apoptosis-related protein caspase-3 was significantly lower, and the expression of Bcl-2 was significantly higher, while the expression of Bax was not signifiantly changed after exercise, compared with the non-exercised group. Expression of these proteins decreased with time after injury, towards the levels observed in sham-operated rats, however at 4 weeks postoperatively, caspase-3 expression remained significantly greater than in sham-operated rats. The present findings indicate that a reduction in apoptosis is one of the mechanisms underlying the improvement of functional recovery by exercise interventions after corticospinal tract injury.

Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

Cardiovascular complications are highly prevalent in patients with diabetes. Zhi-Gan-Cao-Tang (ZGCT), a famous traditional Chinese medicine (TCM) prescription, can be used for the treatment of diabetes with cardiovascular disease complications. ZGCT is composed of nine Chinese herbs: the radix and rhizoma of Glycyrrhiza uralensis Fisch. (Gancao in Chinese, 12 g), the radix of Rehmannia glutinosa Libosch. (Dihuang in Chinese, 50 g), the radix and rhizoma of Panax ginseng C. A. Mey. (Renshen in Chinese, 6 g), the radix of Ophiopogon japonicus (L. f.) Ker-Gawl. (Maidong in Chinese, 10 g), the fructus of Ziziphus jujuba Mill. (Dazao in Chinese, 18 g), the fructus of Cannabis sativa L. (Maren in Chinese, 10 g), Donkey-hide gelatine (Ejiao in Chinese, 6 g), the ramulus of Cinnamomum cassia Presl (Guizhi in Chinese, 9 g), and the fresh rhizoma of Zingiber officinale Rosc. (Shengjiang in Chinese, 9 g). Many of these Chinese herbs are also used in other systems of medicine (Japan, India, European, etc.). However, the effects and effective constituents of ZGCT against diabetic cardiovascular disease remain unclear. This study aimed to investigate the protective effect of ZGCT against diabetic myocardial infarction (DMI) injury in vivo and in vitro and to identify the effective constituents of ZGCT. The in vivo effect on DMI injury was evaluated in a DMI mouse model. The in vitro effect and effective constituent screening experiments were conducted in an H9c2 cardiomyocyte injury model induced by high glucose and hypoxia. It was found that ZGCT significantly reduced myocardial infarction size and serum lactate dehydrogenase (LDH) levels in DMI mice. Myocardial histopathological experiments showed that ZGCT alleviated the disordered arrangement and fracture of muscle fibers and cell disappearance and reduced inflammatory cell infiltration. Cellular experiments showed that ZGCT inhibited cardiomyocyte apoptosis by decreasing the expression of the proapoptotic factor Bax. In addition, it inhibited inflammatory reactions by suppressing the activation of the IκBα/NF-κB pathway and the expression of iNOS. Eight constituents from six Chinese herbs in the recipe of ZGCT were found to enhance the viability of injured cardiomyocytes, and six effective constituents played protective roles through anti-apoptotic and/or anti-inflammatory activities. In addition, one of the effective constituents, glycyrrhizic acid, was verified in vivo to have cardioprotective effect on DMI mice. The TCM prescription ZGCT protects against DMI by inhibiting cardiomyocyte apoptosis and reducing inflammatory reactions. Eight effective constituents of ZGCT were identified. This study provides a scientific basis for the clinical application of ZGCT and is valuable for quality marker research on this prescription. [Display omitted] • The protective effects of ZGCT against DMI in vivo and in vitro were studied. • ZGCT reduced myocardial infarction size and serum LDH levels in DMI mice. • ZGCT had anti-apoptotic and anti-inflammatory effects on injured cardiomyocytes. • Eight effective constituents in ZGCT were identified. • Six effective constituents had anti-apoptotic and/or anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH). Methods: Thirty-six adult Sprague Dawley (SD) male rats were randomly divided into sham operation, ICH and zinc protoporphyrin (ZPP) group. Rats (except for the sham operation group) were given 50 µL stereotactic injection of autologous blood from the femoral artery into the caudate nucleus, to establish an ICH model. In addition, rats in the ZPP group were given 10 mg/kg intraperitoneal injection of ZPP. At day 3 postoperative, neurobehavioral changes and brain water content were evaluated, brain tissue HO-1 expression was detected with immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), brain tissue apoptosis was evaluated with TUNEL method, Caspase 3, Caspase 8 and Caspase 9 activity were detected with colorimetric method, level of TNF-α, IL-1β, IL-6 and IL-8 were measured with the enzyme-linked immunosorbent assay (ELISA), while Bcl-2, Bax, p-NF-κB p65 and p-IκBα protein expression were detected with Western blot. Results: ICH group compared to sham operation: HO-1 positive rate and mRNA expression were increased, neurological deficit score and cell apoptosis rate were increased, Caspase 3, Caspase 8 and Caspase 9 activity were increased, level of TNF-α, IL-1β, IL-6 and IL-8 were increased, Bcl-2 expression was downregulated, Bax, p-NF-κB p65 and p-IκBβ expression were upregulated. The differences were statistically significant (P<0.01). ZPP group compared to ICH: HO-1 positive rate and mRNA expression were decreased, neurological deficit score and cell apoptosis rate were decreased, Caspase 3, Caspase 8, Caspase 9 activity were decreased, level of TNF-α, IL-1β, IL-6 and IL-8 were decreased, Bcl-2 expression was upregulated, Bax, p-NF-κB p65 and p-IκBα expression were downregulated, and the differences were statistically significant (P<0.01). Conclusion: HO-1 inhibitor, ZPP does have a protective effect on ICH rats. This might be due to its inhibition to the inflammatory reaction and neuronal cell apoptosis. [ABSTRACT FROM AUTHOR]

Previous experiments showed that ultra-low-molecular-weight heparin (ULMWH) reduced the infarct and neurologic deficit in rats followed by transient cerebral ischemia, but the mechanisms of its neuroprotective effect are unclear. This study reported the effect of ULMWH on energy metabolism, inflammatory reaction and neuronal apoptosis. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. ULMWH (0.5, 1 mg/kg, i.v.) was administered after the MCAO and reperfusion. 24 h after the reperfusion, Spectrophotometric assay was used to determine the activity of ATPase and the content of lactic acid in the brain. The ICAM-1 and Caspase-3 genes were investigated by RT-PCR. Furthermore, the apoptotic percentage of cells in hippocampus was quantified by flow cytometry. Compared with the model group, ULMWH significantly decreased lactic acid content and increased ATPase activity in ischemic brain. At the same time, ULMWH inhibited the neural apoptosis and decreased the expressions of ICAM-1 and Caspase-3 mRNA in hippocampus. These findings suggest that ULMWH exhibits a neuroprotective effect against cerebral ischemia/reperfusion injury, partly through improving energy metabolism, inhibiting apoptosis and attenuating inflammatory reaction.

Ethnopharmacological relevance Acupuncture is a key part of traditional Chinese medicine, shown to induce favorable neuroplasticity for injuries in the central and peripheral nervous systems. Recent studies report elongated needle therapy (ENT) with BL54 and ST28 may restore acute spinal cord injury (ASCI). However, the precise mechanism for this has not been elucidated. Aim of the study In our current study, we investigated the effects of ENT on inflammation and neuronal apoptosis induced by ASCI, and whether PI3K/Akt and MAPK/ERK signaling pathways are involved in the ENT restoration effect. Materials and methods Rat models of moderate SCI were established in accordance with the modified Allen's method and were treated with ENT continuously for 7 days. Spontaneous activities were evaluated by the Basso Beattie and Bresnahan locomotor scale. Levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, IL-1β, and nuclear factor kappa-β, were determined by enzyme-linked immunosorbent assay. Cell apoptosis was examined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The proportions of cells with positive Bcl-2 and Bax expression were determined by immunohistochemical assays, whilst the expression profiles of p-AKT and p-ERK in spinal cord tissues were evaluated by western blotting. Furthermore, the expression profiles of Cytochrome-C (Cyt-C) and caspase-3 in vivo were analyzed by reverse transcription polymerase chain reaction. The potential inhibitory effects downstream of the Akt and ERK signaling pathways were examined by administration of specific inhibitors LY294002 and PD98059 in vivo. Results As indicated by this study, inflammation as well as PI3K/Akt- and MAPK/ERK signaling pathway-mediated neuronal apoptosis were involved in the course of SCI in rats. The neuro-protective effect of ENT was associated with reduced Bax protein-positive neurons and increased Bcl-2 protein-positive neurons. ENT enhanced recovery of rat activities. Activation of p-Akt and p-ERK in the PI3K/Akt and MAPK/ERK signaling pathways, inhibited expression of the critical component Cyt-C. Cyt-C is required for the mitochondrial apoptosis pathway and cascade of caspase-3, which is involved in activation of neuronal apoptosis through down-regulation of Bax protein and up-regulation of Bcl-2, as determined by TUNEL. The administration of PI3K/Akt and MAPK/ERK signaling pathway specific inhibitors, LY294002 and PD98059, suppressed expression of both p-Akt and p-ERK. Conclusion ENT with BL54 and ST28 points can promote the recovery of ASCI. And the neuro-protective effect of ENT during the restoration of SCI may be associated with the suppression of both inflammation and activation of PI3K/Akt and MAPK/ERK signaling pathways, resulting from down-regulation of Bax protein, up-regulation of Bcl-2, and inhibition of the mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

The objective of this study is to explore the neuroprotective effect and mechanism of picroside II on ERK1/2-COX2 signal transduction pathway after cerebral ischemic injury in rats. Focal cerebral ischemic models were established by inserting monofilament threads into the middle cerebral artery in 200 Wistar rats. Twenty four rats were randomly selected into control group, while the other rats were randomly divided into six groups: model group, picroside group, lipopolysaccharide (LPS) with picroside group, U0126 with picroside group, LPS group, and U0126 group with each group containing three subgroups with ischemia at 6, 12, and 24 h. Neurobehavioral function in the rats was evaluated by modified neurological severity score points (mNSS) test; structure of neurons was observed using hematoxylin-eosin (HE) staining; apoptotic cells were counted using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay; expressions of phosphorylated mitogen/extracellular signal-regulated kinase kinas1/2 (pMEK1/2), phosphorylated extracellular signal-regulated protein kinase1/2 (pERK1/2), and cyclooxygenase (COX2) in the cortex were determined using immunohistochemistry (IHC) and Western blot (WB); and real-time PCR was used to determine the level of COX2 mRNA. The neurological behavioral malfunction appeared in all rats with middle cerebral artery occlusion (MCAO). In the model group, neuron damage was extensive, while the neurobehavioral function score, apoptotic cell index, expression of pMEK1/2, pERK1/2, and COX2 and the level of COX2 mRNA increased significantly when compared to the control group. The peak COX2 mRNA level was in ischemia 12 h, prior to the peak in COX2 protein expression. In the picroside and U0126 groups, the neurological behavioral function was improved, and the number of apoptotic cells and the expression of pMEK1/2, pERK1/2, and COX2 decreased significantly when compared to the model group. In the LPS with picroside group, at ischemia 6 h neuron damage was extensive, and pMEK1/2, pERK1/2, and COX2 expression were much higher than in the model group. But at ischemia 12 and 24 h, the expression of pMEK1/2, pERK1/2, and COX2 decreased slightly, and the neurobehavioral function also improved slightly. In LPS group, neuron damage was extensive, pMEK1/2, pERK1/2, and COX2 expression was still at a high level, and COX2 mRNA peak arrived at ischemic 12 h. Picroside II downregulates COX2 expression after MCAO by inhibiting MEK-ERK1/2 in rats to protect neurons from apoptosis and inflammation. [ABSTRACT FROM AUTHOR]

Objective To study the dynamic expression and distribution of high mobility group box 1 (HMGB-1) in diffuse axonal injury (DAI) in rats and to clarify its involvement in the inflammatory reaction after DAI in rats, in order to provide new targets for the clinical treatment of DAI. Methods A DAI model was established using a coronal rotation device and evaluated by HE, Glees-Marsland silver staining, and Mallory phosphotungstic acid hematoxylin staining. Immunohistochemistry, Western blot and RT-PCR were used to detect the expression and distribution of HMGB-1 in the cortex of DAI rats at 6h, 1d, 3d and 7d. And TUNEL was used to examine the apoptosis of neurons in DAI rats. Results Immunohistochemical results showed that at 6h and 1d after DAI, the number of HMGB-1-positive cells decreased, but at 3 and 7d it began to increase. Western blot also showed that during the early stage after DAI (6h and 1d), the level of HMGB-1 protein in the cortex was significantly lower than that in the control group, but at the late stage (3 and 7d) after DAI it significantly increased compared with that in the control group until 7d. RT-PCR showed that at 6h after DAI there was no significant increase in the level of HMGB-1mRNA, but at 1d there was a slight increase compared with the control group; at 3 and 7d, it showed an obvious significance. TUNEL staining indicated that the significant neuronal apoptosis appeared as early as 6h after DAI, and reached the peak at 3d; it started to decrease at 7d but still remained at a relatively high level. Conclusion The dynamic expression and distribution of HMGB-1 showed significant changes with the time course after DAI in rats. They decreased at the early stage but increased at the late stage. At the early stage, HMGB-1 is mainly passively released by the necrotic neurons, and at the late stage it may be actively secreted by the active inflammatory cells. HMGB-1 may mediate the post-DAI neural cell apoptosis by inducing the inflammatory reaction. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze pathophysiological changes after testicular sperm aspiration (TESA) and microsurgical epididymal sperm aspiration (MESA) procedures. Twenty four mature male Wistar albino rats with a proven breeding history, weighing approximately 200-250 gm were used for the study. Animals were randomly divided into four groups (n = 6), i.e., control, sham-control, unilateral TESA, and MESA. Using a 22G needle, the aspiration procedures were done in testis or caudal epididymis. At the end of 60 days of survival, blood samples were collected and processed for antisperm antibody detection by enzyme-linked immunosorbent assay (ELISA). After euthanasia, testes and epididymides were collected and processed for paraffin embedding. Sections were stained with hematoxylin and eosin, and TUNEL technique. Serum antisperm antibody titer significantly increased in TESA ( P  <  0.001) when compared to MESA. Histomorphometric analysis indicated testicular alterations in TESA and MESA, with significant damage in TESA in both testes ( P < 0.001). Following the MESA procedure, ipsilateral caudal and carpus epididymis showed significant alterations ( P < 0.001) and no such alterations were seen in the ipsilateral caput and intact contralateral epididymis. TUNEL staining revealed an up-regulation of apoptosis in both contra- and ipsilateral testes of TESA. Needle prick had produced drastic and irreversible alterations in testis of TESA. Ensuing processes of immunological and inflammatory reaction had the potential to disrupt spermatogenesis and increase germ cell apoptosis. However, extrapolating conclusions from the experimental model to the clinic needs to be done cautiously. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the role of Buyang Huanwu Decoction fraction in attenuating inflammatory response and cellular apoptosis preventing cerebral ischemia/reperfusion injury. It is inferred that the Buyang Huanwu Decoction fraction contains saponins of Astragalus, safflower flavones and total paeony glycoside. The similarities in the effects between the Buyang Huanwu Decoction fraction and the Ginkgo biloba extract are highlighted.

Previous experiments showed that ultra-low-molecular-weight heparin (ULMWH) reduced the infarct and neurologic deficit in rats followed by transient cerebral ischemia, but the mechanisms of its neuroprotective effect are unclear. This study reported the effect of ULMWH on energy metabolism, inflammatory reaction and neuronal apoptosis. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. ULMWH (0.5, 1 mg/kg, i.v.) was administered after the MCAO and reperfusion. 24 h after the reperfusion, Spectrophotometric assay was used to determine the activity of ATPase and the content of lactic acid in the brain. The ICAM-1 and Caspase-3 genes were investigated by RT-PCR. Furthermore, the apoptotic percentage of cells in hippocampus was quantified by flow cytometry. Compared with the model group, ULMWH significantly decreased lactic acid content and increased ATPase activity in ischemic brain. At the same time, ULMWH inhibited the neural apoptosis and decreased the expressions of ICAM-1 and Caspase-3 mRNA in hippocampus. These findings suggest that ULMWH exhibits a neuroprotective effect against cerebral ischemia/reperfusion injury, partly through improving energy metabolism, inhibiting apoptosis and attenuating inflammatory reaction. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative disease characterized by the production of β-amyloid proteins and hyperphosphorylation of tau protein. Inflammation and apoptotic severity were highly correlated with earlier age at onset of Alzheimer's disease and were also associated with cognitive decline. This study aims to examine whether the traditional Chinese medicine ginsennoside Rd could prevent cognitive deficit and take neuroprotective effects in β-amyloid peptide 1-40-induced rat model of Alzheimer's disease. To produce Alzheimer's disease animal model, aggregated β-amyloid peptide 1-40 injected into hippocampus bilaterally. Ginsennoside Rd protected their cognitive impairment and improved their memory function by daily intraperitoneal injection for 30 days consecutively. In addition, ginsennoside Rd alleviated the inflammation induced by β-amyloid peptide 1-40. Furthermore, ginsennoside Rd played a role in the down-regulation of caspase-3 proteins and reduced the apoptosis that normally followed β-amyloid peptide 1-40 injection. The results of this study showed that the pretreatment of ginsennoside Rd had neuroprotective effects in β-amyloid peptide 1-40-induced AD model rat. [ABSTRACT FROM AUTHOR]

Abstract: A systemic inflammatory reaction may have detrimental effects on the organism, including the central nervous system. Previous studies have indicated that lipopolysaccharide (LPS)-evoked systemic inflammation induces pathological alterations in the mouse midbrain, especially in the substantia nigra. The aim of the present study was to investigate whether the hippocampus is also affected after an intraperitoneal (i.p.) injection of LPS. We focussed on the dynamics of proinflammatory gene expression and the processes leading to neuronal cell death. A systemic inflammatory response in C57BL/6 mice was induced by an i.p. injection of LPS (1mg/kg b.w.). The genetic, biochemical and morphological alterations were analysed up to 96h after LPS administration using quantitative PCR, immunochemical, immunocytochemical and electron microscopic methods. Real-time PCR analysis indicated an altered expression of several genes, mainly responsible for arachidonic acid release and metabolism, in the hippocampus 96h after the systemic administration of LPS. Three hours after LPS treatment, the level of mRNA for iNOS, COX-2 and TNFα was increased; then, after 6–24h, it rose for TLR4 and cPLA2. The expression of 5-LOX and 12-LOX was increased at 12–24 and 24–48h after LPS injection, respectively. Our data demonstrate for the first time the sequential activation of the expression of several pro-inflammatory genes responsible for the maintenance of the inflammatory response. Moreover, the electron microscopy studies presented the stimulation of apoptosis-inducing factor (AIF)-mediated death signalling and cathepsin B-related autophagy or necrosis. These biochemical and morphological alterations in the hippocampus, which were induced by systemic inflammation, may be responsible for the impairment of cognition function observed previously. [ABSTRACT FROM AUTHOR]

The inflammatory response and apoptosis are key factors in cerebral ischemia-reperfusion injury. The severity of the inflammatory reaction and apoptosis has an important impact on the prognosis of stroke. The ultrasmall superparamagnetic iron oxide particle has provided an effective magnetic resonance molecular imaging method for dynamic observation of the cell infiltration process in vivo. The aims of the present study were to investigate the inflammatory response of cerebral ischemia-reperfusion injury in mice using ferumoxytol-enhanced magnetic resonance imaging, and to observe the dynamic changes of inflammatory response and apoptosis. In the present study a C57BL/6n mouse cerebral ischemia-reperfusion model was established by blocking the right middle cerebral artery with an occluding suture. Subsequently, the mice were injected with ferumoxytol via the tail vein, and magnetic resonance scanning was performed at corresponding time points to observe the signal changes. Furthermore, blood samples were used to measure the level of serum inflammatory factors, and histological staining was performed to assess the number of iron-swallowing microglial cells and apoptotic cells. The present results suggested that there was no significant difference in the serum inflammatory factors tumor necrosis factor-α and interleukin 1β between the middle cerebral artery occlusion (MCAO) and MCAO + ferumoxytol groups injected with ferumoxytol and physiological saline. The lowest signal ratio in the negative enhancement region was decreased 24 h after reperfusion in mice injected with ferumoxytol. The proportion of iron-swallowing microglial cells and TUNEL-positive cells were the highest at 24 h after reperfusion, and decreased gradually at 48 and 72 h after reperfusion. Therefore, the present results indicated that ferumoxytol injection of 18 mg Fe/kg does not affect the inflammatory response in the acute phase of cerebral ischemia and reperfusion. Ferumoxytol-enhanced magnetic resonance imaging can be used as an effective means to monitor the inflammatory response in the acute phase of cerebral ischemia-reperfusion injury. Furthermore, it was found that activation of the inflammatory response and apoptosis in the acute stage of cerebral ischemia-reperfusion injury is consistent. [ABSTRACT FROM AUTHOR]