Acute Neurobehavioral and Glial Responses to Explosion Gas Inhalation in Rats.

Military personnel, firefighters, and fire survivors exhibit a higher prevalence of mental health conditions such as depression and post-traumatic stress disorder (PTSD) compared to the general population. While numerous studies have examined the neurological impacts of physical trauma and psychological stress, research on acute neurobehavioral effects of gas inhalation from explosions or fires is limited. This study investigates the early-stage neurobehavioral and neuronal consequences of acute explosion gas inhalation in Sprague-Dawley rats. Rats were exposed to simulated explosive gas and subsequently assessed using behavioral tests and neurobiological analyses. The high-dose exposure group demonstrated significant depression-like behaviors, including reduced mobility and exploration. However, neuronal damage was not evident in histological analyses. Immunofluorescence revealed increased density of radial glia and oligodendrocytes in specific brain regions, suggesting hypoxia and axon damage induced by gas inhalation as a potential mechanism for the observed neurobehavioral changes. These findings underscore the acute impact of explosion gas inhalation on mental health, highlighting the habenula and dentate gyrus of hippocampus as the possible target regions. The findings are expected to support early diagnosis and treatment strategies for brain injuries caused by explosion gas, offering insights into early intervention for depression and PTSD in affected populations.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics.

PURPOSE: To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. METHODS: This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. RESULTS: Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. CONCLUSIONS: Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

[Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway. METHODS: Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were determined. RESULTS: Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05). CONCLUSION: CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1ß and IL-6 in myocardial tissue.

Driving factors on accumulation of cadmium, lead, copper, zinc in agricultural soil and products of the North China Plain.

The accumulation of heavy metals in agricultural soils concerns food security. By using the Geographical Detector, this study investigated the influence of six types of factors (eleven factors) on the accumulation of Cd, Pb, Cu, Zn in agricultural soil and products of the North China Plain and confirmed the dominant factor. The results showed that heavy metals had accumulated in regional agricultural soils and the accumulation of Cd was severe. The accumulation of heavy metals was significantly influenced by policy factors (the management and reduction in usage of fertilizers and pesticides), fertilization factors (application of organic and chemical fertilizers), pesticide factors (application of herbicide and insecticide) and atmospheric deposition factors (heavy metal concentration in atmospheric deposition). The policy factor dominated the other three types of factors. Atmospheric deposition and the excess application of fertilizers and pesticides directly lead to the accumulation of heavy metals. Due to the high concentrations of heavy metals and abundant application amounts, organic fertilizers have contributed high levels of heavy metals to agricultural soils. This study suggests that formulated fertilization and action plans for pesticide reduction could effectively decrease the accumulation of heavy metals in agricultural soils and products in the study area.

NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves.

Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats' lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

Cytotoxicity and inflammatory effects in human bronchial epithelial cells induced by polycyclic aromatic hydrocarbons mixture.

Polycyclic aromatic hydrocarbons (PAHs) are the most common contaminants in the air pollutants. Inhalation exposure to PAHs could increase the risk of respiratory disease, cardiovascular disease and even cancer. However, the biotoxicity of multi-component PAHs from atmospheric pollutants has been poorly studies. The main topic of this study was to investigate the PAHs mixture, which derived from atmospheric pollutants, induced toxic effects and inflammatory effects on human bronchial epithelial cells in vitro. The results showed that PAHs mixture could decrease the cell viability, increase the apoptosis rate, and induce cell cycle arrest at S-phase. Furthermore, the expression of inflammatory factors IL-1ß and IL-6 were increased and NF-κB signaling pathway was activated in PAHs mixture-treated cells. The findings of this study indicate that PAHs mixture-induced cytotoxicity and inflammation may be related to intracellular ROS generation and to the activated NF-κB signaling pathway.

Antihypertensive and Antifibrosis Effects of Acupuncture at PC6 Acupoints in Spontaneously Hypertensive Rats and the Underlying Mechanisms.

Long-term hypertension can lead to both structural and functional impairments of the myocardium. Reversing left ventricular (LV) myocardial fibrosis has been considered as a key goal for curing chronic hypertension and has been a hot field of research in recent years. The aim of the present work is to investigate the effect of electroacupuncture (EA) at PC6 on hypertension-induced myocardial fibrosis in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA groups with WKY rats as a normal control. EA was applied once a day for 8 consecutive weeks. The cardiac fibrosis as well as the underlying mechanisms were investigated. After 8 weeks of EA treatment at PC6, the enhanced myocardial fibrosis in SHRs was characterized by an increased ratio of left ventricular mass index (LVMI), collagen volume fraction (CVF), and elevated content of hydroxyproline (Hyp) as well as the upregulated expression of collagen I and collagen III in myocardium tissue of SHRs. All these abnormal alterations in the SHR + EA group were significantly lower compared to the model group. In addition, EA at PC6 significantly improved the pathological changes of myocardial morphology. Meanwhile, the increased levels of angiotensin II (Ang II) and tumor necrosis factor-α (TNFα) and expression of transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2, and MMP-9 in the serum or heart tissue of SHRs were also markedly diminished by EA. These results suggest that EA at bilateral PC6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by the regulation of the Ang II - TGF-ß1 pathway.

Global gene expression profiling of blast lung injury of goats exposed to shock wave.

PURPOSE: Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. METHODS: In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. RESULTS: Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. CONCLUSION: Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

[Application of shear wave elastography in acupuncture research].

In recent years, a new technique of elastic quantization imaging, the ultrasound-based shear wave elastography (SWE) is arising, which has advantages of real-time, non-invasion, rapid imaging and strong repeatability, and quantifying the elastic properties of soft tissues including thyroid gland, breast, prostate, muscle tendon, ligament, etc.. It has been gradually applied to clinical and experimental researches of acupuncture and has an extensive application prospect. The present paper briefly introduces the application of SWE in accurately locating the acupoint, Deqi from needled acupoints, acupuncture manipulations, and evaluation of efficacy of acupuncture in the treatment of musculofascial diseases.

The Role of Adenosine A2b Receptor in Mediating the Cardioprotection of Electroacupuncture Pretreatment via Influencing Ca2+ Key Regulators.

OBJECTIVE: To investigate the roles played by A2b receptor and the key Ca2+ signaling components in the mediation of the cardioprotection of electroacupuncture pretreatment in the rats subjected to myocardial ischemia and reperfusion. METHODS: SD rats were randomly divided into a normal control (NC) group, ischemia/reperfusion model (M) group, electroacupuncture pretreatment (EA) group, and electroacupuncture pretreatment plus A2b antagonist (EAG) group. The ischemia/reperfusion model was made by ligation and loosening of the left descending branch of the coronary artery in all groups except the NC group. The EA group was pretreated with electroacupuncture at the Neiguan (PC6) point once a day for three consecutive days before the modeling. The elevation of the ST segment, arrhythmia scores, and myocardial infarction size of each group was measured. The relative expression levels of A2b, RyR2, SERCA2a, NCX1, P-PLB(S16)/PLB, and Troponin C/Troponin I proteins in the injured myocardium were detected by multiple fluorescence western blot. RESULTS: The level of ST segment, arrhythmia scores, and infarct size in the M group was significantly higher/larger than that in the NC group after ischemia and reperfusion, while all the three indices mentioned above in the EA group were significantly lower/smaller than those in the M group after reperfusion. The expression of the proteins of adenosine receptor 2b(A2b), ryanodine receptor 2(RyR2), and sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) in the EA group was significantly enhanced as compared with the M group, while in the EAG group, the contents of A2b were significantly lower than those in the EA group, and RyR2 was higher in the EAG group. In comparison with the NC group, the relative expression of NCX1 protein in M, EA, and EAG groups was not changed significantly. The ratio of phosphorylated phospholamban (P-PLB) over phospholamban (PLB) in the M group was significantly lower than that in the NC group, and the ratio in the EA group was significantly increased as compared with the M group, while the ratio of Troponin C/Troponin I in the EA group was significantly decreased in comparison with that in other groups. CONCLUSION: Electroacupuncture pretreatment could reduce ischemia and reperfusion-induced myocardial injury via possibly increasing the A2b content and regulating the key Ca2+ signaling components, namely inhibiting RyR2 and enhancing P-PLB(S16)/PLB ratio and SERCA2a proteins, so as to diminish the intracellular Ca2+ overload and consequently lessen the myocardial injury.

Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation.

The liver possesses a high regenerative capacity. Liver regeneration is a compensatory response overcoming disturbances of whole-body homeostasis provoked by organ defects. Here we show that a vagus-macrophage-hepatocyte link regulates acute liver regeneration after liver injury and that this system is critical for promoting survival. Hepatic Foxm1 is rapidly upregulated after partial hepatectomy (PHx). Hepatic branch vagotomy (HV) suppresses this upregulation and hepatocyte proliferation, thereby increasing mortality. In addition, hepatic FoxM1 supplementation in vagotomized mice reverses the suppression of liver regeneration and blocks the increase in post-PHx mortality. Hepatic macrophage depletion suppresses both post-PHx Foxm1 upregulation and remnant liver regeneration, and increases mortality. Hepatic Il-6 rises rapidly after PHx and this is suppressed by HV, muscarinic blockade or resident macrophage depletion. Furthermore, IL-6 neutralization suppresses post-PHx Foxm1 upregulation and remnant liver regeneration. Collectively, vagal signal-mediated IL-6 production in hepatic macrophages upregulates hepatocyte FoxM1, leading to liver regeneration and assures survival.

[A Potential Role of Adenosine A 2 b Receptor in Mediating Acupuncture Pretreatment Induced Cardioprotection via Influencing Intracellular Calcium Regulator].

It has been shown that ischemia preconditioning (IPC) can attenuate the myocardial injury induced by ischemic and reperfusion. But it was rarely used in clinic due to its inoperability. Previous studies indicate that electroacupuncture (EA) pretreatment can mimic myocardial ischemia preconditioning (MIPC) to produce cardioprotective effect. The activated adenosine A 2 b receptor has been proven to be involved in mediating the cardioprotection of IPC. In the studies on acupuncture analgesia, it was reported that adenosine receptor was activated by acupuncture stimulation, and acupuncture pretreatment can affect the acti-vities of intracellular A 2 b receptor. Based on those mentioned above, it is highly likely that the A 2 b receptor may also participate in the cardioprotection produced by acupuncture pretreatment. In this paper, we comprehensively reviewed relevant studies regarding 1) the cardioprotective effect of IPC and its limitations, 2) the similar cardioprotection produced by both acupuncture pre-treatment and IPC, 3) the mechanism underlying myocardial ischemic injury and intracellular calcium regulation, 4) the acti-vation of adenosine receptors and effects of acupuncture, 5) the relationship between adenosine receptors and intracellular calcium ion, and 6) the effect of acupuncture on adenosine receptors, so as to provide a novel assumption that A 2 b receptor may be a key factor in mediating the cardioprotection of acupuncture pretreatment. Our future research will systematically explore the me-chanism of acupuncture pretreatment in protecting ischemic myocardium from myocardial cell adenosine A 2 b receptor and intracellular calcium signal transduction related factors.

Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers.

BACKGROUND/OBJECTIVE: Insulin signals, via the regulation of key enzyme expression, both suppress gluconeogenesis and enhance lipid synthesis in the liver. Animal studies have revealed insulin signaling favoring gluconeogenesis suppression to be selectively impaired in steatotic livers. However, whether, and if so how, such selective insulin resistance occurs in human steatotic livers remains unknown. Our aim was to investigate selective insulin resistance in human livers with non-alcoholic fatty liver disease (NAFLD). SUBJECTS/METHODS: We examined mRNA expressions of key molecules for insulin signaling, gluconeogenesis and lipogenesis in human liver biopsy samples obtained from 51 non-diabetic subjects: 9 healthy controls and 42 NAFLD patients, and analyzed associations of these molecules with each other and with detailed pathological and clinical biochemistry data. RESULTS: In NAFLD patients, insulin receptor substrate (IRS)-2 expression was decreased, while those of key enzymes for gluconeogenesis were increased. These alterations of IRS-2 and gluconeogenesis enzymes were induced both in simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), while these expression levels did not differ between SS and NASH. Furthermore, alterations in the expressions of IRS-2 and gluconeogenesis enzymes showed strong negative correlations and were concurrently induced in the early histological stage of NAFLD. In contrast, fatty acid synthase (FAS) expression was not decreased in NAFLD, despite IRS-2 downregulation, but correlated strongly with IRS-1 expression. Furthermore, no histological scores were associated with these molecules. Thus, IRS-1 signaling, which is not impaired in NAFLD, appears to modulate FAS expression. CONCLUSION: These analyses revealed that selective insulin resistance is present in human NAFLD livers and occurs in its early phases. The effect of insulin, during the IRS step, on gene expressions for lipogenesis and gluconeogenesis are apparently distinct and preferential downregulation of IRS-2 may contribute to selective resistance to the suppressive effects of insulin on gluconeogenesis.

Neuronal signals regulate obesity induced ß-cell proliferation by FoxM1 dependent mechanism.

Under insulin-resistant conditions such as obesity, pancreatic ß-cells proliferate to prevent blood glucose elevations. A liver-brain-pancreas neuronal relay plays an important role in this process. Here, we show the molecular mechanism underlying this compensatory ß-cell proliferation. We identify FoxM1 activation in islets from neuronal relay-stimulated mice. Blockade of this relay, including vagotomy, inhibits obesity-induced activation of the ß-cell FoxM1 pathway and suppresses ß-cell expansion. Inducible ß-cell-specific FoxM1 deficiency also blocks compensatory ß-cell proliferation. In isolated islets, carbachol and PACAP/VIP synergistically promote ß-cell proliferation through a FoxM1-dependent mechanism. These findings indicate that vagal nerves that release several neurotransmitters may allow simultaneous activation of multiple pathways in ß-cells selectively, thereby efficiently promoting ß-cell proliferation and maintaining glucose homeostasis during obesity development. This neuronal signal-mediated mechanism holds potential for developing novel approaches to regenerating pancreatic ß-cells.

ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity.

Obesity represents chronic inflammatory states promoted by pro-inflammatory M1-macrophage infiltration into white adipose tissue (WAT), thereby inducing insulin resistance. Herein, we demonstrate the importance of an ER stress protein, CHOP, in determining adipose tissue macrophage (ATM) polarity and systemic insulin sensitivity. A high-fat diet (HFD) enhances ER stress with CHOP upregulation in adipocytes. CHOP deficiency prevents HFD-induced insulin resistance and glucose intolerance with ATM M2 predomination and Th2 cytokine upregulation in WAT. Whereas ER stress suppresses Th2 cytokine expression in cultured adipocytes, CHOP knockdown inhibits this downregulation. In contrast, macrophage responsiveness to Th1/Th2 cytokines is unchanged regardless of whether CHOP is expressed. Furthermore, bone marrow transplantation experiments showed recipient CHOP to be the major determinant of ATM polarity. Thus, CHOP in adipocytes plays important roles in ATM M1 polarization by altering WAT micro-environmental conditions, including Th2 cytokine downregulation. This molecular mechanism may link adipose ER stress with systemic insulin resistance.

MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic ß-Cell Proliferation.

Major symptoms of diabetes mellitus manifest, once pancreatic ß-cell numbers have become inadequate. Although natural regeneration of ß-cells after injury is very limited, bone marrow (BM) transplantation (BMT) promotes their regeneration through undetermined mechanism(s) involving inter-cellular (BM cell-to-ß-cell) crosstalk. We found that two microRNAs (miRNAs) contribute to BMT-induced ß-cell regeneration. Screening murine miRNAs in serum exosomes after BMT revealed 42 miRNAs to be increased. Two of these miRNAs (miR-106b-5p and miR-222-3p) were shown to be secreted by BM cells and increased in pancreatic islet cells after BMT. Treatment with the corresponding anti-miRNAs inhibited BMT-induced ß-cell regeneration. Furthermore, intravenous administration of the corresponding miRNA mimics promoted post-injury ß-cell proliferation through Cip/Kip family down-regulation, thereby ameliorating hyperglycemia in mice with insulin-deficient diabetes. Thus, these identified miRNAs may lead to the development of therapeutic strategies for diabetes.

Electroacupuncture ameliorates abnormal defaecation and regulates corticotrophin-releasing factor in a rat model of stress.

OBJECTIVE: To examine the effect of electroacupuncture (EA) treatment on abnormal defaecation in a rat model of chronic heterotypic stress (CHS) and investigate the underlying mechanisms. METHODS: 20 male Sprague-Dawley rats were randomly divided into three groups: normal (n=6), CHS (n=7), and CHS+EA (n=7). Rats in the CHS group and CHS+EA groups received four different types of stressors for 7 days. For rats in the CHS+EA group, EA was applied at ST36 in the bilateral hind legs for 30 min before each stress-loading session. Rats in the normal group did not receive stressors or EA treatment. The faecal pellets of each rat were collected and weighed at a fixed time every day. Protein expression of corticotrophin-releasing factor (CRF) in the hypothalamus and colorectal tissues was measured by Western blotting at the end of the experiment on the 7th day. RESULTS: After 7 consecutive days of CHS, the number of faecal pellets, faecal wet weight, and faecal water content were significantly increased in the CHS group compared with the normal group (p=0.035, p=0.008 and p=0.008, respectively). All three parameters were significantly decreased in CHS+EA versus CHS groups (p=0.030, p=0.011 and p=0.006, respectively). Stress significantly increased CRF expression in both the hypothalamus and colorectal tissues. The excessive CRF responses seen following CHS were significantly suppressed by EA treatment. CONCLUSIONS: EA treatment can ameliorate stress loading induced abnormal defaecation in rats and decrease protein expression of CRF centrally (hypothalamus) and peripherally (colorectal tissues), suggesting a potentially therapeutic role for EA in stress-related responses.

[Development of Researches on Mechanisms of Acupuncture Intervention in Improving Myocar-dial Ischemia by Balancing Interaction between ß-adrenergic Receptor and Acetylcholinergic Receptor Signal Transduction Pathway of Myocardiocytes].

The imbalance of autonomic nervous function after myocardial ischemia (MI) accelerates the development of ischemic myocardial injury. The beta-adrenergic receptor (ß-AR) and muscarinic acetylcholine receptor (M-AChR) are the main receptor types of the cardiomyocyte and the binding sites of the cardiac sympathetic and parasympathetic transmitters. In the present paper, the authors review recent progress of experimental researches on the mechanisms of acupuncture therapy in the prevention and treatment of MI, mainly focusing on the signaling of ß1-AR and M2-AChR subtypes. Results showed that acupuncture could attenuate the injury of myocardial ischemia via down-regulating the over expression of ß1-AR and up-regulating the expression of M2-AChR protein. Correspondingly, acupuncture intervention could reverse the abnormal expression of the intracellular stimulatory G protein and inhibitory G protein caused by MI, and suppress the activity of cellular adenylate cyclase. In addition, acupuncture could also enhance the activity of nitric oxide synthase and the level of nitric oxide in the ischemic cardiomyocytes, and increase the synthesis of cyclic guanosine monophosphate, ultimately reducing the level of cyclic adenosine 3', 5'monophosphate, and lowering the activity of protein kinase A and the inward flow of Ca2+ in cardiomyocytes. In this way, the ischemic myocardial injury is improved at last. However, some results of acupuncture intervention are not identical and need being confirmed further by more approaches.

Pinocembrin protects SH-SY5Y cells against MPP+-induced neurotoxicity through the mitochondrial apoptotic pathway.

Pinocembrin (PB), the most abundant flavonoid in propolis, has been proven to have neuroprotective property against neurotoxicity in vivo and in vitro. Our recent study demonstrated the neuroprotective effect of PB against Aß25-35-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) which mimics Parkinson's disease (PD) with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. We found that pretreatment of SH-SY5Y cells with PB significantly reduced the MPP(+)-induced loss of cell viability, the generation of intracellular ROS, apoptotic rate, and the cleavage of caspase-3. PB strikingly inhibited MPP(+)-induced mitochondrial dysfunctions, including lowered membrane potential, decreased Bcl-2/Bax ratio, and the release of cytochrome c. Overall, these results suggest that PB is intimately involved in inhibiting MPP(+)-induced loss of mitochondrial function and induction of apoptosis that contributes toward neuronal survival. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.

Estradiol synthesis and release in cultured female rat bone marrow stem cells.

Bone marrow stem cells (BMSCs) have the capacity to differentiate into mature cell types of multiple tissues. Thus, they represent an alternative source for organ-specific cell replacement therapy in degenerative diseases. In this study, we demonstrated that female rat BMSCs could differentiate into steroidogenic cells with the capacity for de novo synthesis of Estradiol-17 ß (E2) under high glucose culture conditions with or without retinoic acid (RA). The cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis. Moreover, radioimmunoassay revealed that BMSCs cultured in the present culture system produced and secreted significant amounts of testosterone, androstenedione, and E2. In addition, RA promoted E2 secretion but did not affect the levels of androgen. These results indicate that BMSCs can synthesize and release E2 and may contribute to autologous transplantation therapy for estrogen deficiency.