Hepatic kynurenic acid mediates phosphorylation of Nogo-A in the medial prefrontal cortex to regulate chronic stress-induced anxiety-like behaviors in mice.

Exercise training effectively relieves anxiety disorders via modulating specific brain networks. The role of post-translational modification of proteins in this process, however, has been underappreciated. Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmill exercise, in association with dramatic changes of protein phosphorylation patterns in the medial prefrontal cortex (mPFC). In particular, exercise was proposed to modulate the phosphorylation of Nogo-A protein, which drives the ras homolog family member A (RhoA)/ Rho-associated coiled-coil-containing protein kinases 1(ROCK1) signaling cascade. Further mechanistic studies found that liver-derived kynurenic acid (KYNA) can affect the kynurenine metabolism within the mPFC, to modulate this RhoA/ROCK1 pathway for conferring stress resilience. In sum, we proposed that circulating KYNA might mediate stress-induced anxiety-like behaviors via protein phosphorylation modification within the mPFC, and these findings shed more insights for the liver-brain communications in responding to both stress and physical exercise.

Cardiac Remodeling During Pregnancy With Metabolic Syndrome: Prologue of Pathological Remodeling.

BACKGROUND: The heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders. METHODS: The idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet-feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)-induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat). RESULTS: Pregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery. CONCLUSIONS: These results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.

A novel label-free electrochemiluminescence aptasensor using a tetrahedral DNA nanostructure as a scaffold for ultrasensitive detection of organophosphorus pesticides in a luminol-H2O2 system.

In this work, a new type of Au-tetrahedral DNA nanostructure (Au-TDN) was originally proposed and successfully applied in an electrochemiluminescence aptasensor to detect organophosphorus pesticides (Ops). The aptamers modified with -SH could be covalently bonded with gold nanoparticles (AuNPs) to form a tetrahedron structure, and there were independent probes at each vertex of the tetrahedron, which could increase the probability of specific binding with Ops. The originally designed structure could not only maintain a stable tetrahedral configuration, but also combined with the target to improve the sensitivity of the sensor. Meanwhile, silver nanoparticles (AgNPs) could catalyze the chemical reaction between luminol and H2O2 to generate a variety of intermediates called reactive oxygen species (ROS) for signal enhancement. Factors that had important influences on the aptasensor, such as the concentration of Au-TDN, the incubation time, and the pH value of the buffer, were optimized in this trial. According to the final results, the limit of detection (LOD) of 3 pg mL-1 (S/N = 3) for methyl parathion, the LOD of 0.3 pg mL-1 (S/N = 3) for parathion and the LOD of 0.03 pg mL-1 (S/N = 3) for phoxim were obtained, respectively. Moreover, the novel tetrahedral structure could be replaced by different types of aptamers to expand its application range and lay a foundation for the development of portable rapid detection devices for pesticide residues.

Astragaloside IV relieves gestational diabetes mellitus in genetic mice through reducing hepatic gluconeogenesis.

The glucose intolerance developed during pregnancy is called gestational diabetes mellitus (GDM). GDM has become a severe risk for the health of both mother and baby. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus and has been reported to have anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. C57BL/KsJ-Lepdb/+ female mice were used as the GDM model. The mRNA levels of relative genes in this research were detected by quantitative real-time PCR. The protein levels of relative genes were analyzed by Western blot. Serum lipid level was measured with an ILab Chemistry Analyzer 300 PLUS. Glucose, insulin, and lipid profile levels in the GDM mice model were decreased by AS-IV treatment. AS-IV downregulated the expression of inflammatory genes and upregulated the expressions of anti-oxidant genes in the GDM mice model. AS-IV treatment reduced cAMP accumulation in liver and reduced hepatic gluconeogenesis in GDM mice. This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in a mice model through the regulation of cAMP accumulation and hepatic gluconeogenesis.

Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice.

BACKGROUND: As the most ordinary metabolic disorder during pregnancy, gestational diabetes mellitus (GDM) has become a severe risk for the health of both pregnant female and fetus. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus. It has been proved that AS-IV has anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. METHODS: C57BL/KsJ-Lepdb/+ female mice were used as GDM model. The mRNA levels of relative genes in this research were detected by qRT-PCR. The protein levels of relative genes were analyzed by western blot. Serum concentration of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were analyzed by ELISA. RESULTS: Glucose and insulin levels in GDM mice model were decreased by AS-IV treatment. AS-IV down-regulated the expression of inflammatory gene IL-6 and TNF-α in GDM mice model. AS-IV treatment inhibited the expression of NLR family pyrin domain containing-3 (NLRP3) inflammasome relative proteins in the pancreas of GDM mice. CONCLUSION: This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in mice model through the inhibition of NLRP3 inflammasome in the pancreas.

Examination of the association of physical activity during pregnancy after cesarean delivery and vaginal birth among Chinese women.

BACKGROUND: The goal was to study whether higher physical activity can increase the success rate of Vaginal Birth after Cesarean Delivery (VBAC). METHODS: We enrolled 823 patients with previous cesarean section delivery history (between January 2015 and December 2017) and measured their physical activity during pregnancy. A final number of 519 patients were included for the trial of labor after cesarean delivery (TOLAC). All patients signed informed consent forms. RESULTS: We conducted bivariate analyses and identified that several variables were associated with successful VBAC: Prior history of vaginal birth (odds ratio [OR] 2.4, 95% CI 1.8-3.9); previous indication for primary cesarean delivery (OR 2.2, 95% CI 1.5-3.0); age younger than 40 years (OR 2.1, 95% CI 1.3-3.4); Weight gain less than 20 kg (OR 1.5, 95% CI 1.3-2.4); high pelvic/birth weight score (OR 1.4, 95% CI 1.1-2.0); no induction of labor (OR 1.9, 95% CI 1.4-2.8); and estimated prenatal fetal weight (OR 1.4, 95% CI 1.2-1.5). We also found that the bivariate association between physical activity and VBAC was significant (p = 0.002). In addition, there was higher odds of VBAC in women who had active physical activity of more than 150 min/week (adjusted OR 1.86, 95% CI 1.69-2.07). Lower odds of VBAC was associated with older age, weight gain during pregnancy, induction of labor, and having estimated prenatal fetal weight more than 3500 g. CONCLUSION: Physical activity during pregnancy may influence the success rate of VBAC in Chinese women. Future studies will be needed to prove the robustness of this association using more detailed exposure and outcome definitions.

Naringenin enhances the efficacy of human embryonic stem cell-derived pancreatic endoderm in treating gestational diabetes mellitus mice.

Gestational diabetes mellitus (GDM) is a disease commonly occurs during mid to late pregnancy with pathologies such as hyperglycemia, hyperinsulinemia and mal-development of fetus. We have previously demonstrated that pancreatic endoderm (PE) derived from human embryonic stem cells (hESCs) effectively alleviated diabetic symptoms in a mouse model of GDM, although the clinical efficacy was limited due to oxidative stress. In this study, using the anti-oxidant agent naringenin, we aimed to further enhance the efficacy of hESC-derived PE transplant. Insulin-secreting PE was differentiated from hESCs, which were then transplanted into GDM mice. Naringenin was administered to mice receiving the PE transplant, with sham operated mice serving as negative control, to assess its effect on alleviation of GDM symptoms. We found that naringenin supplement further improved insulin response, glucose metabolism and reproductive outcome of the PE-transplanted female mice. Our new findings further potentiates the feasibility of using differentiated hESCs to treat GDM, in which anti-oxidative agent such as naringenin could greatly enhance the clinical efficacy of stem cell based therapies.

Protective effect of Tanshinone IIA against infarct size and increased HMGB1, NFκB, GFAP and apoptosis consequent to transient middle cerebral artery occlusion.

Acute inflammation plays an important role in brain damage following cerebral ischemia and reperfusion (I/R) injury. The present study employed a rat model of middle cerebral artery occlusion to explore the neuroprotective effects of tanshinone IIA (TSN), which is widely used in China for treating cerebrovascular and cardiovascular diseases. Rats were divided into a sham-operated group and I/R transiently occluded then reperfused groups. Some of the I/R animals were treated daily for 7 or 15 days with two different doses of TSN. After 15 days, triphenyl tetrazolium chloride staining revealed less unstained area indicating fewer lesions in the TSN-treated I/R group relative to the untreated corresponding I/R group. TSN treatment dramatically reduced infarct sizes and reduced content of high mobility group box 1 protein following I/R. Nuclear translocation of NFκB was also attenuated in I/R animals subsequently receiving TSN. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining revealed more apoptosis in the I/R model group and this was reduced in the I/R animals treated with TSN for 15 days. Thus, TSN mitigates the severity of damage effected by I/R.

Identification of a novel Providencia species showing multi-drug-resistant in three patients with hospital-acquired infection.

Providencia species are important opportunistic pathogens for humans and are associated with several infectious diseases. In this study, we found three clinical strains belonging to a novel Providencia species, namely Providencia huashanensis, including strains CRE-3FA-0001T, CRE-138-0026, and CRE-138-0111. These strains were recovered from three patients, and all of them were associated with nosocomial infections, including incision infection, urinary tract infection, and intracranial infection. The three strains showed high-level resistance to many types of antimicrobials, including amikacin, aztreonam, ceftazidime, cefepime, ciprofloxacin, colistin, polymyxin B, imipenem, meropenem, ceftazidime-avibactam, imipenem-relebactam. Investigation of the resistance mechanism revealed that acquired resistance genes such as blaKPC, blaNDM, blaPER, blaOXA, aac, ant, and qnrD, played an important role in the multi-drug-resistant phenotype for the three strains. The phylogenetic trees were reconstructed based on the 16S rRNA gene sequences, multi-locus sequence analysis, and core single nucleotide polymorphisms. The genome sequence of the strains had a range of 83.5%-85.8% average nucleotide identity and 21%-25.5% in silico DNA-DNA hybridization scores with other Providencia type strains. The average nucleotide identity and in silico DNA-DNA hybridization values and the phylogenetic trees indicated that the strains CRE-3FA-0001T, CRE-138-0026, and CRE-138-0111 strains should be considered as a novel species of the genus Providencia, for which the name P. huashanensis sp. nov. is proposed. The type strain is CRE-3FA-0001T = China Center for Type Culture Collection AB 2023186T = Korean Collection for Type Cultures 8373T.

Multiplex nanozymatic biosensing of Salmonella on a finger-actuated microfluidic chip.

A colorimetric biosensor was elaboratively designed for fast, sensitive and multiplex bacterial detection on a single microfluidic chip using immune magnetic nanobeads for specific bacterial separation, immune gold@platinum palladium nanoparticles for specific bacterial labeling, a finger-actuated mixer for efficient immunoreaction and two coaxial rotatable magnetic fields for magnetic nanobead capture (outer one) and magnet-actuated valve control (inner one). First, preloaded bacteria, nanobeads and nanozymes were mixed through a finger actuator to form nanobead-bacteria-nanozyme conjugates, which were captured by the outer magnetic field. After the inner magnetic field was rotated to successively wash the conjugates and push the H2O2-TMB substrate for resuspending these conjugates, colorless TMB was catalyzed into blue TMBox products, followed by color analysis using ImageJ software for bacterial determination. This simple biosensor enabled multiplex Salmonella detection as low as 9 CFU per sample in 45 min.

Physical exercise mediates cortical synaptic protein lactylation to improve stress resilience.

Lactate is a critical metabolite during the body's adaption to exercise training, which effectively relieves anxiety-like disorders. The biological mechanism of lactate in the exercise-mediated anxiolytic effect has, however, not been comprehensively investigated. Here, we report that exercise-induced lactate markedly potentiates the lactylation of multiple synaptic proteins, among which synaptosome-associated protein 91 (SNAP91) is the critical molecule for synaptic functions. Both anatomical evidence and in vivo recording data showed that the lactylation of SNAP91 confers resilience against chronic restraint stress (CRS) via potentiating synaptic structural formation and neuronal activity in the medial prefrontal cortex (mPFC). More interestingly, exercise-potentiated lactylation of SNAP91 is necessary for the prevention of anxiety-like behaviors in CRS mice. These results collectively suggest a previously unrecognized non-histone lactylation in the brain for modulating mental functions and provide evidence for the brain's metabolic adaption during exercise paradigms.

Stress increases hepatic release of lipocalin 2 which contributes to anxiety-like behavior in mice.

Chronic stress induces anxiety disorders via both neural pathways and circulating factors. Although many studies have elucidated the neural circuits involved in stress-coping behaviors, the origin and regulatory mechanism of peripheral cytokines in behavioural regulation under stress conditions are not fully understood. Here, we identified a serum cytokine, lipocalin 2 (LCN2), that was upregulated in participants with anxiety disorders. Using a mouse model of chronic restraint stress (CRS), circulating LCN2 was found to be related to stress-induced anxiety-like behaviour via modulation of neural activity in the medial prefrontal cortex (mPFC). These results suggest that stress increases hepatic LCN2 via a neural pathway, leading to disrupted cortical functions and behaviour.

Physical exercise mediates a cortical FMRP-mTOR pathway to improve resilience against chronic stress in adolescent mice.

Aerobic exercise effectively relieves anxiety disorders via modulating neurogenesis and neural activity. The molecular mechanism of exercise-mediated anxiolysis, however, remains incomplete. On a chronic restrain stress (CRS) model in adolescent mice, we showed that 14-day treadmill exercise profoundly maintained normal neural activity and axonal myelination in the medial prefrontal cortex (mPFC), in association with the prevention of anxiety-like behaviors. Further interrogation of molecular mechanisms revealed the activation of the mechanistic target of the rapamycin (mTOR) pathway within mPFC under exercise training. At the upstream of mTOR, exercise-mediated brain RNA methylation inhibited the expression of Fragile X mental retardation protein (FMRP) to activate the mTOR pathway. In summary, treadmill exercise modulates an FMRP-mTOR pathway to maintain cortical neural activity and axonal myelination, contributing to improved stress resilience. These results extended our understanding of the molecular substrate of exercise-mediated anxiolytic effect during adolescent period.

Dual-ratiometric aptasensor for simultaneous detection of malathion and profenofos based on hairpin tetrahedral DNA nanostructures.

Due to the diversification and complexity of organophosphorus pesticide residues brings great challenges to the detection work. Therefore, we developed a dual-ratiometric electrochemical aptasensor that could detect malathion (MAL) and profenofos (PRO) simultaneously. In this study, metal ions, hairpin-tetrahedral DNA nanostructures (HP-TDN) and nanocomposites were used as signal tracers, sensing framework and signal amplification strategy respectively to develop the aptasensor. Thionine (Thi) labeled HP-TDN (HP-TDNThi) provided specific binding sites for assembling Pb2+ labeled MAL aptamer (Pb2+-APT1) and Cd2+ labeled PRO aptamer (Cd2+-APT2). When the target pesticides were present, Pb2+-APT1 and Cd2+-APT2 were dissociated from the hairpin complementary strand of HP-TDNThi, resulting in reduced oxidation currents of Pb2+ (IPb2+) and Cd2+ (ICd2+), respectively, while the oxidation currents of Thi (IThi) remained unchanged. Thus, IPb2+/IThi and ICd2+/IThi oxidation current ratios were used to quantify MAL and PRO, respectively. In addition, the gold nanoparticles (AuNPs) encapsulated in the zeolitic imidazolate framework (ZIF-8) nanocomposites (Au@ZIF-8) greatly increased the catch of HP-TDN, thereby amplifying the detection signal. The rigid three-dimensional structure of HP-TDN could reduce the steric hindrance effect on the electrode surface, which could greatly improve the recognition efficiency of the aptasensor for the pesticide. Under the optimal conditions, the detection limits of the HP-TDN aptasensor for MAL and PRO were 4.3 pg mL-1 and 13.3 pg mL-1, respectively. Our work proposed a new approach to fabricating a high-performance aptasensor for simultaneous detection of multiple organophosphorus pesticides, opening a new avenue for the development of simultaneous detection sensors in the field of food safety and environmental monitoring.

Research on the experience of National Master of Traditional Chinese Medicine Professor Lu ZhiZheng in treating chronic atrophic gastritis based on data mining technology.

BACKGROUND: The purpose of this research is to summarize the academic expertise of Professor Lu Zhizheng in the treatment of Chronic Atrophic Gastritis, and to explain his clinical reasoning and common prescriptions in the treatment of CAG. METHODS: Professor Lu's outpatient cases of CAG from January 2008 to December 2021 were selected, and the PageRank algorithm was applied on the FangNet platform to analyze the usage frequencies of herbs, their four natures and five flavors according to Traditional Chinese Medicine, core herbs, and herb clustering patterns, with the goal of summarizing the distinguishing features of Professor Lu's academic and clinical approach to CAG. A total of 170 patients from 252 consultations were included in this study. The prescriptions involved a total of 239 herbs, which occurred a cumulative 4339 times. The herb natures were mainly warm, neutral, and slightly cold, and the herb flavors were predominantly sweet, bitter, and pungent. The channel tropism of the selected herbs primarily targeted the spleen, stomach, and lung meridians. Herb rank analysis showed that 34 herbs, including Gancao, Taizishen, Banxia, Huanglian, Shengjiang, Baizhu, Yiyiren, Maiya, Cangzhu, and Kuxingren, were the driver herbs used by Professor Lu for the treatment of CAG. RESULTS: Herb-herb co-occurrence/exclusivity analysis revealed 10 sets of frequently used herb pairs; herb cluster analysis yielded 10 herb clusters. These results reflected the emphasis Professor Lu placed on protecting Qi and Yin while clearing damp-heat. Professor Lu Zhizheng utilized dialectics reinforced with flexible thinking in the treatment of CAG, and emphasized that identifying the pathogenesis and addressing the syndrome should be prioritized. CONCLUSIONS: The characteristic treatment strategy aimed to replenish Qi and nourish Yin, clear away damp-heat, and treat CAG patients comprehensively under the guidance of established principles.

A novel electrochemical aptasensor based on core-shell nanomaterial labeling for simultaneous detection of acetamiprid and malathion.

At present, due to the coexistence of multiple pesticides in vegetables and the enhanced toxicity, a simultaneous detection method for multiple pesticides is urgently needed. In this work, two types of core-shell nanomaterials, Ag-Au core-shell nanoparticles (Ag@Au NPs) and Cu2O-Au core-shell nanoparticles (Cu2O@Au NPs), were synthesized and labeled with acetamiprid aptamer and malathion aptamer to prepare two novel electroactive signal probes, respectively. The two probes were hybridized on the surface of the electrode by the principle of base complementary pairing between the aptamers and the thiolated DNA oligonucleotide sequences, and a dual-signal electrochemical aptasensor for the simultaneous detection of acetamiprid and malathion was established by modified glassy carbon electrode (GCE). The limits of detection (LOD) were calculated to be 43.7 pg mL-1 for acetamiprid and 63.4 pg mL-1 for malathion. The aptasensor determined acetamiprid and malathion in spinach and rape with the recovery rates of 88.9%-112.5% and 98.0%-114.1%, respectively.

Portable electrochemiluminescence detection system based on silicon photomultiplier single photon detector and aptasensor for the detection of tetracycline in milk.

In this work, a portable electrochemiluminescence (ECL) detection system based on silicon photomultiplier (SiPM) single photon detector was proposed for the detection of ECL signals on a screen-printed electrode (SPE). This instrument innovatively used SiPM single photon detector to detect the ECL signal, which solved friability and bloat caused by the high operating voltage and the limitation of detection components in the traditional ECL detection instrument. This detection instrument showed excellent electrochemical and ECL detection performance. On this basis, an aptasensor based on silver (core)-gold (shell) bimetallic nanoparticles (Ag@AuNPs) was constructed for the detection of tetracycline (TET) in milk on SPE. Here, Ag@AuNPs had a significant effect in enhancing luminol ECL signal and immobilizing aptamer. The concentration of TET was detected according to the changes of the ECL signal intensity of the detection instrument. This instrument exhibited an excellent linearity ranging from 0.01 ng/mL to 1,000 ng/mL for the detection of TET, and a limit of detection (LOD) was 0.0053 ng/mL. The developed portable ECL detection instrument provides a new platform for the detection of small molecule contaminants.

Skin-Interfaced Superhydrophobic Insensible Sweat Sensors for Evaluating Body Thermoregulation and Skin Barrier Functions.

Monitoring sweat rate is vital for estimating sweat loss and accurately measuring biomarkers of interest. Although various optical or electrical sensors have been developed to monitor the sensible sweat rate, the quantification of the insensible sweat rate that is directly related to body thermoregulation and skin barrier functions still remains a challenge. This work introduces a superhydrophobic sweat sensor based on a polyacrylate sodium/MXene composite sandwiched between two superhydrophobic textile layers to continuously measure sweat vapor from insensible sweat with high sensitivity and rapid response. The superhydrophobic textile on a holey thin substrate with reduced stiffness and excellent breathability allows the permeation of sweat vapor, while preventing the sensor from being affected by the external water droplets and internal sensible sweat. Integrating the insensible sweat sensor with a flexible wireless communication and powering module further yields a standalone sensing system to continuously monitor insensible sweat rates at different body locations for diverse application scenarios. Proof-of-concept demonstrations on human subjects showcase the feasibility to continuously evaluate the body's thermoregulation and skin barrier functions for the assessment of thermal comfort, disease conditions, and nervous system activity. The results presented in this work also provide a low-cost device platform to detect other health-relevant biomarkers in the sweat (vapor) as the next-generation sweat sensor for smart healthcare and personalized medicine.

[Nuclear factor κB and IKB expression and calcium deposition of atherosclerotic plaques in apolipoprotein E and low density lipoprotein receptor knockout mice].

OBJECTIVE: To observe the histopathological features, nuclear factor-κB (NFκB) and IKB expressions as well as calcium deposition of atherosclerosis plaques (AS) in apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) knockout mice (ApoE(-/-), LDLR(-/-)fed high-fat diet. METHODS: Eight C57BL/6J mice fed with normal diet were used as control, 32 ApoE(-/-) mice and LDLR(-/-) mice were divided into normal diet and high-fat diet groups (n = 8 each). After 4 months, aorta was collected for morphologic (HE, Oil Red O, Von Kossa) and immunohistochemistry (nuclear factor-κB, IKB, macrophage surface molecule-3, α-smooth action protein) analysis. RESULTS: Degree of AS in ApoE(-/-) and LDLR(-/-) mice fed with high-fat diet were significantly severer than those fed with normal diet and AS was more significant in ApoE(-/-) mice than in LDLR(-/-) mice. NFκB and IKB expressions in high-fat diet group were significantly higher than the normal diet group (P < 0.05). Double-labeling of NFκB revealed dominant expression in smooth muscle cells. Calcium deposition was significantly more in ApoE(-/-) mice fed with high-fat diet than mice fed with normal diet (P < 0.05) and was similar in LDLR(-/-) mice fed with high and normal diet (P > 0.05). CONCLUSION: High-fat diet contributes to the formation of AS plagues in ApoE(-/-) and LDLR(-/-) mice joined by upregulated NFκB and IKB expressions and calcium deposition.

[Study on regulation of tanshinone II(A) on GFAP and ATPase and PDI of cerebral ischemia reperfusion injury in rats].

OBJECTIVE: To observe the neuroprotective effect of tanshinone II(A) (Tan II(A)) on the expression of brain tissue glial fibrillary acidic protein (GFAP) and adenosine triphosphatase (ATPase) and protein disulfide isomerase (PDI) of cerebral ischemia reperfusion (I/R) injury of different time in rats, and investigate the neuroprotective and its molecular mechanism of Tan II(A) on brain injury. METHODS: Sixty-four male Sprague-Dawley rats were randomly devided into eight groups (n = 8 per group): Group 1, sham-operated animals without I/R; Group 2, animals with I/R of 3 days; Group 3, animals with I/R of 7 days; Group 4, animals with I/R of 7 days and treatment with low doses of Tan II(A); Group 5, animals with IR of 7 days, treated with high doses of Tan II(A); Group 6, animals with I/R of 15 days; Group 7, animals with IR of 15 days and low doses of Tan II(A) treatment; Group 8, animals with I/R of 15 days, treated with high doses of Tan II(A). The model of focal middle cerebral artery occlusion (MCAO) was established by suture-occluded method. After Tan II(A) treatment, pathological changes of brain tissue in all groups were observed by hematoxylin-eosin staining (HE) and the expression levels of GFAP, ATP and PDI by immunohistochemistry staining. RESULTS: (1) The pathological changes of ischemic injury in low and high dose of Tan II(A) treatment groups were lighter than those in I/R groups, and so were in high dose of Tan II(A) treatment group than in low dose Tan II(A) treatment group. (2) Compared with sham-operated group, expression levels of GFAP in the three different I/R groups increased evidently, while the levels in high dose of Tan II(A) treatment groups were relatively low (P < 0.05). There was no statistically difference between high dose of Tan II(A) treatment group and low dose of Tan II(A) treatment group in either 7 or 15 days treatment groups (P > 0.05). (3) Compared with sham-operated group, expression levels of ATPase and PDI in the three different I/R groups all decreased clearly; Compared with I/R groups, expression levels of ATPase and PDI in Tan II(A) treatment groups increased in the ischemic territory obviously (P < 0.05). CONCLUSIONS: Tan II(A) may have a neuroprotective effect on ischemia-reperfusion injury by inhibiting the production of GFAP to reduce the excessive inflammatory response produced by glial cells in brain and up-regulating the activities of ATPase and PDI in neurons to improve the balance of energy metabolism and maintain the intracellular homeostasis.