Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Cognitive dysfunction in schizophrenia patients caused by downregulation of γ-aminobutyric acid receptor subunits

BACKGROUND The expression pattern of gamma aminobutyric acid(GABA)receptor subunits are commonly altered in patients with schizophrenia,which may lead to nerve excitation/inhibition problems,affecting cognition,emotion,and behavior.AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period.The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy.The recognized cognitive battery tool,the MATRICS Consensus Cognitive Battery,was used to evaluate the scores for various dimensions of cognitive function.The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed.RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups(P<0.05).A significant difference was also found between the case and control groups in terms of cognitive function measures,including attention/alertness and learning ability(P<0.05).Specifically,as the expression levels of GABRA1(α1 subunit gene),GABRB2(β2 subunit gene),GABRD(δsubunit),and GABRE(εsubunit)decreased,the severity of the patients’condition increased gradually,indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia(P<0.05).However,the expression levels of GABRA5(α5 subunit gene)and GABRA6(α6 subunit gene)showed no significant correlation with schizophrenia(P>0.05).CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia.In other words,when GABA receptor subunits are downregulated in patients,cognitive impairment becomes more severe.

Mudskipper interleukin-34 modulates the functions of monocytes/macrophages via the colony-stimulating factor-1 receptor 1

Interleukin-34(IL-34)is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colonystimulating factor-1 receptor(CSF-1R).However,information on the function of IL-34 in fish remains limited.In the present study,we identified an IL-34 homolog from mudskippers(Boleophthalmus pectinirostris).In silico analysis showed that the mudskipper IL-34(BpIL-34)was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper(Epinephelus coioides)homolog.BpIL-34 transcripts were constitutively expressed in various tissues,with the highest level of expression found in the brain.Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues.The recombinant mature BpIL-34 peptide(rBpIL-34)was purified and used to produce anti-rBpIL-34 IgG.Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages(MOs/MФs)was N-glycosylated.In vitro,rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs,as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factorα(BpTNF-α)and BpIL-1βin these cells.Furthermore,the knockdown of mudskipper CSF-1R1(BpCSF-1R1),but not mudskipper BpCSF-1R2,significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФfunction.In conclusion,our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.

Influences of Microwave on the Cognitive Function of Chickling and the Gene Expression of NMDA Receptor Subunit

[Objective] The research aimed to study the effects of microwave on the chick embryo development and the cognitive function of chickling. [Method] The microwave which was transmitted by the permatron and was 2 450 MHz was used to simulate the microwave radiation source to radiate the hatching eggs until the chickling was hatched out. The disposable passive avoidance learning and RT-PCR were respectively used to detect the influences of microwave on the cognitive function of chickling and the expression amounts of NMDA receptor NR1 and NR2 subunits. [Result] After the microwave radiation,the avoidance rate of exposed group was significantly lower than that in the control group. Especially the avoidance rate of highest radiation intensity group was extremely significantly lower than that in the control group. Meanwhile,the body weights of two groups of chickling in the exposed group increased,and the hatching time in one group increased. Via RT-PCR analysis,the expression amount of NR2 subunit increased on the 10th day and the 15th day. The expression amount of NR1 subunit only decreased on the 15th day. [Conclusion] The microwave had the certain influence on the individual development. By changing the structure composition and function of NMDA receptor in the endbrain,the microwave made the self-regulation ability of chickling decline,which had the certain damage on the cognitive function.

The biological function of type I receptors of bone morphogenetic protein in bone

Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.

Functional polymorphism among members of abscisic acid receptor family (ZmPYL) in maize

Pyrabactin resistance 1-like proteins (PYLs) are direct receptors of abscisic acid (ABA). For the redundant and polymorphic functions, some members of the PYL family interact with components of other signaling pathways. Here, 253 positive colonies from a maize cDNA library were screened as interacting proteins with the members of ZmPYL family. After sequencing and function annotation, 17 of 28 interaction combinations were verified by yeast two-hybrid (Y2H). The germination potential, taproot length and proline content of a quartet mutant of Arabidopsis PYL genes were significantly deceased comparing to the wild type (WT) under alkaline stress (pH 8.5) and 100 μmol L–1 methyl jasmonate (MeJA) induction. The malondialdehyde (MDA) content was significantly increased. After germinating in darkness, the characteristics of dark morphogenesis of the quartet mutant seedlings were more obvious than those of the WT. The differential expression of the related genes of photomorphogenesis in the mutant was much more than that in the WT. Three light and two JA responsive cis-affecting elements were identified during the promoter sequences of the AtPYL1 and AtPYL2 genes. These results suggested that functional polymorphism has evolved among the members of ZmPYL family. In response to developmental and environmental stimuli, they not only function as direct ABA receptors but also interact with components of other signaling pathways mediated JA, brassinosteroid (BR), auxin, etc., and even directly regulate downstream stress-related proteins. These signaling pathways can interact at various crosstalk points and different levels of gene expression within a sophisticated network.

Molecular characterization and functional expression of opioid receptor-libe_1 receptor

The opioid receptor-libel receptor (ORL), an orphan receptor whose human and murine complementary DNAs,has been characterized recently. ORL transcripts are particularly abundant in the central nervous system. We demonstrated that ORL expressed in human neuroblastoma SK-N-SH and SH-SY5Y cell lines by radioligand binding assay, reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis in the present study. Stimulation with ORL1 specific agonist, nociceptin/orphanin Fo, increased [34S]GTPrγS binding to SK-N-SH cell membranes (EC50 = 14 ±0.45 nM), and attenuated forskolin-stimulated accumulation of cellular cAMP (EC50= 0.80 ±0.45 nM, indicative that activation of ORL1 activates G proteins and inhibits adenylyl cyclase. Activation of ORL1 receptor was also accessed using CHO:hORL1 cell line by microphysiometer. Treatment of nociceptin/orphanin FQ increased extracellular acidification rate significantly.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

TSH RECEPTOR GENETIC ALTERATIONS IN THE AUTONOMOUSLY FUNCTIONING THYROID ADENOMAS

Objective To determine the relationship between TSH receptor gene mutations and autonomously functioning thyroid adenomas (AFTAs). Methods The thyroid samples from 14 cases of diagnosed AFTAs were analyzed, with normal thyroid specimens adjacent to the tumors as controls. The 155 base pairs DNA fragments which encompassed the third cytoplasmic loop and the sixth transmembrane segments in the TSH receptor gene exon 10 were amplified by Polymerase chain reaction (PCR) and analyzed by the single-strand conformation polymorphism (SSCP). Direct sequencing of the PCR products was performed with Prism Dye Terminator Cycle Sequencing Core Kit. Results 6 of 14 AFTA specimens displayed abnormal migration in SSCP analysis. In sequence analysis of 3 abnormally migrated samples, one base substitution at nucleotide 1957 (A to C) and two same insertion mutations of one adenosine nucleotide between nucleotide 1972 and 1973 were identified. No mutations were found in controls. Conclusion This study confirmed the presence of TSH receptor gene mutations in AFTAs; both one-point substitution mutation and one-base insertion mutation were found to be responsible for the pathogenesis of AFTAs.

Physiological and pharmacological functions of G protein coupled receptor 124:A review

G protein-coupled receptors(GPCRs)are the largest protein superfamily in the body,expressed in various tissues and organs,and are currently one of the most important clinical drug targets.Recently,a class of GPCRs without endogenous ligands(orphan GPCRs)have been discovered.They exhibit different physiological functions in the body and act extensively on the cardiovascular and cerebrovascular systems.Among them,G protein-coupled receptor 124(GPR124)is an orphaned member of the G protein coupled receptor adhesion family that has attracted much attention.It plays a key role in promoting cerebral angiogenesis and maintaining the stability of the blood-brain barrier.It also associated with cardiovascular and cerebrovascular diseases such as cerebral ischemia and atherosclerosis.However,the role of GPR124 in these diseases,the associated signaling pathways,and possible drug intervention targets are still unclear.This article summarizes the physiological effects,pharmacological effects and related signal pathways of GPR124 published in the field of cardiovascular and cerebrovascular diseases published in recent years,in order to provide a reference for the study of the role of GPR124 in the occurrence and development of diseases.

Functional expression of opioid receptor-like receptorand its endogenous specific agonist nociceptin/orphanin FQ during mouse embryogenesis

Expression of opioid receptor-like receptor (ORL1)and its endogenous peptide agonist nociceptin/orphaninFo (N/OFQ) during mouse embryogenesis have been investigated. Transcripts of ORL1 and N/OFQ were detected by RT-PCR in mouse brain of day 8 embryo (E8)and the expression continued afterwards. Northern blotanalysis revealed abundant expression of ORL1 at postnatal day 1 (P1) and N/OFQ at E17 and P1 in the brain butnone was detected in other embryonic tissues. The presence of functional ORL1 in mouse embryonic brain wasalso confirmed by specific binding of [3H] N/OFQ (kd=1.3±0.5 nM and Bmax = 72±9 fmol/mg protein) as wellas by N/OFQ-stimulated G protein activation.

Regulation of neural stem/progenitor cell functions by P2X and P2Y receptors

Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belonging to all three major linages（neurons,astrocytes and oligodendrocytes）of the nervous system（Tang and Illes,2017）.

Elafibranor alleviates alcohol-related liver fibrosis by restoring intestinal barrier function

We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of action of elafibranor(EFN),a dual agonist of peroxisome proliferator-activated receptorα(PPARα)and peroxisome PPARδ(PPARδ).EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis.ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis(ASH),with chronic ASH eventually leading to fibrosis,cirrhosis,and,in some cases,hepatocellular carcinoma.The pathogenesis of ALD is driven by hepatic steatosis,oxidative stress,and acetaldehyde toxicity.Alcohol consumption disrupts lipid metabolism by inactivating PPARα,exacerbating the progression of ALD.EFN primarily activates PPARα,promoting lipolysis andβ-oxidation in ethanol-stimulated HepG2 cells,which significantly reduces hepatic steatosis,apoptosis,and fibrosis in an ALD mouse model.Additionally,alcohol disrupts the gut-liver axis at several interconnected levels,contributing to a proinflammatory environment in the liver.EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy,inhibiting apoptosis and inflammatory responses,and enhancing intestinal barrier function through PPARδactivation.

Expression of c-kit receptor in peripheral blood mononuclear cells in patients with systemic lupus erythematosus

Objective： To determine the expression of c-kit receptor in peripheral blood mononuclear cells （PBMCs） in patients with systemic lupus erythematosus （SLE）, and analyze the relationship between the c-kit expression level of PBMCs and clinical parameters. Methods： Peripheral blood mononuclear cells in 47 patients with SLE and 21 healthy volunteers were collected. Expression of c-kit mRNA in PBMCs were determined with reverse transcription-polymerase chain reaction （RT-PCR）. The protein of c-kit receptor （CDllT） in PBMCs was measured by flow cytometry. Results： Expression of c-kit receptor protein and mRNA in patients with active or inactive SLE （ n = 47） were significantly higher than those in controls. The c-kit receptor of PBMCs in SLE patients were significantly higher than those in healthy controls （ n = 21 ）, the c-kit receptor of PBMCs in active patients （ n = 27） were significantly higher than those in inactive patients （ n = 20） and there was no significant difference was found between patients with inactive SLE and healthy controls（ P 〉 0.05）. The c-kit receptor of PBMCs in SLE have significant association with activity index. Conclusion： Production of c-kit receptor is aberrantly increased in PBMCs in patients with SLE. C-kit receptor might be more closely related to the clinical parameters in SLE patients, which might reflect the clinical status of SLE patients.

Oestrogen-androgen crosstalk in the pathophysiology oferectile dysfunction

<abstract>Ageing in man is associated with a decline in testosterone following changes in the hypothalamo-pituitary testicular axis. This may offset the physiologic equilibrium between oestrogen and androgen and at some point when the ratio of free testosterone to oestradiol reaches a critical level, the oestrogenic gonadotropin suppressive effect predominates with decreased release of FSH and LH. Adding to this endocrinal complexity is the continued peripheral conversion to oestradiol through aromatisation. Although the androgen deficiency is not the sole cause for impotence in the elderly, there is a gradual decrease in nocturnal penile tumescence (NPT) and spontaneous morning erections with ageing. Despite the age related increase in oestrogen levels, the information on the pathophysiological role of the 'female hormone' in erectile dysfunction has been scanty. Together with our identification of oestrogen receptors within the penile cavernosum, we have delineated dysfunctional changes on male erection mediated by oestradiol. These findings parallel the recent concerns over environmental oestrogens on fertility declines in young men. Oestrogenic activity is also present in plants and thereby in human diet. These phytoestrogens are structurally and functionally similar to oestradiol and more potent than the environmental oestrogenic chemicals such as organochlorine and phenolic compounds. Thus in the light of growing concerns of possible compromising effects on sexuality by endogenous and environmental oestrogens, we are faced with the scientific need to delineate their role on the mechanism of male erectile pathway in health and disease for clinical correlates and prognostics.

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction

AIM To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction. METHODS A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha was examined. RESULTS FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating proinflammatory factors such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. CONCLUSION FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses

The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activators of liver X receptors(LXRs),via sterol 27-hydroxylase,is regulated by the rate of flux of cholesterolto the inner mitochondrial membrane,via a complex of cholesterol trafficking proteins.Oxysterols are key signalling molecules,regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production,key features influencing the impact of these cells within atherosclerotic lesions.The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate,but may include steroidogenic acute regulatory protein and translocator protein.There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters(ABCA1,ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages.Thus,molecules which can sustain or improve mitochondrial structure,the function of the electron transport chain,or increase the activity of components of the protein complex involved in cholesterol transfer,may therefore have utility in limiting or regressing atheroma development,reducing the incidence of coronary heart disease and myocardial infarction.

Paired associative stimulation improves synaptic plasticity and functional outcomes after cerebral ischemia

Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cog-nition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China(approval No. TJ-A20151102) on July 11, 2015.

Electroacupuncture treatment improves motor function and neurological outcomes after cerebral ischemia/reperfusion injury

Electroacupuncture(EA)has been widely used for functional restoration after stroke.However,its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood.In this study,we applied EA to the Zusanli(ST36)and Quchi(LI11)acupoints in rats with middle cerebral artery occlusion and reperfusion.We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B,synapsin-1,postsynaptic dense protein 95,and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion.Moreover,EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra.Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA.These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion,possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway.All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine,China(approval No.PZSHUTCM200110002)on January 10,2020.

How functional foods play critical roles in human health

How do functional foods affect human health?To answer this question it is important to understand what happens when food is digested and taken up by the gastrointestinal(GI)tract.The gut is a selective nutrient absorption system and the most important signal transduction and information exchange system within the body.It acts as a signal transducer,a neuroendocrine sensor,and an immunological recognition and presentation system.It is also a complex information exchange system comprising a number of signaling networks involving GI cells and cells immobilized in organs or transported in blood.The bioactivity of functional foods in vivo may be due to their effects on such networks,but this raises the question of what signaling pathways are used by non-nutrients that cannot be absorbed by the gut.The purpose of this review is to describe intestinal nutrient transportation,identify a number of widely expressed receptors and signal transduction pathways,and outline our current understanding of the mechanisms involved in health and disease.At the end of the review,a method for developing a cell communication network is described.This network is convenient for investigating the effects of oral administration of experimental medicines,drugs,or functional foods on cytokines of interest.Because cytokines and chemokines are transported via the circulatory system,a simple 2–3 mL blood sample from a volunteer is a rich source of information.This method may become the gold standard for evaluating the effects of functional foods or medicines in vivo.©2012 Production and hosting by Elsevier B.V.on behalf of Beijing Academy of Food Sciences.