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

Objective To observe the effects of hepatic ischemia-reperfusion (HIR) on blood-brain barrier (BBB) permeability and brain tissue apoptosis in young mice. Methods Twenty-four healthy and clean grade C57BL/6 young mice were randomly divided into the sham operation group, dextran glycoside 10 group, and dextran glycoside 40 group, with 8 mice in each group. The HIR models were established by clamping the left hepatic artery and portal vein in mice of both dextran glycoside 10 and 40 groups. After 60 min of reperfusion, dextran glycoside with a molecular weight of 10 and 40 Kd was injected into the inferior vena cava, respectively. Mice in the sham operation group only underwent abdominal opening and closing, free blood vessels, and other procedures. Immunofluorescence staining was used to observe the permeability of brain tissue BBB (expressed as the pass rate of dextran glycoside), Western blotting was used to detect the indicators related to BBB tight junction protein in brain tissues, including Claudin, Occludin and β-Catenin and tight junction protein 1 (ZO-1), and TUNEL method was used to detect the apoptosis rate of brain tissues. Results Compared with the sham operation group, the dextran glycoside 10 group and the dextran glycoside 40 group had higher passing rates of dextran glycoside and apoptosis rates in the brain tissues of young mice, and the low-dose group had a higher passing rate of dextran glycoside (all P<0. 05) . Compared with the sham operation group, the relative expression levels of Claudin, Occludin, and β-Catenin and ZO-1 proteins decreased (all P<0. 05), and there were no statistically significant differences in the above indicators between the dextran glycoside 10 and 40 groups (all P>0. 05) . Conclusion HIR can lead to increased BBB permeability and increased apoptosis of brain tissues in young mice. [ABSTRACT FROM AUTHOR]

Glucose uptake by peripheral organs is essential for maintaining blood glucose levels within normal range. Impaired glucose uptake is a hallmark of type 2 diabetes (T2D) and metabolic syndrome and is characterized by insulin resistance. Male sex is an independent risk factor for the development of T2D. We tested whether sex and diet are independent variables for differential glucose uptake by various organs. Here, in a longitudinal study, we used 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) to determine baseline differences in whole-body glucose uptake in young male and female mice on chow and high-fat diets. We report that sex and diet are important independent variables that account for differential glucose uptake in brown fat, skeletal muscle, liver, heart, kidney, and the stomach, but not the brain, lungs, pancreas, small intestine, or perigonadal adipose. Of the seven organs analyzed, two organs, namely brown fat, and the heart had the highest concentrations of FDG, followed by the brain, kidneys, and skeletal muscle on chow diet. Young female mice had 47% greater FDG uptake in the brown fat compared to male mice, whereas skeletal muscle FDG uptake was 49% greater in male mice. The high-fat diet inhibited FDG uptake in brown fat, skeletal muscle, and the heart, three major organs involved in uptake, whereas brain uptake was enhanced in both sexes. These foundational and groundbreaking findings suggest that mechanisms of glucose homeostasis are context- and organ-dependent and highlight the need to study sex-specific outcomes and mechanisms for diseases such as T2D, obesity, and metabolic syndrome.

Depression is the most common complication of childhood epilepsy, leading to a poor prognosis for seizure control and poor quality of life. However, the molecular mechanisms underlying epileptic depression have not been completely elucidated. Increasing evidence suggests that oxidative stress and neuroinflammation are major contributors to depression. The positive effects of dietary supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on depression have been previously reported. However, knowledge regarding the effects of EPA and DHA in managing depressive symptoms in pediatric patients with epilepsy is limited. Therefore, this study aims to investigate the effects of EPA and DHA on epileptic depression in a pentylenetetrazole (PTZ)-treated young mouse model. Three-week-old mice were fed a DHA- or EPA-enriched diet for 21 days and treated with PTZ (35 mg/kg, i.p.) every other day for a total of 10 times. EPA was more effective than DHA at alleviating PTZ-induced depressive symptoms. Pathological results revealed that DHA and EPA significantly improved neuronal degeneration in the hippocampus. Analysis of the mechanism revealed that DHA and EPA mitigated PTZ-induced myelin damage by increasing the protein levels of CNPase, Olig2, and MBP. Furthermore, both DHA and EPA reduced neuroinflammation by promoting microglial M2 polarization and suppressing the LCN2-NLRP3 inflammasome pathway. Notably, EPA polarized microglia towards the M2 phenotype. In addition, DHA and EPA decreased oxidative stress by inhibiting NOX2 and enhancing mitochondrial metabolism through the increased expression of mitochondrial respiratory chain complex I-V proteins. These findings suggest that DHA and EPA can be used as effective interventions to improve depression in children with epilepsy, with EPA being a particularly favorable option. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have reported the benefits of docosahexaenoic acid (DHA) on neurodevelopment and cognitive ability, while comparatively less attention has been given to eicosapentaenoic acid (EPA). Additionally, little is known about the effects and mechanisms of DHA and EPA in relation to seizure-induced cognitive impairment in the young rodent model. Current research indicates that ferroptosis is involved in epilepsy and cognitive deficiency in children. Further investigation is warranted to determine whether EPA or DHA can mitigate seizure-induced cognitive deficits by inhibiting ferroptosis. Therefore, this study was conducted to compare the effects of DHA and EPA on seizure-induced cognitive deficiency and reveal the underlying mechanisms focused on ferroptosis in a pentylenetetrazol (PTZ)-kindling young mice model. Mice were fed a diet containing DHA-enriched ethyl esters or EPA-enriched ethyl esters for 21 days at the age of 3 weeks and treated with PTZ (35 mg/kg, i.p.) every other day 10 times. The findings indicated that both EPA and DHA exhibited ameliorative effects on seizure-induced cognitive impairment, with EPA demonstrating a superior efficacy. Further mechanism study revealed that supplementation of DHA and EPA significantly increased cerebral DHA and EPA levels, balanced neurotransmitters, and inhibited ferroptosis by modulating iron homeostasis and reducing lipid peroxide accumulation in the hippocampus through activating the Nrf2/Sirt3 signal pathway. Notably, EPA exhibited better an advantage in ameliorating iron dyshomeostasis compared to DHA, owing to its stronger upregulation of Sirt3. These results indicate that DHA and EPA can efficaciously alleviate seizure-induced cognitive deficiency by inhibiting ferroptosis in PTZ-kindled young mice. [ABSTRACT FROM AUTHOR]

Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A + neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility. [ABSTRACT FROM AUTHOR]

Air pollution has become one of the most serious health risks as a result of industrialization, especially in developing countries. More attention has been drawn to the relationship between obesity/overweight and fine particulate matter (PM2.5). Especially for susceptible populations, the impact of air pollution on children and adolescents has attracted more public attentions. However, the detailed underlying mechanism influencing obesity or overweight under PM2.5 exposure is still unknown. Therefore, young mice were exposed to PM2.5 using the real-ambient exposure system that we previously established in Shijiazhuang city. Compared with the traditionally concentrated air particle (CAP) system, our real-ambient exposure system provides similar PM2.5 concentrations and characteristics as outdoor ambient air and minimizes the influence of external interfering factors. After 8 weeks of exposure to PM2.5, the weight of gonadal white adipose tissue (gWAT) and subcutaneous white adipose tissue (sWAT) was considerably increased, accompanied by a significantly enlarged size of adipocytes in sWAT. Importantly, multiomics analysis indicated altered metabolites involved in the lipid metabolism pathway, and transcriptomic analysis revealed notably changed signaling pathways related to fatty acid metabolism. Moreover, the mtDNA copy number, mitochondrial activity and fatty acid oxidation (FAO) were increased in the liver under PM2.5 exposure. Taken together, our research investigated the hypotrophy of adipose tissue in young mice, supported an imbalance in lipid metabolism based on multiomics analysis, and revealed disordered mitochondrial function under PM2.5 exposure. Our study provided new insight into the hazardous effects of air pollution, and extended our understanding on the underlying mechanism. [ABSTRACT FROM AUTHOR]

Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Depression is the most common complication of childhood epilepsy, leading to a poor prognosis for seizure control and poor quality of life. However, the molecular mechanisms underlying epileptic depression have not been completely elucidated. Increasing evidence suggests that oxidative stress and neuroinflammation are major contributors to depression. The positive effects of dietary supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on depression have been previously reported. However, knowledge regarding the effects of EPA and DHA in managing depressive symptoms in pediatric patients with epilepsy is limited. Therefore, this study aims to investigate the effects of EPA and DHA on epileptic depression in a pentylenetetrazole (PTZ)-treated young mouse model. Three-week-old mice were fed a DHA- or EPA-enriched diet for 21 days and treated with PTZ (35 mg/kg, i.p.) every other day for a total of 10 times. EPA was more effective than DHA at alleviating PTZ-induced depressive symptoms. Pathological results revealed that DHA and EPA significantly improved neuronal degeneration in the hippocampus. Analysis of the mechanism revealed that DHA and EPA mitigated PTZ-induced myelin damage by increasing the protein levels of CNPase, Olig2, and MBP. Furthermore, both DHA and EPA reduced neuroinflammation by promoting microglial M2 polarization and suppressing the LCN2-NLRP3 inflammasome pathway. Notably, EPA polarized microglia towards the M2 phenotype. In addition, DHA and EPA decreased oxidative stress by inhibiting NOX2 and enhancing mitochondrial metabolism through the increased expression of mitochondrial respiratory chain complex I-V proteins. These findings suggest that DHA and EPA can be used as effective interventions to improve depression in children with epilepsy, with EPA being a particularly favorable option.

Severe malaria occurs most in young children but is poorly understood due to the absence of a developmentally‐equivalent rodent model to study the pathogenesis of the disease. Though functional and quantitative deficiencies in innate response and a biased T helper 1 (Th1) response are reported in newborn pups, there is little information available about this intermediate stage of the adaptive immune system in murine neonates. To fill this gap in knowledge, we have developed a mouse model of severe malaria in young mice using 15‐day old mice (pups) infected with Plasmodium chabaudi. We observe similar parasite growth pattern in pups and adults, with a 60% mortality and a decrease in the growth rate of the surviving young mice. Using a battery of behavioral assays, we observed neurological symptoms in pups that do not occur in infected wildtype adults. CD4+ T cells were activated and differentiated to an effector T cell (Teff) phenotype in both adult and pups. However, there were relatively fewer and less terminally differentiated pup CD4+ Teff than adult Teff. Interestingly, despite less activation, the pup Teff expressed higher T‐bet than adults' cells. These data suggest that Th1 cells are functional in pups during Plasmodium infection but develop slowly. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have reported the benefits of docosahexaenoic acid (DHA) on neurodevelopment and cognitive ability, while comparatively less attention has been given to eicosapentaenoic acid (EPA). Additionally, little is known about the effects and mechanisms of DHA and EPA in relation to seizure-induced cognitive impairment in the young rodent model. Current research indicates that ferroptosis is involved in epilepsy and cognitive deficiency in children. Further investigation is warranted to determine whether EPA or DHA can mitigate seizure-induced cognitive deficits by inhibiting ferroptosis. Therefore, this study was conducted to compare the effects of DHA and EPA on seizure-induced cognitive deficiency and reveal the underlying mechanisms focused on ferroptosis in a pentylenetetrazol (PTZ)-kindling young mice model. Mice were fed a diet containing DHA-enriched ethyl esters or EPA-enriched ethyl esters for 21 days at the age of 3 weeks and treated with PTZ (35 mg/kg, i.p.) every other day 10 times. The findings indicated that both EPA and DHA exhibited ameliorative effects on seizure-induced cognitive impairment, with EPA demonstrating a superior efficacy. Further mechanism study revealed that supplementation of DHA and EPA significantly increased cerebral DHA and EPA levels, balanced neurotransmitters, and inhibited ferroptosis by modulating iron homeostasis and reducing lipid peroxide accumulation in the hippocampus through activating the Nrf2/Sirt3 signal pathway. Notably, EPA exhibited better an advantage in ameliorating iron dyshomeostasis compared to DHA, owing to its stronger upregulation of Sirt3. These results indicate that DHA and EPA can efficaciously alleviate seizure-induced cognitive deficiency by inhibiting ferroptosis in PTZ-kindled young mice.

Research shows that across life, the incidence of mental illness is highest in the young. In the context of the COVID-19 pandemic, mental health issues of the young in particular have received global attention. The rostral anterior cingulate cortex (rACC) plays an important role in psychiatric disorders and chronic pain-psychiatric comorbidities. However, it remains unknown whether or how the afferent and efferent circuits of the rACC change with aging. In this study, we microinjected a retrograde tracer virus and an anterograde trans-monosynaptic virus into the rACC of young and middleaged mice (both male and female), and systematically and quantitatively analyzed the whole-brain afferent and efferent connections of rACC at different ages and sexes. Notably, in young and middle-aged mice, afferents of the rACC belong to four groups of brain structures arising mainly from the amygdala [mainly basolateral amygdaloid nucleus (BLA)] and cerebral cortex (mainly orbital cortex), with a small part originating from the basal forebrain and thalamus. In contrast, efferents of the rACC belong to four groups of brain structures mainly projecting to the thalamus (mainly ventral anteriorlateral/ ventromedial thalamic nucleus (VAL/VM)], with a very small part projecting to the amygdala, basal forebrain, and cerebral cortex. Compared with young mice, the BLA-rACC circuit in middle-aged mice (male and female) did not change significantly, while the rACC-VAL/VM circuit in middle-aged mice (male and female) decreased significantly. In conclusion, this study comprehensively analyzed the input-output neural projections of rACC in mice of different ages and sexes and provided preliminary evidence for further targeted research. [ABSTRACT FROM AUTHOR]

To investigate the effects and mechanism of budesonide suspension on epithelial-mesenchymal transition and airway remodeling in asthmatic young rats. Asthmatic infant rats (n=36) were randomly divided into three groups-model group, budesonide 1 group, and budesonide 2 groups. The three groups were given aerosol inhalation of normal saline, budesonide suspension 0.1 mg, budesonide suspension 0.2 mg, 1 time/d, for a total of 14 days, detected and observed the changes of epithelial-mesenchymal transition and airway remodeling in the rats. The total number of leukocytes and eosinophils in the bronchoalveolar lavage fluid of the budesonide group 1 and budesonide group 2 were lower than those of the model group (P<0.05), and the budesonide group 2 were lower than the budesonide group 1 (P<0.05). The serum tumor necrosis factor (TNF)-琢 and heme oxygenase (HO)-1 levels in budesonide group 1 and budesonide group 2 were lower than those in the model group (P<0.05), and the budesonide group 2 were lower than budesonide group 1 (P<0.05). The bronchial wall thickness (WAt/Pi), the number of bronchial wall smooth muscle cell nuclei (N/Pi) and the bronchial wall smooth muscle thickness (WAm/Pi) of the budesonide group 1 and budesonide group 2 were higher than those of the model group, and the budesonide group 2 were higher than the budesonide group 1 (P<0.05). The relative expression levels of E-cadherin and NF-资B protein in lung tissues of budesonide group 1 and budesonide group 2 were lower than those of the model group (P<0.05), and budesonide group 2 were lower than budesonide group 1 (P<0.05). The application of budesonide suspension in asthmatic young mice can inhibit epithelial-mesenchymal transition and airway remodeling, and can also inhibit the release of TNF-琢 and HO-1, and reduce the infiltration of acidic granulocytes and leukocytes, thereby reduce the infiltration of acidic granulocytes and leukocytes. So as to play lung protective effect, and there are dose-dependent. [ABSTRACT FROM AUTHOR]

Rationale: Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. Methods: Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and GABAergic transmission in the hippocampus. Objectives: To determine the contribution of hippocampal NRG1 to fear memory forgetting and low-frequency stimulation (LFS)–induced LTD. Results: Administration of NRG1 in the hippocampus accelerated forgetting of contextual fear memories. Furthermore, NRG1 had no effect on low-frequency stimulation–induced LTD in young mice but significantly facilitated the induction of LTD and GABAergic transmission in adult animals. More importantly, NRG1-facilitated LTD induction in adult mice could be blocked by inhibition of GABAA receptors and NMDAR activation. Conclusion: These findings suggest a role for NRG1 in fear memory forgetting and hippocampal LTD, providing a potential target for the development of drug-assisted PTSD therapy. [ABSTRACT FROM AUTHOR]

Changes in the plasma metabolism of young ICR mice after exposure to nano-TiO2 at different doses were measured to investigate the mechanism of its toxic side-effects and to identify its toxicity-related biological targets. Mice were assigned randomly to control group and nano-TiO2 (10, 30, 100, or 300 mg⋅kg-1 ) exposure groups. Plasma data were analyzed using metabonomics technology to identify potential biomarkers. Topology of biomarkers was determined using the KEGG database. Contents of cholic acid, deoxycholic acid, ursodeoxycholic acid and taurocholic acid in plasma were measured by targeted quantitative methods to find the biomarkers corresponding to the toxic effects of TiO2. Forty-nine metabolites were screened from plasma. The toxicity of nano-TiO2 resulted mainly from an abnormality of phospholipids and bile-acid compounds. The toxicity of nano-TiO2 in mice after 28 d exposure may be related to the abnormal metabolism of phospholipids and bile-acid compounds. [ABSTRACT FROM AUTHOR]

Tau phosphorylation is associated with cognitive impairment in young mice. However, the underlying mechanism and targeted interventions remain mostly unknown. We set out to determine the potential interactions of Tau, interleukin 6 (IL-6) and mitochondria following treatment of anesthetic sevoflurane and to assess their influences on synapse number and cognition in young mice. Sevoflurane (3% for 2 ​h) was given to wild-type, Tau knockout, IL-6 knockout, and cyclophilin D (CypD) knockout mice on postnatal (P) day 6, 7 and 8. We measured amounts of phosphorylated Tau, IL-6, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, postsynaptic density 95 (PSD-95), synaptophysin, N-cadherin, synapse number, and cognitive function in the mice, employing Western blot, electron microscope and Morris water maze among others. Here we showed that sevoflurane increased Tau phosphorylation and caused IL-6 elevation, mitochondrial dysfunction, synaptic loss and cognitive impairment in young wild-type, but not Tau knockout, mice. In young IL-6 knockout mice, sevoflurane increased Tau phosphorylation but did not cause mitochondrial dysfunction, synaptic loss or cognitive impairment. Finally, sevoflurane increased Tau phosphorylation and IL-6 amount, but did not induce synaptic loss and cognitive impairment, in young CypD knockout mice or WT mice pretreated with idebenone, an analog of co-enzyme Q10. In conclusion, sevoflurane increased Tau phosphorylation, which caused IL-6 elevation, leading to mitochondrial dysfunction in young mice. Such interactions caused synaptic loss and cognitive impairment in the mice. Idebenone mitigated sevoflurane-induced cognitive impairment in young mice. These studies would promote more research to study Tau in young mice.

Objective: To compare the differences of glycogen metabolism in different brain regions between young mice and old mice, and lay the foundation for further studies. Methods: The tissues of cortex, hippocampus and striatumof male C57BL/6J young mice (8 weeks old) and old mice (18 months old) were separately collected. The glycogen levels in these tissues were analyzed with a glycogen assay kit. Western blot was used to detect the expression levels of glycogen metabolism related enzymes. Results: Compared to young mice, glycogen levels in the cortex and striatum in old mice were significantly increased, but glycogen level in the hippocampus showed no significant change. Among key enzymes of glycogenesis, the expression of glycogen synthase 1 (GYS1) in the cortex and striatum in old mice was obviously increased, but it didn't show obvious difference in the hippocampus; the expression of glycogen branch enzyme 1 (GBE1) in the cortex was decreased, however, there were no significant changes in the hippocampus and striatum. Among key enzymes of glycogenolysis, the expression of glycogen phosphorylase, brain form (PYGB) in the cortex, hippocampus and striatum was increased, but there were no significant differences in the expression of glycogen debranch enzyme (AGL) in these regions. The expression of glucose transporter 1 in these regions was not significantly changed between young mice and old mice. In addition, among monocarboxylic acid transporters, the levels of monocarboxylic acid transporter 1 (MCT1) in these brain regions in old mice were significantly increased. The levels of monocarboxylic acid transporter 4 (MCT4) in the cortex were obviously increased, but there were no significant differences in other brain regions.Conclusion: Generally, brain glycogen levels in old mice were higher than that in young mice. The expressions of enzymes in the pathway of brain glycogen metabolismin old mice were significantly different from that in young mice, and the glycogen metabolism differences were highly heterogeneous among various brain regions. [ABSTRACT FROM AUTHOR]

Gel-forming mucins are the main organic component responsible for physical properties of the mucus hydrogels. While numerous biological functions of these mucins are well documented, specific physiological functions of each mucin are largely unknown. To investigate in vivo functions of the gel-forming mucin Muc5b, which is one of the major secreted airway mucins, along with Muc5ac, we generated mice in which Muc5b was disrupted and maintained in the absence of environmental stress. Adult Muc5b-deficient mice displayed bronchial hyperplasia and metaplasia, interstitial thickening, alveolar collapse, immune cell infiltrates, fragmented and disorganized elastin fibers and collagen deposits that were, for approximately one-fifth of the mice, associated with altered pulmonary function leading to respiratory failure. These lung abnormalities start early in life, as demonstrated in one-quarter of 2-day-old Muc5b-deficient pups. Thus, the mouse mucin Muc5b is essential for maintaining normal lung function.

Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of inflammatory bowel disease (IBD) in children. It is important to determine whether helminth therapy would be of value in pediatric IBD and whether triggering immunological memory to the worm would be anticolitic. Three-week-old (young) and eight-week-old (adult) Balb/c mice were infected with H. diminuta, and infectivity and T helper 2 (Th2) immunity were assessed. Other mice received H. diminuta with or without a crude worm extract (HdE) 28-42 days postinfection (dpi) with or without dinitrobenzene sulphonic acid [DNBS, 1.5 mg (young) or 3 mg (adults), ir], and colitis was assessed 72 h later. Infected young mice developed Th2 immunity and expelled H. diminuta; expulsion was delayed by ~2 days compared with adult mice. Colitis, as gauged by macroscopic disease and histopathology scores, was less severe in young mice infected 10 days, but not 8 days, before DNBS. Protection against DNBS-induced colitis was accompanied by an increased capacity to make interleukin (IL)-4 and IL-10. Mice infected with H. diminuta were not protected from DNBS-colitis when challenged 28 days later; however, injection of these mice with HdE coincident with DNBS resulted in less disease and increased splenic IL-4 and IL-10. Using a boost (500 µg HdE, 28 dpi) and repeat HdE (100 µg, 42 dpi) regimen with infected mice suppressed DNBS-colitis, as did adoptive transfer of splenic CD4+ T cells from infected mice with low-dose HdE challenge. Should these data translate to IBD, then helminth therapy could be of value in pediatric-onset IBD, and defining the antigen(s) that elicit antihelminth immunological memory could serve as an anticolitic approach in previously infected individuals. [ABSTRACT FROM AUTHOR]

Hepatic ischemic reperfusion (HIR) is a common pathophysiological process in many surgical procedures such as liver transplantation (LT) and hepatectomy. And it is also an important factor leading to perioperative distant organ damage. Children undergoing major liver surgery are more susceptible to various pathophysiological processes, including HIR, since their brains are still developing and the physiological functions are still incomplete, which can lead to brain damage and postoperative cognitive impairment, thus seriously affecting the long-term prognosis of the children. However, the present treatments of mitigating HIR-induced hippocampal damage are not proven to be effective. The important role of microRNAs (miRNAs) in the pathophysiological processes of many diseases and in the normal development of the body has been confirmed in several studies. The current study explored the role of miR-122-5p in HIR-induced hippocampal damage progression. HIR-induced hippocampal damage mouse model was induced by clamping the left and middle lobe vessels of the liver of young mice for 1 h, removing the vessel clamps and re-perfusing them for 6 h. The changes in the level of miR-122-5p in the hippocampal tissues were measured, and its influences on the activity as well as apoptotic rate of neuronal cells were investigated. Short interfering RNA modified with 2'-O-methoxy substitution targeting long-stranded non-coding RNA (lncRNA) nuclear enriched transcript 1 (NEAT1) as well as miR-122-5p antagomir were used to further clarify the role played by the corresponding molecules in hippocampal injury in young mice with HIR. The result obtained in our study was that the expression of miR-122-5p in the hippocampal tissue of young mice receiving HIR is reduced. Upregulated expression of miR-122-5p reduces the viability of neuronal cells and promotes the development of apoptosis, thereby aggravating the damage of hippocampal tissue in HIR young mice. Additionally, in the hippocampal tissue of young mice receiving HIR, lncRNA NEAT1 exerts some anti-apoptotic effects by binding to miR-122-5p, promoting the expression of Wnt1 pathway. An essential observation of this study was the binding of lncRNA NEAT1 to miR-122-5p, which upregulates Wnt1 and inhibits HIR-induced hippocampal damage in young mice. • Hepatic I/R injury causes hippocampal tissue damage in young mice with increasedlncRNA NEAT1 and decreased miR-122-5p • lncRNA NEAT1 can act as ceRNA, bind to miR-122-5p and regulate the expression of downstream Wnt1/β-catenin signaling pathway • lncRNA NEAT1/miR-122-5p/Wnt1 can play a protective role during hippocampal tissue injury in young mice with hepatic I/R [ABSTRACT FROM AUTHOR]

To investigate the neuron toxicities of low-dose exposure to bisphenol A (BPA) in children, mice were used as an animal model. We examined brain cell damage and the effects of learning and memory ability after BPA exposure in male mice (4 weeks of age) that were divided into four groups and chronically received different BPA treatments for 8 weeks. The comet assay and hippocampal neuron counting were used to detect the brain cell damage. The Y-maze test was applied to test alterations in learning and memory ability. Long term potentiation induction by BPA exposure was performed to study the potential mechanism of performance. The percentages of tail DNA, tail length and tail moment in brain cells increased with increasing BPA exposure concentrations. Significant differences in DNA damage were observed among the groups, including between the low-dose and control groups. In the Y-maze test, the other three groups qualified for the learned standard one day earlier than the high-exposed group. Furthermore, the ratio of qualified mice in the high-exposed group was always the lowest among the groups, indicating that high BPA treatment significantly altered the spatial memory performance of mice. Different BPA treatments exerted different effects on the neuron numbers of different regions in the hippocampus. In the CA1 region, the high-exposed group had a significant decrease in neuron numbers. A non-monotonic relationship was observed between the exposure concentrations and neuron quantity in the CA3 region. The hippocampal slices in the control and medium-exposed groups generated long-term potentiation after induction by theta burst stimulation, but the low-exposed group did not. A significant difference was observed between the control and low-exposed groups. In conclusion, chronic exposure to a low level of BPA had adverse effects on brain cells and altered the learning and memory ability of adolescent mice. [ABSTRACT FROM AUTHOR]

Subcutaneous daily injection (with neglect of aseptics) of 0.5 ml solution of soybean cream substitute (10% volume in distilled water) during 30 days caused systemic amyloidosis in 30-day-old mice. All the known methods for induction of systemic amyloidosis are based on the use of old animals, as senile tissue bradytrophy allows effective simulation of amyloidosis. [ABSTRACT FROM AUTHOR]

Air pollution has become one of the most serious health risks as a result of industrialization, especially in developing countries. More attention has been drawn to the relationship between obesity/overweight and fine particulate matter (PM2.5). Especially for susceptible populations, the impact of air pollution on children and adolescents has attracted more public attentions. However, the detailed underlying mechanism influencing obesity or overweight under PM2.5 exposure is still unknown. Therefore, young mice were exposed to PM2.5 using the real-ambient exposure system that we previously established in Shijiazhuang city. Compared with the traditionally concentrated air particle (CAP) system, our real-ambient exposure system provides similar PM2.5 concentrations and characteristics as outdoor ambient air and minimizes the influence of external interfering factors. After 8 weeks of exposure to PM2.5, the weight of gonadal white adipose tissue (gWAT) and subcutaneous white adipose tissue (sWAT) was considerably increased, accompanied by a significantly enlarged size of adipocytes in sWAT. Importantly, multiomics analysis indicated altered metabolites involved in the lipid metabolism pathway, and transcriptomic analysis revealed notably changed signaling pathways related to fatty acid metabolism. Moreover, the mtDNA copy number, mitochondrial activity and fatty acid oxidation (FAO) were increased in the liver under PM2.5 exposure. Taken together, our research investigated the hypotrophy of adipose tissue in young mice, supported an imbalance in lipid metabolism based on multiomics analysis, and revealed disordered mitochondrial function under PM2.5 exposure. Our study provided new insight into the hazardous effects of air pollution, and extended our understanding on the underlying mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Si, Gao, Yang, Zhu, Han, Li, Wang, Li, Zhao, Chen, Zheng and Jiang.)

Recent studies show that myosin light chain kinase (MLCK) plays a pivotal role in development of cerebral edema, a known complication following traumatic brain injury (TBI) in children and a contributing factor to worsened neurologic recovery. Interferon-stimulated gene 15 (ISG15) is upregulated after cerebral ischemia and is neuroprotective. The significant role of ISG15 after TBI has not been studied. Postnatal Day (PND) 21 and PND24 mice were subjected to lateral closed-skull injury with impact depth of 2.0 or 2.25 mm. Behavior was examined at 7 d using two-object novel recognition and Wire Hang tests. Mice were sacrificed at 6 h, 12 h, 24 h, 48 h, 72 h, and 7 d. ISG15 and MLCK were analyzed by Western blot and immunohistochemistry, blood-brain barrier (BBB) disruption with Evans Blue (EB), and cerebral edema with wet/dry weights. EB extravasation and edema peaked at 72 h in both ages. PND21 mice had more severe neurological deficits, compared with PND24 mice. PND24 mice showed peak ISG15 expression at 6 h, and PND21 mice at 72 h. MLCK peaked in both age groups at 12 h and co-localized with ISG15 on immunohistochemistry and co-immunoprecipitation. These studies provide evidence, ISG15 is elevated following TBI in mice, preceding MLCK elevation, development of BBB disruption, and cerebral edema. [ABSTRACT FROM AUTHOR]

Research shows that across life, the incidence of mental illness is highest in the young. In the context of the COVID-19 pandemic, mental health issues of the young in particular have received global attention. The rostral anterior cingulate cortex (rACC) plays an important role in psychiatric disorders and chronic pain-psychiatric comorbidities. However, it remains unknown whether or how the afferent and efferent circuits of the rACC change with aging. In this study, we microinjected a retrograde tracer virus and an anterograde trans-monosynaptic virus into the rACC of young and middle-aged mice (both male and female), and systematically and quantitatively analyzed the whole-brain afferent and efferent connections of rACC at different ages and sexes. Notably, in young and middle-aged mice, afferents of the rACC belong to four groups of brain structures arising mainly from the amygdala [mainly basolateral amygdaloid nucleus (BLA)] and cerebral cortex (mainly orbital cortex), with a small part originating from the basal forebrain and thalamus. In contrast, efferents of the rACC belong to four groups of brain structures mainly projecting to the thalamus (mainly ventral anterior-lateral/ventromedial thalamic nucleus (VAL/VM)], with a very small part projecting to the amygdala, basal forebrain, and cerebral cortex. Compared with young mice, the BLA-rACC circuit in middle-aged mice (male and female) did not change significantly, while the rACC-VAL/VM circuit in middle-aged mice (male and female) decreased significantly. In conclusion, this study comprehensively analyzed the input-output neural projections of rACC in mice of different ages and sexes and provided preliminary evidence for further targeted research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Yu, Yao, Zhu, Dai, He, Liu, Xu, Shao, Fang and Shen.)

Objective: To observe the effect of electroacupuncture (EA) on the proliferation of endogenous neural stem cells in the hippocampus of young mice with Alzheimer's disease (AD), so as to explore its mechanisms underlying improvement of AD., Methods: Forty 1.5-month-old APP/PS1 transgenic male mice were randomly divided into an EA group and a model group, 20 mice in each group, and other 20 C57BL/6J male mice of the same age were used as the normal control group. EA (intermittment wave 10 Hz, 2 mA) was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Shenshu" (BL 23) for 20 min, once a day, 6 days a week for 16 weeks. H.E. staining was used to assess histopathological changes of neurons of the hippocampal dentate gyrus. Immunohistochemical stain was used to detect the expression of 5-bromodeoxyuridine (BrdU)-positive in the hippocampus, and immunofluorescence double-labeled technique was used to detect the number of proliferated positive neurons of hippocampal neural stem cells. The expression levels of brain derived neurotrophic factor (BDNF) and Nestin mRNA and protein were detected by using real-time PCR and Western blot, separately., Results: The immunoactivity of BrdU, and the expression levels of BDNF and Nestin mRNA and protein in the hippocampus in the model group were significantly lower than in the normal control group ( P <0.01, P <0.05), and considerably higher in the EA group than in the model group ( P <0.01, P <0.05). The number of BrdU/NeuN dual labeled neurons was slightly increased in the model group than in the normal control group ( P >0.05), and evidently increased in the EA group relevant to the model group ( P <0.05), suggesting a proliferation of hippocampal neural stem cells. After modeling, the neurons of hippocampal dentate gyrus were arranged loosely and irregularly and their structure was fuzzy, with an appearance of different degrees of nuclear pyknosis, whereas in the EA group, the neuronal contour was clear and the nuclear structure was relatively distinct., Conclusion: EA can activate the proliferation of neural stem cells in the hippocampus in AD mice, which may contribute to its function in improving the neuronal structure by upregulating the expression of BDNF.

T-2 toxin is a kind of group A trichothecenes mycotoxins, frequently detected in various foods and feeds, having high toxic effects on both humans and animals. The present study aims to investigate the toxic effects of T-2 toxin exposure to ICR mice during pregnancy and lactation on liver glycolipid metabolism of young mice. The pregnant mice were given 0, 0.005 and 0.05 mg of T-2 toxin/kg bw daily through oral gavage from late gestation (GD 14) to the lactation (LD 21). Liver and serum samples of the young mice were collected on postnatal day 21 (PND 21), PND 28 and PND 56. The results showed that T-2 toxin increased the contents of triglycerides (TG), total cholesterol (T-CHO) and glucose in serum of young mice on PND 21 and PND 28. In addition, obvious lipid droplets of liver in T-2 toxin treatment groups were observed, especially in 0.05 mg group of PND 21and PND 28. Compared with the control group, T-2 treatment also increased the expressions of genes associated with liver glycolipid metabolism, such as PEPCK , Glut2 , Fas , Acox1 , Hmgcr , PPARα , Srebp1 and CD36. These results demonstrated T-2 toxin exposure to pregnant mice could cause liver glycolipid metabolism disruption in the young mice and the toxic effects weakened on PND 56. • Maternal exposure to T-2 toxin to mice resulted in significant accumulation of lipids in young mice. • Maternal exposure to T-2 toxin to mice caused hepatic glycolipid metabolism disorder in young mice. • Maternal exposure to T-2 toxin to mice disrupted bile acid metabolism in young mice. [ABSTRACT FROM AUTHOR]

The aging of organisms leads to a decreased ability of tissue to regenerate after injury. The regeneration of the bladder urothelium after induced desquamation with biopolymer chitosan has been studied in young mice but not in old mice. Chitosan is a suitable inducer of urothelial desquamation because it is known to be non-toxic. We used chitosan for desquamation of urothelial cells in order to compare the dynamics of urothelial regeneration after injury between young and old mice. Our aim was to determine whether the urothelial function and structure of old mice is restored as fast as in young mice, and to evaluate the inflammatory response due to chitosan treatment. We discovered that the urothelial function restored comparably fast in both age groups and that the urothelium of young and old mice recovered within 5 days after injury, although the onset of proliferation and differentiation appeared later in old mice. Acute inflammation markers showed some differences in the inflammatory response in young versus old mice, but in both age groups, chitosan caused short-term acute inflammation. In conclusion, the restoration of urothelial function is not impaired in old mice, but the regeneration of the urothelial structure in old mice slightly lags behind the regeneration in young mice. [ABSTRACT FROM AUTHOR]

Tau phosphorylation is associated with cognitive impairment in young mice. However, the underlying mechanism and targeted interventions remain mostly unknown. We set out to determine the potential interactions of Tau, interleukin 6 (IL-6) and mitochondria following treatment of anesthetic sevoflurane and to assess their influences on synapse number and cognition in young mice. Sevoflurane (3% for 2 ​h) was given to wild-type, Tau knockout, IL-6 knockout, and cyclophilin D (CypD) knockout mice on postnatal (P) day 6, 7 and 8. We measured amounts of phosphorylated Tau, IL-6, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, postsynaptic density 95 (PSD-95), synaptophysin, N-cadherin, synapse number, and cognitive function in the mice, employing Western blot, electron microscope and Morris water maze among others. Here we showed that sevoflurane increased Tau phosphorylation and caused IL-6 elevation, mitochondrial dysfunction, synaptic loss and cognitive impairment in young wild-type, but not Tau knockout, mice. In young IL-6 knockout mice, sevoflurane increased Tau phosphorylation but did not cause mitochondrial dysfunction, synaptic loss or cognitive impairment. Finally, sevoflurane increased Tau phosphorylation and IL-6 amount, but did not induce synaptic loss and cognitive impairment, in young CypD knockout mice or WT mice pretreated with idebenone, an analog of co-enzyme Q10. In conclusion, sevoflurane increased Tau phosphorylation, which caused IL-6 elevation, leading to mitochondrial dysfunction in young mice. Such interactions caused synaptic loss and cognitive impairment in the mice. Idebenone mitigated sevoflurane-induced cognitive impairment in young mice. These studies would promote more research to study Tau in young mice., Competing Interests: The authors declared no conflict of interests related to the studies. Dr. Zhongcong Xie is a consultant for Baxter, Novartis, Shanghai Jiaotong University and Tongji University., (© 2020 The Authors.)

Anesthetic sevoflurane induces mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in young mice, but the underlying mechanism remains to be determined. Cyclophilin D (CypD) is a modulatory factor for the mitochondrial permeability transition pore (mPTP). We, therefore, set out to evaluate the role of CypD in these sevoflurane-induced changes in vitro and in young mice. Wild-type (WT) and CypD knockout (KO) young (postnatal day 6, 7, and 8) mice received 3% sevoflurane 2 h daily and the neural progenitor cells (NPCs) harvested from the WT or CypD KO mice received 4.1% sevoflurane. We used immunohistochemistry and immunocytochemistry imaging, flow cytometry, Western blot, RT-PCR, co-immunoprecipitation, and Morris Water Maze to assess the interaction of sevoflurane and CypD on mitochondria function, neurogenesis, and cognition in vitro and in WT or CypD KO mice. We demonstrated that the sevoflurane anesthesia induced accumulation of CypD, mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in WT mice or NPCs harvested from WT mice, but not in CypD KO mice or NPCs harvested from CypD KO mice. Furthermore, the sevoflurane anesthesia reduced the binding of CypD with Adenine nucleotide translocator, the other component of mPTP. These data suggest that the sevoflurane anesthesia might induce a CypD-dependent mitochondria dysfunction, impairment of neurogenesis, and cognitive impairment in young mice and NPCs., (Copyright © 2020 Zhang, Lu, Liang, Liufu, Dong, Zheng and Xie.)

Gel-forming mucins are the main organic component responsible for physical properties of the mucus hydrogels. While numerous biological functions of these mucins are well documented, specific physiological functions of each mucin are largely unknown. To investigate in vivo functions of the gel-forming mucin Muc5b, which is one of the major secreted airway mucins, along with Muc5ac, we generated mice in which Muc5b was disrupted and maintained in the absence of environmental stress. Adult Muc5b-deficient mice displayed bronchial hyperplasia and metaplasia, interstitial thickening, alveolar collapse, immune cell infiltrates, fragmented and disorganized elastin fibers and collagen deposits that were, for approximately one-fifth of the mice, associated with altered pulmonary function leading to respiratory failure. These lung abnormalities start early in life, as demonstrated in one-quarter of 2-day-old Muc5b-deficient pups. Thus, the mouse mucin Muc5b is essential for maintaining normal lung function., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Background: Aging is an unavoidable, physiological process that reduces the complexity and the plasticity of the synaptic contacts in Central Nervous System (CNS), having profound implications for human well-being. The term "cognitive reserve" refers to central cellular adaptations that augment the resilience of human brain to damage and aging. The term "Cognitive training" indicates the cultural, social and physical stimulations proposed as add-on therapy for the cure of central neurological diseases. "Cognitive training" reinforces the "cognitive reserve" permitting to counteract brain impairments and rejuvenating synaptic complexity. The research has begun investigating the clinical impact of the "cognitive training" in aged people, but additional work is needed to definitively assess its effectiveness. In particular, there is a need to understand, from a preclinical point of view, whether "cognitive training" promotes compensatory effects or, alternatively, if it elicits genuine recovery of neuronal defects. Although the translation from rodent studies to the clinical situation could be difficult, the results from pre-clinical models are of high clinical relevance, since they should allow a better understanding of the effects of environmental interventions in aging-associated chronic derangements in mammals., Conclusion: Data in literature and the recent results obtained in our laboratory concerning the impact of environmental stimulation on the presynaptic release of noradrenaline, glutamate and gamma amino butyric acid (GABA) suggest that these neurotransmitters undergo different adaptations during aging and that they are differently tuned by "cognitive training". The impact of "cognitive training" on neurotransmitter exocytosis might account for the cellular events involved in reinforcement of "cognitive reserve" in young and old animals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of inflammatory bowel disease (IBD) in children. It is important to determine whether helminth therapy would be of value in pediatric IBD and whether triggering immunological memory to the worm would be anticolitic. Three-week-old (young) and eight-week-old (adult) Balb/c mice were infected with H. diminuta, and infectivity and T helper 2 (Th2) immunity were assessed. Other mice received H. diminuta with or without a crude worm extract ( HdE) 28-42 days postinfection (dpi) with or without dinitrobenzene sulphonic acid [DNBS, 1.5 mg (young) or 3 mg (adults), ir], and colitis was assessed 72 h later. Infected young mice developed Th2 immunity and expelled H. diminuta; expulsion was delayed by ~2 days compared with adult mice. Colitis, as gauged by macroscopic disease and histopathology scores, was less severe in young mice infected 10 days, but not 8 days, before DNBS. Protection against DNBS-induced colitis was accompanied by an increased capacity to make interleukin (IL)-4 and IL-10. Mice infected with H. diminuta were not protected from DNBS-colitis when challenged 28 days later; however, injection of these mice with HdE coincident with DNBS resulted in less disease and increased splenic IL-4 and IL-10. Using a boost (500 μg HdE, 28 dpi) and repeat HdE (100 μg, 42 dpi) regimen with infected mice suppressed DNBS-colitis, as did adoptive transfer of splenic CD4 + T cells from infected mice with low-dose HdE challenge. Should these data translate to IBD, then helminth therapy could be of value in pediatric-onset IBD, and defining the antigen(s) that elicit antihelminth immunological memory could serve as an anticolitic approach in previously infected individuals. NEW & NOTEWORTHY This study demonstrates that juvenile mice are protected from colitis by infection with the tapeworm Hymenolepis diminuta and that using worm antigen to trigger an immunological memory response in previously infected mice can be used to limit the severity of colitis.

Background: Angiotensin converting enzyme inhibitors (ACEi) are the current standard of care treatment for cardiac dysfunction in Duchenne muscular dystrophy patients. We previously showed treatment with an ACEi plus mineralocorticoid receptor (MR) antagonist improves limb and respiratory skeletal muscles, in addition to cardiac muscles, in a dystrophic mouse model at 20 weeks-of-age., Objective: To determine whether previously observed preclinical benefits of an ACEi plus MR antagonist on dystrophic skeletal muscles can be reproduced by increasing ACEi dosage alone. We also compared functional and histological outcome measures at 10 and 20 weeks-of-age., Methods: Dystrophin deficient utrophin haplo-insufficient ( utrn +/- ; mdx ) "het" mice were treated with 10, 20, or 50 mg/kg × day of the ACEi lisinopril from 4 to 10 weeks-of-age via water bottles and compared with C57BL/10 wild-type control mice and untreated hets. Data from 10 week-old het mice were also compared to data collected from an untreated het group at 20 weeks-old. In vivo cardiac and grip strength measurements, in vitro diaphragm and extensor digitorum longus muscle force measurements, and histopathological analyses were performed. One-way ANOVA followed by Dunnett post hoc comparison was used to determine significance., Results: ACEi treatment reduced skeletal muscle damage but had no significant effect on muscle force. Body weight, heart rate, grip strength and blood pressure were unaffected by treatment. Limb muscle histopathology was more informative at 10 than 20 weeks-of-age., Conclusions: These results suggest increased ACEi dosage alone cannot improve all dystrophic parameters. Further optimization of MR antagonists in 20 week-old mice is warranted.