Myocardial ischemia-reperfusion injury (MIRI) remains a critical clinical condition with limited preventive and therapeutic strategies, underscoring the need for novel interventions. The gut-heart axis and exosomal crosstalk hold therapeutic promise for cardioprotection, yet the fundamental question of which specific gut cells release the beneficial exosomes is unanswered. This study aimed to elucidate whether ginseng polysaccharides WGPA exert remote cardiac protection by regulating intestinal immune homeostasis, specifically through promoting the release of exosomes from regulatory T cells (Tregs). Using integrated in vivo and in vitro models, we evaluated the protective effects of WGPA against MIRI. The results demonstrated that WGPA pretreatment significantly attenuated myocardial injury and improved cardiac function. Mechanistically, WGPA selectively activated intestinal Tregs and enhanced the release of HSP70-enriched exosomes. These exosomes entered systemic circulation and were delivered to the heart, where surface HSP70 interacted with TLR4 on cardiomyocytes, activating downstream protective signaling pathways and ultimately suppressing cardiomyocyte death and inflammatory responses. Our study reveals for the first time a complete mechanism by which medicinal plant polysaccharides confer cross-organ cardioprotection via the “intestinal Tregs–exosome–heart” axis, providing a novel theoretical basis and a potential intervention strategy for the prevention and treatment of MIRI.

Alzheimer's disease is characterized by the presence of amyloid-beta plaques, neurofibrillary tangles, and chronic neuroinflammation. Effective therapies capable of restoring neuronal loss, a key pathological feature of Alzheimer's disease are lacking. Our previous studies have demonstrated that overexpression of neuronal differentiation 1 (NeuroD1) in astrocytes can convert astrocytes into neurons in Alzheimer's disease models and this astrocyte-to-neuron conversion technology can rescue pathological features in models of stroke and epilepsy. This study investigated whether NeuroD1-mediated in vivo reprogramming of reactive astrocytes into functional neurons could rescue neurodegeneration and cognitive decline in amyloid precursor protein/presenilin 1 transgenic Alzheimer's disease model mice. Using retro-orbital delivery of AAV-PHP.eB-GFAP-NeuroD1-GFP, we achieved broad astrocyte-to-neuron conversion throughout the brain of 7-month-old Alzheimer's disease mice. Three months post-treatment, immunostaining revealed significant neuronal regeneration in the cortex and hippocampus, accompanied by a marked reduction in neuroinflammatory markers. The converted neurons exhibited mature electrophysiological properties, including action potentials and synaptic activity, which correlated with increased neuronal density in the hippocampus. Morris water maze test demonstrated that NeuroD1-treated mice exhibited restored spatial learning and memory compared with control animals. These findings demonstrate that NeuroD1-driven neuroregeneration via gene therapy not only replenishes neuronal populations but also reduces key pathological features related to Alzheimer's disease, including neuroinflammation and amyloid plaque burden, ultimately reducing cognitive impairment. Our findings highlight in vivo astrocyte-to-neuron reprogramming through systemic astrocyte-to-neuron delivery as a promising and transformative strategy for treating Alzheimer's disease and related neurodegenerative disorders.

Cleavage of amyloid precursor protein (APP) produces toxic amyloid-beta peptides, which play a critical role in the pathogenesis of Alzheimer's disease. Neuronal loss is a key feature of Alzheimer's disease. Despite the importance of APP in the proliferation of neural progenitors and the survival of adult-born granule cells in the dentate gyrus, little is known about the effect of APP deficiency on neuronal electrophysiological activities and the survival of newly born neurons. Utilizing whole-cell patch-clamp recording in combination with retroviral labeling and immunofluorescent staining in Alzheimer's disease model mice with App knockout (App(-/-)), we show that APP deficiency increased the number of adult-born granule cells at 4 weeks post-injection, but did not affect their intrinsic excitability or miniature current activity. In contrast, at 10 weeks post-injection, adult-born granule cells showed increased abundance and intrinsic excitability that were associated with abnormal dendritic morphology, increased miniature excitatory- and inhibitory-synaptic transmission, and decreased potassium-chloride-cotransporter 2 expression. Compared with adult-born granule cells at 10 week post-injection, mature granule cells exhibited decreased intrinsic excitability and potassium-chloride-cotransporter 2 expression alongside increased apoptosis in App(-/-) mice. Additionally, although App(-/-)mice showed abnormal freezing behavior and elevated mature granule cell activation during contextual fear conditioning, adult-born granule cells were not recruited in either App(-/-) or wild-type control mice. Taken together, these findings suggest that APP is required for adult-born granule cell maturation and that APP deficiency induces excitotoxicity in adult-born granule cells at 10 weeks post-injection, promoting subsequent apoptosis of mature granule cells.

Steroid hormones are powerful endocrine regulators, but little is known about how environmental conditions modulate steroidogenesis to reprogram developmental fates. Here, we use the Drosophila prothoracic gland (PG) to investigate how a nutrient restriction checkpoint (NRC) ensures or blocks developmental progression and sexual maturation via regulating steroidogenesis. Extensive transcriptome analysis of the PG reveals that pre-NRC starvation significantly downregulates mitochondria-associated genes. Pre-NRC starvation reduces prothoracicotropic neuropeptide hormone signaling, insulin signaling, and TORC1 activity in PG cells, which prevent mitochondrial fragmentation and import of Disembodied, a key steroidogenic enzyme. Ultimately, pre-NRC starvation causes severe mitophagy and proteasome dysfunction, blocking steroidogenesis and metamorphosis. By contrast, post-NRC starvation does not impair mitochondrial homeostasis in PG cells but reduces sit expression and induces moderate autophagy to promote steroidogenesis, leading to precocious metamorphosis. This study constitutes a paradigm for exploring how steroid hormone levels are controlled in response to environmental stress during developmental checkpoints. The prothoracic gland is the principal steroidogenic gland in Drosophila. Here Zhang et al. perform transcriptomic analysis and show that starvation prior to the nutrient restriction checkpoint alters mitochondrial homeostasis in the gland and blocks steroid hormone production.

BackgroundIdiopathic Pulmonary Fibrosis (IPF), an interstitial lung disease of unknown etiology, remains incurable with current therapies, which fail to halt disease progression or restore lung function. However, Feibi Recipe No. 2 (FBR2), a clinically validated traditional Chinese medicine formula, exhibits potential as an IPF treatment.ObjectiveThis study aimed to investigate the regulatory effect of FBR2 on ferroptosis through the SIRT3/p53 pathway and its therapeutic potential in improving IPF.MethodsPulmonary fibrosis was induced in C57BL/6J mice by intratracheal instillation of Bleomycin (BLM), followed by FBR2 treatment via gavage. Assessments encompassed histopathology, ELISA for cytokine detection, IHC and Western blot for protein expression analysis, and qRT-PCR for gene expression quantification. Transmission electron microscopy (TEM) was used to observe mitochondrial morphology. The roles of Erastin and the SIRT3 inhibitor 3-TYP were also explored to elucidate FBR2’s mechanisms of action.ResultsFBR2 treatment significantly mitigated BLM-induced lung injury in mice, as evidenced by improved body weight and survival rates, and reduced levels of inflammatory cytokines, including IL-6 and TNF-α. FBR2 decreased collagen deposition in lung tissue, as shown by Masson’s staining and IHC detection of Col-I and α-SMA, confirming its anti-fibrotic effects. It also reduced iron and MDA levels in lung tissue, increased GSH-Px activity, improved mitochondrial morphology, and enhanced the expression of GPX4 and SLC7A11, indicating its ferroptosis-inhibitory capacity. Furthermore, FBR2 increased SIRT3 levels and suppressed p53 and its acetylated forms, promoting the translocation of p53 from the nucleus to the cytoplasm where it co-localized with SIRT3. The protective effects of FBR2 were reversed by Erastin, confirming the central role of ferroptosis in pulmonary fibrosis treatment. The use of 3-TYP further confirmed FBR2’s intervention in ferroptosis and cellular senescence through the SIRT3/p53 pathway.ConclusionFBR2 shows therapeutic potential in a BLM-induced pulmonary fibrosis mouse model, with its effects mediated through modulation of the ferroptosis pathway via the SIRT3/p53 mechanism. This study provides novel evidence for the targeted treatment of IPF and offers further insights into its pathogenesis.

Context-triggered retrieval of drug withdrawal memories (CTR-DWM) is a major cause of drug relapse. Most studies of the context-triggered retrieval of morphine withdrawal memories (CTR-MWM) have mainly focused on the functional interactions within the central structures of the brain. It remains unknown how an increase in corticosterone, which is an important response under drug withdrawal state, participates in CTR-MWM. The present results show that corticosterone contributes to CTR-MWM; within the basolateral amygdala (BLA), it is the mineralocorticoid receptor (MR), rather than the glucocorticoid receptor (GR), activated by corticosterone that mediates CTR-MWM; MR of BLA neurons projecting to the nucleus accumbens core (BLA→NAcC) mediates CTR-MWM; MR increases presynaptic glutamate release and participates in dopamine D1 receptor -induced increase in presynaptic glutamate release and postsynaptic AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) currents; MR increases intrinsic excitability of BLA→NAcC neurons during CTR-MWM. These results suggest that corticosterone contributes to CTR-MWM by activating BLA→NAcC neurons through MR pathways, uncovering a link between a systemic hormonal response and a specific CTR-MWM process.

Two microglia phenotypes, M1 pro-inflammatory and M2 anti-inflammatory phenotypes, exert distinct functions post-intracerebral hemorrhage (post-IH). The M1-to-M2 switch is noted within 7 days, but precise timing remains undetermined. This research sought to examine the specific timing of the M1-to-M2 transition and examine the effect of Sheng-Di-Da-Huang Decoction (SDDHD) on M2 microglia post-IH. Rats were grouped into sham, IH and dose-varied SDDHD treatment cohorts. Rats of IH group had an intrastriatum injection of collagenase IV (0.2 U), while those of sham group were only injected with saline. All rats underwent neurological score assessment and magnetic resonance imaging (MRI) scans at different time points after procedure. The expression markers (iNOS for M1; Arg1, IL-4, and IL-10 for M2) were assessed across days. M1 markers (iNOS) peaked at day 3, whereas M2 markers (Arg1, IL-4 and IL-10) rose progressively, suggesting the M1-to-M2 switch around day 3. SDDHD decreased iNOS expression and elevated Arg1, IL-4 and IL-10 expression, improving neurological outcomes. SDDHD exhibits a bidirectional regulation of microglia, promoting M2 transformation while inhibiting M1, thereby enhancing neurological recovery post-IH.

Ischemic stroke is one of the top-ranked causes of death and disability in the world, but still lacking efficacy treatment options. Excitotoxicity caused by NMDA receptors (NMDARs) hyperactivation plays a key role in brain injury after ischemic stroke. GluN2B, the regulatory subunit of NMDARs, plays an important role in brain injury induced by ischemic stroke, and specific antagonists of GluN2B can ameliorate brain damage induced by ischemic stroke in rats. However, over half a century after Memantine (the first NMDA partial inhibitor for Alzheimer's clinical treatment) was identified, only a few additional NMDA partial inhibitors, especially those specifically targeting GluN2B, have been discovered. In this study, by using whole patch-clamp technique and multiple molecular biological methods, we discovered a new specific GluN2B partial antagonist, named FLY26, and further determined its effects on alleviating the brain injury caused by ischemic stroke in rats. Our experiment results showed FLY26 suppressed the excitotoxicity caused by overactivation of NMDARs in SH-SY5Y cells, and ameliorated brain damage of middle cerebral artery occlusion (MACO) rats, within the dosage range of 1.5-6.0 mg/kg, via BDNF/TrkB signaling pathway. Our results indicated that FLY26 is a promising lead compound for the development of novel, specific GluN2B partial antagonist. Our results indicated that FLY26 is a promising lead compound for the development of novel, specific GluN2B partial antagonist, which may offer better safety profile as a therapeutic intervention for ischemic stroke.

BAI1, BAI2, and BAI3 (for ‘Brain-specific Angiogenesis Inhibitor-1, -2, and -3’) are adhesion-GPCRs implicated in neuronal development. The precise roles of individual BAIs remain unclear. BAIs interact with two sets of ligands, secreted C1ql proteins and membrane-bound RTN4R proteins (a.k.a. NoGo receptors), but which of these ligands regulate specific functions of BAIs is incompletely understood. To address these key questions, we here systematically examine the functions of the three BAIs in neuronal development using hippocampal neuron-glia cultures, genetic knockouts, and rescue experiments. In a direct comparison, we demonstrate that deletions of BAI1 or BAI3, but not of BAI2, increase axonal and dendritic arborizations but decrease excitatory synapse formation, while inhibitory synapse formation remains unaffected. Since biochemical and cellular assays reveal that only BAI3 binds to both RTN4Rs and C1qls, we analyzed the role of these two ligands in controlling BAI3 functions using rescue experiments. We find that RTN4R-binding to BAI3 is essential for restricting axonal and dendritic arborizations and for enabling excitatory synapse formation, whereas C1ql-binding to BAI3 is only required for synapse organization as monitored in hippocampal neuron-glia cultures. Thus, BAI1 and BAI3 perform diverse functions that shape multiple facets of neuronal development and that require their interaction with RTN4Rs.

BACKGROUND:General anesthesia may involve shared neural mechanisms. The periaqueductal gray (PAG) plays a critical role in physiologic, instinctive behaviors, as well as sleep-wake regulation. However, the role of the dorsomedial PAG (dmPAG) in regulating the anesthesia-awakening state remains unclear. The study aims to investigate the role of dmPAG glutamatergic neurons in promoting arousal under multiple general anesthetics. METHODS:Multiple general anesthetics, including sevoflurane, propofol, ketamine, and dexmedetomidine, were administered to mice of both sexes. Calcium imaging was employed to monitor activity changes in glutamatergic neurons within the dmPAG during anesthesia and arousal. Optogenetic and chemogenetic approaches were used to manipulate neuronal activity and evaluate their effects on anesthesia induction, maintenance, and recovery. Additionally, electroencephalogram recordings were analyzed to assess alterations in spectral power and the burst suppression ratio under anesthesia. RESULTS:Glutamatergic neuronal activity in the dmPAG was suppressed during sevoflurane anesthesia but increased during wakefulness, with similar patterns observed for all intravenous anesthetics tested. Optogenetic activation of dmPAG glutamatergic neurons significantly prolonged anesthesia induction time (green fluorescent protein [GFP] vs. ChR 2 , 218.8 ± 50.83 s vs. 372.5 ± 40.18 s, P < 0.001) and shortened emergence time (GFP vs. ChR 2 , 230.8 ± 40.44 s vs. 135 ± 19.82 s, P < 0.001) under sevoflurane anesthesia. Electroencephalogram changes characteristic of wakefulness were observed during maintained anesthesia, with the burst suppression ratio decreasing (GFP vs. ChR 2 : 50.08 ± 8.21% vs. 2.15 ± 3.38%, P < 0.001). Chemogenetic activation produced similar effects, while chemogenetic inhibition potentiated the anesthetic effects of all tested anesthetics. CONCLUSIONS:The findings suggest that glutamatergic neurons in the dmPAG may act as a common neural substrate for multiple anesthetic agents, playing a critical role in both the loss and the recovery of consciousness.

Microglia are innate immune cells in the central nervous system (CNS) and play critical roles in proper brain development and function. During postnatal development, microglia have a highly plastic morphology and change rapidly in response to the temporal brain environment. However, their dynamics and phenotypes during this period are still not fully elucidated. Here, we systematically elucidated microglial density and morphological changes during postnatal development as well as in pathological obese conditions. Our results demonstrated a spatiotemporal distribution of microglia in different brain regions associated with gradually increased microglial complexity during postnatal development. Moreover, microglia become reactive in most brain regions of obese mice, but their morphological diversity has a region-specific manner, with an obvious alteration in the hypothalamus. Overall, our data emphasized the morphological dynamics of microglia following developing time windows and provided the basic information for future investigations.

Introduction:Sleep deprivation often leads to marked neurobehavioral and cognitive deficits, yet few well-defined interventions exist to address these effects. Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, possesses sedative, hypnotic, analgesic, and sympathetic-blocking properties, closely mimic natural sleep state. In this study, we aim to investigate whether DEX protects hippocampal tissue against rapid eye movement sleep deprivation (RSD)-induced injury in rats and to explore the underlying molecular mechanisms. Methods:In this study, a rapid eye movement sleep deprivation (RSD) rat model was created using a modified multi-platform method. The influence of dexmedetomidine (DEX) on hippocampal tissue morphology, the BDNF/TrkB signaling pathway, and cognitive function was then evaluated. Group comparisons were analyzed using one-way ANOVA followed by appropriate post hoc tests. Results:In comparison with the control group, DEX significantly alleviated the impaired spatial learning and memory as reflected escape latency and increased the time spent in the garget quadrant. ANA-12 reversed these improvements, indicating DEX's cognitive benefits. HE staining showed that DEX protected neurons from RSD-induced injury by preserving structural integrity and TUNEL assay demonstrated reduced neuron apoptosis in the DEX group. Co-treatment with ANA-12 abolished these protective effects, resulting in neuronal damage and apoptosis levels similar to those observed in RSD rats. Moreover, compared with the level of TNA alpha in RSD rats, IL 6, IL 1beta and MDA levels were lower in the hippocampus of DEX group, while SOD activity was enhanced. Western blot analysis revealed that DEX increased hippocampal BDNF (0.586 ± 0.036 vs 0.315 ± 0.034, ~1.86‑fold, P < 0.01), TrkB (0.774 ± 0.039 vs 0.518 ± 0.033, ~1.49‑fold, P < 0.01) and pro-TrkB expression. However, co-administration of ANA‑12 abolished these effects, returning expression levels close to those in the RSD group, implying that DEX's neuroprotection is mediated via the BDNF/TrkB pathway. Conclusion:These findings indicate that DEX exerts neuroprotective effects in RSD by activating the BDNF/TrkB pathway, offering valuable evidence for DEX-based therapeutic approaches to sleep deprivation-related brain injury.

Intestinal homeostasis relies on the continuous renewal of intestinal stem cells (ISCs), which could be epigenetically regulated. While protein arginine methyltransferase 5 (Prmt5) is known to play a key role in multiple organs as an epigenetic modifier, its specific function in maintaining intestinal homeostasis remains to be elucidated. Here, we show that Prmt5 is highly expressed in mouse crypts. The deletion of Prmt5 results in ISCs deficiency, ectopic localization of Paneth cells, and spontaneous colitis. Mechanistically, Prmt5 sustains a high level of H3K27ac accumulation by inhibiting Hdac9 expression in the intestinal epithelium, and maintains the stemness of ISCs in a cell-autonomous manner. Notably, inhibition of histone deacetylases can rescue both self‐renewal and differentiation capacities of Prmt5‐depleted ISCs. These findings highlight Prmt5 as a critical regulator in intestinal epithelium development and tissue homeostasis.

To investigate the impact of florfenicol on soil microbial community structure and diversity, an indoor florfenicol exposure model was established. Soil samples were collected at different concentrations of florfenicol (0, 0.05, 0.5, 5, and 50 mg/kg) on days 0, 7, 30, and 60. High-throughput sequencing was employed to examine the changes in soil microbial community structure, diversity, and abundance. The analysis revealed a total of 31874 operational taxonomic units ( OTUs ) in the soil samples, averaging 9524 OTUs per sample. The number of soil microbial community OTUs declined with increasing florfenicol concentration. The microbial species richness and diversity showed a decreasing trend at day 7, while the treatment group with 50 mg/kg florfenicol at 60 days exhibited the lowest richness index. Examination of the soil microbial community structure identified 50 phyla and 1303 genera. At the phylum level, the abundance of Actinobacteria and Bacteroides decreased with increasing florfenicol concentration. Similarly, at the genus level, some of the dominant genera displayed a decline in abundance with the rise of florfenicol concentration. Cluster analysis demonstrated significant temporal and concentration variability. The results indicate differences in the composition, diversity, dominance, abundance, and evenness of soil bacterial communities among different groups. Florfenicol has a significant negative impact on the structure and diversity of soil microbial communities. The findings of this study provide a scientific basis for the rational use of florfenicol in livestock farming to maintain a healthy and stable soil microecological environment.

Objective To observe the clinical efficacy of acupuncture intervention at different time for patients with sudden hearing loss.Methods According to the timing of acupuncture intervention,86 patients were divided into early exposure group(n=43)and late exposure group(n=43).The early exposure group was given acupuncture treatment within 14 days of onset,and the late exposure group was given acupuncture treatment after 14 days of onset.After propensity score matching(PSM,a statistical matching technique for observational data)processing by using SPSS26.0 software,outcomes of 30 cases in the early exposure group and 30 cases in the late exposure group were analyzed.In addition to receiving basic treatment with drugs for vascular dilatation,thrombolysis,nourishing nerve,etc.,all patients of the two groups were treated with neck acupuncture("Neck Seven Meridian Lines"acupuncture),once every other day except Sundays,for a total of 12 time.Before,after the treatment and 3 months after the treatment,the total score of the Tinnitus Handicap Inventory(THI,0,2 and 4 points for each of the 25 items,total scores=100 points)scale was used to evaluate the improvement of tinnitus symptoms caused by hearing loss.The clinical therapeutic effect was evaluated according to the efficacy grading criteria in the Guidelines for Diagnosis and Treatment of Sudden Deafness(2015)and the changes of pure tone audiometry curve.Multivariate Logistic regression was used to analyze the effect of factors that might influence efficacy before propensity score matching.Results The THI scores of patients in both groups decreased strikingly after the treatment and 3 months'follow-up(P<0.05).Compared with the same time-points of the late exposure group,the total THI scores of post-treatment and 3 months'follow-up were evidently lower in the early exposure group(P<0.05).The effective rate of the early exposure group(22/30,80.00%)was significantly higher(P<0.05)than that of the late exposure group(16/30,53.33%).The classification of sudden deafness and the application of traditional Chinese medicine in this study were not independent factors affecting the total effective rate.Conclusion The time point of acupuncture intervention is an important factor affecting the effect on hearing and tinnitus disability of patients with sudden deafness.The earlier acupuncture treatment is accepted,the better the therapeutic effect is.

Microglia are resident immune cells in the brain that interact with neurons to maintain the homeostasis of the central nervous system (CNS). Studies show that the microglial surface expresses potassium channels that regulate microglial activation, while abnormalities in these potassium channels can lead to neural diseases. Currently, whole-cell patch-clamp recordings of microglia are mostly performed on cultured primary microglia from fetal or newborn mice due to difficulties in conducting electrophysiological evaluations on acutely isolated microglia. This study introduces an easy-to-follow protocol for isolating hippocampal microglia from adult mice and performing whole-cell patch-clamp recordings on the isolated cells. Briefly, the brain was removed from a mouse after decapitation, the hippocampus was dissected bilaterally, and microglia were isolated using an adult mouse brain dissociation kit. The microglia were then purified using a magnetic-activated cell sorting (MACS) method and seeded onto coverslips. Successful microglial isolation was confirmed by immunofluorescent staining with anti-CD11 and anti-Iba1 antibodies. A cover slip was placed in a recording chamber, and the whole-cell potassium currents of the acutely isolated microglia were recorded under voltage-clamp conditions.

Osteoarthritis is the most prevalent age-related degenerative joint disease and a leading cause of pain and disability in aged people. Its etiology is multifaceted, involving factors such as biomechanics, pro-inflammatory mediators, genetics, and metabolism. Beyond its evident impact on joint functionality and the erosion of patients’ quality of life, OA exhibits symbiotic relationships with various systemic diseases, giving rise to various complications. This review reveals OA’s extensive impact, encompassing osteoporosis, sarcopenia, cardiovascular diseases, diabetes mellitus, neurological disorders, mental health, and even cancer. Shared inflammatory processes, genetic factors, and lifestyle elements link OA to these systemic conditions. Consequently, recognizing these connections and addressing them offers opportunities to enhance patient care and reduce the burden of associated diseases, emphasizing the need for a holistic approach to managing OA and its complications.

Type 2 diabetes mellitus (T2DM) is prevalent in the world while research on its pathogenesis and treatment is still unsatisfactory. Active ingredients of traditional Chinese medicines including Eclipta prostrata have been gradually applied to cure various diseases and many in vitro studies have revealed that E. Prostrata has a good hypoglycemic effect. The main objective of this research was to investigate the isolation of E. Prostrata flavonoids (EPFs) and saponins (EPSs), chemical constituents and their hypoglycemic effect on IR-HepG2 cells as well as the potential mechanisms. We determined of the Chemical Constituent was using UPLC-HESI/MS/MS to clarify its chemical substance basis; We established of insulin resistant HepG2 cell line (IR-HepG2) model to evaluate on insulin resistance; We examined Glucose and lipid metabolism, regulate antioxidant system, mitochondrial function as well as APN/AMPK and IRS-1/PI3K/AKT signaling pathway in IR-HepG2 cells treated with EPFs and EPSs to further explore the mechanisms of EPFs and EPSs hypoglycemic activity. The results showed that E. Prostrata extractions treatment could promote glucose uptake and glycogen synthesis, reduce lipid accumulation, improve mitochondrial function and reduce ROS production in IR-HepG2 cells. In particular, both EPFs and EPSs perform preferable activation in glucose consumption than metformin hydrochloride (MET). Further results suggest that EPFs and EPSs may play a role in lowering blood glucose through APN/AMPK and IRS-1/PI3K/AKT signaling pathways. These results suggested that E. Prostrata extractions ideal hypoglycemic activity and worthy of further study.

BACKGROUND: Accumulated evidence suggests that brain regions that promote wakefulness also facilitate emergence from general anesthesia (GA). Glutamatergic neurons in the substantia innominata (SI) regulate motivation-related aversive, depressive, and aggressive behaviors relying on heightened arousal. Here, we hypothesize that glutamatergic neurons in the SI are also involved in the regulation of the effects of sevoflurane anesthesia. METHODS: With a combination of fiber photometry, chemogenetic and optogenetic tools, behavioral tests, and cortical electroencephalogram recordings, we investigated whether and how SI glutamatergic neurons and their projections to the lateral hypothalamus (LH) regulate sevoflurane anesthesia in adult male mice. RESULTS: Population activity of glutamatergic neurons in the SI gradually decreased upon sevoflurane-induced loss of consciousness (LOC) and slowly returned as soon as inhalation of sevoflurane discontinued before recovery of consciousness (ROC). Chemogenetic activation of SI glutamatergic neurons dampened the animals’ sensitivity to sevoflurane exposure, prolonged induction time (mean ± standard deviation [SD]; 389 ± 67 seconds vs 458 ± 53 seconds; P = .047), and shortened emergence time (305 seconds, 95% confidence interval [CI], 242–369 seconds vs 207 seconds, 95% CI, 135–279 seconds; P = .004), whereas chemogenetic inhibition of these neurons facilitated sevoflurane anesthesia. Furthermore, optogenetic activation of SI glutamatergic neurons and their terminals in LH induced cortical activation and behavioral emergence from different depths of sevoflurane anesthesia. CONCLUSIONS: Our study shows that SI glutamatergic neuronal activity facilitates emergence from sevoflurane anesthesia and provides evidence for the involvement of the SI-LH glutamatergic pathway in the regulation of consciousness during GA.