Disruption of IDO signaling pathway alleviates chronic unpredictable mild stress-induced depression-like behaviors and tumor progression in mice with breast cancer.

Women with breast cancer (BC) are often combined with psychological disorder such as depression and anxiety. Depression is associated or correlated with increased toxicity and severity of physical symptoms. However, the mechanism of BC progression related to the regulation of emotion-related circuitry remains to be further explored. The study aims to investigate indoleamine 2,3-dioxygenase (IDO) pathway mechanism underlying stress-induced progression of BC. BC cell line 4T1 was subcutaneously inoculated into BALB/c mice, and they then received daily chronic unpredictable mild stressors (CUMS) for 12 weeks. Depression-like behavior tests were conducted, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and novelty suppressed feeding test (NSF). The levels of 5-Hydroxytryptamine (5-HT) and inflammatory factors, IL-6, CXCL1, IL-10 and IL-4 were measured by enzyme linked immunosorbent assay (ELISA) of mouse serum. Immunohistochemical staining was performed to detect Ki67- or FOXP3-positive tumor cells. The status of IDO signaling pathway was assessed by immunoblotting analysis. CUMS induced depression-like behaviors, decreased the level of 5-HT, promoted tumor progression, enhanced the immunohistochemical staining of Ki-67, and promoted the activation of IDO signaling pathway in BC mice. The IDO signaling pathway was disrupted in mice by lentiviral transduction of shRAN-IDO. Lentivirus-mediated IDO knockdown attenuated CUMS-induced depression-like behaviors, increased the level of 5-HT, inhibited tumor progression, and reduced the immunohistochemical staining of Ki-67 in BC mice. The present study suggests that disruption of IDO signaling pathway alleviates CUMS-induced depression-like behaviors and inhibits tumor progression in BC mice.

Zn-Shik-PEG nanoparticles alleviate inflammation and multi-organ damage in sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by excessive formation of reactive oxygen species (ROS) and dysregulated inflammatory response. Previous studies have reported that shikonin (Shik) possess prominent anti-inflammatory and antioxidant effects and holds promise as a potential therapeutic drug for sepsis. However, the poor water solubility and the relatively high toxicity of shikonin hamper its clinical application. To address this challenge, we constructed Zn2+-shikonin nanoparticles, hereafter Zn-Shik-PEG NPs, based on an organic-inorganic hybridization strategy of metal-polyphenol coordination to improve the aqueous solubility and biosafety of shikonin. Mechanistic studies suggest that Zn-Shik-PEG NPs could effectively clear intracellular ROS via regulating the Nrf2/HO-1 pathway, meanwhile Zn-Shik-PEG NPs could inhibit NLRP3 inflammasome-mediated activation of inflammation and apoptosis by regulating the AMPK/SIRT1 pathway. As a result, the Zn-Shik-PEG NPs demonstrated excellent therapeutic efficacies in lipopolysaccharide (LPS) as well as cecal ligation puncture (CLP) induced sepsis model. These findings suggest that Zn-Shik-PEG NPs may have therapeutic potential for the treatment of other ROS-associated and inflammatory diseases.

[Virtual screening and antiepileptic activity evaluation of COX-2 inhibitory components in Trachelospermi Caulisetfolium].

This study investigated the potential active components against cyclooxygenase-2(COX-2) from Trachelospermi Caulisetfolium and explored the pharmacodynamic material basis.A pharmacophore-based virtual screening method was adopted to establish a COX-2 ligands-based HipHop pharmacophore model on the basis of the information on compounds with COX-2 inhibitory activity reported in published research articles.The reported components in Trachelospermi Caulisetfolium were collected to establish the compound library and matched with the pharmacophores.Subsequently, the matched small molecule compounds underwent molecular docking with COX-2 targets(PDB ID: 3 LN1), and the interaction of potential active monomers and COX-2 was further explored by molecular dynamics.The antiepileptic effect of active monomer arctigenin(15) was determined based on the pentylenetetrazole(PTZ)-induced seizure model, and its modulatory effect on the COX-2 level was evaluated.A compound library containing 118 chemical constituents in Trachelospermi Caulisetfolium was established by literature retrieval.The preferred pharmacophore 04 was selected through test set verification for virtual screening of the compound library of Trachelospermi Caulisetfolium.After matching, six potential constituents with COX-2 inhibitory activity were obtained.The interaction of five compounds with COX-2 and COX-1 was analyzed by molecular docking, and 10 ns molecular dynamics was performed on two compounds.Compound 15 could prolong the latent time of PTZ-induced seizures at medium and high doses, improve the anxiety-and depression-like behaviors induced by PTZ, reduce the expression level of COX-2, and decrease the number of COX-2 immuno-posi-tive cells in the hippocampal CA1 region.The results showed that it was reasonable to investigate the components in Trachelospermi Caulisetfolium with COX-2 inhibitory activity based on virtual screening and activity evaluation.

Research progress in biological activities of succinimide derivatives.

Succinimides are well recognized heterocyclic compounds in drug discovery which produce diverse therapeutically related applications in pharmacological practices. Researches in medicinal chemistry field have isolated and synthesized succinimide derivatives with multiple medicinal properties including anticonvulsant, anti-inflammatory, antitumor and antimicrobial agents, 5-HT receptor ligands and enzyme inhibitors. Simultaneously, SAR (Structure-Activity Relationship) analysis has been gradually possessed, along with a great deal of derivatives have been derived for potential targets. In this article, we comprehensively summarize the biological activities and SAR for succinimide derivatives, along with the featuring bioactive molecules reported in patents, wishing to provide an overall retrospect and prospect on the succinimide analogues.

14-3-3 proteins are required for hippocampal long-term potentiation and associative learning and memory.

14-3-3 is a family of regulatory proteins highly expressed in the brain. Previous invertebrate studies have demonstrated the importance of 14-3-3 in the regulation of synaptic functions and learning and memory. However, the in vivo role of 14-3-3 in these processes has not been determined using mammalian animal models. Here, we report the behavioral and electrophysiological characterization of a new animal model of 14-3-3 proteins. These transgenic mice, considered to be a 14-3-3 functional knock-out, express a known 14-3-3 inhibitor in various brain regions of different founder lines. We identify a founder-specific impairment in hippocampal-dependent learning and memory tasks, as well as a correlated suppression in long-term synaptic plasticity of the hippocampal synapses. Moreover, hippocampal synaptic NMDA receptor levels are selectively reduced in the transgenic founder line that exhibits both behavioral and synaptic plasticity deficits. Collectively, our findings provide evidence that 14-3-3 is a positive regulator of associative learning and memory at both the behavioral and cellular level.

Modulation of GluK2a subunit-containing kainate receptors by 14-3-3 proteins.

Kainate receptors (KARs) are one of the ionotropic glutamate receptors that mediate excitatory postsynaptic currents (EPSCs) with characteristically slow kinetics. Although mechanisms for the slow kinetics of KAR-EPSCs are not totally understood, recent evidence has implicated a regulatory role of KAR-associated proteins. Here, we report that decay kinetics of GluK2a-containing receptors is modulated by closely associated 14-3-3 proteins. 14-3-3 binding requires PKC-dependent phosphorylation of serine residues localized in the carboxyl tail of the GluK2a subunit. In transfected cells, 14-3-3 binding to GluK2a slows desensitization kinetics of both homomeric GluK2a and heteromeric GluK2a/GluK5 receptors. Moreover, KAR-EPSCs at mossy fiber-CA3 synapses decay significantly faster in the 14-3-3 functional knock-out mice. Collectively, these results demonstrate that 14-3-3 proteins are an important regulator of GluK2a-containing KARs and may contribute to the slow decay kinetics of native KAR-EPSCs.

Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Preeclampsia-Induced Apoptosis of Placental Trophoblastic Cells Via Inhibiting the Mitochondrial Unfolded Protein Response.

Preeclampsia is a serious obstetric complication. Currently, there is a lack of effective preventive approaches for this disease. Recent studies have identified transcutaneous auricular vagus nerve stimulation (taVNS) as a potential novel non-pharmaceutical therapeutic modality for preeclampsia. In this study, we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt. Our results showed that taVNS promoted the release of acetylcholine (ACh). ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS (mtROS), presumably through M3AChR. This reduced the release of pro-apoptotic proteins (cleaved caspase-3, NF-κB-p65, and cytochrome C) and helped preserve the morphological and functional integrity of mitochondria, thus reducing the apoptosis of placental trophoblasts, improving placental function, and relieving preeclampsia. Our study unravels the potential pathophysiological mechanism of preeclampsia. In-depth characterization of the UPRmt is essential for developing more effective therapeutic strategies for preeclampsia targeting mitochondrial function.

Rules of acupoint selection in treatment of inflammatory bowel disease with acupuncture-moxibustion based on complex network analysis. / åŸºäºŽå¤æ‚ç½‘ç»œåˆ†æžé’ˆç¸æ²»ç–—ç‚Žæ€§è‚ ç— çš„é€‰ç©´è§„å¾‹.

OBJECTIVES: To analyze the rules of acupoint selection and compatibility of acupuncture and moxibustion in treatment of inflammatory bowel disease (IBD) based on complex network technology and provide the reliable evidences for acupoint selection in treatment of this disease with acupuncture and moxibustion. METHODS: The clinical studies on acupuncture-moxibustion treatment of IBD were searched from the databases including CNKI, Wanfang, VIP, PubMed and Embase. The studies were screened and the acupoint prescriptions were extracted to set up the database of acupuncture-moxibustion treatment for IBD. Using Microsoft Excel 2021 software, the use times of acupoint, the use frequency (%) of acupoint, meridian tropism and the use of special point were imported. With SPSS Modeler 18.0 software adopted, the association rules were analyzed on the acupoint prescriptions. The acupoint co-occurrence network diagram, k-core network diagram, and community analysis diagram were drawn by Gephi 0.9.5 software. RESULTS: A total of 156 studies were included, composed of 175 acupoint prescriptions, 75 acupoints, with 1 378 use times in total and around 8 acupoints in one prescription. Regarding the top use frequency, Tianshu (ST25), Zusanli (ST36), Guanyuan (CV4), Zhongwan (CV12) and Pishu (BL20) were listed. The top meridians involved were the foot-yangming stomach meridian, the foot-taiyang bladder meridian and the Conception Vessel. The front-mu point had been used with the highest frequency among the special points. ST36 and ST25 were a pair of points with the highest frequency in treatment. The k-core hierarchical analysis was adopted to optimize acupoint prescriptions, and 22 core acupoints were obtained, i.e. ST25, ST36, CV4, CV12, BL20, Dachangshu (BL25), Shangjuxu (ST37), Shenshu (BL23), Qihai (CV6), Sanyinjiao (SP6), Mingmen (GV4), Xingjian (LR2), Yinlingquan (SP9), Neiting (ST44), Taichong (LR3), Xiajuxu (ST39), Shuifen (CV9), Shenque (CV8), Ganshu (BL18), Weishu (BL21), Hegu (LI4) and Quchi(LI11), which were classified into three core acupoint groups by community analysis. CONCLUSIONS: Through complex network analysis, it is found that the local acupoints on the chest and abdomen are generally selected in treatment with acupuncture-moxibustion for IBD, the combination of the nearby and distal points is considered simulta-neously, and the acupoint prescription is modified according to syndrome/pattern differentiation；and among special points, the front-mu point is widely used in treatment. All of these rules provide the ideas for the acupoint selection of acupuncture-moxibustion in treatment of IBD.

Acupuncture and related acupoint therapies for smoking cessation: An umbrella review and updated meta-analysis.

INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Plasmonic Au-Cu nanostructures: Synthesis and applications.

Plasmonic Au-Cu nanostructures composed of Au and Cu metals, have demonstrated advantages over their monolithic counterparts, which have recently attracted considerable attention. Au-Cu nanostructures are currently used in various research fields, including catalysis, light harvesting, optoelectronics, and biotechnologies. Herein, recent developments in Au-Cu nanostructures are summarized. The development of three types of Au-Cu nanostructures is reviewed, including alloys, core-shell structures, and Janus structures. Afterwards, we discuss the peculiar plasmonic properties of Au-Cu nanostructures as well as their potential applications. The excellent properties of Au-Cu nanostructures enable applications in catalysis, plasmon-enhanced spectroscopy, photothermal conversion and therapy. Lastly, we present our thoughts on the current status and future prospects of the Au-Cu nanostructures research field. This review is intended to contribute to the development of fabrication strategies and applications relating to Au-Cu nanostructures.

[Discussion on acupuncture analgesia from the perspective of acupuncture regulating mind].

To explore the regulating effect of acupuncture on pain based on the three dimensions of pain (pain sensation, pain emotion and pain cognition). The pain sensation is related to the body, the pain emotion is related to the seven emotions, the pain cognition is related to the mind of the five zang, and the three dimensions of pain interact with each other. Through the two ways of "regulating qi to treat mind" and "treating mind to regulate qi ", acupuncture comprehensively acts on pain sensation, pain emotion and pain cognition to achieve comprehensive regulation of pain.

[The rules of acupoint selection of acupuncture and moxibustion for aphasia based on data mining].

OBJECTIVE: To explore the rules of acupoint selection for aphasia treated with acupuncture and moxibustion using data mining technology. METHODS: From January 1, 2000 to April 1, 2022, the articles for clinical researches of acupuncture and moxibustion for aphasia published in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase were searched. Using Microsoft Excel 2021, the database was set up to analyze the use frequency of acupoint, meridian tropism, acupoint distribution and the use of specific points. SPSS26.0 was adopted for factor analysis, SPSS Modeler 18.0 was for association rule analysis of prescriptions, and Gephi 0.9.5 was to plot the co-occurrence network diagrams of acupoints and meridians. RESULTS: A total of 140 articles were collated, including 146 acupuncture and moxibustion prescriptions and 189 acupoints. The total use frequency of these acupoints was 1 211. Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Baihui (GV 20) and Yamen (GV 15) were the top 5 acupoints of the high use frequency for aphasia treated with acupuncture and moxibustion. Among 189 acupoints collected, the extra points and empirical points were mostly selected. The top 3 involved meridians were the governor vessel, the gallbladder meridian of foot-shaoyang and the conception vessel. These acupoints were mostly distributed on the head, face and neck region. The use frequency of five-shu points was the highest among the specific points. The acupoint combinations of high frequency referred to Yuye (EX-HN 13)-Jinjin (EX-HN 12), Yuye (EX-HN 13)-Lianquan (CV 23)-Jinjin (EX-HN 12), and Fengchi (GB 20)-Yuye (EX-HN 13)-Jinjin (EX-HN 12). Factor analysis extracted 10 common factors for acupoint compatibility in treatment of aphasia with acupuncture and moxibustion. CONCLUSION: In clinical treatment of aphasia with acupuncture and moxibustion, the local acupoints are preferred. The core acupoints include Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Baihui (GV 20) and Yamen (GV 15). The acupoint prescription is modified flexibly according to syndrome differentiation to enhance the therapeutic effect.

[Research on mechanisms of acupoint sensitization in gastric ulcer mice from perspective of dorsal root ganglion neuronal excitability].

OBJECTIVE: To investigate the relationship between acupoint sensitization on the body surface and neuronal intrinsic excitability of the medium- and small-size dorsal root ganglion (DRG) neurons from the perspective of ion channel kinetics in mice with gastric ulcer. METHODS: Male C57BL/6J mice were randomly divided into control (n=32) and model groups (n=34). The gastric ulcer model was established by injection of 60% glacial acetic acid (0.2 mL/100 g) into the gastric wall muscle layer and submucosa near the pylorus in the minor curvature of the stomach. In contrast, the same dose of normal saline was injected in the same way in the control group. Six days after modeling, Evans blue (EB) solution was injected into the mouse's tail vein for observing the number and distribution of the exudation blue spots on the body surface. Histopathological changes of the gastric tissue were observed by H.E. staining. Then, whole-cell membrane currents and intrinsic excitability of medium- and small-size neurons in the spinal T9-T11 DRGs were measured by in vitro electrophysiology combining with biocytin-ABC method. RESULTS: In the control group, EB exudation blue spots were not obvious, while in the model group, the blue spots on the body surface were densely distributed in the area of spinal T9-T11 segments, the epigastric region, and the skin around "Zhongwan" (CV12) and "Huaroumen" (ST24) regions, and near the surgical incision region. Compared with the control group, the model group had a high level of eosinophilic infiltrates in the submucosa of gastric tissues, severe gastric fossa structure damage, gastric fundus gland dilation and other pathological manifestations. The number of exudation blue spots was proportional to the degree of inflammatory reaction in the stomach. In comparison with the control group, the spike discharges of type II of medium-size DRG neurons in T9-T11 segments were decreased, and the current of whole-cell membrane was increased, basic intensity was decreased (P<0.05), discharge frequency and discharge number were increased (P<0.01,P<0.000 1); while the discharges of type I small-size DRG neurons were decreased, those of type II neurons increased, the whole-cell membrane current was decreased, and discharge frequency and discharge number were decreased (P<0.01, P<0.000 1). CONCLUSION: Both the medium- and small-size DRG neurons from the spinal T9-T11 segments involve in gastric ulcer-induced acupoint sensitization via their different spike discharge activities. And intrinsic excitability of these DRG neurons can not only dynamically encode the plasticity of acupoint sensitization, but also can help us understand the neural mechanism of acupoint sensitization induced by visceral injury.

[Relationship between acupoint sensitization and changes in dorsal root ganglion neuron excitability in myocardial ischemia mice].

OBJECTIVE: To investigate the relationship between the sensitization state of acupoints on the surface of the myocardial ischemia (MI) model mice and the changes in the electrophysiological properties of the dorsal root ganglion (DRG) neurons in the corresponding spinal cord segment, and its underlying mechanism. METHODS: Sixty-eight male C57BL/6J mice were randomly divided into control and model groups (34 mice in each group). The model group received an intraperitoneal injection of 160 mg/kg isoproterenol (ISO) to establish the MI model, and the control group received an injection of the same dose of normal saline as the model group. After modeling for about 6 days, MI proportion was measured by HE staining to verify the pathological changes in the heart tissue. Evans blue (EB) dye was injected into the tail vein of mice to reflect the size, location, distribution, and number of exudates on the body surface. Then, whole-cell membrane currents, intrinsic excitability and membrane properties of different types of DRG neurons were evaluated by electrophysiological experiment in vitro. RESULTS: Compared with the control group, the heart size was larger, with pathological outcomes showing enlarged myocardial hypertrophy, destroyed structure of cardiomyocytes, with mononuclear cell infiltration among the cardiomyocytes in the model group. Compared with the control group, the number of EB exudation points was significantly increased (P<0.01), which were mainly concentrated in the epidermis near the T1-T5 segment of the spinal cord, "Feishu" (BL13), "Jueyinshu" (BL14) and "Xinshu" (BL15) in the model group. Compared with the control group, the rheobase and action potential amplitude (APA) of DRG medium-sized neurons were obviously decreased (P<0.01, P<0.05), while the whole-cell membrane currents, the spike numbers, the average instantaneous frequency, and the average discharge frequency were markedly increased (P<0.01). There were no significant alterations in the membrane properties and intrinsic excitability induced by depolarized currents of small-sized neurons between groups. Compared with the control group, the whole-cell membrane currents, spike numbers, and the average instantaneous frequency were significantly increased in the model group(P<0.05, P<0.01) while rheobase was significantly decreased (P<0.05) in DRG medium-sized neurons labeled with biotin and CGRP. CONCLUSION: After the mice were modeled by ISO, the DRG medium-size neurons in the T1-T5 segment of the spinal cord may mediate the sensitization of acupoints on the body surface through their different neuronal membrane properties and intrinsic excitabilities.

Aß damages learning and memory in Alzheimer's disease rats with kidney-yang deficiency.

Previous studies demonstrated that Alzheimer's disease was considered as the consequence produced by deficiency of Kidney essence. However, the mechanism underlying the symptoms also remains elusive. Here we report that spatial learning and memory, escape, and swimming capacities were damaged significantly in Kidney-yang deficiency rats. Indeed, both hippocampal Aß(40) and 42 increases in Kidney-yang deficiency contribute to the learning and memory impairments. Specifically, damage of synaptic plasticity is involved in the learning and memory impairment of Kidney-yang deficiency rats. We determined that the learning and memory damage in Kidney-yang deficiency due to synaptic plasticity impairment and increases of Aß(40) and 42 was not caused via NMDA receptor internalization induced by Aß increase. ß-Adrenergic receptor agonist can rescue the impaired long-term potential (LTP) in Kidney-yang rats. Taken together, our results suggest that spatial learning and memory inhibited in Kidney-yang deficiency might be induced by Aß increase and the decrease of ß(2) receptor function in glia.

NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21).

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36.

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynaptic µ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

[Effect of electroacupuncture on mood and estrogen receptor α expression in mice with polycystic ovary syndrome induced by bisphenol A exposure].

OBJECTIVE: To compare the effect of electroacupuncture (EA) on "Guanyuan" (CV4) or sensitization points in mice with polycystic ovary syndrome (PCOS), so as to explore its mechanisms underlying improvement of PCOS. METHODS: In the first part of this study, 26 female ICR mice were randomized into control group (8 mice) and model group (18 mice). The PCOS model was established by gavage of bisphenol A (BPA) at a dose of 100 mg/kg, and the control group were gavage of equal volume of corn oil, once daily, 5 days a week for 4 conse-cutive weeks. Evans blue (EB) dye (0.1 mL/10 g) was injected into the caudal vein after modeling. The size, number and distribution of EB exudation points at the skin were observed. In the second part of this study, 32 mice were randomized into control, model, EA-CV4 and EA-sensitization points groups (8 mice in each group). EA (2 Hz, 2 mA) was applied to the sensitization points or CV4 for 20 min, once daily, 5 days a week for 4 conse-cutive weeks. The body weight was measured once a week for 8 consecutive weeks. The behavior changes were evaluated by open field test and elevated plus maze test. H.E. staining was used to observe the histopathologic changes of the ovary tissue. Serum level of estradiol (E2) was measured by ELISA. The expressions of estrogen receptor α (ER-α) in ovarian and uterine tissues were detected by Western blot and immunofluorescence. RESULTS: (1) In PCOS mice, the EB exudation points were found to overlap the lower abdomen, lumbosacral, chest, back and lower limbs regions, and the number of EB points was significantly more than that of the control group (P<0.01). (2) After the intervention and compared with the control group, the ovaries showed polycystic changes and an increase of atresia follicles with a larger diameter, the activity time in the central area, the total distance of movement, the times of open-arm entries, the duration in open-arm, the serum E2 content and the expression of ER-α in ovarian tissue were significantly decreased (P<0.01, P<0.05), while the mice's body weight and the expression of ER-α in uterine tissue were increased (P<0.05) in the model group. After the intervention and compared with the model group, a small number of normal follicles and corpus luteum were observed under microscope, the activity time in the central area, the total distance of movement, the times of open-arm entries, the duration in open-arm, the serum E2 content and the expression of ER-α in ovarian tissue were significantly increased (P<0.05, P<0.01), while the mice's body weight and the expression of ER-α in uterine tissue was decreased (P<0.05) in both EA-CV4 and EA-sensitization points groups. CONCLUSION: EA at sensitization points and CV4 can regulate the expression of estrogen and ER-α in PCOS mice, and improve the anxiety like behavior. EB exudation points on the body surface can not only reflect the functional changes of organs, but also treat diseases through body surface stimulation, suggesting a dual role in diagnosis and treatment.

Advances in Anti-Osteoporosis Polysaccharides Derived from Medicinal Herbs and Other Edible Substances.

Osteoporosis is a common metabolic bone disease, and treatment is required for the prevention of low bone mass, deterioration of microstructural bone tissue, and fragility fractures. Osteoporosis therapy includes calcium, vitamin D, and drugs with antiresorptive or anabolic action on the bone. Therapy for osteoporosis does not include taking non-steroidal anti-inflammatory drugs (NSAID), but pain associated with osteoporotic fractures can be treated by taking non-steroidal anti-inflammatory drugs (NSAID). Recently, polysaccharides extracted from medicinal herbs and edible substances (PsMHES) have attracted attention on account of their safety and promising anti-osteoporosis effects, whereas a systematic review about their potential in anti-osteoporosis is vacant to date. Herein, we reviewed the recent progress of PsMHES with anti-osteoporosis activities, looking to introduce the advances in the various pharmacological mechanisms and targets involved in the anti-osteoporosis effects, extraction methods, main mechanism involved in Wnt/[Formula: see text]-catenin pathways and RANKL (Receptor Activator for NF[Formula: see text]B ligand or TNFSF25) pathways, and Structure-Activity Relationships (SAR) analysis of PsMHES. Typical herbs likeAchyranthes bidentate and Morinda officinalis used for the treatment of osteoporosis are introduced; their traditional uses in traditional Chinese medicine (TCM) are discussed in this paper as well. This review will help to the recognition of the value of PsMHES in anti-osteoporosis and provide guidance for the research and development of new anti-osteoporosis agents in clinic.

[Effects of early electroacupuncture on the expression of Iba-1 and TNF-α in Parkinson's disease mice].

OBJECTIVE: To observe the effect of early electroacupuncture(EA) intervention on ionized calcium binding adapter molecule 1 (Iba-1), tyrosine hydroxylase (TH) and tumor necrosis factor-α (TNF-α) in Parkinson's disease (PD) mice, so as to explore its neuroinflammation mechanism in treating PD. METHODS: A total of 24 male C57BL/6J mice (9 weeks old) were randomly divided into control, model and EA groups, with 8 mice in each group. The PD model was established by long-term low dose subcutaneous injection of rotenone. Started at the same time with modeling, EA (2 Hz/100 Hz, 1 mA) was applied to "Shenting"(GV24), bilateral "Tianshu"(LI11), "Quchi"(ST25), and "Shangjuxu"(ST37) for 15 min, once a day for 8 weeks. The motor function was assessed by rotorod test and step length test. The expression levels of Iba-1 and TH proteins in substantia nigra pars compacta (SNpc) was detected by Western blot and immunohistochemistry. The expression level of TNF-α protein in colon tissue was examined by Western blot and immunofluorescence staining. RESULTS: Compared with the control group, the fall latency shortened at 4, 6, and 8 weeks after modeling (P<0.01) and the step length of hind limbs shortened at 5 and 7 weeks after modeling (P<0.01), the expression levels of Iba-1 in SNpc and TNF-α in colon tissue were increased (P<0.01), and the expression level of TH in SNpc was decreased (P<0.01) in the model group. Compared with the model group, the fall latency prolonged at 6 and 8 weeks after modeling (P<0.01) and the step length of hind limbs prolonged at 5 and 7 weeks after modeling (P<0.01), the expression levels of Iba-1 in SNpc and TNF-α in colon tissue were decreased (P<0.01, P<0.05), and the expression level of TH in SNpc was increased (P<0.05, P<0.01) in the EA group. CONCLUSION: Early EA intervention can delay the occurring time of motor disfunction, alleviated the loss of substantia nigra dopaminergic neurons, and exerted a good neuroprotective effect on the degenerative changes in rotenone-induced PD mice, which may be related to its effects in alleviating the intestinal inflammation, inhibiting the activation of microglia, thereby reducing the neuroinflammation.