Electroacupuncture Inhibits Neural Ferroptosis in Rat Model of Traumatic Brain Injury via Activating System Xc-/GSH/GPX4 Axis.

BACKGROUND: Ferroptosis is an iron-dependent regulating programmed cell death discovered recently that has been receiving much attention in traumatic brain injury (TBI). xCT, a major functional subunit of Cystine/glutamic acid reverse transporter (System Xc-), promotes cystine intake and glutathione biosynthesis, thereby protecting against oxidative stress and ferroptosis. OBJECTIVE: The intention of this research was to verify the hypothesis that electroacupuncture (EA) exerted an anti-ferroptosis effect via an increase in the expression of xCT and activation of the System Xc-/GSH/GPX4 axis in cortical neurons of TBI rats. METHODS: After the TBI rat model was prepared, animals received EA treatment at GV20, GV26, ST36 and PC6, for 15min. The xCT inhibitor Sulfasalazine (SSZ) was administered 2h prior to model being prepared. The degree of neurological impairment was evaluated by means of TUNEL staining and the modified neurological severity score (mNSS). Specific indicators of ferroptosis (Ultrastructure of mitochondria, Iron and ROS) were detected by transmission electron microscopy (TEM), Prussian blue staining (Perls stain) and flow cytometry (FCM), respectively. GSH synthesis and metabolism-related factors in the content of the cerebral cortex were detected by an assay kit. Real-time quantitative PCR (RT-QPCR), Western blot (WB), and immunofluorescence (IF) were used for detecting the expression of System Xc-/GSH/GPX4 axisrelated proteins in injured cerebral cortex tissues. RESULTS: EA successfully relieved nerve damage within 7 days after TBI, significantly inhibited neuronal ferroptosis, upregulated the expression of xCT and System Xc-/GSH/GPX4 axis forward protein and promoted glutathione (GSH) synthesis and metabolism in the injured area of the cerebral cortex. However, aggravation of nerve damage and increased ferroptosis effect were found in TBI rats injected with xCT inhibitors. CONCLUSIONS: EA inhibits neuronal ferroptosis by up-regulated xCT expression and by activating System Xc-/GSH/GPX4 axis after TBI, confirming the relevant theories regarding the EA effect in treating TBI and providing theoretical support for clinical practice.

Template-Free Synthesis of Boron-Doped Graphitic Carbon Nitride Porous Nanotubes for Enhanced Photocatalytic Hydrogen Evolution.

The photocatalytic activity of g-C3N4 can be enhanced by improving photoinduced carrier separation and exposing sufficient reactive sites. In this study, we synthesized B-doped porous tubular g-C3N4 (BCNT) using a H3BO3-assisted supramolecular self-template method, wherein H3BO3 helped in B-doping, building a porous structure, and maintaining one-dimensional nanotubes. The tubular structure had an ultrathin tube wall and large aspect ratio, which are conducive to the directional transmission and separation of photogenerated carriers; moreover, the abundant pore structure of the tube wall could fully expose the reactive sites. The introduction of B and the cyano group modulated the bandgap of g-C3N4 and elevated the position of the conduction band, thus enhancing the photoreduction ability and effectively improving the hydrogen evolution performance. Consequently, the hydrogen evolution of BCNT-2 (220.8, 53.2 µmol·h-1) was 1.82 and 1.54 times that of ultrathin g-C3N4 nanosheets (CNN, 121.3, 34.6 µmol·h-1) under simulated sunlight and LED lamp irradiation, respectively. Thus, this work provides in-depth insights into the rational design of one-dimensional g-C3N4 nanotubes with high hydrogen evolution activity under visible irradiation.

Mitochondria and NLRP3 inflammasome in cardiac hypertrophy.

Cardiac hypertrophy is the main adaptive response of the heart to chronic loads; however, prolonged or excessive hypertrophy promotes myocardial interstitial fibrosis, systolic dysfunction, and cardiomyocyte death, especially aseptic inflammation mediated by NLRP3 inflammasome, which can aggravate ventricular remodeling and myocardial damage, which is an important mechanism for the progression of heart failure. Various cardiac overloads can cause mitochondrial damage. In recent years, the mitochondria have been demonstrated to be involved in the inflammatory response during the development of cardiac hypertrophy in vitro and in vivo. As the NLRP3 inflammasome and mitochondria are regulators of inflammation and cardiac hypertrophy, we explored the potential functions of the NLRP3 inflammasome and mitochondrial dysfunction in cardiac hypertrophy. In particular, we proposed that the induction of mitochondrial dysfunction in cardiomyocytes may promote NLRP3-dependent inflammation during myocardial hypertrophy. Further in-depth studies could prompt valuable discoveries regarding the underlying molecular mechanisms of cardiac hypertrophy, reveal novel anti-inflammatory therapies for cardiac hypertrophy, and provide more desirable therapeutic outcomes for patients with cardiac hypertrophy.

Effects of Aire on perforin expression in BMDCs via TLR7/8 and its therapeutic effect on type 1 diabetes.

AIMS: Type 1 diabetes, as a kind of autoimmune diseases, usually results from the broken-down of self-tolerance. Autoimmune regulator (Aire), as a transcription factor, induces peripheral tolerance by regulating Toll-like receptor (TLR) expression in dendritic cells (DCs). Several studies have recently identified a small population of perforin-expressing DCs, which is an important population of tolerogenic DCs (tolDCs) that restricts autoreactive T cells in vivo through a perforin-mediated mechanism. Thus, the present study explored the specific relationship among Aire, perforin-expressing DCs and immune tolerance, as well as their roles in type 1 diabetes. METHODS: We conducted studies based on the Aire-overexpressing bone marrow-derived dendritic cell (BMDC) model. And through in vitro and in vivo experiments to observe that Aire-overexpressing BMDCs which express perforin induce immune tolerance and treat type 1 diabetes via TLR7/8. RESULTS: Aire enhances the expression of perforin in BMDCs after treatment with the TLR7/8 ligand as well as promotes the expression of TLR7/8 and myeloid differentiation primary response gene 88 (MyD88)-dependent pathway molecules. Aire-overexpressing BMDCs mediate apoptosis of allogeneic CD8+ T cells via perforin in vitro. Moreover, Aire-overexpressing BMDCs enhance the therapeutic effect of type 1 diabetes in non-obese diabetic (NOD) mice via perforin and induce apoptosis of autoreactive CD8+ T cells in vivo. CONCLUSIONS: These results provide an experimental basis for comprehensively elucidating the role and significance of Aire expression in peripheral DCs, thereby providing new ideas for the treatment of autoimmune diseases by using Aire as a target to induce the production of perforin-expressing DCs.

Aire and Fezf2, two regulators in medullary thymic epithelial cells, control autoimmune diseases by regulating TSAs: Partner or complementer?

The expression of tissue-specific antigens (TSAs) in medullary thymic epithelial cells (mTECs) is believed to be responsible for the elimination of autoreactive T cells, a critical process in the maintenance of central immune tolerance. The transcription factor autoimmune regulator (Aire) and FEZ family zinc finger 2(Fezf2) play an essential role in driving the expression of TSAs in mTECs, while their deficiency in humans and mice causes a range of autoimmune manifestations, such as type 1 diabetes, Sjögren's syndrome and rheumatoid arthritis. However, because of their regulatory mechanisms, the expression profile of TSAs and their relationship with special autoimmune diseases are still in dispute. In this review, we compare the roles of Aire and Fezf2 in regulating TSAs, with an emphasis on their molecular mechanisms in autoimmune diseases, which provides the foundation for devising improved diagnostic and therapeutic approaches for patients.

[Effect of electroacupuncture on behavior and cell apoptosis of brain tissue in traumatic brain injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on behavior, pathomorphology and brain cell apoptosis in traumatic brain injury (TBI) rats, so as to explore its mechanisms underlying treatment of TBI. METHODS: Male SD rats were randomly divided into control (n=10), sham (n=30), model (n=30) and EA (n=30) groups, the latter three groups were further divided into 3, 7, 14 d subgroups （n=10）. TBI model was established by using a free fall brain injury striking device after exposing the local cranial bone (to induce the left parietal cerebral contusion). Twenty-four hours after modeling, EA (2 Hz, 1 mA) was applied at "Quchi"(LI11), "Neiguan"(PC6), "Zusanli"(ST36) and "Yongquan" (KI1) combined with acupuncture at "Shuigou"(GV26) and "Baihui"(GV20) for 15 min, once a day for 14 consecutive days. After 3, 7, and 14 days treatment, the behavioral function (balance, walking, nerve, and limb retraction) of the rats was evaluated. The histopathological changes of the injured brain tissue were observed by HE staining. TUNEL method was used to detect the apoptosis of cells in the brain injury area. RESULTS: After modeling, the scores of balance and walking in the model group were higher than those in the sham group (P<0.01, P<0.05), the neurological function score and the right limb retraction force were lower than those in the sham group(P<0.01). After 3 days treatment, the neurological function score and the right limb retraction force in the EA group were higher than those in the model group (P<0.05). After 7 and 14 days treatment, the scores of balance and walking function in the EA group were lower than those in the model group (P<0.05, P<0.01), while the scores of nerve function and right limb retraction force were higher (P<0.05, P<0.01). HE staining showed that modeling induced pathological changes such as the inflammatory cell infiltration, interstitial edema, necrosis, nuclear pyknosis and nuclear lysis were relatively milder in the EA group on the 7th and 14th day. Compared with the sham group, the cell apoptosis of brain injury area was higher in the model group (P<0.01); while it was lower on day 7 and 14 in the EA group in comparison with the model group (P<0.01, P<0.05). CONCLUSION: EA can improve the behavioral function, reduce the apoptosis of brain cells in the injured area, and promote the rehabilitation of craniocerebral injury.

Therapeutic effects of acupuncture in rheumatoid arthritis are associated with centromere protein F expression.

OBJECTIVE: The objective of this study is to study the critical role of CENPF in regulation of rheumatoid arthritis with acupuncture treatment. METHODS: PCA was used to analyze the different expression genes between AP treatment group and control group. Volcano plot and random forest model were used to analyze the decreased and increased expression genes. RT-qPCR and IF were used to measure the expression of CENPF in CIA model rat with or without AP treatment. The expression of MCP-1, TNF-α and IL-6 was measured by western blotting. The pathology character and arthritis index were used to analyze the severity of joint injury. RESULTS: PCA data showed that the expression of genes was different between AP treatment group and control group from GEO datasets. Volcano plot and random forest model analysis indicated that CENPF is the most significantly increased expression gene after AP treatment. RT-qPCR and IF assay showed that CENPF is reduced expression in CIA model rat, while CENPF is upregulated expression in CIA model rat with AP treatment. Furthermore, overexpression of CENPF reduced the increasing of MCP-1, TNF-α and IL-6 in CIA model rat. On the contrary, CENPF deficiency induced the expression of MCP-1, TNF-α and IL-6 in CIA model rat. Additionally, the expression of MCP-1, TNF-α and IL-6 in CIA model rat was suppressed, whereas knockdown of CENPF antagonized the decrease of MCP-1, TNF-α and IL-6 in CIA model rat with AP treatment. CONCLUSIONS: CENPF may be a key gene in regulation of the therapeutic effects of acupuncture in rheumatoid arthritis. Rheumatoid arthritis is a globally common autoimmune inflammatory disease found especially in China. Acupuncture (AP), a traditional Chinese medicine (TCM) treatment method, is commonly used for treating rheumatoid arthritis. Many studies have demonstrated that acupuncture alone or in combination with other treatments is beneficial to treat clinical situation of rheumatoid arthritis, thus improving function and quality of life. In this study, we found that centromere protein F (CENPF) is a key gene in rheumatoid arthritis with acupuncture treatment by using differentially expressed genes (DEGs) and random forest model analysis of GSE57983 and GSE77298. Acupuncture helps to up-regulate the expression of CENPF in tissues in rheumatoid arthritis. Functionally, overexpression of CENPF inhibits monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and Interleukin (IL)-6 expressions whereas deficiency of CENPF facilitates MCP-1, TNF-α, and IL-6 expressions in a collagen-induced arthritis (CIA) rat model. Furthermore, knocked down CENPF with acupuncture treatment antagonizes the inhibition of MCP-1, TNF-α, and IL-6 expressions in a CIA rat model. CENPF could be a crucial biomarker in regulating function of acupuncture in treating rheumatoid arthritis.

Species-resolved sequencing of low-biomass or degraded microbiomes using 2bRAD-M.

Microbiome samples with low microbial biomass or severe DNA degradation remain challenging for amplicon-based or whole-metagenome sequencing approaches. Here, we introduce 2bRAD-M, a highly reduced and cost-effective strategy which only sequences ~ 1% of metagenome and can simultaneously produce species-level bacterial, archaeal, and fungal profiles. 2bRAD-M can accurately generate species-level taxonomic profiles for otherwise hard-to-sequence samples with merely 1 pg of total DNA, high host DNA contamination, or severely fragmented DNA from degraded samples. Tests of 2bRAD-M on various stool, skin, environmental, and clinical FFPE samples suggest a successful reconstruction of comprehensive, high-resolution microbial profiles.

MDSCs interactions with other immune cells and their role in maternal-fetal tolerance.

MDSCs (myeloid-derived suppressor cells) are a population of immature and heterogeneous bone marrow cells with immunosuppressive functions, and they are mainly divided into two subgroups: granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). Immunosuppression is the main and most important function of MDSCs, and they mainly exert an inhibitory effect through endoplasmic reticulum stress and some enzymes related to inhibitors, as well as some cytokines and other factors. In addition, MDSCs also interact with other immune cells, especially NK cells, DCs and Tregs, to participate in immune regulation. A large number of MDSCs are found during normal pregnancy. Combined with their immunosuppressive effects, these results suggest that MDSCs are likely to be closely related to maternal-fetal immune tolerance. This review mainly shows the interaction of MDSCs with other immune cells and the important role of MDSCs in maternal-fetal tolerance. The current research shows that MDSCs are mainly mediated by STAT3, HLA-G, CXCR2, Arg-1 and HIF1-α in immune regulation during pregnancy. Interpreting maternal-fetal tolerance from the perspective of MDSCs provides a special perspective for research on immune regulation and maternal-fetal tolerance of MDSCs to obtain a more comprehensive understanding of immune regulation and immune tolerance.

Easy Fabrication of Amorphous Covalent Organic Nanospheres Using Schiff-Base Chemistry for Iodine Capture.

Designing a strategy for easy fabrication of amorphous porous organic polymers (POPs) with regularly nanospherical structure using common chemical raw materials is highly imperative to promote the practical application for iodine capture. Uniform covalent organic nanospheres (CONs), defined as CON-TT, were easily prepared at room temperature via a Schiff base condensation reaction of tri(4-aminophenyl) methane (TAPM) and terephthalaldehyde (TPA) catalyzed by acetic acid. The obtained CON-TT exhibits a uniform nanospherical shape, high specific surface area, effective imine sorption sites and abundant benzene rings. An excellent reversible iodine adsorption capacity of 4.80 g g-1 is achieved, which can be attributed to the hybrid of physisorption and chemisorption process. We anticipate that this work can provide general guidance for the industrial large-scale preparation of other CONs for iodine capture.

Effect of acupuncture treatment on cognitive impairment after traumatic brain injury in adults: A protocol for systematic review.

BACKGROUND: Acupuncture has been widely used to treat cognitive impairment after traumatic brain injury (TBI). But its efficiency has not been scientifically and methodically evaluated. The objective of this study is to evaluate the efficiency and safety of the acupuncture treatment for cognitive impairment after TBI in adults. METHODS: This protocol of systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. We will conduct the literature searching in the following electronic databases: the Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, the Chinese Science Citation Database (CSCD), China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), Wanfang, and the Chinese Scientific Journal Database (VIP). The time limit for retrieving studies is from establishment to November 2021 for each database. All published randomized controlled trials related to this review will be included. Review Manager (V.5.3.5) will be implemented for the assessment of bias risk and data analyses. The selection of the studies, data abstraction, and validations will be performed independently by 2 researchers. RESULTS: This review will assess the clinical efficacy and safety, as well as the acupoints characteristics of acupuncture on CI of TBI in adults. CONCLUSION: This review will summarize the current evidence of acupuncture on CI of TBI outcomes and provide guidance for clinicians and patients to select acupuncture for CI of TBI in adults. TRAIL REGISTRATION NUMBER: This protocol of systematic review has been registered on INPLASY website (No. INPLASY2021110113).

Effect of Earthworm on Wound Healing: A Systematic Review and Meta-Analysis.

Background: Earthworm, also called dilong (Chinese language), has been used as a traditional Chinese medicine for thousands of years. Recently, some scientists believe that earthworm extracts (EE) can promote wound healing. However, its effectiveness remains controversial. We conducted a meta-analysis to evaluate the effect of EE on wound healing based on the healing rate. Methods: We comprehensively reviewed literature that mentioned EE for wound healing in the PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, and WanFang database that have been published until January 2021. We computed weighted mean difference (WMD) for analysis with RevMan 5.3 software in animal and human models groups. Two researchers independently selected studies and evaluated the risk of bias with the Cochrane Collaboration tool. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO (CRD42020168400). Results: From 2,486 articles, we selected 16 studies for analysis. EE treatment was associated with improvements in wound healing performance based on wound healing rate (mouse model: weighted mean difference (WMD) = 3.55, 95% confidence interval (CI): 2.34-4.77, p < 0.00001; rat model: WMD = 17.29, 95% CI: 5.75-28.82, p = 0.003; rabbit model: WMD = 19.29, 95% CI: 9.95-28.64, p < 0.0001). Clinical studies also confirmed that EE could reduce healing time in hospital (WMD = -8.94, 95% CI: -17.75 to -0.14, p = 0.05). Conclusion: The results of this meta-analysis demonstrated the efficacy of EE on wound healing process. As a corollary, EE can be a useful natural product for wound healing drug development. Systematic Review Registration : https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=168400, identifier CRD42020168400.

[Effect of Jiannao Anshen acupuncture on insomnia: a functional magnetic resonance imaging study].

OBJECTIVE: To observe the efficacy of Jiannao Anshen acupuncture (acupuncture for brain-invigorating and mind-calming) on insomnia, and the dynamic changes of functional magnetic resonance imaging (fMRI) before and after acupuncture, to provide neuroimaging basis of acupuncture for insomnia. METHODS: A total of 58 participants were included. Of them, 29 patients with insomnia were included into an observation group, and 29 healthy participants were included into a control group. The patients in the observation group were treated with Jiannao Anshen acupuncture at Baihui (GV 20), bilateral Sishencong (EX-HN 1), Fengfu (GV 16), Fengchi (GB 20), Qiangjian (GV 18), occipital sideline, Anmian (Extra), Yiming (EX-HN 14) and Dazhui (GV 14); treatment was given once a day, 10 days as a course of treatment, and a total of 2 courses of treatment was given. The resting-state fMRI data was collected in the observation group before and after treatment. The participants in the control group received no treatment, and the resting-state fMRI data was collected only once. The resting-state fMRI data in the observation group before treatment and in the control group, also the observation group before and after treatment were compared. The Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), daytime insomnia symptom scale (DISS), hyperarousal scale (HAS), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), digit symbol test, mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and the A, B speed of trail making test (NCT) were observed in the observation group before and after treatment. The clinical efficacy of the observation group was evaluated. RESULTS: The total effective rate was 89.7% (26/29) in the observation group. In the observation group, the scores of PSQI, ISI and DISS, the A, B speed of NCT were all decreased after treatment (P<0.01, P<0.05). Before treatment, compared with the control group, functional connectivity in ventral dorsal prefrontal cortex, dorsal anterior cingulate cortex, inferior parietal lobe, dorsal lateral prefrontal cortex, dorsal anterior cingulate cortex, left ventral anterior cingulate gyrus and right ventral anterior cingulate gyrus was reduced in the observation group; compared before treatment, the functional connectivity in lingual gyrus, cerebellar area 6, frontal lobe, insular lobe and anterior cingulate gyrus, premotor gyrus and posterior cingulate gyrus was increased after treatment in the observation group. After treatment, the functional connection intensity of left ventral caudate nucleus and insular lobe was negatively correlated with HAMD score in the observation group (r =-0.55, P<0.05), and the functional connection intensity of left ventral caudate nucleus and anterior cingulate gyrus was negatively correlated with HAMA score in the observation group (r =-0.47, P<0.05). CONCLUSION: The Jiannao Anshen acupuncture could effectively improve the sleep quality in patients with insomnia, and acupuncture could enhance the connection of left dorsal, right ventral and left ventral caudate nucleus with brain area.

AIRE-overexpressing BMDCs suppress TFH cells through ICOSL to prevent and attenuate autoimmune diabetes in NOD mice.

The strong genetic association between autoimmune regulator (AIRE) and autoimmune diseases indicates its critical role in immune tolerance. AIRE deficiency is thought to promote the development of follicular helper T (TFH) cells, which are considered to be essential in B cell proliferation. Excessive TFH cell generation is a key step towards the development of autoimmune diseases, including type 1 diabetes. However, the potential mechanism by which AIRE contributes to the generation and function of the TFH cell population has remained elusive. We show that AIRE reduced TFH cell generation by inhibiting the expression of inducible costimulatory ligand (ICOSL), interleukin (IL)-6 and IL-27 in dendritic cells (DCs). To understand the precise impact of AIRE-overexpressing bone marrow-derived DCs (AIRE-BMDCs) on type 1 diabetes progression and the associated molecular mechanisms, we transferred AIRE-BMDCs to recipient NOD mice and found that transplantation of AIRE-BMDCs can prevent or delay the onset of diabetes, attenuate diabetes after the establishment of overt hyperglycaemia, and lead to the inhibition of autoreactive pathological TFH cells and germinal centre (GC) B cells. To further determine the potential mechanism underlying this TFH cell depletion, BMDCs were cotransferred with recombinant mouse ICOSL (ICOSLG protein). We demonstrated that NOD mice were more susceptible to diabetes when they received AIRE-BMDCs and ICOSLG than when they received only mock-vehicle BMDCs (GFP-BMDCs). In addition, we did not observe the reversal of diabetes in any mice subjected to this cotransfer system. A single cycle of ICOSLG treatment temporarily promoted TFH cell proliferation and GC development. Our results reveal a mechanistic role of AIRE-BMDCs in the initiation of TFH cell differentiation, and the AIRE-mediated decrease in ICOSL expression in BMDCs plays a critical role. The effect of decreased ICOSL expression in type 1 diabetes will guide the design and evaluation of parallel studies in patients.

The Role of AIRE Deficiency in Infertility and Its Potential Pathogenesis.

The increasing number of patients with infertility is recognized as an emerging problem worldwide. However, little is known about the cause of infertility. At present, it is believed that infertility may be related to genetic or abnormal immune responses. It has long been indicated that autoimmune regulator (AIRE), a transcription factor, participates in immune tolerance by regulating the expression of thousands of promiscuous tissue-specific antigens in medullary thymic epithelial cells (mTECs), which play a pivotal role in preventing autoimmune diseases. AIRE is also expressed in germ cell progenitors. Importantly, the deletion of AIRE leads to severe oophoritis and age-dependent depletion of follicular reserves and causes altered embryonic development in female mice. AIRE-deficient male mice exhibit altered apoptosis during spermatogenesis and have a significantly decreased breeding capacity. These reports suggest that AIRE deficiency may be responsible for infertility. The causes may be related to the production of autoantibodies against sperm, poor development of germ cells, and abnormal ovarian function, which eventually lead to infertility. Here, we focus on the potential associations of AIRE deficiency with infertility as well as the possible pathogenesis, providing insight into the significance of AIRE in the development of infertility.

Effect of electroacupuncture treatment on functional constipation in adults: A protocol for systematic review.

BACKGROUND: Electroacupuncture has been widely used to treat functional constipation. But its efficiency has not been scientifically and methodically evaluated. The objective of this study is to evaluate the efficiency and safety of the electroacupuncture treatment for functional constipation in adults. METHODS: This protocol of systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will conduct the literature searching in the following electronic databases: the Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, the Chinese Science Citation Database (CSCD), China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), Wanfang, and the Chinese Scientific Journal Database (VIP). The time limit for retrieving studies is from establishment to July 2020 for each database. All published randomized controlled trials (RTCs) related to this review will be included. Review Manager (V.5.3.5) will be implemented for the assessment of bias risk and data analyses. The selection of the studies, data abstraction, and validations will be performed independently by 2 researchers. RESULTS: This review will assess the clinical efficacy and safety, as well as the acupoints characteristics of electroacupuncture on functional constipation (FC) in adults. CONCLUSION: This review will summarize the current evidence of electroacupuncture on FC outcomes and provide guidance for clinicians and patients to select electroacupuncture for FC in adults. TRAIL REGISTRATION NUMBER: This protocol of systematic review has been registered on PROSPERO website (No. CRD42019146715).

[Effect of electroacupuncture at different stages on the expression of Fas and FasL in brain tissue of rats with traumatic brain injury].

OBJECTIVE: To investigate the expression of apoptosis-related proteins Fas and FasL in the brain tissue of rats with traumatic brain injury and the effect of electroacupuncture on the expression of Fas and FasL, so as to explore the effective time window of electroacupuncture in the treatment of traumatic brain injury. METHODS: Sprague-Dawley rats were randomly divided into blank group, sham-operation group, model group, and electroacupuncture treatment groups 1, 2, and 3. Traumatic brain injury was induced by the modified Feeney free-fall impact device, and for the rats in the electroacupuncture treatment groups 1, 2, and 3, electroacupuncture started at 4 hours and on days 3 and 7, respectively, after modeling and lasted to day 14. The Morris water maze test was used to evaluate learning and memory ability, and immunofluorescence assay and Western blot were used to observe the changes in the expression of Fas and FasL in traumatic brain tissue. RESULTS: Compared with the blank group and the sham-operation group, the model group had a lower percentage of time spent in the target quadrant from the 3rd day folowing modeling; after electroacupuncture intervention, the electroacupuncture treatment groups showed a gradual increase in the time spent in the target quadrant, and on day 7,10 and 14, electroacupuncture treatment group 1 had a significantly higher percentage than the model group (P<0.05). On day 14, electroacupuncture treatment group 2 had a significantly higher percentage than the model group (P<0.05). After electroacupuncture intervention, all groups except the blank group and the sham-operation group had increases in the expression of Fas and FasL in brain tissue, which reached the highest level on day 7 after modeling and then tended to decrease; compared with electroacupuncture treatment groups 2 and 3 and the model group, electroacupuncture treatment group 1 had significant reductions in the expression of Fas and FasL (P<0.05, P<0.01); compared with electroacupuncture treatment group 3 and the model group, electroacupuncture treatment group 2 had significant decreases in the expression of Fas and FasL (P<0.05) on day 14 after modeling; compared with the model group, electroacupuncture treatment group 3 had significant reductions in the expression of Fas and FasL in brain tissue on day 14 after modeling (P<0.05). CONCLUSION: Early electroacupuncture intervention can regulate the apoptosis receptor pathway by down-regulating Fas and FasL to exert a therapeutic effect on traumatic brain injury and help with the recovery of cognition and memory ability after traumatic brain injury.

[Effect of electroacupuncture on neuronal apoptosis in rats with traumatic brain injury based on PI3K/Akt signaling pathway].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on neuronal apoptosis in rats with traumatic brain injury (TBI), and to explore the action mechanism of EA on improving the brain nerve function of TBI. METHODS: A total of 88 6-week-old SD rats were randomly divided into a sham operation group, a model group, an EA group and a LY294002+EA group, 22 rats in each group. The TBI model on the left side was established by the improved Feeney's free fall method. After modeling for 24 h, the rats in the EA group and LY294002+EA group were treated with acupuncture at "Baihui" (GV 20) for 10 min and pricking acupuncture at "Shuigou" (GV 26) for 20 s; EA was applied at "Neiguan" (PC 6) and "Zusanli" (ST 36) on the right side (discontinuous wave, 2 Hz of frequency, 1 mA of intensity) for 10 min, once a day for 3 days. After 3 days of intervention, the TUNEL method was used to detect the level of neuron apoptosis in left cerebral cortex; the Western blot method was used to detect the expression of Akt, p-Akt, Bcl-2, Bax, Cyt-C and Caspase-9 in the left cerebral cortex. RESULTS: After 3-day treatment, compared with the sham group, the number of neuronal apoptosis in the left cortex was increased in the model group (P<0.01), and the expression of Bax, Cyt-C and Caspase-9 protein was increased (P<0.01), and the expression of p-Akt/Akt, Bcl-2 was decreased (P<0.01). Compared with the model group, the number of neuronal apoptosis in the left cortex was decreased in the EA group (P<0.01), and the expression of Bax, Cyt-C and Caspase-9 was decreased (P<0.01), and the expression of p-Akt/Akt and Bcl-2 was increased (P<0.01). Compared with the LY294002+EA group, the number of neuronal apoptosis in the left cortex was decreased in the EA group (P<0.01), and the expression of Bax, Caspase-9 and Cyt-C was decreased (P<0.01, P<0.05), and the expression of p-Akt/Akt and Bcl-2 was increased (P<0.01). CONCLUSION: EA could significantly reduce the neuronal apoptosis in rats with TBI, and its mechanism may be related to the activation of PI3K/Akt signaling pathway.

Whitening Activity of Constituents Isolated from the Trichosanthes Pulp.

Whitening cosmetics market has a bright future, and pure natural whitening products of traditional Chinese medicine have always been a research hotspot. In this research, the whitening active ingredient of Chinese medicine Trichosanthes pulp was isolated and purified for the first time, and its whitening mechanism was clarified. Chromatographic methods such as silica gel, ODS, and HPLC were used to isolate and purify them. B16 cells were used to measure the antioxidant activity, tyrosinase activity, and melanin removal activity. A total of 20 compounds were isolated, including p-hydroxybenzaldehyde (1), salicylic acid (2), vanillic acid (3), isovanillic acid (4), protocatechuate (5), trans-cinnamic acid (6), 4-coumaric acid (7), trans-ferulic acid (8), drechslerol-B (9), cyclotucanol 3-palmitate (10), 5-acetoxymethyl-2-furaldehyde (11), 5-hydroxymethylfurfural (12), diosmetin (13), apigenin (14), chrysoeriol (15), luteolin (16), 4'-hydroxyscutellarin (17), quercetin (18), 3',5-dihydroxy-7-(ß-D-glucopyranosyloxy)-4'-methoxyflavone (19), and cofloxacin-7-O-ß-D-glucoside (20). Among them, compounds 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 have good antioxidant repairing effects; compounds 3, 4, 5, 6, and 7 have high black inhibition; compounds 1, 2, 3, 4, 5, 6, 7, 8, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 have obvious tyrosine acidase inhibitory activity. The results laid foundation for the further development and utilization of Trichosanthes pulp resources and also provide a basis for the development of natural whitening cosmetics.

Trichromatic-emission and dual-ratio semiconducting polymer dots as fluorescent probe for simultaneous quantification of Cu2+ and pH in vitro and in vivo.

Novel dual-ratio semiconducting polymer dots (Pdots) with trichromatic-emission in the red, green and blue primary-color regions, are designed as lysosome-targeting nanoprobes for the simultaneous detection and multicolor imaging of pH and Cu2+ in HeLa cells and zebrafish without cross-interference.