Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats. / S1脑区CXCL1/CXCR2å‚ä¸Žé’ˆåˆºæ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ç—›çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

Advances of research on mechanisms of acupuncture underlying improvement of ischemic stroke by regulating neuronal mitochondria. / é’ˆåˆºè°ƒæŽ§ç¼ºè¡€æ€§å’ä¸­åŽç¥žç»å ƒçº¿ç²’ä½“çš„ä½œç”¨æœºåˆ¶ç ”ç©¶è¿›å±•.

Acupuncture has a positive effect in the treatment of ischemic stroke (IS). A number of studies have confirmed that the role of acupuncture in the treatment of IS, which is closely related to its functions of regulating mitochondrial functions. In the present article, we review the mechanisms of acupuncture underlying improvement of mitochondria in the treatment of IS from 4 aspects： 1) protecting mitochondrial structure integrity, 2) regulative effect on mitochondrial functional activities, including regulating energy metabolism, reducing oxidative stress, suppressing calcium overload, and regulating mitochondrial membrane potential changes, 3) regulating mitochondrial quality control system, including promoting mitochondrial biosynthesis, regulating mitochondrial dynamics and apoptosis, and 4) regula-ting mitochondria-related apoptosis pathways. All of these may provide a theoretical basis for acupuncture in the treatment of IS and a reference for further research.

Evidence for Quantum Stripe Ordering in a Triangular Optical Lattice.

Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.

Pathological pathway analysis in an experimental rheumatoid arthritis model and the tissue repair effect of acupuncture at ST36.

Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the face of inflammation-induced cartilage and bone damage, RA treatment remains insufficient. While research evidence indicates that acupuncture can exert anti-inflammatory and analgesic effects, improve the joint function of RA patients, and delay the disease, data on whether it can promote RA repair are lacking. Findings from the present work demonstrated that both the antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) models can simulate joint swelling of RA. The AIA model was more stable than the CIA model, with a higher incidence of successful arthritis modeling. Moreover, the AIA mice model could simulate the signal molecules and related pathological processes of the autoimmune response in RA, as well as major pathways related to RA and antigen immune response mechanisms. Manual acupuncture (MA) at Zusanli (ST36) significantly improved paw redness and swelling, pain, and inflammatory cell infiltration in the joints in AIA mice. The therapeutic effect of MA on AIA is achieved primarily through the regulation of steroid hormone biosynthesis, cell metabolism, and tissue repair processes. MA at ST36 can increase the gene contents of tissue repair growth factors, including PEG3, GADD45A, GDF5, FGF5, SOX2, and ATP6V1C2 in the inflammatory side joints of AIA mice, as well as the gene expression of the anti-inflammatory cytokine IL-10. In conclusion, acupuncture may alleviate RA in the joints via modulating the tissue healing process.

[Current situation and prospect of researches on regularities and mechanisms of acupuncture-moxibustion in alleviating chronic inflammatory response].

The inflammatory response plays an important role in the onset, development and prognosis of inflammatory diseases and a variety of chronic diseases. Long-term uncontrolled inflammatory response may lead to dysfunction or loss of organ tissue function. Clinical practice and evidence-based medicine suggest that acupuncture can effectively alleviate the inflammatory status of various inflammatory diseases and chronic diseases. Stimulation of acupoints related to internal organs and target organs can initiate neuromodulation by modulating the microenvironment of acupoints. After integration of acupuncture stimulus information in the central nervous system, neurotransmitters, hormones, etc. are released and ultimately act on immune cells through neuro-endocrine-immune pathways, such as the vagus-mediated cholinergic anti-inflammatory pathway, vagus nerve-adrenal medullary-dopamine pathway, somatic sympathetic nerve pathway, and hypothalamic-pituitary-adrenal axis, etc. Ultimately, the intracellular signaling pathways and polarization balance of monocytes/macrophages and T cell subsets are regulated and the immune homeo-stasis of target organs of the body realizes. Therefore, we proposed that the anti-inflammatory action of acupuncture may be one of the universal therapeutic strategies for multiple diseases, and a powerful interpretation of acupuncture in regulating the balance of yin and yang. The elucidation of its anti-inflammatory action rules and mechanism may better realize the clinical transformation of acupuncture and moxibustion precision treatment.

The autonomic nervous system: A potential link to the efficacy of acupuncture.

The autonomic nervous system (ANS) is a diffuse network that regulates physiological systems to maintain body homeostasis by integrating inputs from the internal and external environment, including the sympathetic, parasympathetic, and enteric nervous systems (ENS). Recent evidence suggests that ANS is one of the key neural pathways for acupuncture signal transduction, which has attracted worldwide attention in the acupuncture field. Here, we reviewed the basic and clinical research published in PubMed over the past 20 years on the effects of acupuncture on ANS regulation and homeostasis maintenance. It was found that acupuncture effectively alleviates ANS dysfunction-associated symptoms in its indications, such as migraine, depression, insomnia, functional dyspepsia, functional constipation. Acupuncture stimulation on some specific acupoints activates sensory nerve fibers, the spinal cord, and the brain. Using information integration and efferents from a complex network of autonomic nuclei of the brain, such as the insular cortex (IC), prefrontal cortex, anterior cingulate cortex (ACC), amygdala (AMG), hypothalamus, periaqueductal gray (PAG), nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), nucleus ambiguus (AMB), acupuncture alleviates visceral dysfunction, inflammation via efferent autonomic nerves, and relieves pain and pain affect. The modulating pattern of sympathetic and parasympathetic nerves is associated with acupuncture stimulation on specific acupoints, intervention parameters, and disease models, and the relationships among them require further exploration. In conclusion, ANS is one of the therapeutic targets for acupuncture and mediates acupuncture's actions, which restores homeostasis. A systemic study is needed to determine the rules and mechanisms underlying the effects of acupoint stimulation on corresponding organs mediated by specific central nervous networks and the efferent ANS.

[Common research strategy and outlook for the development of acupuncture translational medicine].

To explore the common questions of acupuncture translational medicine study and the development strategy of its translational application. It is believed that the research on the individual and common mechanisms of acupuncture effects, and the common molecule of acupoint and parameter research for the effect onset of acupuncture may promote clinical translation and instrument research and development. The study of meridian theory should be fully applied to clinical practice to build a meridian diagnostic system with clinical significance. Using evidence-based medicine, the clinical research of acupuncture can be transformed into clinical guidelines to provide the effective regimens for clinical practice. The communication and cooperation should be enhanced between the basic research and clinical application in the field of acupuncture. It is suggested that the promotion of acupuncture translational medicine research is contribute to the overall development of acupuncture discipline, and to better service for the human health engineering.

[Acupoit is the "transducer" in the physiochemical information coupling response of acupuncture].

Acupoint is the initial response site of acupuncture stimulus and also the source link of the effect onset of acupuncture. Acupuncture is a mechanical physical stimulus. How is the mechanical force of acupuncture transduced into neuroelectrical and biochemical signals at acupoint? How does the physiochemical information of acupoint launch acupuncture effect? All of these remain the common and crucial questions in the study of acupuncture effect mechanism. Physical changes are induced in the local tissue of acupoint by needling techniques, such as the deformation and displacement of muscle fibers, which may act on the nerve ending receptors and produce electroneurographic signals. Besides, these changes may activate the mechanosensitive ion channels of the cytomembrane in acupoint site. Through cellular signal transduction, the physical signals may be transformed into chemical ones to trigger the physiochemical coupling response of acupoint microenvironment. Eventually, acupuncture effect is generated via nerves and body fluids. "The mechanical force of acupuncture", through "the physiochemical transduction", promotes the body's perception and transmits acupuncture signals. It suggests that acupoint is the "transducer" in the physiochemical information coupling response of acupuncture.

[Progress of researches on acupuncture-moxibustion treatment of cartilage damage of osteoarthritis].

Cartilage damage is the key pathological mechanism in the progressive development of osteoarthritis(OA). Slowing down cartilage damage and accelerating cartilage repair are strategies for effective treatment of OA. Acupuncture and moxibustion therapies are widely used in relieving symptoms of OA and have a protective effect on cartilage. In this paper, we reviewed the mechanisms of acupuncture and moxibustion underlying relieving cartilage damage from three aspects: 1) promoting chondrocyte homeostasis by inhibiting apoptosis and improving cellular autophagy, 2) regulating extracellular matrix (ECM) metabolism (inhibiting decomposition and promoting synthesis) by suppressing the release of inflammatory factors and the activity of proteolytic enzymes, and 3) improving OA microenvironment by reducing the number of macrophagocyte 1 (M1) and increasing the ratio of M2/M1 in the local inflammatory locus. In addition, most studies on the mechanisms of acupuncture and moxibustion underlying remission of OA focus on the improvement of pathological changes, such as joint histopathology, cartilage morphology, synovial inflammatory reaction and infiltration, subchondral bone remodeling, etc., thus, the exact functions of acupuncture and moxibustion in ameliorating cartilage injury remain unknown. In view of the important role of mitochondrial dysfunction in promoting OA development and cartilage damage and the current use of tissue engineering methods of chondrocytes and mesenchymal stem cells to repair articular cartilage injury, it is highly recommended that future studies should pay more attention to these aspects.

["Acupuncture network drug"--transformation and application strategies of exosomes based on characteristics of network regulation of acupuncture therapy].

Although the basic mechanism of acupuncture-moxibustion has been revealed from many aspects, there are still many shackles in the transformation of the related research achievements. The transformation of academic achievements of experimental acupunctology is an urgent issue to be solved at present. Network regulation is the basic action mode of acupuncture therapy. In the present paper, we proposed that the "acupuncture network drug" could carry a variety of effective active ingredients which may be the core component of network regulation of acupuncture therapy. The "exosomes", polyvesicle derived from the intracellular lysosomal microparticles invagination, contain complex RNAs and proteins and exist in the body fluids and function in secreting abundant activate substances to participate in intercellular communication, which is the research hotspot in the field of frontier life science in the world. They play an important role in the diagnosis and treatment of diseases, and drug development, etc.. Our studies using rats with adjuvant arthritis and mice with sepsis displayed that after intraperitoneal administration of serum exosomes derived from normal animals receiving acupuncture intervention, an acupuncture-like analgesic effect and an anti-inflammatory effect were achieved, respectively. It is thus possible that acupuncture network drugs could be developed from serum exosomes secreted by exosome autogenous living cells after acupuncture intervention by virtue of the characteristics of low immunogenicity and may have great advantages in drug development and modification. It is also expected to provide new ideas for the transformation of experimental research results and to in depth give explanations about the underlying mechanisms of acupuncture therapy.

Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway.

OBJECTIVE: To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways. METHODS: Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot. RESULTS: Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05). CONCLUSIONS: Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

Wake-Promoting Effect of Bloodletting Puncture at Hand Twelve Jing-Well Points in Acute Stroke Patients: A Multi-center Randomized Controlled Trial.

OBJECTIVE: To assess the effect and safety of bloodletting puncture at hand twelve Jing-Well points (HTWPs) in acute stroke patients with conscious disturbance. METHODS: In this multi-center and randomized controlled trial, 360 patients suffered from ischemic or hemorrhagic stroke with conscious disturbance within 48 h from the onset of symptom were divided into bloodletting (180 cases) and control (180 cases) groups using a block randomization. Patients in both groups received routine Western medicine, and patients in the bloodletting group received additional bloodletting puncture at HTWPs on admission immediately before conventional treatment. The primary outcome measure was Glasgow Coma Scale (GCS) score and the secondary outcomes included blood pressure, respiratory rate and pulse rate. All variables were evaluated at baseline (before bloodletting), 0 (after bloodletting immediately), 15, 30, 50 and 80 min post bloodletting. RESULTS: At 80 min post bloodletting, the proportion of patients with improved consciousness in the bloodletting group was greater than the control group (P<0.05). In the separate analysis of moderate consciousness disturbance subgroup, bloodletting therapy benefited ischemic patients, and improved the eye and language response of GCS score at 15, 30, 50, 80 min post bloodletting (P<0.05 or P<0.01). No significant differences were observed regarding the secondary outcomes between two groups (P>0.05). CONCLUSION: The bloodletting puncture at HTWPs was safe and could improve conscious levels of ischemic stroke patients, highlighting a first-aid intervention for acute stroke. (Registration No. ChiCTR-INR-16009530).

Initiation of Acupoint Molecular Mechanisms for Manual Acupuncture Analgesia-Nuclear Factor κB Signaling Pathway.

OBJECTIVE: To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA). METHOD: A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund's adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11-7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted. RESULT: (1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1ß (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P<0.05 or P<0.01), and the expression of NFκB p65 (Rela), NFκB p50 (Nfkb1) were increased in the control+MA7 group (P<0.05). (2) CFA+MA groups showed increased PWL from day 1 to 7 (P<0.01 vs. CFA), and the Western blot results were consistent with immunohistochemistry, the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups (P<0.05). (3) Compared with the CFA+DMSO+MA group, the PWL of the CFA+ BAY 11-7082+MA group decreased significantly and continued until day 5 and 7 (P<0.05 and P<0.01, respectively), and the NFκB p65 expression of CFA+BAY 11-7082+MA was significantly reduced compared with CFA+DMSO+MA (P<0.01). CONCLUSION: Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect, which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.

[Research advances in the mechanism of acupuncture in regulating tumor immunosuppression].

As a characteristic therapy in traditional Chinese medicine, acupuncture has shown potential advantages in anti-tumor therapy, and one of the therapeutic effects of acupuncture is to improve the immunosuppressive conditions in patients with tumor. Based on the immunoregulatory effect of acupuncture, this article summarized the mechanism of acupuncture in regulating tumor immune status from the following aspects: stimulating the activation of natural killer cells, increasing the number of CD8+ T cells, and adjusting the balance between T helper 1 cells and T helper 2 cells and between regulatory T cells and T helper 17 cells. With reference to existing evidence, we believe that acupuncture can regulate the body's immunosuppressive conditions through a variety of targets, but further clinical and basic studies are needed to clarify its regulatory effect on tumor immune microenvironment and related mechanism of action.

[Progress of research on acupuncture treatment of nonspecific low back pain].

Nonspecific low back pain (NLBP) is a heterogeneous disease with no definite pathological anatomical causes. Although acupuncture treatment of NLBP has been included in the international clinical guidelines for low back pain in many countries, the grade strength is still low, and the Results of clinical efficacy evaluation are controversial. Moderate evidence from international studies indicates that acupuncture treatment of NLBP has a clear short-term analgesic effect and can improve pain related depression symptoms to a certain extent, but the exploration of efficacy rules is relatively insufficient, and there is no specific operational scheme to guide the acupuncture treatment of NLBP. Domestic clinical studies are quite distinctive in the aspects of dose-effect acupoint selection, characteristic needling Methods, and acupuncture apparatuses, but lack of systematic research, and have low quality and weak evidence. In terms of the underlying mechanisms, acupuncture may achieve analgesic effect through anti-inflammation, relieving central sensitization, and improving the damage of local multifidus muscles and bones. However, due to the heterogeneity of NLBP disease, the current elaboration on the mechanism of acupuncture treatment of NLBP may not reach a consensus, and it is still worth further exploration.

Current Tracking on Effectiveness and Mechanisms of Acupuncture Therapy: A Literature Review of High-Quality Studies.

The scientific evidence of acupuncture studies has been improved in recent years, and one of the important manifestations is that more and more acupuncture clinical trials and mechanism researches have been published in the source periodicals of Science Citation Index (SCI). This study summarized the dominant diseases of acupuncture focusing on of acupuncture efficacy and mechanisms, and discussed the existing problems, highlighting the direction of future developments. Most clinical studies were published in journals with journal impact factor (JIF) score of 10 or above, and majority of the basic researches had JIF scores of 5 to 10. The above literature were further divided according to the International Classification of Diseases (ICD). The most concerned diseases in these articles were neurological diseases, musculoskeletal system and connective tissue diseases, tumor and digestive system diseases. The therapeutic effect and mechanism of acupuncture on each kind of disease were summarized. The results showed that the therapeutic effect of acupuncture on nerve injury focused on the anti-oxidation pathway, neuroprotective and anti-inflammatory processes. The antiinflammatory effect also played an important role in the treatment of musculoskeletal diseases. The analgesic effect was underlined in most of these studies. Clinical trials were well carried out on acupuncture curative effect of tumor complications and side effects of chemo-radiotherapy, but the potential mechanisms have not been clarified. Somato-visceral reflex was suggested to be strongly associated with the effects of acupuncture changing the motor activity of the gastrointestinal tract. Functional magnetic resonance imaging studies indicated that non-specific effects play important roles in acupuncture analgesia. Lines of evidence have pointed out that the regulation of neuro-endocrine-immune networks may be a common switch of acupuncture on different nerve system diseases.

[Research advances in the clinical effect of bloodletting puncture at well-points in treatment of acute central nervous injury].

Bloodletting puncture at twelve well-points is a characteristic emergency therapy in traditional Chinese medicine. This article reviewed the research advances in the clinical effect of this therapy in the treatment of acute central nervous injury and its mechanism of action over the past 30 years, and it is found that this therapy can effectively improve disturbance of consciousness, neurological defects, and cerebral edema caused by stroke, traumatic brain injury, and carbon monoxide poisoning. The mechanism involves the improvement of cerebral blood flow and tissue oxygen supply, repair of the blood-brain barrier, and regulation of local ion balance. Well-designed clinical trials and in-depth research on biological mechanisms should be performed in future to promote and guide its clinical application.

Two pairs of enantiomeric propylated flavonoids and a new lignan from the aerial parts of Abrus precatorius.

Two pairs of novel enantiomeric flavonoids (1a, 1b and 2a, 2b), along with one new lignan (3), were isolated from the aerial parts of Abrus precatorius. All of these enantiomeric flavonoids featured an unprecedented propylated flavonoid skeleton representing a new family of flavonoid, and the new lignan was found to have an attractive arachidate ester side chain. Their structures were extensively elucidated by means of detailed NMR and mass spectroscopic analysis. Moreover, biological evaluation of antibacterial activity for these compounds against Bacillus cereus and Escherichia coli were conducted.

Rhodomyrtosone B, a membrane-targeting anti-MRSA natural acylgphloroglucinol from Rhodomyrtus tomentosa.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Rhodomyrtus tomentosa are traditionally used in the treatment of infectious diseases such as wound infections in Chinese traditional medicine. The mechanisms of the activity of rhodomyrtosone B (RDSB), a natural acylphloroglucinol isolated from the leaves of Rhodomyrtus tomentosa, are still not understood. We provided a detailed investigation of the antibacterial action of RDSB against bacteria in vitro and in vivo. MATERIALS AND METHODS: The antibacterial activity of RDSB was tested by the microdilution method against a panel of bacteria, and a time-killing assay was carried out according to CLSI guidelines. The cytotoxic potential of RDSB was evaluated against mammalian cells, and its haemolytic activity towards rabbit red blood cells (RBCs) was assessed. The mode of action of RDSB was investigated by targeting bacterial membranes, and its resistance was evaluated using a sequential passaging method. The antibacterial activities in vivo were assessed against MRSA in a mouse skin infection mode. RESULTS: RDSB exhibited distinct antibacterial activities against selected Gram-positive pathogens responsible for serious infections, even including methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 0.62-1.25 µg/mL and vancomycin-resistant Enterococcus faecium (VRE) with an MIC of 2.5 µg/mL. RDSB displayed much more rapid bactericidal activity against MRSA than that of vancomycin. The membrane-targeting experiments revealed that RDSB exhibited significant antibacterial activity with the perturbation of bacterial membrane potential and an increase in membrane permeability. In particular, RDSB had weak cytotoxicity to mammalian cells (IC50 >14 µg/mL) and has advantageous specificity against selected Gram-positive bacterial membranes rather than RBCs. Notably, RDSB displayed in vitro antibacterial activities against MRSA without drug-resistance and profoundly attenuated the skin ulcer formation in a murine model of MRSA infection under a single dose of 40 µg RDSB per mouse. CONCLUSION: RDSB has profound antibacterial activity against drug-resistant bacteria (MRSA and VRE) and low cytotoxicity. It is bactericidal in nature, and an increase in membrane permeability resulting from membrane perturbation is one of its modes of action. RDSB represents a promising natural antibiotic to combat drug-resistant (MRSA and VRE) infections.

Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network.

The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA) on the neuroendocrine-immune (NEI) network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund's adjuvant (CFA) model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli) acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.