Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress and Mitochondrial Dysfunction.

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.

Polygenic adaptation contributes to the invasive success of the Colorado potato beetle.

How invasive species cope with novel selective pressures with limited genetic variation is a fundamental question in molecular ecology. Several mechanisms have been proposed, but they can lack generality. Here, we addressed an alternative solution, polygenic adaptation, wherein traits that arise from multiple combinations of loci may be less sensitive to loss of variation during invasion. We tested the polygenic signal of environmental adaptation of Colorado potato beetle (CPB) introduced in Eurasia. Population genomic analyses showed declining genetic diversity in the eastward expansion of Eurasian populations, and weak population genetic structure (except for the invasion fronts in Asia). Demographic history showed that all populations shared a strong bottleneck about 100 years ago when CPB was introduced to Europe. Genome scans revealed a suite of genes involved in activity regulation functions that are plausibly related to cold stress, including some well-founded functions (e.g., the activity of phosphodiesterase, the G-protein regulator) and discrete functions. Such polygenic architecture supports the hypothesis that polygenic adaptation and potentially genetic redundancy can fuel the adaptation of CPB despite strong genetic depletion, thus representing a promising general mechanism for resolving the genetic paradox of invasion. More broadly, most complex traits based on polygenes may be less sensitive to invasive bottlenecks, thus ensuring the evolutionary success of invasive species in novel environments.

[Progress of the application of PET technology in acupuncture research].

To further investigate the application of positron emission tomography (PET) technology in acupuncture research field, with "PET" and "acupuncture" as keywords, the related literature published from 1997 to 2018 was searched in PubMed, CNKI and WANFANG database; then the literature was classified and analyzed. The results showed that in clinical and experimental studies, whether in physiological or pathological conditions, PET technology has verified the specificity of acupoints, bidirectional regulation of acupoints, and the clinical effect of qi-arrival from the level of brain functional activity. It has deeply revealed the central mechanism underlying that acupuncture has multi-target, multi-channel and multi-level overall effects. The purpose of this study is to provide objective scientific basis for acupuncture research, and then potentially guide the clinical practice.

Polydatin effectively attenuates disease activity in lupus-prone mouse models by blocking ROS-mediated NET formation.

BACKGROUND: Neutrophil extracellular trap (NET) formation has been described to be closely involved in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the effect of polydatin (PD) on NET formation and its effects on disease activity in lupus-prone mouse models. METHODS: In vitro, neutrophils from SLE patients and healthy people stimulated with phorbol 12-myristate 13-acetate (PMA) or phosphate-buffered saline (PBS) were treated with PD, and reactive oxygen species (ROS) production and NET formation examined. In vivo, pristane-induced lupus (PIL) mice were treated with vehicle, PD, mycophenolate mofetil (MMF) or cyclophosphamide (CYC) while MRL/lpr mice were treated with vehicle or PD. Proteinuria, serum autoantibodies, ROS production, NET formation and kidney histopathology were tested. RESULTS: Consistent with previous findings, blood neutrophils from SLE patients showed increased spontaneous NET formation. Both in vivo and in vitro, PD treatment significantly inhibited ROS production and NET release by neutrophils. In MRL/lpr mouse model, PD administration reduced the proteinuria, circulating autoantibody levels, and deposition of NETs and immune complex in the kidneys. In addition, PD treatment ameliorated lupus-like features in PIL mice as MMF or CYC did. CONCLUSIONS: PD treatment inhibited ROS-mediated NET formation and ameliorated lupus manifestations in both PIL mice and MRL/lpr mice. These results highlight the involvement of NETosis in SLE pathogenesis and reveal that PD might be a potential therapeutic agent for SLE or other autoimmune diseases.

Isorhamnetin, the active constituent of a Chinese herb Hippophae rhamnoides L, is a potent suppressor of dendritic-cell maturation and trafficking.

Dendritic cells (DCs) have been recognized as major targets of immunosuppressive therapies for their significant roles in connecting innate and adaptive immunity. Isorhamnetin (Iso), one of the most common flavonoid compounds extracted from the Chinese herb Hippophae rhamnoides L, has been proved to have anti-inflammatory, anticarcinogenic, and antioxidant activities in many chronic inflammatory conditions, but the effects of Iso on DCs have rarely been reported before. Here we investigated the functions and the mechanisms of Iso on bone marrow-derived DCs (BMDCs) including maturation, phagocytosis, and trafficking. Our data showed that Iso effectively inhibited the maturation of lipopolysaccharide (LPS)-treated BMDCs by down regulation of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß and IL-12p70, up regulation of IL-10, and depression of costimulatory molecules CD40, CD80, and CD86, while had no effects on phagocytosis. Furthermore, Iso inhibited the migration of LPS-treated BMDCs, which may be due to its inhibition on chemokine receptor 7 (CCR7) expression. These findings strongly suggest that Iso is a potent immunosuppressive agent by inhibiting DC activation and trafficking, and may be used to prevent or treat chronic inflammation, autoimmune diseases, and graft rejections.

[Meridian differentiation of low back pain in Neijing (Inner Canon of Yellow Emperor)].

There are various contents about diagnosis and treatment of low back pain in Neijing (Inner Canon of Yellow Emperor), which are closely related to meridians and collaterals, forming a complete theoretical system of meridian differentiation for low back pain. Its theory and application are interpreted in this paper from five main aspects, including 18 meridians and collaterals densely distributing in the tendons and bones of the waist, the pathogenesis of low back pain lying in the disorders of the meridian qi and blood, the nature of low back pain being reflected by the color and shape of meridians and collaterals, the disordered meridians of low back pain being first identified based on syndrome differentiation, the acupuncture prescription being selected according to meridian differentiation. The purpose of this paper is to guide clinical practice, explore the advantages and characteristics of meridian differentiation, and provide theoretical reference and evidence for promoting the standardization of TCM.

[Hypothalamic Transcription Profiles Associated with Twirling-reducing Needling in Rats with Stress-induced Prehypertension].

OBJECTIVE: To observe the effect of twirling-reducing needling on changes of profile of differentially-expressed genes in the hypothalamus in rats with stress-induced prehypertension (SI-PHT), so as to explore its mechanism under-lying improvement of prehypertension. METHODS: Wistar male rats were randomly divided into blank control group (n=12), model group (n=12) and acupuncture group (n=10). The SI-PHT model was established by planta-electric-shock stimulation (30 V, 5 s) plus noise stimulation (80-100 db, 50 ms), twice daily, continuously for 11 days. Manual acupuncture stimulation (twirling-reducing needling) was applied to bilateral "Taichong" (LR 3) and "Quchi" (LI 11) for about 1 min (60 cycles/min), followed by retaining the needles for 20 min during modeling preparation, once daily for 11 days. The systolic blood pressure (SBP) and behavior changes were recorded before intervention and on the 3rd, 5th, 7th, 9th and 11th day during modeling. The expression (Fold change,|FC| ≥ 1.5) profile of genes in the hypothalamus was analyzed using Affymetrix GeneChip Rat Gene 2.0 ST Array, followed by analyzing the differentially-expressed genes involving the related biological process,molecular function, and signaling pathways by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), separately. RESULTS: After modeling, the systolic pressure levels were remarkably increased from the 3rd day to the 11th day in both model and acupuncture groups relatively to their respective baseline levels (P<0.01), and were significantly lower in the acupuncture group than in the model group (P<0.01) from the 5th day to the 11th day. Meanwhile, 93 genes were up-regulated and 153 down-regulated in the model group relative to the control group (P<0.05,|FC| ≥ 1.5), while in comparison with the model group, 59 genes were up-regulated and 86 down-regulated in the acupuncture group (P<0.05,|FC| ≥ 1.5). The expression levels of the 40 differen-tially-expressed genes (24 up-regulated and 16 down-regulated) in the model group were evidently reversed after acupuncture stimulation (P<0.05,|FC| ≥ 1.5). After acupuncture stimulation, the expression of acyl-CoA synthetase medium-chain family member 3 (Acsm 3) gene was down-regulated, and chorionic gonadotropin-alpha (Cgα), crystal (Cry) αB and thyroid stimulating hormone beta (Tshß) genes and the autoimmune thyroid disease (AITD) pathway were up-regulated (P<0.05,|FC| ≥ 1.5), suggesting an involvement of fatty acid biosynthetic processing, G-protein coupled receptor protein signaling, and hormone activity, etc. in acupuncture-induced blood-pressure lowering. CONCLUSIONS: Twirling-reducing needling of acupuncture can lower blood pressure in prehypertension rats, which may be related to its effects in regulating expression of Acsm 3, Cgα, CryαB, Tshß genes and in activating AITD pathway.

[Application of gene chip technology for acupuncture research over the past 15 years].

To explore the application of gene chip technology in the acupuncture research so as to provide evidences for the mechanism of acupuncture for regulating bodies. The literature on the application of gene chip technology in the acupuncture field from 2001 to 2016 was collected in PubMed, Springer, CNKI and WANFANG databases, which was analyzed and summarized. There were some achievements of the technology for acupuncture research, focusing on the five aspects, including the study of the relationship between meridian-point and viscera, the influencing factors of acupuncture effect, the effect and mechanism of acupuncture analgesia, the mechanism of acupuncture anti-aging, the effect and mechanism of acupuncture for diseases of each system. Gene chip technology plays an important role in researching acupuncture mechanism. It is an important technology for genomics study of acupuncture. However, there are also some disadvantages such as high cost, deficient data mining, non-uniform observation objects, deficient professionals, etc. All those need further resolution so as to promote the application of this technology in the acupuncture researching field.