A haplotype-resolved gap-free genome assembly provides novel insight into monoterpenoid diversification in Mentha suaveolens 'Variegata'.

Mentha is a commonly used spice worldwide, which possesses medicinal properties and fragrance. These characteristics are conferred, at least partially, by essential oils such as menthol. In this study, a gap-free assembly with a genome size of 414.3 Mb and 31,251 coding genes was obtained for Mentha suaveolens 'Variegata'. Based on its high heterozygosity (1.5%), two complete haplotypic assemblies were resolved, with genome sizes of 401.9 and 405.7 Mb, respectively. The telomeres and centromeres of each haplotype were almost fully annotated. In addition, we detected a total of 41,135 structural variations. Enrichment analysis demonstrated that genes involved in terpenoid biosynthesis were affected by these structural variations. Analysis of volatile metabolites showed that M. suaveolens mainly produces piperitenone oxide rather than menthol. We identified three genes in the M. suaveolens genome which encode isopiperitenone reductase (ISPR), a key rate-limiting enzyme in menthol biosynthesis. However, the transcription levels of ISPR were low. Given that other terpenoid biosynthesis genes were expressed, M. suaveolens ISPRs may account for the accumulation of piperitenone oxide in this species. The findings of this study may provide a valuable resource for improving the detection rate and accuracy of genetic variants, thereby enhancing our understanding of their impact on gene function and expression. Moreover, our haplotype-resolved gap-free genome assembly offers novel insights into molecular marker-assisted breeding of Mentha.

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery.

Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.

Real-Time Detection of Ferulic Acid Effects on Rat Left Ventricle Using Pressure-Volume Conductivity Catheter.

Decreased cardiac function can have a negative impact on other organs. The left ventricular pressure-volume relationship is considered to be a valid method for evaluating cardiac function. Real-time monitoring of cardiac function is important for drug evaluation. Under closed-chest conditions, the miniature transducer, which is an important component of the pressure-volume catheter, enters the left ventricle of the rat through the right carotid artery. The device visualizes the changes in cardiac function during the experiment in the form of a pressure-volume loop. The actual volume of the ventricle is calculated by altering the conductivity of the blood by injecting 50 µL of a 20% sodium chloride solution into the rat's left jugular vein. The actual volume of the rat's ventricular cavity is calculated by measuring the conductivity of the blood in a known volume using a pressure-volume conductance catheter. This protocol allows for continuous observation of the effects of drugs on the heart and will promote the rationale for the use of specialty ethnic drugs in cardiovascular disease.

Real-Time Detection of Dynamic Affinity between Biomolecules Using Surface Plasmon Resonance (SPR) Technology.

Surface plasmon resonance (SPR) technology is a sensitive precise method for detecting viruses, pathogenic molecular proteins, and receptors, determining blood types, and detecting food adulteration, among other biomolecular detections. This technology allows for the rapid identification of potential binding between biomolecules, facilitating fast and user-friendly, non-invasive screening of various indicators without the need for labeling. Additionally, SPR technology facilitates real-time detection for high-throughput drug screening. In this program, the application field and basic principles of SPR technology are briefly introduced. The operation process is outlined in detail, starting with instrument calibration and basic system operation, followed by ligand capture and multi-cycle analysis of the analyte. The real-time curve and experimental results of binding quercetin and calycosin to KCNJ2 protein were elaborated upon. Overall, SPR technology provides a highly specific, simple, sensitive, and rapid method for drug screening, real-time detection of related pharmacokinetics, virus detection, and environmental and food safety identification.

Assembly and analysis of the mitochondrial genome of Prunella vulgaris.

Prunella vulgaris (Lamiaceae) is widely distributed in Eurasia. Former studies have demonstrated that P. vulgaris has a wide range of pharmacological effects. Nevertheless, no complete P. vulgaris mitochondrial genome has been reported, which limits further understanding of the biology of P. vulgaris. Here, we assembled the first complete mitochondrial genome of P. vulgaris using a hybrid assembly strategy based on sequencing data from both Nanopore and Illumina platforms. Then, the mitochondrial genome of P. vulgaris was analyzed comprehensively in terms of gene content, codon preference, intercellular gene transfer, phylogeny, and RNA editing. The mitochondrial genome of P. vulgaris has two circular structures. It has a total length of 297, 777 bp, a GC content of 43.92%, and 29 unique protein-coding genes (PCGs). There are 76 simple sequence repeats (SSRs) in the mitochondrial genome, of which tetrameric accounts for a large percentage (43.4%). A comparative analysis between the mitochondrial and chloroplast genomes revealed that 36 homologous fragments exist in them, with a total length of 28, 895 bp. The phylogenetic analysis showed that P. vulgaris belongs to the Lamiales family Lamiaceae and P. vulgaris is closely related to Salvia miltiorrhiza. In addition, the mitochondrial genome sequences of seven species of Lamiaceae are unconservative in their alignments and undergo frequent genome reorganization. This work reports for the first time the complete mitochondrial genome of P. vulgaris, which provides useful genetic information for further Prunella studies.

Integrating UPLC-Q-Exactive Orbitrap/MS, network pharmacology and experimental validation to reveal the potential mechanism of Tibetan medicine Rhodiola granules in improving myocardial ischemia-reperfusion injury.

ETHNOPHARMACOLOGY RELEVANCE: Rhodiola granules (RG) is a traditional Tibetan medicine prescription that can be used to improve the symptoms of ischemia and hypoxia in cardiovascular and cerebrovascular diseases. However, there is no report on its use to improve myocardial ischemia/reperfusion (I/R) injury, and its potential active ingredients and mechanism against myocardial ischemia/reperfusion (I/R) injury remain unclear. AIM OF THE STUDY: This study aimed to reveal the potential bioactive components and underlying pharmacological mechanisms of RG in improving myocardial I/R injury through a comprehensive strategy. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap/MS technology was used to analyze the chemical components of RG, the potential bioactive components and targets were tracked and predicted by the SwissADME and SwissTargetPrediction databases, and the core targets were predicted through the PPI network, as well the functions and pathways were determined by GO and KEGG analysis. In addition, the molecular docking and ligation of the anterior descending coronary artery-induced rat I/R models were experimentally validated. RESULTS: A total of 37 ingredients were detected from RG, including nine flavones, ten flavonoid glycosides, one glycoside, eight organic acids, four amides, two nucleosides, one amino acid, and two other components. Among them, 15 chemical components, such as salidroside, morin, diosmetin, and gallic acid were identified as key active compounds. Ten core targets, including AKT1, VEGF, PTGS2, and STAT3, were discovered through the analysis of the PPI network constructed from 124 common potential targets. These possible targets were involved in the regulation of oxidative stress and HIF-1/VEGF/PI3K-Akt signaling pathways. Furthermore, molecular docking confirmed that the potential bioactive compounds in RG have good potential binding abilities to AKT1, VEGFA, PTGS2, STAT3, and HIF-1α proteins. Then, the animal experiments showed that RG could significantly improve the cardiac function of I/R rats, reduce the size of myocardial infarction, improve the myocardial structure, and reduce the degree of myocardial fibrosis, inflammatory cell infiltration, and myocardial cell apoptosis rate in I/R rats. In addition, we also found that RG could decrease the concentration of AGE, Ox-LDL, MDA, MPO, XOD, SDH, Ca2+, and ROS, and increase the concentration of Trx, TrxR1, SOD, T-AOC, NO, ATP, Na+k+-ATPase, Ca2+-ATPase, and CCO. Moreover, RG could significantly down-regulate the expressions of Bax, Cleaved-caspase3, HIF-1α, and PTGS2, as well up-regulate the expressions of Bcl-2, VEGFA, p-AKT1, and p-STAT3. CONCLUSION: In summary, we revealed for the first time the potential active ingredients and mechanisms of RG for myocardial I/R injury therapy through a comprehensive research strategy. RG may synergistically improve myocardial I/R injury through anti-inflammatory, regulating energy metabolism, and oxidative stress, improving I/R-induced myocardial apoptosis, which may be related to the HIF-1/VEGF/PI3K-Akt signaling pathway. Our study provides new insights into the clinical application of RG and also provides a reference for the development and mechanism research of other Tibetan medicine compound preparations.

Artificial intelligence for drug discovery: Resources, methods, and applications.

Conventional wet laboratory testing, validations, and synthetic procedures are costly and time-consuming for drug discovery. Advancements in artificial intelligence (AI) techniques have revolutionized their applications to drug discovery. Combined with accessible data resources, AI techniques are changing the landscape of drug discovery. In the past decades, a series of AI-based models have been developed for various steps of drug discovery. These models have been used as complements of conventional experiments and have accelerated the drug discovery process. In this review, we first introduced the widely used data resources in drug discovery, such as ChEMBL and DrugBank, followed by the molecular representation schemes that convert data into computer-readable formats. Meanwhile, we summarized the algorithms used to develop AI-based models for drug discovery. Subsequently, we discussed the applications of AI techniques in pharmaceutical analysis including predicting drug toxicity, drug bioactivity, and drug physicochemical property. Furthermore, we introduced the AI-based models for de novo drug design, drug-target structure prediction, drug-target interaction, and binding affinity prediction. Moreover, we also highlighted the advanced applications of AI in drug synergism/antagonism prediction and nanomedicine design. Finally, we discussed the challenges and future perspectives on the applications of AI to drug discovery.

Preclinical anti-apoptotic properties of salidroside for hypoxic-ischemic cerebral damage: a systematic review and meta-analysis / 数字中医药（英文）

@#【Objective】   As the main active ingredient of Tibetan medicine Hongjingtian (Rhodiolae Crenulatae Radix et Rhizoma), salidroside (Sal) has a good anti-apoptotic potential. Currently, there are some conflicting results on the anti-apoptotic mechanisms of Sal. Here we conducted a systematic review and meta-analysis to provide the preclinical evidence of its anti-apoptotic properties in preventing and treating hypoxic-ischemic cerebral damage(HICD). 【Methods】   The literature on the anti-apoptotic potential of Sal in the treatment of HICD from January 1, 1980 to November 9, 2021 was searched online using Chinese databases including Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database, and English databases including PubMed and Web of Science. The quality of the included articles was evaluated by the Cochrane Collaboration network bias risk assessment criteria, and meta-analysis was performed using RevMan 5.3 software. 【Results】  A total of 40 articles were finally included. Among the 40 articles, 30 were about in vivo animal experiments and 17 about in vitro cell experiments, and 7 of them included both animal and cell experiments. After analysis, it was found that Sal had significant effects on disease-related indicators of HICD (P < 0.05), such as cerebral infarctsize and brain water content. As to in vivo studies, Sal mainly affects the expressions of apoptotic factors through antiinflammation, anti-oxidation, activation of complement pathway, and regulation of signal transduction and autophagy, thus exerting anti-apoptotic potential in treating HICD. While for in vitro studies, Sal plays the anti-apoptotic role in HICD models mainly through anti-oxidation, anti-inflammation, reduction of Ca2+ overload, regulation of mitochondrial function, signal transduction, and C3 complement. 【Conclusion】  Sal can take anti-apoptotic effects to prevent and treat HICD through mechanisms such as anti-inflammation, anti-oxidation, enhanced autophagy, complement and signal transduction, regulation of mitochondrial membrane potential, and reduction of Ca2 + overload.

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique.

Potassium channels on the myocardial cell membrane play an important role in the regulation of cell electrophysiological activities. Being one of the main ion channels, voltage-gated potassium (Kv) channels are closely associated with some serious heart diseases, such as drug-induced myocardial damage and myocardial infarction. In the present study, the whole-cell patch-clamp technique was employed to determine the effects of 1.5 mM 4-aminopyridine (4-AP, a broad-spectrum potassium channel inhibitor) and aconitine (AC, 25 µM, 50 µM, 100 µM, and 200 µM) on the Kv channel current (IKv) in H9c2 cardiomyocytes. It was found that 4-AP inhibited the IKv by about 54%, while the inhibitory effect of AC on the IKv showed a dose-dependent trend (no effect for 25 µM, 30% inhibitory rate for 50 µM, 46% inhibitory rate for 100 µM and 54% inhibitory rate for 200 µM). Due to the characteristics of higher sensitivity and precision, this technique will promote the exploration of cardiotoxicity and the pharmacological effects of ethnomedicine targeting ion channels.

Real-Time Dynamic Collection of Hippocampal Extracellular Fluid from Conscious Rats Using a Microdialysis System.

A variety of central nervous system (CNS) diseases are associated with changes in the composition of hippocampal extracellular fluid (HECF). However, difficulty in obtaining HECF in real time from conscious rats has long restricted the evaluation of CNS disease progression and the effectiveness of ethnomedicine therapy. Encouragingly, a brain microdialysis technique can be used for continuous sampling with the advantages of dynamic observation, quantitative analysis, and a small sampling size. This allows the monitoring of changes in the extracellular fluid content for compounds from traditional herbs and their metabolites in the brain of living animals. The aim of this study was thus to accurately implant a cerebrospinal fluid microdialysis probe into the hippocampal region of Sprague Dawley (SD) rats with a three-dimensional brain stereotaxic apparatus, cutting off molecular weights greater than 20 kDa. The high-quality HECF was then obtained from conscious rats using a microdialysis sampling control system with an adjustable sampling rate from 2.87 nL/min - 2.98 mL/min. In conclusion, our protocol provides an efficient, rapid, and dynamic method to obtain HECF in awake rats with the help of microdialysis technology, which provides us with unlimited possibilities to further explore the pathogenesis of CNS-related diseases and evaluate drug efficacy.

Emerging biotechnology applications in natural product and synthetic pharmaceutical analyses.

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.

Dynamic Continuous Blood Extraction from Rat Heart via Noninvasive Microdialysis Technique.

Dynamic analysis of blood components is of great importance in understanding cardiovascular diseases and their related diseases, such as myocardial infarction, arrhythmia, atherosclerosis, cardiogenic pulmonary edema, pulmonary embolism, and cerebral embolism. At the same time, it is urgent to break through the continuous heart blood sampling technique in live rats to evaluate the effectiveness of distinctive ethnic medicine therapy. In this study, a blood microdialysis probe was implanted in the right jugular vein of rats in a precise and noninvasive surgical procedure. Cardiac blood samples were then collected at a rate of 2.87 nL/min to 2.98 mL/min by connecting to an online microdialysis sample collection system. Even more momentously, the acquired blood samples can temporarily be stored in microdialysis containers at 4 °C. The microdialysis-based online continuous blood collection program from rat heart has greatly guaranteed the quality of blood samples, advancing and invigorating the scientific rationality of the research on systemic cardiovascular diseases and evaluating ethnomedicine therapy from the perspective of hematology.

Tumor imaging and photothermal therapy in second near infrared window: A systematic review and meta-analysis.

Background: Second near-infrared window (NIR-II, 1000-1700 nm) technology for tumor imaging and photothermal therapy (PTT) is an innovative method for tumor diagnosis and treatment. The NIR-II probe can specifically identify tumor cells, and effectively convert light energy into heat energy under the irradiation of NIR laser, thus achieving the integration of non-invasive tumor diagnosis and treatment. In the present study, we conducted a systematic review and meta-analysis of preclinical investigations to corroborate the efficacy and safety of photothermal therapy. Methods: Relevant preclinical data were retrieved by searching PubMed, Web of Science, CNKI, WANFANG and VIP information databases. And the acquired data were analyzed by RevMan Version 5.3 software. Results: According to the inclusion criteria, forty-two articles relating to NIR-II tumor imaging and PTT were recruited for further in-depth analysis. The NIR-II photoacoustic and fluorescence imaging could quickly and accurately identify tumor in mice, manifesting higher signal intensity on tumor site than that of normal tissue. After PTT, the tumor volume of mice decreased miraculously [RR=8.49, 95%CI (4.64, 15.55), P<0.00001], and even disappeared completely [RR=7.01, 95%CI (3.04, 16.13), P<0.00001] with no potential risk of affecting the blood routine. Conclusions: PTT guided by NIR-II imaging can effectively diagnose the tumor lesion and eliminate it with the advantages of non-invasive and higher biosafety.

Standardized Rat Coronary Ring Preparation and Real-Time Recording of Dynamic Tension Changes Along Vessel Diameter.

As a key event of cardiovascular system diseases, coronary artery disease (CAD) has been widely regarded as the main culprit of atherosclerosis, myocardial infarction, and angina pectoris, which seriously threaten the life and health of people all over the world. However, how to record the dynamic biomechanical characteristics of isolated blood vessels has long puzzled people. Meanwhile, precise positioning and isolation of coronary arteries to measure in vitro dynamic vascular tension changes have become a trend in CAD drug development. The present protocol describes the macroscopic identification and microscopic separation of rat coronary arteries. The contraction and dilation function of the coronary artery ring along the vessel diameter was monitored using the established multi myograph system. The standardized and programmed protocols of coronary ring tension measurement, from sampling to data acquisition, tremendously improve the repeatability of the experimental data, which ensures the authenticity of vascular tension records after physiological, pathological, and drug intervention.

Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction.

Objective: Danggui Buxue decoction (DBD), consisting of Angelicae Sinensis Radix (ASR) and Astragali Radix (AR), is a famous prescription with the function of antivasoconstriction. This study intends to probe its mechanisms on the relaxation of the middle cerebral artery (MCA). Methods: Vascular tension of rat MCA was measured using a DMT620 M system. First, the identical series of concentrations of DBD, ASR, and AR were added into resting KCl and U46619 preconstricted MCA. According to the compatibility ratio, their dilatation effects were further investigated on KCl and U46619 preconstricted vessels. Third, four K+ channel blockers were employed to probe the vasodilator mechanism on KCl-contracted MCA. We finally examined the effects of DBD, ASR, and AR on the vascular tone of U46619-contracted MCA in the presence or absence of Ca2+. Results: Data suggested that DBD, ASR, and AR can relax on KCl and U46619 precontracted MCA with no effects on resting vessels. The vasodilator effect of ASR was greater than those of DBD and AR on KCl-contracted MCA. For U46619-contracted MCA, ASR showed a stronger vasodilator effect than DBD and AR at low concentrations, but DBD was stronger than ASR at high concentrations. Amazingly, the vasodilator effect of DBD was stronger than that of AR at all concentrations on two vasoconstrictors which evoked MCA. The vasodilator effect of ASR was superior to that of DBD at a compatibility ratio on KCl-contracted MCA at low concentrations, while being inferior to DBD at high concentrations. However, DBD exceeded AR in vasodilating MCA at all concentrations. For U46619-constricted MCA, DBD, ASR, and AR had almost identical vasodilation. The dilation of DBD and AR on KCl-contracted MCA was independent of K+ channel blockers. However, ASR may inhibit the K+ channel opening partially through synergistic interactions with Gli and BaCl2. DBD, ASR, and AR may be responsible for inhibiting [Ca2+]out, while ASR and AR can also inhibit [Ca2+]in. Conclusion: DBD can relax MCA with no effects on resting vessels. The mechanism may be related to ASR's inhibition of KATP and Kir channels. Meanwhile, the inhibition of [Ca2+]out by DBD, ASR, and AR as well as the inhibition of [Ca2+]in by ASR and AR may contribute to dilate MCA.

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment.

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.

Salvia miltiorrhiza improves type 2 diabetes: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetes refers to any group of metabolic diseases characterized by high blood sugar and generally thought to be caused by insufficient production of insulin, impaired response to insulin. Globally, patients with type 2 diabetes account for more than 85% of the total diabetic patients, and due to factors, such as obesity, aging, environment and lifestyle, the incidence of diabetes is rising. Salvia miltiorrhiza (SM) is a medicine used to treat diabetes in China. In recent years, it has been reported that SM has the effect of improving type 2 diabetes. However, there is no systematic review of its efficacy and safety yet. Therefore, we propose a systematic review to evaluate the efficacy and safety of SM for T2D. METHODS: Six databases will be searched: China National Knowledge Infrastructure (CNKI), China Biological Medicine (CBM), China Scientific Journals Database (CSJD), Wanfang database, PubMed, and EMBASE. The information is searched from January 2010 to July 2020. Languages are limited to English and Chinese. The primary outcomes include 2 hour plasma glucose, fasting plasma glucose, hemoglobin A1c, homeostasis model assessment of insulin resistance, and fasting plasma insulin. The secondary outcomes include clinical efficacy and adverse events. RESULTS: This systematic review will evaluate the efficacy and safety of Salvia miltiorrhiza in the treatment of type 2 diabetes. CONCLUSION: This systematic review provides evidence as to whether Salvia miltiorrhiza is effective and safe for type 2 diabetes. ETHICS: Ethical approval is not necessary as this protocol is only for systematic review and does not involve in privacy data or an animal experiment. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020110046.

Potential applications of microfluidics based blood brain barrier (BBB)-on-chips for in vitro drug development.

The human blood-brain barrier (BBB) is a complex multi-dimensional reticular barrier system composed of cerebral microvascular endothelial cells, pericytes, astrocytes and a variety of neurons. The conventional in vitro cell culture model fails to truly present the dynamic hemodynamics of BBB and the interaction between neurons. And it is even more impossible to explore brain-related multi-organ diseases, which brings huge obstacles to explore diseases of the central nervous system and the interaction between brain-related multi-organs, and evaluate drug efficacy. Miniaturized microfluidics based BBB chips are being commonly used to co-culture a variety of cells on a small-sized chip to construct a three-dimensional (3D) BBB or BBB-related organ disease models. By combining with other electrophysiological, biochemical sensors or equipment and imaging systems, it can in real time and quickly screen disease-related markers and evaluate drug efficacy. This review systematically summarized the research progress of in vitro BBB and BBB-related organ chips, and analyzed the obstacles of BBB models in depth. Parallelly combined with the current research trends and hot spots, we give the further improvement measures of microfluidic BBB chips.

Is gastrointestinal motility related to alkaloids of Charred Semen Arecae?

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Arecae (SA) is one of the most commonly used Traditional Chinese Medicine. Charred Semen Arecae (CSA) is the processed product of SA. Alkaloids are considered as pharmacological mechanisms of SA and CSA on gastrointestinal motility. Recent studies have shown alkaloids decreased quickly after procession. However, the promoting on gastrointestinal motility were not decreased. Is gastrointestinal motility related to alkaloids of CSA? This study explored the effects of SA, CSA, Semen Arecae-Removal (SA-R), and Charred Semen Arecae-Removal (CSA-R) on gastrointestinal motility, Gastric Inhibitory Polypeptide (GIP), Glucagon Like Peptide-1 (GLP-1), gastric juice and bile in rats. MATERIAL AND METHODS: Rats were randomly divided into six groups, including the Control group, SA group, CSA group, SA-R group, CSA-R group, and Positive drug group (Mosapride). Alkaloids of samples were knocked out by using the "target constituent removal" strategy. Gastric residue and intestinal propulsion rate were evaluated in rats. Serum levels of GIP and GLP-1 were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Gastric juice and bile were examined, respectively. RESULTS: CSA-R and SA-R have been investigated by the Preparative Thin-layer Chromatography (PTLC) method. Intestinal propulsion and gastric residue assessments confirmed the effectiveness of CSA and CSA-R. CSA-R was higher than SA-R in the GLP-1, pepsin activity, the secretion of bile, Bilirubin (BIL), and Cholesterol (CHO). The statistical comparison demonstrated that there is no difference between the CSA group and CSA-R group. CONCLUSIONS: After processing, the promoting gastrointestinal motility might be not related to alkaloids. Maillard reaction could be produced to promote the secretion of GLP-1, bile, and CHO for gastrointestinal motility. Our findings provide a pharmacological reference for the clinical application of SA and CSA in the treatment of digestive diseases.

The efficacy and safety of acupuncture for perimenopause symptom compared with different sham acupuncture control groups: A protocol of systematic review and meta-analysis.

BACKGROUND: Perimenopause is a period that every woman must go through, most people are more or less affected by perimenopausal symptoms, it to affect women's health, work, life, and economy. As acupuncture treatment is more and more increasing in perimenopausal symptoms, there have also been many clinical trials about it. But the results of the trials are inconsistent. Therefore, we will conduct a systematic review and meta-analysis of the safety and efficacy of perimenopausal symptoms treated with acupuncture. METHODS: The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. RCT study on different acupuncture interventions for perimenopausal symptoms will be searched in 8 databases (PubMed, EMBASE, the Cochrane Library, the web of science, CBM, CNKI, WAN FANG, and VIP). Besides, the search will also be performed on the clinical trial research platform if necessary. The primary outcome that will be extracted: the Flushes per 24 hours, the Frequency of hot flashes, the severity of hot flashes, the menopause-related symptom score, the treatment efficacy, the adverse event. Endnote software X8 will be used for study selection, STATA 13.0 and Review Manager software 5.3 will be used for analysis and synthesis. These studies selection, data extraction, and risk of bias assessment will be conducted by 2 independent reviewers. RESULTS: This study will provide the results: 1. the primary and secondary outcome indicators of different acupuncture intervention measures (traditional hand acupuncture, moxibustion, ear acupuncture, laser, acupressure points) for perimenopausal symptoms. 2. The effects of different control groups (medicine control, routine care, waiting, and sham acupuncture control) on the analysis results will be reported, especially the effects of different sham acupuncture control (invasive/noninvasive) on the analysis results. CONCLUSION: This systematic review and meta-analysis study hopes to provide useful evidence for better use of different types of acupuncture in treat perimenopausal symptoms and better design of control groups in related clinical trials. In addition, the research conclusion will be published in peer journals.OSF REGISTRATION NUMBER DOI 10.17605/OSF.IO/VZCKU Ethics and dissemination This conclusion of the study will be published in peer journals. The ethical approval is not required because there is no direct involvement of human.