The Effect of Sn-2 Palmitate on Blood Glucose, Lipids and Body Composition in Middle-Aged and Elderly Adults: A Randomized, Double-Blinded Controlled Trial.

Sn-2 palmitate is widely used in infant formula. However, little is known about its effects on metabolism and body composition in middle-aged and elderly adults. In a double-blinded, randomized controlled trial, we enrolled Chinese adults aged 45-75 years with self-reported constipation. Individuals were randomly assigned in a 1:1 ratio to a 1,3-dioleoyl-2-palmitoyl-glycerol (OPO)-enriched oil (66% palmitic acid in the sn-2 position) or a control vegetable oil (24% palmitic acid in the sn-2 position) daily for 24 weeks. Skim milk powder was used as the carrier for both fats. Interviews and body composition were performed at baseline, week 4, week 12 and week 24. A fasting blood draw was taken except at week 4. This study was a secondary analysis and considered exploratory. A total of 111 adults (83 women and 28 men, mean age 64.2 ± 7.0 years) were enrolled, of whom 53 were assigned to the OPO group and 57 to the control group. During the intervention, blood glucose, triglyceride, the triglyceride-glucose index, total cholesterol, low-density lipoprotein cholesterol and remnant cholesterol remained stable, while high-density lipoprotein cholesterol decreased in both groups (p = 0.003). No differences in change were observed between the groups (all p > 0.05). From baseline to week 24, the level of visceral fat increased slightly (p = 0.017), while body weight, total body water, protein, soft lean mass, fat-free mass, skeletal muscle and skeletal muscle mass index (SMI) decreased in two groups (p < 0.01). At weeks 4, 12 and 24, the SMI decreased less in the OPO group than in the control group, with a trend towards significance (p = 0.090). A 24-week daily intake of sn-2-palmitate-enriched oil had no adverse impact on fasting blood glucose, lipids and body composition compared with the control vegetable oil in Chinese adults (funded by Chinese Nutrition Society National Nutrition Science Research Grant, National Key Research and Development Program of China and Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd.; ChiCTR1900026480).

The efficacy of Omega-3 polyunsaturated fatty acids for severe burn patients: A systematic review and trial sequential meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Severe burns lead to metabolic changes, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Omege-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties. In the absence of substantial evidence for use on major burns, we systematically reviewed the efficacy of omega-3 PUFAs for patients with severe burns. METHODS: We comprehensively searched MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, Wang Fang Data, Chinese Biomedicine Database, and Science Direct databases to collect randomised controlled trials of omega-3 PUFAs administered to patients with burns from January 2000 to June 2023. Two researchers independently screened the literatures, extracted the data, and assessed the risk of bias in the included studies. The outcomes were mortality, the risk of severe sepsis, septic shock, and multiple organ dysfunction syndrome. Data synthesis was conducted using Review Manager. Trial sequential analyses (TSA) for outcomes were performed. RESULTS: Three randomised controlled trials involving 140 patients were included. Of these, 71 patients received omega-3 PUFAs. The results showed that omega-3 PUFAs significantly reduced the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome (RR = 0.38, 95 % CI [0.19, 0.75], P = 0.005), C-reactive protein levels (MD = -39.70[-81.63, 2.23], P = 0.06), and improved respiratory outcomes. However, there was no difference in 14-day mortality (RR = 1.10, 95%CI [0.59, 2.05], P = 0.75). TSA showed that the results for the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome are insufficient and inconclusive. CONCLUSIONS: Omega-3 PUFAs may reduce inflammatory response and risk of sepsis, septic shock, and multiple organ dysfunction syndrome in severe burns patients and may shorten hospital stay but cannot reduce risk of death. Due to the limitation of the quantity and quality of the included studies, the evidence level is low, and the conclusions need to be verified by larger scale and higher quality randomised controlled trials.

Design and evaluation of an intelligent physical examination system in improving the satisfaction of patients with chronic disease.

Background: and Purpose: Enhancing patient satisfaction remains crucial for healthcare quality. The utilization of artificial intelligence (AI) in the Internet of Health Things (loHT) can streamline the medical examination process. Most Traditional Chinese Medicine (TCM) examinations are non-invasive and contribute significantly to patient satisfaction. Our aim was to establish an intelligent physical examination system that amalgamates TCM and Western medicine and to conduct a preliminary investigation into its effectiveness in enhancing the satisfaction of patients with chronic diseases. Materials and methods: Experts from clinical departments, the equipment department, and the software development department were invited to participate in group discussions to determine the design principles and organizational structure of the intelligent physical examination system. This system integrates TCM and Western medicine. We compared the satisfaction levels of patients examined using the intelligent physical examination system with those examined using the traditional medical examination system. Results: An intelligent physical examination system, combining TCM and Western medicine, was developed. A total of 106 patients were finally enrolled (intelligent group vs. control group) to evaluate satisfaction. There were no statistically significant differences between the intelligent group and the control group in age, gender, education, or income level. We identified significant differences in five aspects of satisfaction: 1) the physical examination environment; 2) the attitude and responsiveness of doctors; 3) the attitude and responsiveness of nurses; 4) the effectiveness of obtaining results; and 5) the information regarding physical examination and medical advice (p < 0.05). Furthermore, these differences remained statistically significant even after adjusting for age, gender, education, and income level. Conclusions: The intelligent physical examination system effectively capitalized on the advantages of combining AI with the integration of TCM and Western medicine, substantially optimizing the medical examination process. In comparison to the traditional physical examination system, the intelligent system significantly enhanced patient satisfaction. Future improvements could involve integrating chronic disease follow-up technology into the system.

Global trends in research related to functional dyspepsia and anxiety or depression over the past two decades: a bibliometric analysis.

Background and purpose: Functional dyspepsia (FD) is a prevalent global disorder of the upper digestive tract characterized by functional impairment. It often coexists with anxiety/depression, significantly impairing occupational productivity and overall quality of life. This study aimed to identify emerging patterns and prominent themes within FD and anxiety/depression research through bibliometric analysis to help explore new innovative avenues for investigating this type of FD. Methods: A comprehensive review of literature encompassing FD and anxiety/depression was conducted using the Science Citation Index Extension of the Web of Science Core Collection from 2003 to 2023. Information extracted comprised "Full Record and Cited References." Bibliometric analysis of relevant publications, including country, institution, author, journal, citations, and keywords, was conducted using CiteSpace, VOSviewer, and Bibliometrix package in R and Excel. Results: Studies related to FD and anxiety/depression have demonstrated an ascending trajectory since 2003. Our bibliometric analysis identified 338 studies published by 2023. NEUROGASTROENTEROLOGY AND MOTILITY emerged as the most prolific journal, while GASTROENTEROLOGY retained pre-eminence within the top 10 published journals. China emerged as the most prolific country, with two institutions within the top 10 in terms of volume of publications. The Mayo Clinic stood as the foremost institution in terms of publication volume, with the Chengdu University of Traditional Chinese Medicine exhibiting robust collaborative engagement. Eminent author influence was attributed to Talley NJ of Newcastle University, Australia. Clusters of extensively cited papers and prevalent keywords delineate the status and trend of FD and anxiety/depression research. This encompasses FD, anxiety, depression, sleep disorders, and functional gastrointestinal disorders. Furthermore, the timeline view map or trend-term analysis suggested that duodenal low-grade inflammation ("duodenal eosinophilia" and "mast cells") might be a new concern associated with FD and anxiety/depression. Conclusion: Employing bibliometric analysis, this study revealed prevalent focal areas and new trends within FD and anxiety/depression research. These insights serve as valuable guidance for scholars seeking to delve into new research avenues.

Ziqi Dihuang decoction ameliorates thrombosis in septic rats by inhitbiting plasminogen activator inhibitor-1.

Introduction: Sepsis is now a global medical burden with high morbility and mortality. The focus of this study was to evaluate the effects of Ziqi Dihuang (ZQDH) decoction on inflammatory and thrombosis-related parameters in septic rats. Mothods: A rat model of sepsis was established by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly divided into Sham group, CLP group, ZQDH-1ow group (0.735 g/kg) and ZQDH-high group (1.47 g/kg). Rats in ZQDH groups were given ZQDH decoction by gavage for 7 days before CLP. White blood cells (WBC), inflammatory cell infiltration of liver, kidney and lung, as well as serum levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and reactive oxygen species (ROS) were used to assess systemic inflammatory response. Coagulation and fibrinolytic indexes included platelet count, coagulation function, fibrin deposition, and levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in serum, liver, kidney and lung. Results: LPS rats showed significant changes in inflammatory and thrombosis-related parameters such as increased WBC and inflammatory factors, decreased platelet counts, and increased tPA and PAI-1 concentrations in serum and organs. ZQDH decoction pretreatment can significantly inhibit the infiltration of inflammatory cells in the lung, and inhibit the production of TNF-α, IL-6 and ROS in a dose-dependent manner. ZQDH decoction also ameliorated thrombocytopenia, renal fibrin deposition, and tPA and PAI-1 levels in serum and organs. Conclusion: These results suggest that ZQDH decoction can dose-dependently relieve systemic inflammatory injury and regulate fibrinolysis system in septic rats, which may be mediated by PAI-1.

DLAT is a promising prognostic marker and therapeutic target for hepatocellular carcinoma: a comprehensive study based on public databases.

Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients.

Efficacy of omega-3 fatty acids for hospitalized COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging expert consensuses and guidelines recommend that omega-3 fatty acids may have anti-inflammatory effects in hospitalized patients with coronavirus disease (COVID-19). However, these recommendations are based on pathophysiological studies of inflammation rather than direct clinical evidence. We conducted this systematic review and meta-analysis to evaluate the efficacy of omega-3 fatty acid supplementation in hospitalized patients with COVID-19. METHODS AND STUDY DESIGN: We retrieved literature from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), WANFANG, Chinese Biomedical Literature Database, and Cochrane Library databases up to May 1, 2023. Data from studies comparing omega-3 fatty acids with a placebo or other pharmaceutical nutrients were analyzed. RESULTS: Of 3032 records, 42 full-text articles were reviewed, five eligible studies were identified, and one study was found in the references. In total of six studies involving 273 patients were included, pooled, and analyzed. Compared to the control group, omega-3 fatty acid intervention reduced the overall mortality of hospitalized patients with COVID-19 (RR=0.76; 95% CI, [0.61, 0.93]; p=0.010). No serious or unexpected drug-related adverse events were observed. No statistical significance was observed in inflammatory markers such as CRP (MD=-9.69; 95% CI, [-22.52, 3.15]; p=0.14; I2=97%) and IL-6; however, the neutrophil/lymphocyte ratio was significantly lower in the omega-3 FAs group on day 7 of intervention (p < 0.001). CONCLUSIONS: Omega-3 fatty acid administration may be associated with reduced mortality in hospitalized patients with COVID-19. Given the small sample size of enrolled studies, more rigorous and large-scale trials are urgently needed in the future to verify its efficacy.

Identification of Fangji Huangqi Tang as a potential herbal formula for Sjogren syndrome treatment via network pharmacology and experimental validation.

Fangji Huangqi Tang (FHT) is a well-known Chinese herbal formula that is prescribed as treatment for rheumatoid diseases. In this study, we aimed to investigate the potential therapeutic targets, efficacy, and safety of FHT in the treatment of Sjogren's syndrome (SS). The Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in SS. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological functions of the DEGs. Subsequently, an FHT-herb-active compound-target network was constructed to identify the relationship between the active compounds in FHT and the related targets. Then, enrichment analysis involving the DEGs and protein-protein interaction (PPI) network analysis were performed to analyze the biological functions of potential targets and screen hub genes. Further, molecular docking was employed to verify the binding affinity between the active compounds and the hub targets, and in vivo experiments involving NOD/LtJ mice were conducted to verify the therapeutic effects of FHT on SS-like symptoms. Finally, inhibition of PIK3CK/Akt pathway by FHT was validated by WB and rt-qPCR. A total of 1836 DEGs were identified in SS based on the GSE159574 dataset, and 114 targets of the active compounds in FHT were screened. Further, via network pharmacology analysis and molecular docking, six active compounds and five hub targets were obtained, and enrichment analysis showed that the anti-SS effect of FHT was predominantly associated with immune cells, such as T cells and neutrophils. In vivo, FHT effectively reduced lymphocyte infiltration foci, increased saliva flow rate, and inhibited increases in the levels of SS-related autoantibodies (anti-SSA and anti-SSB). Furthermore, the biosafety of FHT was verified via the serological examination of liver and kidney function. WB and rt-qPCR analysis confirmed that FHT could inhibit the expression of PIK3CG and the activation of PIK3CG/Akt pathway. Via network pharmacological analysis, molecular docking, and in vivo verification, we demonstrated the multicomponent and multitarget characteristics of FHT in SS treatment, thereby providing novel insights into the pathogenesis of SS and the therapeutic targets of FHT for SS.

Phytochemistry and biological activities of corynanthe alkaloids.

Medicinal plants constitute a source for designing clinically useful drugs targeting diseases through various mechanisms. Plant secondary metabolites can be used as lead compounds of drugs. Corynanthe alkaloids are highly abundant natural bioactive substances of various core structures possessing important properties such as nerve excitation and antimalarial and analgesic effects. In this review, we summarize and review the state-of-the-art corynanthe-type alkaloid research focusing on phytochemistry, pharmacology, and structural chemistry. Approximately 120 articles reporting 231 alkaloids classified into simple corynanthe, yohimbine, oxindole corynanthe, mavacurane, sarpagine, akuammiline, strychnos, and ajmaline-type groups were compiled. Relevant biological properties discussed include antiviral, antibacterial, anti-inflammatory, antimalarial, muscle-relaxant, vasorelaxant, and analgesic activities and activities affecting the main nervous and cardiac systems, as well as NF-κB inhibitory and Na+-glucose cotransporter inhibitory properties. This review provides insights and a reference for future studies, thus paving the way for the discovery of drugs based on corynanthe alkaloids.

Enteral glutamine supplements for patients with severe burns: A systematic review and meta-analysis.

PURPOSE: Our previous study in 2009 concluded that glutamine may shorten the length of hospital stay (LOS) in patients with severe burns. Recent large-scale studies have suggested a decline in the effectiveness of glutamine in treating patients with severe burns over the last decade. Therefore, we conducted this systematic review and meta-analysis to update the status of glutamine uses in patients with severe burns. METHODS: We retrieved related literature prior to December 2022 from the PubMed, Web of Science, Cochrane Library, Embase, SinoMed, Wanfang, and CNKI databases. Terms such as glutamine, enteral and burn were linked for searching. Adults patients with severe burns were included and non-randomized controlled trials were excluded. Data from studies that compared enteral glutamine for severe burns with a control group were extracted. The primary outcomes of mortality and infectious morbidities were pooled and analyzed. The modified Jadad scale and Cochrane collaboration's tool were used to assess the risk of bias in RCTs, and the Review Manager 5.4 was used to pool and analyze the data. RESULTS: Six randomized controlled trials involving 1398 patients were included in the analysis. There were no significant differences in overall mortality (risk ratio (RR) = 0.37; 95% confidence interval (CI): 0.06 - 2.37; p = 0.300) or infectious morbidities (RR = 0.73; 95% CI: 0.41 - 1.31; p = 0.290). The incidence of multiple organ dysfunction syndrome was similar between the 2 groups (RR = 0.27; 95% CI: 0.03 - 2.24; p = 0.220). The LOS (mean difference (MD) = -8.97; 95% CI: -15.22 to -2.71; p = 0.005) and LOS/total burn surface area (MD = -0.27; 95% CI: -0.54 to 0.00; p = 0.050) decreased in the enteral glutamine group. The incidence of wound infection was significantly reduced (RR = 0.42; 95% CI: 0.16 - 1.06; p = 0.070). CONCLUSION: Compared to the control group, enteral glutamine administration may not improve the mortality, although it may be associated with a shorter LOS, a lower LOS/total burn surface area ratio, and may reduce the risk of wound infection in patients with severe burns.

Arctiin alleviates functional constipation by enhancing intestinal motility in mice.

Functional constipation (FC), a common symptom that is primarily associated with intestinal motility dysfunction, is a common problem worldwide. Arctiin (Arc) is a lignan glycoside isolated from the Chinese herbal medicine Arctium lappa L., which is a health food in China. The present study aimed to evaluate the laxative effects of Arc against FC in mice. A model of FC induced by loperamide (5 mg/kg) was established in male Institute of Cancer Research (ICR) mice. Arc was administered at a dose of 100 mg/kg as a protective agent. The faecal status, intestinal motility and histological analyses were evaluated. Furthermore, the levels of gastrointestinal motility-associated neurotransmitters, such as motilin (MTL), nitric oxide (NO), and brain-derived neurotrophic factor (BDNF) and the protective effect of Arc on interstitial cells of Cajal (ICC) were assessed. Arc treatment reversed the loperamide-induced reduction in faecal number and water content and the intestinal transit ratio in ICR mice. Histological analysis confirmed that Arc administration mitigated colonic injury. Moreover, Arc treatment increased levels of motilin and brain-derived neurotrophic factor while decreasing nitric oxide levels and ICC injury in the colon of FC mice. Arc decreased inflammation induction and aquaporin expression levels. Owing to its pro-intestinal motility property, Arc was shown to have a protective effect against FC and may thus serve as a promising therapeutic strategy for the management of FC.

New Type of Tannins Identified from the Seeds of Cornus officinalis Sieb. et Zucc. by HPLC-ESI-MS/MS.

There is a lack of information on the compound profile of Cornus officinalis Sieb. et Zucc. seeds. This greatly affects their optimal utilization. In our preliminary study, we found that the extract of the seeds displayed a strong positive reaction to the FeCl3 solution, indicating the presence of polyphenols. However, to date, only nine polyphenols have been isolated. In this study, HPLC-ESI-MS/MS was employed to fully reveal the polyphenol profile of the seed extracts. A total of 90 polyphenols were identified. They were classified into nine brevifolincarboxyl tannins and their derivatives, 34 ellagitannins, 21 gallotannins, and 26 phenolic acids and their derivatives. Most of these were first identified from the seeds of C. officinalis. More importantly, five new types of tannins were reported for the first time: brevifolincarboxyl-trigalloyl-hexoside, digalloyl-dehydrohexahydroxydiphenoyl (DHHDP)-hexdside, galloyl-DHHDP-hexoside, DHHDP-hexahydroxydiphenoyl(HHDP)-galloyl-gluconic acid, and peroxide product of DHHDP-trigalloylhexoside. Moreover, the total phenolic content was as high as 79,157 ± 563 mg gallic acid equivalent per 100 g in the seeds extract. The results of this study not only enrich the structure database of tannins, but also provide invaluable aid to its further utilization in industries.

Goat milk powder supplemented with branched-chain fatty acid: influence on quality and microstructure.

BACKGROUND: Branched-chain fatty acid (BCFA) is effective in preventing and helping to treat neonatal necrotizing enterocolitis. It is essential to supplement goat-milk powder for formula-fed preterm infants with BCFA. In this study, the quality and microstructures of milk powders supplemented with different concentrations of BCFA were evaluated, using goat milk powder without BCFA as the control group (CG). RESULTS: In comparison with the CG, goat milk powder supplemented with BCFA exhibited smaller fat globules and a significant drop in overall particle size. During 16 weeks of storage, BCFA-supplemented groups showed suitable moisture content and viscosity and good solubility. The BCFA also helped reduce the number of folds on the surface of the milk powder particles. CONCLUSION: The findings of this study indicate that goat milk powders with BCFA exhibit differences in quality and microstructure in comparison with ordinary goat milk powder, which is relevant for the future development and application of BCFA in foods. © 2022 Society of Chemical Industry.

Meiocyte size is a determining factor for unreduced gamete formation in Arabidopsis thaliana.

Polyploidy, the presence of more than two sets of chromosomes within a cell, is a widespread phenomenon in plants. The main route to polyploidy is considered through the production of unreduced gametes that are formed as a consequence of meiotic defects. Nevertheless, for reasons poorly understood, the frequency of unreduced gamete formation differs substantially among different plant species. The previously identified meiotic mutant jason (jas) in Arabidopsis thaliana forms about 60% diploid (2n) pollen. JAS is required to maintain an organelle band as a physical barrier between the two meiotic spindles, preventing previously separated chromosome groups from uniting into a single cell. In this study, we characterized the jas suppressor mutant telamon (tel) that restored the production of haploid pollen in the jas background. The tel mutant did not restore the organelle band, but enlarged the size of male jas tel meiocytes, suggesting that enlarged meiocytes can bypass the requirement of the organelle band. Consistently, enlarged meiocytes generated by a tetraploid jas mutant formed reduced gametes. The results reveal that meiocyte size impacts chromosome segregation in meiosis II, suggesting an alternative way to maintain the ploidy stability in meiosis during evolution.

Modulation of cerebral cortex activity by acupuncture in patients with prolonged disorder of consciousness: An fNIRS study.

Background and objective: Acupuncture is a promising non-pharmacological therapy for patients with prolonged disorder of consciousness (PDOC); however, its underlying mechanism remains uncertain. This study aimed to reveal the modulatory effects of acupuncture on the cerebral cortex activity among patients with PDOC. Materials and methods: Twenty-eight PDOC patients were randomly assigned to the treatment (n = 14) or control (n = 14) group. The treatment group received one session of acupuncture, while the control group received one session of sham acupuncture. All patients underwent evaluation of the functional connectivity and activation response of the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1) via functional near-infrared spectroscopy. We further explored the potential correlation of the consciousness level and activation response/functional connectivity with acupuncture. Results: Compared to the control group, a single session of acupuncture significantly tended to enhance resting-state functional connectivity (rsFC) in DLPFC-M1, DLPFC-M1, and S1-S1. And the activation level of the DLPFC (both sides) in the acupuncture group is significantly higher than those in sham acupuncture group. However, no significant correlation was found between the consciousness level and activation response/functional connectivity. Conclusion: One session of acupuncture has a significant modulation of rsFC and activation in the DLPFC, M1, and S1 with PDOC patients. Acupuncture-evoked effect may have some functional significance in PDOC patients. This is an important step toward exploring the acupuncture effects on PDOC patients.

[Scalp acupuncture regulates hypothalamic V1aR/CaMKâ ¡/AQP4 signaling pathway in rats with focal cerebral ischemia].

OBJECTIVE: To observe the effect of scalp acupuncture on the expression of argarginine vasopressin receptor-1a(V1aR), phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ), and aquaporin 4(AQP4) at hypothalamus in middle cerebral artery occlusion (MCAO) rats, so as to explore the molecular mechanisms of scalp acupuncture reducing encepha-ledema in acute ischemic stroke. METHODS: A total of 96 male SD rats were randomly divided into normal， model, inhibitor and scalp acupuncture groups, with 24 rats in each group. The MCAO model was established by thread occlusion method. The inhibitor group was intraperitoneally injected with V1aR inhibitor (30 µg/kg)，once a day for 7 consecutive days. In the scalp acupuncture group, acupuncture was applied to bilateral "parietal and temporal anterior oblique line", with rapid insertion of 2 needles at 15° to 20°, twisting at 100 r/min for 1 min, and retaining the needles for 30 min, once a day for 7 consecutive days. The neurologic deficit score (NDS) and neurological score (NS) were evaluated before and after intervention. The positive expression of p-CaMKⅡ and AQP4 proteins in hypothalamus was detected by immunohistochemistry. The water content of left brain tissue was determined by BIIiot method. The expression of V1aR mRNA in hypothalamus was detected by real-time PCR. RESULTS: Compared with the normal group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP4 positive expression levels were significantly increased (P<0.01) in the model group. Compared with the model group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP4 positive expression levels were significantly decreased (P<0.01) in the inhibitor and scalp acupuncture groups. CONCLUSION: Regulating the signaling pathway of V1aR/CaMKⅡ/AQP4 in hypothalamus may be one of the molecular mechanisms of scalp acupuncture reducing encephaledema in acute ischemic stroke.

Selection of bionic Co-former improves the dissolution of Neohesperidin via Co-amorphous solid dispersion with Naringin.

The co-amorphous solid dispersion (c-ASD) is a useful method to enhance water solubility of poorly soluble drugs. The objective of this study was to improve the dissolution of Neohesperidin (NE) via binary c-ASD which, to the best of our knowledge, has not yet been reported. Since NE and Naringin (NA) co-exist abundantly in Chinese herbal medicine Fructus Aurantii Immaturus, it was hypothesised that NA served as a co-former of NE-NA c-ASD to improve the dissolution profile of NE. Hence, NA was selected to prepare c-ASD with NE at a weight ratio of 4:10, 10:10, 10:4 by lyophilisation. They were characterised according to thermal properties, molecular interactions, dissolution properties and physical stability. We found that the 10:10 ratio was the most potent in enhancing the dissolution behaviour of NE; whereby NE and NA are highly synchronous in pair-wise solvation process. A molecular mixture was achieved through the intermolecular H-bond and pi-pi stacking force formed between NE and NA and was stable for 7 -months. We concluded that the NE-NA co-amorphous binary system is a promising strategy to improve the dissolution behaviour and stabilise the amorphous state of NE. Bionic co-former selection may be an innovative and effective way to accurately determine the appropriate co-former of poorly water soluble substances.

Demethyleneberberine blocked the maturation of IL-1ß in inflammation by inhibiting TLR4-mitochondria signaling.

Demethyleneberberine (DMB) is a natural product from traditional Chinese medicinal herb the rhizome of Coptis chinensis Franch., which has been reported to possess multiple pharmacological activities, especially anti-inflammation and immunoregulation. However, the potential mechanism of DMB in inflammation is still a mystery. In this study, a mouse model of ulcerative colitis (UC) was induced by Dextran sulfate sodium salt (DSS), and in vitro experiments were performed in RAW264.7 macrophages and the primary intestinal macrophages which obtained from Toll-Like receptor 4 (TLR4) and NOD-Like receptor protein 3 (NLRP3) knockout fetal mouse. Mitochondrial was increased by overexpression of peroxlsome proliferator-activated receptor-γ coactlvator-1α (PGC-1α) and exhausted by adding Ethidium Bromide (EtBr) in RAW264.7 to evaluate the function of mitochondria in the maturation of IL-1ß. Additionally, the safety of DMB (50 mg/kg/d) in mice was assessed by orally administrating for 98 days. DMB siginificantly improved colon atrophy, colonic tissue mass score, neutrophil infiltration and histological damage, which was mainly attributed to the anti-inflammatory effect of DMB. Further in vitro analysis showed that DMB blocked the excessive mitochondrial biosynthesis and maintained the homeostasis of mitochondria in inflammatory response. Moreover, the maturation of IL-1ß was suppressed by DMB in a mitochondria dependent manner. Crucially, DMB was a candidate agent for UC with free of toxicity and side effects. These findings demonstrated that DMB ameliorated inflammatory response by inhibiting TLR4-mitochondria signaling, and revealed the effectiveness and mechanism of DMB for alleviation of UC and provided an additional strategy for UC intervention.

Isolation and Bioinspired Total Synthesis of Rugosiformisin A, A Skeleton-Rearranged Abietane-Type Diterpenoid from Isodon rugosiformis.

Rugosiformisin A, a skeleton-rearranged abietane-type diterpenoid with a spiro[4.5]decane motif, was isolated from Isodon rugosiformis. Its structure was unambiguously established via NMR spectroscopic analysis and single-crystal X-ray diffraction. A bioinspired asymmetric synthesis of rugosiformisin A was achieved in 15 steps with 2.7% overall yield. The synthesis features an iridium-catalyzed asymmetric polyene cyclization and a semipinacol rearrangement.