Improvement of amphipathic properties with molecular structure unfolding and activation of cottonseed protein as ultra stable and safe emulsifier by deamidation.

By-product cottonseed proteins are excellent options for numerous applications due to their superior properties and lower cost. However, its complex folded structure and large molecular weight lead to lower reactivity and insufficient amphiphilicity. Cottonseed protein isolate (CPI) is less-soluble in water. Therefore, we improved the amphiphilicity of CPI with associated hydrolysis, molecular structure unfolding, and activation by alkaline-induced deamidation (at 24, 36, and 72 h) and produced three cottonseed protein hydrolysates CPH 24, 36, and 72. FTIR/UV-CD measurements confirmed the conformational changes and conversion of the structural content. Particle size decreased 2503.4-771.8 nm, while surface hydrophobicity (133.5-326.7), carboxyl content (1.13 × 10Ö¾3-2.09 × 10Ö¾3), and flexibility increased, signifying hydrolysis, unfolding, and amphiphilicity improvement. Longer deamidation (CPH 72) exhibited the best properties, its prepared emulsions were long-term stable under all the environmental stresses without visible phase separation after at least 40 days of storage except at pH 4. Compared to CPI, it had smaller droplets (939.3-264.9 nm) and larger absolute ζ-potential (-26.5 to -58.0 mV). From the in-vitro cytotoxicity test, deamidated CPI is extremely safer than commonly used synthetic surfactants. This research provides a new method for producing multifunctional emulsifiers from CPI, which could be utilized in the development of functional foods/non-foods.

Identification of in vivo metabolites of Citri Sarcodactylis Fructus by UHPLC-Q/Orbitrap HRMS.

INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.

[Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin].

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

The role of Keap1/Nrf2/HO-1 signal pathway in liver injury induced by rare earth neodymium oxide in mice / 中华劳动卫生职业病杂志

Objective: To investigate the role of Keap1/Nrf2/HO-1 signaling pathway in liver injury induced by neodymium oxide (Nd(2)O(3)) in mice. Methods: In March 2021, forty-eight SPF grade healthy male C57BL/6J mice were randomly divided into control group (0.9% NaCl), low dose group (62.5 mg/ml Nd(2)O(3)), medium dose group (125.0 mg/ml Nd(2)O(3)), and high dose group (250.0 mg/ml Nd(2)O(3)), each group consisted of 12 animals. The infected groups were treated with Nd(2)O(3) suspension by non-exposed tracheal drip and were killed 35 days after dust exposure. The liver weight of each group was weighed and the organ coefficient was calculated. The content of Nd(3+) in liver tissue was detected by inductively coupled plasma mass spectrometry (ICP-MS). HE staining and immunofluorescence was used to observe the changes of inflammation and nuclear entry. The mRNA expression levels of Keap1, Nrf2 and HO-1 in mice liver tissue were detected by qRT-PCR. Western blotting was used to detect the protein expression levels of Keap1 and HO-1. The contents of catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were detected by colorimetric method. The contents of interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. The data was expressed in Mean±SD. Two-independent sample t-test was used for inter-group comparison, and one-way analysis of variance was used for multi-group comparison. Results: Compared with the control group, the liver organ coefficient of mice in medium and high dose groups were increased, and the Nd(3+) accumulation in liver of mice in all dose groups were significantly increased (P<0.05). Pathology showed that the structure of liver lobules in the high dose group was slightly disordered, the liver cells showed balloon-like lesions, the arrangement of liver cell cords was disordered, and the inflammatory exudation was obvious. Compared with the control group, the levels of IL-1β and IL-6 in liver tissue of mice in all dose groups were increased, and the levels of TNF-α in liver tissue of mice in high dose group were increased (P<0.05). Compared with the control group, the mRNA and protein expression levels of Keap1 in high dose group were significantly decreased, while the mRNA expression level of Nrf2, the mRNA and protein expression levels of HO-1 were significantly increased (P<0.05), and Nrf2 was successfully activated into the nucleus. Compared with the control group, the activities of CAT, GSH-Px and T-SOD in high dose group were significantly decreased (P<0.05) . Conclusion: A large amount of Nd(2)O(3) accumulates in the liver of male mice, which may lead to oxidative stress and inflammatory response through activation of Keap1/Nrf2/HO-1 signal pathway. It is suggested that Keap1/Nrf2/HO-1 signal pathway may be one of the mechanisms of Nd(2)O(3) expose-induced liver injury in mice.

Effect of Solitaire FR Stent Thrombectomy Combined with the Suction Thrombus on the Clinical Effect and Prognosis of Acute Middle Cerebral Artery Occlusion.

To determine the curative effect and prognosis of Solitaire FR stent thrombectomy integrated with the suction thrombus on the treatment of acute middle cerebral artery occlusion (AMCAO). Based on the treatment, patients suffering from AMCAO were separated into the Solitaire FR group (Solitaire FR stent + suction thrombus) and suction group (suction thrombus). Modified thrombolysis in cerebral infarction grading, National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale score, and safety performance were compared between the two groups. The operation time in the suction group was obviously shorter than the Solitaire FR group (P < 0.05). Significant differences were observed in the NIHSS scores 1 week and 4 weeks after the operation between the Solitaire FR group and the suction group (P < 0.05). The NIHSS scores 1 week and 4 weeks after operation were significantly lower than those before operation (P < 0.05). NIHSS scores 1 week after operation did not show obvious difference (P > 0.05). The Solitaire FR group showed obvious lower NIHSS scores than the suction group 4 weeks after surgery (P < 0.05). Statistically obvious difference in cerebral infarction grading of modified thrombolysis between the Solitaire FR group and the suction group were observed (P < 0.05). The recanalization rate of the Solitaire FR group was obviously higher than the suction group (P < 0.05). The difference in the monthly modified Rankin Scale score was obvious (P < 0.05). The good prognosis rate of the Solitaire FR group was obviously higher than the suction group (P < 0.05). No obvious differences in the incidence of internal bleeding, reocclusion, and 3-month postoperative mortality were observed (P > 0.05). These results showed that the treatment of the Solitaire FR stent + suction thrombus in AMCAO patients has a good thrombus recanalization rate and is helpful in improving the prognosis and safety performance.

The complete chloroplast genome sequence of traditional Chinese medicine Uncaria macrophylla (Rubiaceae).

Uncaria macrophylla (Rubiaceae) is a medicinal vine plant of the Rubiaceae family that was distributed in East Asia and Southeast Asia. The first complete chloroplast genome of Uncaria macrophylla was sequenced and assembled in this study. The genome is 155,138 bp in length and contained 129 encoded genes in total, including 79 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The phylogenomic analysis showed that U. macrophylla was closely related to Uncaria rhynchophylla according to the current sampling extent.

Effects of natural dihydrochalcones in sweet tea (Lithocarpus polystachyus) on diabetes: a systematical review and meta-analysis of animal studies.

Sweet tea (Lithocarpus polystachyus Rehd.), a natural functional food highly rich in dihydrochalcones including trilobatin, phlorizin and phloretin, is reported to possess numerous biological activities especially for treating diabetes. Here, the aim of this systematical review and meta-analysis is to assess the effect of dihydrochalcones in sweet tea (DST) on diabetes and summarize their possible mechanisms. We searched in eight databases including Embase, PubMed, Cochrane, Web of Science, WanFang database, VIP database, China National Knowledge Infrastructure and China Biology Medicine from Jan 2000 to Nov 2021 and ultimately included 21 animal studies in this review. A total of 10 outcome measurements including blood lipid indexes, blood glucose, insulin resistance indicators and oxidative stress biomarkers were extracted for meta-analysis using RevMan 5.4 software. DST significantly decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), blood glucose (BG), homeostasis model assessment of insulin resistance (HOMA-IR) and malondialdehyde (MDA), and increased high-density lipoprotein cholesterol (HDL-c), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in diabetic animal models. In summary, DST could treat diabetes by regulation of blood glucose/lipid metabolism, oxidative/carbonyl stress, inflammatory response etc.

Effect of Vitamin D Supplementation on the Prognosis of Post-stroke Fatigue: A Retrospective Cohort Study.

Objective: We aimed to evaluate the effect of vitamin D supplementation in post-stroke fatigue (PSF) patients with vitamin D deficiency on fatigue symptoms and outcomes. Methods: Patients with primary acute ischemic stroke (AIS) were recruited consecutively from July 2016 to June 2018. Post-stroke fatigue patients were screened out with the Fatigue Severity Scale (FSS) questionnaire, serum concentrations of 25-hydroxyvitamin D [25-(OH)-D] were assessed with enzyme-linked immunosorbent assay (ELISA), and neurological function was evaluated with FSS and modified Rankin Scale (mRS) scoring criteria. Post-stroke fatigue patients with vitamin D deficiency were divided into two groups: a study group in which patients received vitamin D supplementation (cholecalciferol, 600 IU/day) along with usual care, and a control group in which patients received usual care alone. At the end of 1 and 3 months after treatment, all PSE patients accepted re-measurement of serum vitamin D and re-evaluation of fatigue and neurological function. Results: A total of 532 AIS patients were consecutively recruited to participate in this study. Patients without PSF, non-vitamin D deficiency, pre-stroke fatigue, or vitamin D supplementation were excluded from the study. In addition, patients who were lost to follow-up were also excluded. Finally, 139 out of 532 (26.1%) patients with PSF and vitamin D deficiency received vitamin D supplementation treatment. Fatigue Severity Scale score was significantly lower in the study group than in the control group at 1 month (t = -4.731, p < 0.01) and 3 months (t = -7.937, p < 0.01) after treatment. One month after treatment, mRS score in the study group was lower than that in the control group without statistical difference (t = -0.660, p > 0.05), whereas mRS was significantly higher in the study group than in the control group at 3 months after treatment (t = -4.715, p < 0.01). Conclusions: Our results indicated that vitamin D supplementation could improve fatigue symptoms and neurological outcomes in PSF patients with vitamin D deficiency. Subject to replication in other settings, a randomized controlled trial (RCT) might be undertaken to validate the potential beneficial impact of vitamin D supplementation in post-stroke patients found to be vitamin D deficient.

Protopanaxadiol improves endometriosis associated infertility and miscarriage in sex hormones receptors-dependent and independent manners.

Background: Patients with endometriosis (EMs) have high risks of infertility and spontaneous abortion. How to remodel the fertility of patients with EMs has always been the hot spot and difficulty in the field of reproductive medicine. As an aglycone of ginsenosides, protopanaxadiol (PPD) possesses pleiotropic biological functions and has high medicinal values. We aimed to investigate the effect and potential mechanism of PPD in the treatment of EMs-associated infertility and spontaneous abortion. Methods: The EMs mice models were constructed by allotransplantation. The pregnancy rates, embryo implantation numbers and embryo resorption rates of control and EMs were counted. RNA sequencing, qRT-PCR, enzyme linked immunosorbent assay (ELISA) and FCM analysis were performed to screen and confirm the expression of endometrial receptivity/decidualization-related molecules, inflammation cytokines and NK cell function-related molecules in vitro and/or in vivo. The SWISS Target Prediction, STRING and Cytoscape were carried out to predict the potential cellular sensory proteins, the protein-protein interaction (PPI) network between sensory proteins and fertility-related molecules, respectively. Micro-CT detection, liver and kidney function tests were used to evaluate the safety. Results: Here, we observe that PPD significantly up-regulates endometrial receptivity-related molecules (e.g., Lif, Igfbp1, Mmps, collagens) and restricts pelvic inflammatory response (low levels of IL-12 and IFN-γ) of macrophage, and further remodel and improve the fertility of EMs mice. Additionally, PPD increases the expression of decidualization-related genes and Collagens, and promotes the proliferation, residence, immune tolerance and anagogic functions of decidual NK cells (low levels of CD16 and NKp30, high levels of Ki67, VEGF, TGF-ß) in pregnant EMs mice, and further triggers decidualization, decidual NK cell-mediated maternal-fetal immune tolerance and angiogenesis, preventing pregnant EMs mice from miscarriage. Mechanically, these effects should be dependent on ESRs, PGR and other sensory proteins (e.g., AR). Compared with GnRHa (the clinic first-line drug for EMs), PPD does not lead to the decline of serum estrogen and bone loss. Conclusion: These data suggest that PPD prevents EMs-associated infertility and miscarriage in sex hormones receptors-dependent and independent manners possibly, and provides a potential therapeutic strategy with high efficiency and low side effects to remodels the fertility of patients with EMs.

[Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism].

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Current advances in environmental stimuli regulating the glycyrrhizic acid biosynthesis pathway.

Glycyrrhizic acid, the main active ingredient of licorice, has good antibacterial, anti-tumor, anti-viral, anti-inflammatory, and immunostimulatory activities. However, the content of glycyrrhizic acid fluctuates greatly in different licorice cultivars, and production depends on plant sources, which greatly limits its development and applications. Therefore, increasing glycyrrhizic acid content has become a research priority. In recent years, regulation of the glycyrrhizic acid biosynthesis pathway has been analyzed, the downstream synthesis pathway in licorice has been fully investigated, some key genes have been cloned, polymorphisms have been studied, and the content of glycyrrhizic acid was shown to be regulated by environmental stimuli. This work has provided a basis for studying the regulation mechanism of the glycyrrhizic acid synthesis pathway. This review summarizes and discusses relevant research to provide a current understanding of the glycyrrhizic acid synthesis pathway and its regulation in licorice.

How to improve CHMs quality: Enlighten from CHMs ecological cultivation.

Chinese herbal medicines (CHMs) are one of the important bioresources of medicine, which works by unlocking nature's ability to prevent diseases and recover from illnesses. Recently, it has ascended to the world stage and become a global icon. Nowadays, a considerable of researches have focused on the quality evaluation of CHMs. However, it is difficult to meet the reasonable needs of human beings for safe drug use to evaluate the quality of a huge number of inferior goods for the CHMs contaminated by pesticides and heavy metals. Hence to explore an eligible medicinal plant cultivation pattern, which can provide high quality CHMs sustainably, is most promising. This review analyzed the situation and characteristics of medicinal plant resources in different periods, including wild-harvested and cultivated resources during different stages, putting forward that ecological cultivation must be the way to develop medicinal plant cultivation and to obtain high quality CHMs.

How to improve CHMs quality: Enlighten from CHMs ecological cultivation / 中草药·英文版

Chinese herbal medicines (CHMs) are one of the important bioresources of medicine, which works by unlocking nature's ability to prevent diseases and recover from illnesses. Recently, it has ascended to the world stage and become a global icon. Nowadays, a considerable of researches have focused on the quality evaluation of CHMs. However, it is difficult to meet the reasonable needs of human beings for safe drug use to evaluate the quality of a huge number of inferior goods for the CHMs contaminated by pesticides and heavy metals. Hence to explore an eligible medicinal plant cultivation pattern, which can provide high quality CHMs sustainably, is most promising. This review analyzed the situation and characteristics of medicinal plant resources in different periods, including wild-harvested and cultivated resources during different stages, putting forward that ecological cultivation must be the way to develop medicinal plant cultivation and to obtain high quality CHMs.

A target-oriented algorithm for maintaining serum calcium stability automatically in regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation (RCA) for renal replacement therapy is widely practiced in critically ill patients. However, concern exists regarding its labor-intensiveness for monitoring and the associated hypocalcemia. In this study, we provided an algorithm for prescribing RCA and evaluated its safety in patients. METHODS: During 18 hemofiltration treatments with calcium-free replacement solution, participants were randomized to receive algorithm-based or trial-and-error RCA protocol. The effluent volume, post-filter and in vivo ionized calcium (iCa), and calcium in the sera and effluents were periodically measured at an interval of 1 to 2 h. RESULTS: For patients received algorithm-based RCA protocol, no one had a serum iCa less than 0.9 mmol/L, and none needed calcium supplement adjustment to maintain serum calcium stability. For patients accepted trial-and-error protocol, all patients had a serum iCa below 0.9 mmol/L, their serum iCa and calcium levels fluctuated dramatically, and all patients need additional calcium supplement adjustment during RCA. None of the participants showed a post-filter iCa > 0.4 mmol/L. CONCLUSION: We provided a safe algorithm for calculating calcium supplementation doses that could maintain serum calcium stability without additional adjustment during RCA.

New lathyrane diterpenoids with anti-inflammatory activity isolated from the roots of Jatropha curcas L.

ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha curcas L. (Euphorbiaceae), as a drought resistant shrub mainly cultivated in tropical and subtropical areas worldwide, is widely used as traditional medicine to cure arthritis, dysentery, abscess and pneumonia in Asian, African and South American folklores. The methanolic extracts of the roots have been revealed the anti-inflammatory activity in vivo and vitro. AIM OF STUDY: This research aimed to provide promising anti-inflammatory candidates from the roots of J. curcas. In addition, RNA-Seq was conducted to give targeted genes involved in the anti-inflammatory action. MATERIALS AND METHODS: The diterpenoids were isolated from the CH2Cl2 fraction of the methanolic extract from the roots of J. curcas by column chromatography (CC): silica gel, Sephadex LH-20, ODS, semi-preparative reversed-phase high-performance liquid chromatography (HPLC). The structures were identified based on HR-ESI-MS and 1D, 2D-NMR spectroscopic analysis. Their anti-inflammatory effects were tested on lipopolysaccharide (LPS, 500 ng/mL)-stimulated murine RAW264.7 macrophages. Furthermore, we conducted transcriptome-wide RNA sequencing to profile gene expression alterations in LPS-induced RAW264.7 cells upon treatment with jatrocurcasenone I (4) and analyzed the underlying genes targeted by this compound. RESULTS: Six diterpenoids were obtained from J. curcas, and four of them were identified to be new lathyrane diterpenoids: jatrocurcasenones F-I (1-4). Compounds 3 and 4 exhibited potent inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 cells with IC50 values of 11.28 µM and 7.71 µM, respectively. Western blotting analysis showed that the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were suppressed with the supplementation of 3 and 4. The results of RNA-seq showed that 4 (20 µM) exhibited regulation on the 587 differentially expressed genes (DEGs) induced by LPS (500 ng/mL). Transcriptome-wide RNA sequencing indicated that the protective activity of 4 supplementation was most likely driven by modulating expression levels of IL-1α, IL-1ß, IL-1f6, IL-6, IL-1rn, IL-27, Ccl2, Ccl5, Ccl7, Ccl9, Ccl22, Cxcl10, Tnfsf12, Tnfsf15, Lta, Trim25, Bcl2a1a, Dusp1, Dusp2, Ptgs2, Edn1 and Nr4a1. CONCLUSIONS: This study offered four new lathyrane diterpenoids, of them, jatrocurcasenone I (4) showed significant anti-inflammatory activity. RNA-Seq suggested that jatrocurcasenone I (4) could be a candidate drug for the prevention inflammation-mediated diseases by modulating 24 candidate DEGs.

[Mechanism of salicylic acid ameliorates salt-induced changes in Andrographis paniculata].

In this study, Andrographis paniculata seedlings were used as experimental materials to study the effects of salicylic acid(SA) on the growth and effective component accumulation of A. paniculata under NaCl stress. The results showed that with the increase of NaCl concentration, the growth of A. paniculata seedlings was significantly inhibited, and the content of carotene and carotenoid decreased. The activity of antioxidant enzyme was enhanced. At the same time, the contents of proline, proline and soluble protein were on the rise. The contents of andrographolide, new andrographolide and deoxyandrographolide showed an upward trend, while deoxyandrographolide showed a downward trend. Treatment with 100 mmol·L~(-1) NaCl+5 mg·L~(-1) SA showed a significant increase in antioxidant enzyme activity in A. paniculata leaves. Treatment with 100 mmol·L~(-1) NaCl+10 mg·L~(-1) SA showed significant changes in soluble protein and proline content in A. paniculata leaves, while MDA content in A. paniculata leaves significantly decreased. 10 mg·L~(-1) SA had the best effect on the growth of A. paniculata seedlings under salt stress. Under the treatment of 50 mmol·L~(-1) NaCl+10 mg·L~(-1) SA, fresh weight, dry weight and leaf dry weight of A. paniculata seedlings reached the highest level, which were 1.02, 1.09 and 1.11 times of those in the control group, respectively. The concentrations of NaCl and 10 mg·L~(-1) SA were significantly higher than those of the control group. Four key enzyme genes of A. paniculata diterpene lactone synthesis pathway were selected to explore the molecular mechanism of salicylic acid to alleviate salt stress. With the increase of salt stress, the relative expressions of HMGR, GGPS and ApCPS were up-regulated, indicating that salt stress may enhance the synthesis of A. paniculata diterpene lactone through MVA pathway. SA can effectively promote the growth and development of A. paniculata under salt stress, improve its osmotic regulation and antioxidant capacity, improve its salt tolerance, and alleviate the effects of salt stress on A. paniculata.

Safety of the Xuesaitong injection in China: results from a large-scale multicentre post-marketing surveillance study in a real-world setting.

OBJECTIVE: The safety profile of traditional Chinese medicine injections has emerged as the greatest challenge to their clinical application. The authors aimed to perform a post-marketing surveillance study in a real-world setting to evaluate the safety of the Xuesaitong (XST) injection in China. METHODS: This multi-centre, post-marketing, observational study enrolled patients who received XST injections in 42 centres in China between March 2015 and November 2017. Adverse drug reactions (ADRs) and adverse drug events (ADEs) were collected and evaluated in a post-marketing database. Logistic regression analysis was performed to analyse the risk factors for ADRs. RESULTS: A total of 30,008 consecutive patients with a mean age of 62.29 ± 14.58 years were included in this post-marketing study. The incidences of ADEs and ADRs were 0.5% and 0.33%, respectively. The most common clinical manifestations were damage to skin and appendages (47.66%). There were four new kinds of ADEs found in the present monitoring study. The majority of ADRs were type B (62.62%) and occurred within 24 h after XST injection treatment. No severe ADRs were reported in this analysis. Multivariate logistic regression analysis showed that the hospital level (OR = 0.607; 95% CI = 0.407-0.906; p = .0144), hypertension (OR = 1.979; 95% CI, 1.323-2.959; p = .0009) and solvent type (OR = 2.951; 95% CI, 1.608-5.417; p = .0005) were risk factors for ADR occurrence. CONCLUSION: XST injection is well tolerated and has a favourable safety profile for patients in a real-world setting. This post-marketing study provided further evidence of the safety of XST injections for clinical applications.

Inhibiting Matrix Metalloproteinase-2 Activation by Perturbing Protein-Protein Interactions Using a Cyclic Peptide.

We report on a cyclic peptide that inhibits matrix metalloproteinase-2 (MMP2) activation with a low-nM-level potency. This inhibitor specifically binds to the D570-A583 epitope on proMMP2 and interferes with the protein-protein interaction (PPI) between proMMP2 and tissue inhibitor of metalloproteinases-2 (TIMP2), thereby preventing the TIMP2-assisted proMMP2 activation process. We developed this cyclic peptide inhibitor through an epitope-targeted library screening process and validated its binding to proMMP2. Using a human melanoma cell line, we demonstrated the cyclic peptide's ability to modulate cellular MMP2 activities and inhibit cell migration. These results provide the first successful example of targeting the PPI between proMMP2 and TIMP2, confirming the feasibility of an MMP2 inhibition strategy that has been sought after for 2 decades.

YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4.

BACKGROUND: Newly identified lncRNA zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) is identified as an oncogenic gene. However, the role of ZFPM2-AS1 in small cell lung cancer (SCLC) is poorly comprehended. METHODS: The expression of genes in SCLC tissues and cells was measured by qRT-PCR. Colony formation, EdU, CCK-8, transwell and wound healing as well as in vivo assays revealed the function of ZFPM2-AS1 in SCLC. ChIP, luciferase reporter, RIP and RNA pull down assays demonstrated the binding relation among genes. RESULTS: ZFPM2-AS1 was significantly upregulated in SCLC tissues and cells. ZFPM2-AS1 deficiency attenuated SCLC cell proliferation, invasion and migration. In addition, ZFPM2-AS1 was transcriptionally activated by Yin Yang 1 (YY1) factor. Further, miR-3612 was confirmed as downstream miRNA of ZFPM2-AS1. Moreover, TNF receptor associated factor 4 (TRAF4) was the target gene of miR-3612 in SCLC. ZFPM2-AS1, miR-3612 and TRAF4 jointly constituted a competing endogenous RNA (ceRNA) network in SCLC. Finally, TRAF4 could countervail ZFPM2-AS1 downregulation-mediated function on SCLC cell proliferation and invasion in vitro and tumor growth in vivo. CONCLUSION: Our study elucidated the oncogenic effect of ZFPM2-AS1 in SCLC progression, indicating it may be a therapeutic target for SCLC.

[Literature research and discussion of Chinese medicinal properties of Morinda citrifolia].

Noni is a dry and mature fruit of Morinda citrifolia, which is widely distributed in the islands in the southern Pacific Ocean and the Indochina Peninsula in Asia. It is edible and has been used as a natural medicine for thousands of years. At present, Noni has been legally introduced into China, but there is no clear standard of traditional Chinese medicine properties and clinical application of traditional Chinese medicine, which greatly limits the application of compatibility with traditional Chinese medicine in China. This article appllied our pioneering modern research technology of new herbal medicine outside of China, theoretically studied the traditional Chinese medicine properties of Noni, and scientifically guided the reasonable compatibility and application of Noni with traditional Chinese medicine. The Web of Science and PubMed databases were selected to access the literatures on Noni. The retrieval time was August 1, 2018, with Noni or Morinda citrifolia as the search term. A total of 862 articles were retrieved. By reading the titles and abstracts of the articles, in addition to repetitive and irrelevant literature, 251 scientific research literatures with reasonable design and high credibility were selected, including 25 clinical trials, 94 pharmacological experiments, and 51 chemical composition literatures. Through analysis of scientific research literatures, led by clinical experiments, supported by pharmacological experiments, combined with the research progress of chemical components, the medicinal properties were studied under the guidance of traditional Chinese medicine theory. The Chinese medicine property of Noni is flat, with acid and sweet flavor.The channel tropisms of Noni included kidney, liver and spleen. The function of Noni included tonifying kindey and liver, strengthening tendon and bone, yiqi yangyin. The clinical application of Noni is used for liver and kidney deficiency, waist and knee weakness, weak muscles and bones; Qi and Yin deficiency, tiredness and thirst. Taken as fruit pulp or dry powder, the equivalent of dried product is 1-4 g. Noni is also distributed in Taiwan, Hainan in China. Hainan, Yunnan have been cultivated and introduced. Give Noni a clear Chinese medicine property, and lay a theoretical foundation for the compatibility of Noni with traditional Chinese medicine, which can enrich the Chinese medicine resources and promote the development of Chinese medicine.