Integrating transcriptomics and network pharmacology to reveal the mechanisms of total Rhizoma Coptidis alkaloids against nonalcoholic steatohepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) has emerged as a major cause of cirrhosis and hepatocellular carcinoma, posing a significant threat to public health. Rhizoma Coptidis, a traditional Chinese medicinal herb has been shown to have significant curative effects on liver diseases. Total Rhizoma Coptidis Alkaloids (TRCA) is a primarily alkaloid mixture extracted from Rhizoma Coptidis, and its constituents are widely accepted to have hepatoprotective effects. AIM OF THE STUDY: This work aimed to investigate the efficacy and potential mechanisms of TRCA in ameliorating NASH through both in vitro experiments and in vivo mouse models. MATERIALS AND METHODS: The study employed a mice model induced by a high-fat diet (HFD) to evaluate the effectiveness and pharmacological mechanisms of TRCA in alleviating NASH. Transcriptomic sequencing and network pharmacology were used to explore the possible targets and mechanisms of TRCA to ameliorate NASH. Further validation was performed in free fatty acid (FFA)-induced human hepatocytes (LO2) and human hepatocellular carcinoma cells (HepG2). RESULTS: TRCA effectively ameliorated the main features of NASH such as lipid accumulation, hepatitis and hepatic fibrosis in the liver tissue of mice induced by HFD, as well as improved glucose tolerance and insulin resistance in mice. Combined with transcriptomic and network pharmacological analyses, 68 core targets associated with the improvement of NASH by TRCA were obtained. According to the KEGG results, the core targets were significantly enriched in the PI3K-AKT signaling pathway whereas TRCA ameliorated the aberrant down-regulation of the PI3K-AKT signaling pathway induced by HFD. Furthermore, the five highest-ranked genes were obtained by PPI network analysis. Moreover, our findings suggest that TRCA may impede the progression of HFD-induced NASH by regulating the expression of PPARG, MMP9, ALB, CCL2, and EGFR. CONCLUSIONS: TRCA can ameliorate HFD-induced liver injury by modulating aberrant downregulation of the PI3K-AKT signaling pathway. Key proteins such as PPARG, MMP9, ALB, CCL2, and EGFR may be critical targets for TRCA to ameliorate NASH. This finding supports using Rhizoma Coptidis, a well-known herbal medicine, as a potential therapeutic agent for NASH.

Online semi-supervised learning for motor imagery EEG classification.

OBJECTIVE: Time-consuming data labeling in brain-computer interfaces (BCIs) raises many problems such as mental fatigue and is one key factor that hinders the real-world adoption of motor imagery (MI)-based BCIs. An alternative approach is to integrate readily available, as well as informative, unlabeled data online, whereas this approach is less investigated. APPROACH: We proposed an online semi-supervised learning scheme to improve the classification performance of MI-based BCI. This scheme uses regularized weighted online sequential extreme learning machine (RWOS-ELM) as the base classifier and updates its model parameters with incoming balanced data chunk-by-chunk. In the initial stage, we designed a technique that combines the synthetic minority oversampling with the edited nearest neighbor rule for data augmentation to construct more discriminative initial classifiers. When used online, the incoming chunk of data is first pseudo-labeled by RWOS-ELM as well as an auxiliary classifier, and then balanced again by the above-mentioned technique. Initial classifiers are further updated based on these class-balanced data. MAIN RESULTS: Offline experimental results on two publicly available MI datasets demonstrate the superiority of the proposed scheme over its counterparts. Further online experiments on six subjects show that their BCI performance gradually improved by learning from incoming unlabeled data. SIGNIFICANCE: Our proposed online semi-supervised learning scheme has higher computation and memory usage efficiency, which is promising for online MI-based BCIs, especially in the case of insufficient labeled training data.

Hydrophobic-action-driven removal of six organophosphorus pesticides from tea infusion by modified carbonized bacterial cellulose.

The abuse of organophosphorus pesticides (OPPs) in tea planting makes it easy to transfer from tea into its infusion, bringing potential health risks to consumers. Thus, it is essential to adopt reliable techniques to remove OPPs from tea infusion. In this study, three treatment methods were used to modify carbonized bacterial cellulose (CBC) to improve its adsorption performance. Among them, CBC treated by hydrazine hydrate (N-CBC) had the best adsorption effect, whose removal rate for dicrotophos is 13 times that of CBC. The in-depth study of adsorption mechanism proved that hydrophobic interaction dominated the adsorption of OPPs onto N-CBC. The pseudo-second-order kinetic model and Langmuir isotherm model were more suitable to describe the process. Additionally, there were no significant changes in tea infusion quality after N-CBC treatment. This work clarifies that N-CBC benefitted from simple preparation method, excellent adsorption performance and unique adsorption mechanism has potential applications in tea infusion.

Supplementation of graded levels of rumen-protected choline to a pelleted total mixed ration did not improve the growth and slaughter performance of fattening lambs.

Choline is an essential nutrient in ruminant diets, which contributes to the fundamental biological functions of the animal. However, choline is easily degraded in the rumen before it can be absorbed. Rumen-protected choline (RPC) supplementation might support the fast growth of ruminants. This study aimed to investigate the effects of supplementing graded levels of RPC in a pelleted total mixed ration for fattening lambs. Sixty three-month-old male Small Tail Han and northeast fine wool sheep hybrid lambs with a liveweight of 15.3 ± 1.8 kg (mean ± SD) were fed designated diets and randomly assigned into five treatment groups (n = 12 per group). The five treatments were the rate of RPC supplementation at 0, 1.25, 2.50, 3.75, and 5.00 g (equivalent to 0, 0.31, 0.63, 0.94, and 1.25 g of choline chloride, respectively)/kg basal diet and the RPC-supplemented feed was offered for 112 days after 12 days of adaptation. Average daily gain, dry matter intake, and nutrient digestibility were similar across treatments. The rumen pH was quadratically significant among treatments, with the lowest and highest pH observed from the 2.5 and 5 g/kg RPC supplement groups, respectively (P = 0.02). After feeding, the ruminal ammonia concentrations among treatments were different (P < 0.05), with the highest value observed from the 5 g/kg RPC supplement group. Microbial crude protein level was different, with the highest value recorded from the 0 g/kg RPC supplement group (P = 0.028). A linear effect (P < 0.05) was observed from short-chain fatty acid values among treatments before and after feeding. Serum albumin (P = 0.003) and albumin/globulin ratio (P = 0.002) had a quadratic effect, with the highest value found in the 0 g/kg RPC supplement group. Abdominal fat was higher in RPC-supplemented groups (P < 0.05) compared to the control group. Drip loss was 65% higher in RPC-supplemented groups compared to the control group (P = 0.012). Overall, the study results showed an effect of RPC on ruminal parameters, but the supplementation of low-level RPC did not improve the growth and slaughter performance of fattening lambs.

Phosphorus dendron nanomicelles as a platform for combination anti-inflammatory and antioxidative therapy of acute lung injury.

Rationale: Development of novel nanomedicines to inhibit pro-inflammatory cytokine expression and reactive oxygen species (ROS) generation for anti-inflammatory therapy of acute lung injury (ALI) remains challenging. Here, we present a new nanomedicine platform based on tyramine-bearing two dimethylphosphonate sodium salt (TBP)-modified amphiphilic phosphorus dendron (C11G3) nanomicelles encapsulated with antioxidant drug curcumin (Cur). Methods: C11G3-TBP dendrons were synthesized via divergent synthesis and self-assembled to generate nanomicelles in a water environment to load hydrophobic drug Cur. The created C11G3-TBP@Cur nanomicelles were well characterized and systematically examined in their cytotoxicity, cellular uptake, intracellular ROS elimination, pro-inflammatory cytokine inhibition and alveolar macrophages M2 type repolarization in vitro, and evaluated to assay their anti-inflammatory and antioxidative therapy effects of ALI mice model through pro-inflammatory cytokine expression level in bronchoalveolar lavage fluid and lung tissue, histological analysis and micro-CT imaging detection of lung tissue injury in vivo. Results: The nanomicelles with rigid phosphorous dendron structure enable high-capacity and stable Cur loading. Very strikingly, the drug-free C11G3-TBP micelles exhibit excellent cytocompatibility and intrinsic anti-inflammatory activity through inhibition of nuclear transcription factor-kappa B, thus causing repolarization of alveolar macrophages from M1 type to anti-inflammatory M2 type. Taken together with the strong ROS scavenging property of the encapsulated Cur, the developed nanomicelles enable effective therapy of inflammatory alveolar macrophages in vitro and an ALI mouse model in vivo after atomization administration. Conclusion: The created phosphorus dendron nanomicelles can be developed as a general nanomedicine platform for combination anti-inflammatory and antioxidative therapy of inflammatory diseases.

Quickly and efficiently remove multiple pesticides in tea infusions by low-cost carbonized bacterial cellulose.

Soaking tea leaves make tea consumers exposure to pesticide residues more easily. However, there are few studies on the removal of pesticides in tea infusions. Therefore, a low-cost carbonized bacterial cellulose material was prepared by direct calcination method, and used to remove multiple pesticides in tea infusions quickly and efficiently. CBC-350 has the best removal efficiency for 9 pesticides and then screened the best adsorption conditions. The adsorption isotherm experiment was carried out and indicated that the adsorption process was in consist with the Freundlich model. The thermodynamic parameters are also calculated. Moreover, the adsorption mechanism was discussed, which suggests that π-π interaction and hydrophobic action are the driving force during the adsorption process. Exhilaratingly, the CBC-350 also has excellent adsorption capacity compared to other adsorbents and can be reused at least five times.

Polysaccharide extracted from Taraxacum platycarpum root exerts immunomodulatory activity via MAPK and NF-κB pathways in RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum platycarpum Dahlst. (Korean dandelion) is a medicinal herb used in traditional medicine in Korea to treat various disease such as furuncles, mammitis, hepatitis, jaundice. Moreover, a decoction prepared from T. platycarpum leaves and stems is an effective treatment for cancer, glycosuria, liver disease, pleurodynia, and stomach problems. AIM OF THE STUDY: The main objective of this work was to study the composition and structural properties of polysaccharides (TPP) from Taraxacum platycarpum Dahlst. root and investigate the immunostimulatory activity on RAW264.7 cells. MATERIALS AND METHODS: TPP was extracted from T. platycarpum using hot water extraction, ethanol precipitation method and its fractionated using DEAE-Sepharose fast flow column. The composition, molecular weight, and structural characterization of TPP and its fractions were evaluated by various techniques. Further, the immunostimulatory activity of polysaccharides was tested on murine macrophage cell line RAW264.7 by various in vitro assays. The structure effect of TPP on RAW264.7 cells was studied by the removal of sulfate (desulfation) and protein (deproteinization) contents from TPP. RESULTS: We obtained three fractions namely TPP-1, TPP-2, and TPP-3 which mainly consisted of carbohydrates (75.55, 52.71, and 48.41%), sulfate (8.42, 15.19, and 27.67%), uronic acid (1.27, 6.56, and 4.39%), and protein (8.15, 24.85, and 9.73%). The average molecular weight of the fractions was 56.7, 108.2, and 132.3 × 103 g/mol, respectively. The polysaccharides activate the RAW264.7 cell to produce a significant amount of NO and upregulate the various mRNA expression by the activation of MAPK and NF-κB pathways via TLR4, TLR2, and CR3 receptors. The structurally modified deproteinated derivative (DP-TPP-2) more effectively decreases the NO production which means the protein content of TPP-2 mainly contributes to the RAW264.7 cells activation. The structure of DP-TPP-2 primarily consists of 1 â†’ 2)-Galp, 1 â†’ 6)-Glup, 1 â†’ 2) - Rhap, and 1 â†’ 5) - Arap glycosidic linkages. CONCLUSIONS: The present study demonstrated that the polysaccharide isolated from T. platycarpum shows admirable immunostimulatory by the activation of MAPK and NF-κB pathways through TLR4, TLR2, and CR3 receptors. The protein content of polysaccharides mainly contributes to the RAW264.7 cells activation. Our study results could be useful for developing a new immunostimulant agent.

The effectiveness of acupuncture and moxibustion for treating tenosynovitis: A systematic review and meta-analysis protocol.

BACKGROUND: De Quervain's tenosynovitis is an overuse disease that involves a thickening of the abductor pollicis longus and extensor pollicis brevis tendons. Evidence shows that acupuncture and moxibustion (AM) could remarkably relieve the pain of De Quervain's tenosynovitis patients. The aim of this protocol is to determine the efficacy and safety of AM for treating De Quervain's tenosynovitis. METHODS: Several online databases including PubMed, Cochrane Library, Embase, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, WangFang Database, Chinese Scientific Journal Database will be searched from their establishment to July 1, 2020. We will include all randomized controlled trials using AM as the method for treating De Quervain's tenosynovitis, regardless of blinding or publication types. The selection of studies, data extraction and the assessment of the studies quality will be conducted by 2 reviewers separately. When there is sufficient available data for meta-analysis, we will use the RevMan V.5.3 statistical software for data synthesis. The total effective rate, range of motion of wrist ulnar deviation will be the primary outcomes, and the secondary outcomes contain Visual Analog Scale, Coney Wrist Score and side effects. We will express the result by using Risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data. RESULTS: The results of this study be presented in corresponding journal or conferences. CONCLUSIONS: This study is designed to provide sufficient evidence to assess the exact effectiveness of AM on De Quervain's tenosynovitis. PROSPERO REGISTRATION NUMBER: CRD42020158764.

Inducing inflammatory response in RAW264.7 and NK-92 cells by an arabinogalactan isolated from Ferula gummosa via NF-κB and MAPK signaling pathways.

The polysaccharide isolated from F. gummosa (FGP) was found homogenous with a weight average molecular weight (Mw) of 50.0 × 103 g/mol and radius of gyration (Rg) of 105.3 nm. The FGP was an arabinogalactan with a backbone formed of →6)-ß-Galp-1→ residues having random branching points at C-3 extended with either ß-Galp-(1→3)-ß-Galp-(1→ or α-Araf-(1→ side chain residues. FGP exhibited proliferative effect on RAW264.7 cells and induced macrophages to exert proinflammatory response releasing NO and up-regulating the transcription of cytokines including TNF-α, IL-1ß, IL-6 and IL-12. The FGP induced NK-92 cells to up-regulate the expressions of TNF-α, IFN-γ, granzyme-B, perforin, NKG2D and FasL. The presence of p-NF- κB, p-ERK, p-JNK and p-p38 in RAW264.7 and NK-92 cells indicated their activation through NF-κB and MAPKs signaling pathways. These findings suggested that polysaccharides from F. gummosa are potent in boosting immune system and thus may be considered for further studies of biomedical applications.

Ensemble classifier based on optimized extreme learning machine for motor imagery classification.

OBJECTIVE: Designing an effective classifier with high classification accuracy and strong generalization capability is essential for brain-computer interface (BCI) research. In this study, an extreme learning machine (ELM) based method is proposed to improve the classification accuracy of motor imagery electroencephalogram (EEG). APPROACH: The proposed method constructs an ensemble classifier based on optimized ELMs. Particle swarm optimization is used to simultaneously optimize the input weights and hidden biases of ELM to avoid the randomness and instability of classification result when ELM uses randomly generated parameters, and majority voting strategy is used to fuse the classification results of multiple base classifiers to avoid the negative impact of ELM with local optimal parameters on classification result. The proposed method was compared with four competing methods in experiments based on two public EEG datasets and some existing methods reported in the literature using the same datasets as well. MAIN RESULTS: The results indicate that the proposed method achieved significant higher classification accuracies than those of the competing methods on both two-class and four-class motor imagery data. Moreover, compared to the existing methods, it still obtained superior average accuracies of two-class classification and performed better for the subjects with relatively poor accuracies on both two-class and four-class classifications. SIGNIFICANCE: The significant accuracy improvement demonstrates the superiority of the proposed method. It can be a promising candidate for accurate classification of motor imagery EEG in BCI systems.

A higher efficiency removal of neonicotinoid insecticides by modified cellulose-based complex particle.

Cellulose as an eco-friendly material is extensive in the nature. In this study, modified cellulose-based complex particle (MCCP) was produced through hydrothermal carbonization with methacrylic acid in the stirring and sand bath circumstance. The activated modified carbon-based porous particle (AMCCP) was prepared by treating with potassium hydroxide at high temperature, showing higher efficiency in removing neonicotinoids than MCCP. The AMCCP was fully characterized via scanning electron microscopy, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller analysis. The Brunauer-Emmett-Teller analysis showed the prepared AMCCP has smaller aggregated particles with higher surface area than MCCP. The adsorption kinetic and the adsorption isotherm of AMCCP were studied, revealing that the pseudo-second-order kinetic model and the Langmuir model correlated with the experimental data better. The maximum adsorption capacity of AMCCP is 142.36 mg/g for acetamiprid. The adsorption process is spontaneous, favorable, and endothermic in nature. After five regeneration time, the adsorption efficiency of the AMCCP is still over 95%.

Protective effect of Shouwu Yizhi decoction against vascular dementia by promoting angiogenesis.

Shouwu is a traditional Chinese medicine (TCM) with neuroprotective effect. Shouwu Yizhi decoction (SYD) was designed based on TCM theory. However, little is known about the roles of SYD in Vascular dementia (VaD). The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion (I/R) rat model to induce VaD. SYD administration (54 mg·kg-1) for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion (MCAO) rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test. Moreover, SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats, thereby alleviating VaD. Mechanistically, SYD caused increases in the expression of vascular endothelial growth factor (VEGF), CD34 and CD31, compared with the MCAO rats in coronal hippocampus. Simultaneously, the expression level of miR-210 was elevated significantly after SYD administration, compared with the vehicle rats (P < 0.01). The expression of Notch 4 at both mRNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats (P < 0.05). Overall, the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced miR210 expression to activate Notch pathway, and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats, ultimately enhancing the cognition and memory of MCAO rats. Therefore, our findings preliminarily identified the effect and the mechanism of action for SYD on VaD in rats. SYD could be a potential candidate in treatment of VaD.

Peri-operative use of sorafenib in liver transplantation: a time-to-event meta-analysis.

AIM: To evaluate whether the application of sorafenib during the peri-operative period of liver transplantation improves prognosis in liver cancer patients. METHODS: We searched PubMed, EMBASE and MEDLINE for eligible articles. A total of 4 studies were found that fulfilled the previously agreed-upon standards. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. RESULTS: Out of the 104 studies identified in the database, 82 were not clinical experiments, and 18 did not fit the inclusion standards. Among the remaining 4 articles, only 1 was related to the preoperative use of sorafenib, whereas the other 3 were related to its postoperative use. As the heterogeneity among the 4 studies was high, with an I(2) of 86%, a randomized effect model was applied to pool the data. The application of sorafenib before liver transplantation had a hazard ratio (HR) of 3.29 with a 95% confidence interval (CI) of 0.33-32.56. The use of sorafenib after liver transplantation had an HR of 1.44 (95%CI: 0.27-7.71). The overall pooled HR was 1.68 (95%CI: 0.41-6.91). CONCLUSION: The results showed that the use of sorafenib during the peri-operative period of liver transplantation did not improve patient survival significantly. In fact, sorafenib could even lead to a worse prognosis, as its use may increase the hazard of poor survival.

Two new rhamnopyranosides of neolignans from Sanguisorba officinalis.

Two new rhamnopyranosides of neolignans, (7S,8R)-4,9,5',9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan-7-O-α-l-rhamnopyranoside (1) and (7S,8R)-4,9,9'-trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-7-O-α-l-rhamnopyranoside (2), together with a known compound (7S,8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (3), were isolated from the 80% EtOH extract of the roots of Sanguisorba officinalis. Their structures were characterized by spectroscopic analysis including 1D NMR, 2D NMR, and HR-ESI-MS, and chemical method.

Experimental study on the effect of Kang-Lai-Te induced apoptosis of human hepatoma carcinoma cell HepG2.

BACKGROUND: Kang-Lai-Te (KLT) is extracted from the traditional Chinese herbal medicine Semen Coicis, which has been used in China as an effective clinical drug for over a thousand years. It contains numerous ingredients with anti-tumor effects. In our previous studies on transplanted hepatomas in rats, KLT could stop the cells in the G2+M stage of cell cycle and then reduce the number of cells entering the stage G0 and G1, but the mechanism of the anti-proliferative effect was unknown. In this experiment, we examined whether KLT inhibits HepG2 cell growth, if so, tried to explore its mechanism. METHODS: KLT at different concentrations was used for the treatment of hepatocellular carcinoma cells in vitro, respectively. The proliferation inhibitory rate was evaluated by MTT assay, induction of cell apoptosis rate and the protein levels of Fas and Fas ligand (FasL) were determined by flow cytometry (FCM), and the expression of Fas and FasL mRNA was detected by real-time fluorescent quantitative RT-PCR. RESULTS: KLT produced an obvious time and dose-dependent inhibitory effect on HepG2 cells, and marked apoptosis was detected by FCM. The protein of Fas increased by 11.01%, 18.71%, 28.71% and 37.15%; the protein of FasL increased by 1.49%, 1.91%, 3.27% and 3.38% in comparison with the control (P<0.05). Real-time fluorescent quantitative RT-PCR showed that treating HepG2 cells with KLT caused the upregulation of Fas and FasL mRNA. CONCLUSION: KLT inhibits HepG2 growth by inducing apoptosis, which may be mediated through activation of the Fas/FasL pathway.

Chinese herb related molecules of cancer-cell-apoptosis: a minireview of progress between Kanglaite injection and related genes.

Many kinds of Chinese herb had been confirmed to have the character of anti-tumor, clinical reports about anti-tumor effects of Chinese herb had also been found in recent years, but most of the reports were focused on the clinical treatment of effectiveness for Chinese herb, on the other hand, review about Chinese herbal related with molecules on cancer-cell-apoptosis was seldom, many scientists could not believe such kinds of clinical describes about anti-tumor effects for Chinese herb, because these describes were lack of molecular biology evidence. Kanglaite(KLT) injection is an anti-tumor new drug which extracts from Chinese medicine-coix seed with modern advanced pharmaceutical technology, it is also a new biphase extended-spectrum anticancer medicine, the food and drug administration(FDA) of United States also approved a phase II trial of KLT to test its efficacy in treating non-small-cell lung cancer. Some studies show it could inhibit some anti-apoptotic gene and activate some pro-apoptotic gene, its injection solution is one of the new anticancer medicine that can significantly inhibit a various kinds of tumor cells, so it has become the core of research that how to further explore KLT injection to promote tumor cell apoptosis by impacting on related genes. In this review, the relationship between KLT and some tumor cell apoptosis molecules had been discussed and reviewed generally.

[The effects of twenty-one traditional Chinese medicines on tyrosinase].

OBJECTIVE: To study the effects of 21 kinds of traditional Chinese medicines on tyrosinase. METHODS: The catalytic reactive velocity of tyrosinase was determined by vision spectrophotometry so as to evaluate the upregulation of traditional Chinese medicines extracts. RESULTS: 21 time-curves of catalytic reaction of tyrosinase were obtained. CONCLUSION: 13 kinds of traditional Chinese medicines extracts in vitro showed a upregulation to tyrosinase activity (P < 0.01). Scutellaria baicalensis and Cremastra appendiculata showed a better upregulation to tyrosinase activity.