Mitochondrial folate pathway regulates myofibroblast differentiation and silica-induced pulmonary fibrosis.

BACKGROUND: Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment. METHODS: The experiments were conducted in TGF-ß treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo. RESULTS: By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-ß stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice. CONCLUSION: Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.

Study on the preparation and luminescence properties of SrGe4 O9 :Mn4+ red phosphors for plant illumination.

In this study, SrGe4 O9 :Mn4+ red phosphors for plant illumination were prepared using a high-temperature solid-phase method. The samples were characterized and analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), fluorescence spectroscopy, and other techniques. The phase structure, apparent morphology, and luminescence properties of the SrGe4 O9 :Mn4+ red phosphors were investigated. The results indicated that the dopant Mn4+ was incorporated into the matrix structure by substituting some Ge4+ ions without any changes in the crystal structure of the SrGe4 O9 matrix. The samples comprised micron-scale particles and exhibited high purity and uniform distribution of elements. The SrGe4 O9 :Mn4+ phosphors exhibited relatively strong red light emission at 660 nm under the excitation of a 430-nm blue light, and the luminescence intensity was the highest when the Mn4+ doping amount was 1%. Proper doping of Ti4+ or Sn4+ could effectively improve the luminescence intensity of the SrGe4 O9 :Mn4+ phosphors. The light-emitting diode (LED) device packaging showed that the SrGe4 O9 :Mn4+ red phosphors could be used for plant growth illumination.

Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment / 中国中药杂志

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

Correlation between lactate dehydrogenase and QTc interval prolongation in maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: Corrected QT (QTc) interval prolongation is one of the common causes of sudden cardiac death in patients with maintenance hemodialysis (MHD) patients. However, there are few studies on QTc prolongation in MHD patients. The concentration of lactate dehydrogenase (LDH) in hemodialysis population increased, and LDH was associated with the mortality of MHD patients. This study aimed to investigate the relationship between QTc interval prolongation and LDH in MHD patients. METHODS: This is a cross-sectional observational study. Patients who underwent MHD for more than 3 months in the Second Affiliated Hospital of Nantong University from November 2012 to November 2019 with complete data were selected as the research subjects. The patients were divided into the normal QTc interval group and the QTc interval prolongation group. The general data of patients and clinical laboratory indicators were collected retrospectively from the electronic medical record system. Pearson correlation analysis and binary logistic regression were used to analyze the correlation between LDH and QTc interval prolongation; the cut-off value of LDH predicting QTc interval prolongation was calculated by receiver operating characteristic (ROC) curve. RESULTS: The LDH level in the prolonged QTc interval group was significantly higher than that in the normal group (301.96±110.91 vs. 215.39±67.65, t=-8.03, P<0.001). QTc interval and LDH (r=0.386) were positively correlated. Binary logistic regression analysis showed that LDH, serum potassium <4 mmol/L, serum phosphorus, and left ventricular end-diastolic diameter (LVDd) were independent related factors for QTc interval prolongation. The ROC curve results showed that LDH =220 U/L was the best cutoff point for predicting QTc interval prolongation in MHD patients, with a sensitivity of 81.45% and a specificity of 59.35%. Binary logistic regression analysis showed that the LDH >220 U/L group was 6.34 times more likely to have QTc interval prolongation than the LDH ≤220 U/L group (OR 6.34, 95% CI: 3.47-11.58, P<0.001). CONCLUSIONS: LDH in MHD patients is closely related to QTc interval prolongation. Serum LDH, ionic calcium, serum phosphorus and potassium may predict QTc interval prolongation. Monitoring related indicators can remind clinicians to intervene as soon as possible to reduce the potential risk of arrhythmia and sudden cardiac death (SCD).

[Clinical efficacy of Longjintonglin Capsules on chronic prostatitis with damp-heat stasis syndrome Re-evaluation based on multicenter real-world study].

OBJECTIVE: To re-evaluate the clinical efficacy of Longjintonglin Capsules (LJTL) in the treatment of chronic prostatitis with damp-heat stasis syndrome. METHODS: This multicenter real-world study included 1 352 cases of chronic prostatitis with damp-heat and stagnation syndrome treated with LJTL (3 capsules once, tid, 30 minutes after meals, for 2 four-week courses) in addition to routine treatment. Before and after treatment, we analyzed the NIH-CPSI scores, the scores of Chinese medicine symptom quantitative classification and changes in individual symptom scores, and observed adverse reactions to medication. RESULTS: The total effectiveness rate of LJTL was 93.64%. Compared with the baseline, the NIH-CPSI scores were significantly decreased after treatment (ï¼»24.27 ± 6.04ï¼½ vs ï¼»8.17 ± 4.21ï¼½, P < 0.05), and so were the scores on the pain symptoms (ï¼»9.63 ± 3.65ï¼½ vs ï¼»3.02 ± 2.23ï¼½, P < 0.05), voiding symptoms (ï¼»5.65 ± 2.15ï¼½ vs ï¼»1.62 ± 1.36) and quality of life (ï¼»8.96 ± 2.32ï¼½ vs ï¼»3.16 ± 1.89ï¼½, P < 0.05). The effectiveness rate of LJTL was 95.9% on the Chinese medicine symptom frequent urination, 90.4% on painful urination, and 91.4% scanty dark urine, with a total effectiveness rate of 82.4% － 95.9%, all with statistically significant difference in comparison with the baseline (P < 0.05). CONCLUSION: Longjintonglin Capsules combined with routine treatment can significantly improve the clinical symptoms of chronic prostatitis with damp-heat stasis syndrome, especially effective on the symptoms of frequent urination, painful urination and scanty dark urine. Besides, it recommendable for its antidepressant and antianxiety effects, and the effect of improving the quality of life of the chronic prostatitis patients with damp-heat stasis.

Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes.

BACKGROUND: A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PURPOSE: This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. METHODS: Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aß production pathway and tau phosphorylation kinase cascade were examined in these two models. RESULTS: Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.

Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting GSK3ß signaling pathway.

Podocyte injury following abnormal podocyte autophagy plays an indispensable role in diabetic nephropathy (DN), therefore, restoration of podocyte autophagy is considered as a feasible strategy for the treatment of DN. Here, we investigated the preventive effects of sarsasapogenin (Sar), the main active ingredient in Anemarrhena asphodeloides Bunge, on the podocyte injury in diabetic rats, and tried to illustrate the mechanisms underlying the effects in high glucose (HG, 40 mM)-treated podocytes (MPs). Diabetes model was established in rats with single streptozocin (60 mg· kg-1) intraperitoneal administration. The rats were then treated with Sar (20, 60 mg· kg-1· d-1, i.g.) or a positive control drug insulin (INS) (40 U· kg-1· d-1, i.h.) for 10 weeks. Our results showed that both Sar and insulin precluded the decreases of autophagy-related proteins (ATG5, Beclin1 and LC3B) and podocyte marker proteins (podocin, nephrin and synaptopodin) in the diabetic kidney. Furthermore, network pharmacology was utilized to assess GSK3ß as the potential target involved in the action of Sar on DN and were substantiated by significant changes of GSK3ß signaling in the diabetic kidney. The underlying protection mechanisms of Sar were explored in HG-treated MPs. Sar (20, 40 µM) or insulin (50 mU/L) significantly increased the expression of autophagy- related proteins and podocyte marker proteins in HG-treated MPs. Furthermore, Sar or insulin treatment efficiently regulatedphosphorylation at activation and inhibition sites of GSK3ß. To sum up, this study certifies that Sar meliorates experimental DN through targeting GSK3ß signaling pathway and restoring podocyte autophagy.

Sarsasapogenin ameliorates diabetes-associated memory impairment and neuroinflammation through down-regulation of PAR-1 receptor.

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.

High-continuity genome assembly of the jellyfish Chrysaora quinquecirrha.

The Atlantic sea nettle ( Chrysaora quinquecirrha) has an important evolutionary position due to its high ecological value. However, due to limited sequencing technologies and complex jellyfish genomic sequences, the current C. quinquecirrha genome assembly is highly fragmented. Here, we used the most advanced high-throughput chromosome conformation capture (Hi-C) technology to obtain high-coverage sequencing data of the C. quinquecirrha genome. We then anchored these data to the previously published contig-level assembly to improve the genome. Finally, a high-continuity genome sequence of C. quinquecirrha was successfully assembled, which contained 1 882 scaffolds with a N50 length of 3.83 Mb. The N50 length of the genome assembly was 5.23 times longer than the previously released one, and additional analysis revealed that it had a high degree of genomic continuity and accuracy. Acquisition of the high-continuity genome sequence of C. quinquecirrha not only provides a basis for the study of jellyfish evolution through comparative genomics but also provides an important resource for studies on jellyfish growth and development.

Meta-analysis of Oral Chinese Medicine for Adjuvant Treatment of Primary Hepatic Carcinoma and Screening of Basic Chinese Herbs / 中国实验方剂学杂志

Objective:To systematically evaluate the efficacy of oral Chinese herbal prescriptions combined with transcatheter arterial chemoembolization （TACE） against primary hepatic carcinoma （PHC） and screen the basic Chinese herbs，in order to provide certain reference for clinical medication. Method:The randomized controlled trials concerning the treatment of PHC with oral Chinese herbal prescriptions plus TACE were retrieved from CBM，China National Knowledge Infrastructure （CNKI），Chongqing Weipu Database for Chinese Technical Periodicals （VIP），and Wanfang Data Knowledge Service Platform.The quality of the included trials was evaluated by Cochrane handbook，and the Meta-analysis was performed using RevMan 5.3.The enumeration data were expressed by odds ratio （OR），the measurement data by mean difference （MD） or standardized mean difference （SMD），and the effect size by 95% confidence interval （CI）.The data of oral Chinese herbal prescriptions involved in trials were sorted out and subjected to association rule analysis and frequency analysis based on the Traditional Chinese Medicine Inheritance Support System （TCMISS），for exploring the basic Chinese herbs and their dosages against PHC. Result:A total of 75 randomized controlled trials were included，involving 7 406 cases. As revealed by the Meta-analysis，oral Chinese herbal prescriptions combined with TACE was significantly better than TACE alone in improving the short-term curative effect ［OR=2.05，95%CI（1.83，2.29）］，decreasing alpha fetoprotein （AFP） ［MD=-59.02，95%CI（-79.03，-39.01）］，ameliorating liver function ［SMD=-1.23，95%CI（-1.58，-0.88）］，boosting immunity ［SMD=1.08，95%CI（0.84，1.32）］，adjusting Karnofsky Performance Status （KPS） scale score ［OR=2.7，95%CI（1.11，11.02）］，elevating survival rate ［OR=2.31，95%CI（1.96，2.71）］，and reducing adverse reactions ［OR=0.38，95%CI（0.34，0.43）］.Data mining results showed that the basic Chinese herbs against PHC were Bupleuri Radix，Paeoniae Alba Radix，Atractylodis Macrocephalae Rhizoma，Poria，and Glycyrrhizae Radix et Rhizoma，with their clinical dosages listed as follows：6-15 g for Bupleuri Radix，10-15 g for Paeoniae Alba Radix，9-15 g for Atractylodis Macrocephalae Rhizoma，10-15 g for Poria，and 3-10 g for Glycyrrhizae Radix et Rhizoma. Conclusion:The oral Chinese herbal prescriptions combined with TACE produce better effects in treatment of PHC as compared with TACE alone.These five basic Chinese herbs have anti-cancer effect，and their dosages are within the ranges stipulated in 2020 edition of <italic>Chinese Pharmacopoeia.</italic>This Meta-analysis has provided certain reference for clinical medication.

Application of an extreme learning machine network with particle swarm optimization in syndrome classification of primary liver cancer / 中西医结合学报

OBJECTIVE@#By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes.@*METHODS@#From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used "TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information" as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models.@*RESULTS@#The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%.@*CONCLUSION@#Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

Application and progress of data mining in study of compatibility law of traditional Chinese medicine / 中国中药杂志

Data mining is an important method to obtain the key information from a large amount of data, and it is widely applied in the research on the modernization of traditional Chinese medicine(TCM). The compatibility law of herbs is a key issue in the research of TCM prescriptions. This reflects the flexibility and effectiveness of TCM prescriptions, and it is also a crucial link to the development of TCM modernization. Therefore, it is the core purpose of the research on TCM prescriptions to find the compatibility law of herbs and clarify the scientific connotation. Data mining, as an effective method and an important approach, has formed a standardized system in the research of compatibility law of herbs, which can reveal the relationship between different Chinese herbs and summarize the internal rules in compatibility. Two hundred and twenty two effective papers were sorted out and categorized in this article. The results showed that data mining was mainly applied in finding the core Chinese herb pairs, summarizing the utility and attributes of TCM prescriptions, revealing the relationship between prescriptions, Chinese herbs and syndromes, finding the optimal dose of Chinese herbs, and producing the new prescriptions. The problems of data mining in research of herbs compatibility rules were summarized, and its development and trend in current researches were discussed in this article to provide useful references for the in-depth study of data mining in the compatibility law of Chinese herbs.

Sarsasapogenin alleviates diabetic nephropathy through suppression of chronic inflammation by down-regulating PAR-1: In vivo and in vitro study.

BACKGROUND: Sarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known. PURPOSE: This study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN. METHODS: Streptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar. RESULTS: Sar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs. CONCLUSION: Sar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.

Efficacy and antiparasitic mechanism of 10-gingerol isolated from ginger Zingiber officinale against Ichthyophthirius multifiliis in grass carp.

Ichthyophthirius multifiliis is a ciliate parasite of freshwater fish with a global distribution and results in severe economic losses in aquaculture. The present study aimed to investigate the efficacy and antiparasitic mechanism of active compounds isolated from Zingiber officinale against I. multifiliis. Three compounds were isolated from the Z. officinale extract and identified as 10-gingerol, 6-dehydroshogaol, and 6-dehydro-10-gingerol. 10-gingerol demonstrated the greatest antiparasitic efficacy in vitro. 10-gingerol resulted in 100% mortalities of theronts, nonencysted tomonts, and encysted tomonts at concentrations of 2, 8, and 16 mg/L, respectively. 10-gingerol significantly reduced theronts infectivity (p < 0.05) at a concentration of 1 mg/L, and it was effective in treating infected grass carp and protecting naïve fish from I. multifiliis infestation at a concentration of 4 mg/L. The antiparasitic mechanism might be attributed to the increase of intracellular osmotic pressure, accumulation of free radicals, and membrane damage of I. multifiliis post 10-gingerol treatment. The study demonstrated that 10-gingerol had the potential as a therapeutic agent against I. multifiliis.

Effect of zinc substitution in hydroxyapatite coating on osteoblast and osteoclast differentiation under osteoblast/osteoclast co-culture.

Zinc is an essential trace element required for bone remodelling process, but its role in such process remains to be elucidated. In particular, inconsistent results have been reported on the effect of Zn on osteoclastic responses, and supplement of receptor activator of nuclear factor kappa-B ligand (RANKL) factors has been commonly adopted. Co-culture is a suitable approach to elucidating the role of Zn in bone remodelling process, by better imitating the cellular environment as the presence of osteoblasts plays critical role in modulating osteoclastic functions. In this study, zinc-substituted HA coatings have been deposited using a liquid precursor plasma spraying process at two different concentrations (1, 2 wt.%). The effect of zinc substitution on osteoblastic and osteoclastic differentiation has been studied in vitro. In particular, a cultivation regime was designed to first induce osteoblastic differentiation of rat bone marrow stromal cells (BMSCs) for 14 days, and then induce osteoclastic differentiation of osteoclast-like precursor RAW 264.7 cells through the aid of the osteoblasts formed for additional 14 days, in the absence of the external addition of RANKL. The results showed that Zn substitution moderately promoted the BMSC differentiation into the osteoblasts and reduced the osteoclastic activity in early time (1 day co-culture). However, promotion of the osteoclastic activity were observed at later stages, as indicated by the significantly enhanced expressions of trap5b and IL-1 (8- and 15-day co-culture) and moderate stimulation of the nucleus integration and formation of the multinucleated cells (14-day co-culture). Such stimulating effect of the osteoclastic activity was absent under mono-culture of RAW 264.7 cell, with simple RANKL supplementation. The results suggest that both the zinc and the presence of MSC/osteoblast play profound and highly interacted roles on osteoclast differentiation and activity, which is critical in modulating the bone remodelling process.

Improving hygroscopicity of fermented Cordyceps powder based on particle design technology of traditional Chinese medicine / 中国中药杂志

Commonly used dosage forms of fermented Cordyceps powder products are capsules and tablets. The hygroscopicity of the powder,as one of the important parameters in the tableting process,has important effects on the tabletting process of the tablets. How to improve the hygroscopicity of powder is of great significance for the development of new composite particles. Therefore,particle design technology was used in this study to prepare composite particle powder,and its hygroscopicity was compared with fermented Cordyceps powder and physically mixed powder. By preparing three different types of powders,the equilibrium moisture absorption,particle size,scanning electron micrograph,angle of repose,contact angle and compression degree were compared to observe the effect of traditional Chinese medicine particle design technology on improving the hygroscopicity of the fermented Cordyceps powder. The results showed that the equilibrium moisture absorption was 21. 2%,19. 6%,14. 5% respectively for the fermented Cordyceps powder,physically mixed powder and composite particle powder; the median diameter was(49. 751± 0. 280),(59. 183± 0. 170),(12. 842±0. 080) μm,respectively; the mode diameter was(185. 479±1. 372),(173. 964± 1. 104),(61. 671± 0. 979) μm,respectively. In the scanning electron micrograph of the composite particle powder,it can be clearly seen that the fermented Cordyceps powder had hydrophobic gas phase nano-silica with a fixed shape and uniform size. The angle of repose was(50. 63 ± 0. 75) °,(49. 25 ± 0. 43) °,(48. 33±0. 84) ° respectively; the contact angle was(7. 4±0. 2) °,(8. 2±0. 3) °,(15. 0±2. 6) ° respectively; and the compression degree was(38. 2±1. 3) %,(35. 8±0. 2) %,(32. 5±2. 6) % respectively. This study showed that after treatment by the vibrating ultrafine pulverizer,the fermented Cordyceps powder particles had obvious and uniform small particle hydrophobic gas phase nano-silica adhered to form a partially wrapped coating structure,which reduced the contact surface of fermented Cordyceps powder with the outside world,thereby reducing the hygroscopicity of the composite particle powder. It further demonstrated that the hygroscopicity of fermented Cordyceps powder can be improved by particle design.

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats.

Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in albuminuria, kidney weight index, serum uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (fibronectin and collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in interleukin-18, NLRP3, and activated caspase 1 levels as well as advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate diabetic nephropathy in rats via inhibition of NLRP3 inflammasome activation and AGEs-RAGE interaction.

Sarsasapogenin suppresses Aß overproduction induced by high glucose in HT-22 cells.

The aim of this study is to investigate effects and potential mechanisms of sarsasapogenin (Sar), an active component purified from Rhizoma Anemarrhenae, on high glucose-induced amyloid-beta (Aß) peptide overproduction in HT-22 cells. HT-22 cells were divided into normal glucose; high glucose (HG); HG co-treated with low, middle, and high concentration of Sar (1, 5, 25 µmol/L); and peroxisome proliferator-activated receptor γ (PPARγ) agonist (10 µmol/L pioglitazone). After treatment for 24 h, protein expression of Aß and ß-site Aß precursor protein cleaving enzyme 1 (BACE1) and activated PPARγ level were determined by Western blot; Aß42 levels were also measured by using both immunofluorescence and ELISA methods. BACE1 activity and mRNA level were assessed by fluorospectrophotometry and quantitative PCR, respectively. Cell viability was assayed with a CCK-8 kit. Elevated Aß expression and Aß42 level were found in HG-treated HT-22 cells, accompanied by increased BACE1 protein and mRNA levels as well as enzymatic activity, which was markedly attenuated by three concentrations of Sar and pioglitazone. Moreover, HG reduced nuclear PPARγ levels, which was reversed by middle and high concentrations of Sar as well as pioglitazone. PPARγ antagonist GW9662 (20 µmol/L) pretreatment reversed the effect of Sar on BACE1 protein expression in HG-cultured HT-22 cells. Additionally, Sar suppressed HG-induced decreases in cell viability of HT-22 cells. High glucose can induce an increase in Aß levels and a decrease in cell viability in HT-22 cells, while co-treatment with Sar improves these results, which is mediated likely through activation of PPARγ and subsequent downregulation of BACE1.

Combined effects of Chinese medicine feed and ginger extract bath on co-infection of Ichthyophthirius multifiliis and Dactylogyrus ctenopharyngodonid in grass carp.

Dactylogyrus ctenopharyngodonid and Ichthyophthirius multifiliis are two important ectoparasites of freshwater fish. Co-infection by the two parasites leads to high fish mortality and results in heavy economic losses. This study aimed to evaluate the efficacy of medicated feed and a ginger extract bath against D. ctenopharyngodonid and I. multifiliis on grass carp and investigate the hematological response of grass carp co-infected by the two parasites. These results demonstrated that red blood cell (RBC) and thrombocyte percentage among leucocytes significantly decreased after grass carp were co-infected by D. ctenopharyngodonid and I. multifiliis. The monocyte and neutrophil percentages significantly increased with the increment of parasite mean intensities, while the lymphocyte percentage decreased. The activities of serum acid phosphatase (ACP), alkaline phosphatase (AKP), lysozyme (LZM), and superoxide dismutase (SOD) significantly increased after co-infection. When grass carp treated with medicated feed containing 4% of Astragalus membranaceus, Allium sativum, Morus alba, and Glycyrrhiza uralensis, the activities of ACP, AKP, LZM, and SOD were significantly enhanced, and the mean intensities of D. ctenopharyngodonid and I. multifiliis were significantly decreased. When grass carp was treated with medicated feed and a 4-mg/L ginger extract bath, all parasites were eliminated during 28 days. The bath of ginger extract at a concentration of 4 mg/L kept a low mean intensity of I. multifiliis and D. ctenopharyngodonid, then the two parasites were eliminated by oral administration of the medicated feed with an immunostimulant (Chinese medicine compound).