Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

[Research progress in chemical constituents, pharmacological effects, and clinical application of Curcuma wenyujin and prediction of its quality markers].

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.

Increased interbrain synchronization and neural efficiency of the frontal cortex to enhance human coordinative behavior: A combined hyper-tES and fNIRS study.

Coordination is crucial for individuals to achieve common goals; however, the causal relationship between coordination behavior and neural activity has not yet been explored. Interbrain synchronization (IBS) and neural efficiency in cortical areas associated with the mirror neuron system (MNS) are considered two potential brain mechanisms. In the present study, we attempted to clarify how the two mechanisms facilitate coordination using hypertranscranial electrical stimulation (hyper-tES). A total of 124 healthy young adults were randomly divided into three groups (the hyper-tACS, hyper-tDCS and sham groups) and underwent modulation of the right inferior frontal gyrus (IFG) during functional near-infrared spectroscopy (fNIRS). Increased IBS of the PFC or neural efficiency of the right IFG (related to the MNS) was accompanied by greater coordination behavior; IBS had longer-lasting effects on behavior. Our findings highlight the importance of IBS and neural efficiency of the frontal cortex for coordination and suggest potential interventions to improve coordination in different temporal windows.

Manual Therapy for a Chronic Non-Specific Low Back Pain Rat Model.

Chronic low back pain (CLBP) is a highly prevalent condition worldwide and a major cause of disability. The majority of patients with CLBP are diagnosed with chronic non-specific low back pain (CNLBP) due to an unknown pathological cause. Manual therapy (MT) is an integral aspect of traditional Chinese medicine and is recognized as Tuina in China. It involves techniques like bone-setting and muscle relaxation manipulation. Despite its clinical efficacy in treating CNLBP, the underlying mechanisms of MT remain unclear. In animal experiments aimed at investigating these mechanisms, one of the main challenges is achieving normative MT on CNLBP model rats. Improving the stability of finger strength is a key issue in MT. To address this technical limitation, a standardized procedure for MT on CNLBP model rats is presented in this study. This procedure significantly enhances the stability of MT with the hands and alleviates common problems associated with immobilizing rats during MT. The findings of this study are of reference value for future experimental investigations of MT.

The influence of residual pectin composition and content on nanocellulose films from ramie fibers: Micro-nano structure and physical properties.

In this study, cellulose nanofibril (CNF) films from ramie fibers were prepared with different pectin compositions and contents, and the influence of residual pectin on the overall performances of CNF films was evaluated. There was no significant effect of the residual pectin composition on the properties of obtained CNF films. However, when the content of residual pectin was increased from 0.45 % to 9.16 %, the surface area and water absorption of CNF films were increased from 0.2223 to 0.3300 m2/g, and from 93.51 % to 122.42 %, respectively. Pectin covers the CNF surface and act as a physical barrier between the cellulose fibrils; thus the nanocellulose films with high pectin content will have a loose and porous structure, resulting in a high surface area and a high water absorption. Besides, with the residual pectin content decreasing from 9.16 % to 0.45 %, the UVA light transmittance and tensile strength of CNF films were increased from 30.6 % to 59.9 %, and from 37.67 to 100.26 MPa, respectively. After removal of amorphous pectins in CNFs, the low pectin containing CNFs are able to pack more compactly to form a strong and thin film. This paper provides guidance for the preparation of CNF films with different performance requirements.

[Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing].

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Ecological risk assessment of potentially toxic elements in selenium-rich soil with different land-use types.

Dashan Village area is one of the representative areas in China with high selenium concentration in the natural environment. A total of 133 topsoil samples have been collected in the Dashan Village area to explore the potential toxic elements (PTEs) background concentrations in soils under different land-use types for a comprehensive PTEs risk assessment (arsenic, cadmium, chromium, copper, mercury, nickel, lead, selenium and zinc). The results show that the geometric mean concentrations of As, Cr, Cu, Hg, Ni, Pb, Se and Zn found in the soil of the Dashan Village area were lower than the control standard for soil contamination risk in agricultural land. However, the geometric mean concentrations of Cd exceeded their corresponding standard values. For different land-use types, geometric mean concentrations of As, Cd, Cu, Hg, Ni and Pb in the arable soils were higher than in woodland soils and tea garden soils. Based on the potential ecological risk assessment, the woodland, arable and tea garden were at low-risk levels. Cadmium posed the highest ecological risk, while the other PTEs were of low risk in soils. Multiple statistical analyses and geostatistical analysis indicated that the concentrations of Cr, Ni, Pb, Cu, Zn and Se originated mainly from natural sources, while the concentrations of Cd, As and Hg could be influenced by anthropogenic activities. These results provide scientific support for the safe utilization and ecological sustainability of selenium-rich land resources.

Structurally diverse glycosides with α-glucosidase inhibitory properties from water extract of the leaves of Cyclocarya paliurus.

In this work we investigated the chemical constituents of water extract of the leaves of Cyclocarya paliurus. Two new megastigmane glycosides (3 and 8), three aliphatic alcohol glycosides (9-11), and two aromatic glycosides (12 and 13), along with fourteen known compounds were isolated, and their in vitro inhibitory activity against α-glucosidase was evaluated. Compounds 13 and 15-18 displayed inhibitory activity with IC50 values varying from 27.05 to 96.58 µM, and the structure-activity relationship among isolated compounds was discussed.

Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing / 中国中药杂志

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Effects of residual pectin composition and content on the properties of cellulose nanofibrils from ramie fibers.

In this study, a series of pretreatment methods (pectin extraction) were employed to prepare cellulose nanofibrils (CNFs) with different pectin composition and contents from ramie fibers. The comprehensive effects of residual pectin on the final properties of CNFs were investigated. The residual pectin did not have a significant effect on the size distribution of the obtained CNFs. While the presence of pectin led to higher zeta potential value, improved dispersion stability and enhanced storage modulus of the CNF dispersion, with the sodium carbonate extraction method showing the greatest impact. The possible mechanism for enhanced dispersion stability of CNFs is the formation of self-assembled hierarchical pectin-hemicellulose/lignin-cellulose nanostructures, offering abundant electrostatic repulsion and steric hindrance between the nanoparticles. This work provides guidelines for the tailored production of CNFs to meet the requirements for different applications.

Association of Vitamin D Supplementation with Cardiovascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: low vitamin D status has been associated with an increased incidence of cardiovascular events. However, whether vitamin D supplementation would reduce the incidence of cardiovascular events remains unclear. PURPOSE: To perform a systematic review and meta-analysis of the effect of vitamin D supplementation on the mortality and incidence of cardiovascular events. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from their inception until 3 May 2022. STUDY SELECTION: Two authors searched for randomized clinical trials that reported vitamin D supplementation's effect on cardiovascular events outcomes. DATA EXTRACTION: Two authors conducted independent data extraction. DATA SYNTHESIS: We identified 41,809 reports; after exclusions, 18 trials with a total of 70,278 participants were eligible for analysis. Vitamin D supplementation was not associated with the mortality of cardiovascular events (RR 0.96, 95% CI 0.88-1.06, I2 = 0%), the incidence of stroke (RR 1.05, 95% CI 0.92-1.20, I2 = 0%), myocardial infarction (RR 0.97, 95% CI 0.87-1.09, I2 = 0%), total cardiovascular events (RR 0.97, 95% CI 0.91-1.04, I2 = 27%), or cerebrovascular events (RR 1.01, 95% CI 0.87-1.18, I2 = 0%). LIMITATION: Cardiovascular events were the secondary outcome in most trials and thus, might be selectively reported. CONCLUSION: In this meta-analysis of randomized clinical trials, vitamin D supplementation was not associated with a lower risk of cardiovascular events than no supplementation. These findings do not support the routine use of vitamin D supplementation in general.

Ultrasound-assisted deep eutectic solvents extraction of glabridin and isoliquiritigenin from Glycyrrhiza glabra: Optimization, extraction mechanism and in vitro bioactivities.

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.

Corosolic acid and its structural analogs: A systematic review of their biological activities and underlying mechanism of action.

BACKGROUND: The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature. PURPOSE: This systematic review aims to summarize the medical applications of CA and its analogues. METHODS: A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. 'corosolic acid', 'ursolic acid', 'oleanolic acid', 'maslinic acid', 'asiatic acid', 'betulinic acid', 'extraction', 'pharmacokinetic', 'pharmacological' were used to extract relevant literature. The PRISMA guidelines were followed. RESULTS: At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared. CONCLUSION: CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.

Novel technologies and models for studying pharmacological activities of traditional Chinese medicine for promoting blood circulation and removing blood stasis / 中国药理学与毒理学杂志

OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine (TCM) for promoting blood circulation and removing blood stasis, as exemplified by cryptotanshinone and salvi?anolic acid B, exerted striking effects on modulating angiogenesis and vascular permeability, which suggests that they may be effective in treating vascular leak-driven diseases (e.g. tumor, cerebral cavernous malformation and diabetic reti?nopathy). However, the lack of reliable and advanced technologies and models sets up difficult hurdles for better under?standing the role of TCM for promoting blood circulation and removing blood stasis. To this end, this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases. METHODS Two-photon laser scanning fluorescence micros?copy was used to observe the interactions between neutrophils and blood vessels in a real-time manner. Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils. RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels. CCM2ECKO (deletion of CCM2 in endothelial cells) mice were employed to establish the cerebral cavernous malformation (CCM) animal model. Micro-computed tomography (micro-CT) was utilized to assess the CCM lesion. Müller cell-knockout mouse model was used to study the progression of dia?betic retinopathy. Vascular permeability in this model was assessed by fluorescein angiography. RESULTS The interac?tions between neutrophils and endothelial cells involve a series of complicated processes, including rolling, adhesion, intraluminal crawling and transmigration, which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner. Dynamic flow system was capable of recapitulating the biological behaviors of neutro?phils in vitro. Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model. In terms of CCM studies, specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion. The size and number of CCM lesions could be visualized and quantified by micro-CT. Furthermore, the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy. Vascular leak could be monitored at different time points using fluorescein angiography. CONCLUSION An array of high technol?ogies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases. The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms, with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.

Sources, Fraction Distribution and Health Risk Assessment of Selenium (Se) in Dashan Village, a Se-Rich Area in Anhui Province, China.

Soil, rock, potable water, animal food and human hair samples were collected from the Dashan village, a typical selenium (Se)-rich area of China. Se content and fraction distribution were determined to trace the source of soil Se and evaluate the potential health risk to humans. Total Se contents in soils ranged from 0.60 to 10.46 mg kg- 1. The fractions of soil Se followed the order: residual Se (R-Se) > organic-bound Se (O-Se) > acid soluble Se (A-Se) > exchangeable Se (E-Se) > water soluble Se (W-Se). Total Se contents in rocks ranged from 0.07 to 24.8 mg kg- 1. The dietary Se intake of local residents was estimated to be 261.2 µg day- 1 and hair Se content varied from 0.34 to 1.35 mg kg- 1, suggesting that the potential health risk should be concerned. Weathering of carbonaceous rock was speculated to be the primary source of soil Se according to the contents of Se in rocks, the distribution of Se in soil profiles and the relationships between Se and other elements in soils and parent rocks.

Improvement of Curvulamine Production by Precursors Co-addition Strategy in Liquid Culture of Marine-Derived Fungus Curvularia sp. IFB-Z10.

Curvulamine, a novel scaffold alkaloid with remarkable selective antibacterial activity, is produced by marine fungus Curvularia sp. IFB-Z10. However, its deep pharmaceutical research and application are severely restricted by the low yield, which needs to be solved urgently. The purpose of this study was to improve curvulamine production via precursors co-addition strategy and further reveal the regulation mechanism. In this work, the optimal precursors co-addition conditions were firstly obtained, and curvulamine production achieved 166.74 mg/L with the supply of 250 mg/L alanine and 200 mg/L proline at 60 h, which was 4.08 times that of control. It was observed that under alanine and proline stimulation, fungus exhibited the morphology of a small-diameter compact pellet. Furthermore, the organic acid levels in central carbon metabolism (CCM) were declined with precursors supplement. Besides, precursors also induced the critical biosynthetic gene transcriptions. The above findings collectively promoted curvulamine synthesis. Finally, Curvularia sp. IFB-Z10 fermentation process was successfully established by feeding alanine and proline at 0.021 g/L/h and 0.017 g/L/h rate from 60 to 72 h, and curvulamine production reached 133.58 mg/L in a 5-L bioreactor. The information acquired would facilitate the enhancement of curvulamine yield in submerged fermentation and the research on synthesis regulation of other alkaloids.

Effects of electroacupuncture plus drug anesthesia on pain and stress response in patients after radical surgery for stomach cancer / 针灸推拿医学（英文版）

Objective: To observe the effect of electroacupuncture plus drug anesthesia on pain and stress response in patients after radical surgery for stomach cancer.Methods: A total of 60 patients were randomized into a control group and an observation group by the random number table, with 30 cases in each group. The control group was given conventional drug anesthesia. The observation group was given additional electroacupuncture intervention. Before anesthesia and 2 h, 12 h and 24 h after surgery, the visual analog scale (VAS) was scored, the heart rate, the mean arterial pressure, and the levels of serum β-endorphin (β-EP) and adrenocorticotrophic hormone (ACTH) were measured. Results: Two hours, 12 h and 24 h after surgery, the VAS scores of both groups were higher than those before anesthesia (all P<0.05), and the VAS scores in the observation group were lower than those in the control group at the same time points (all P<0.05). Two hours, 12 h and 24 h after surgery, the heart rates and mean arterial pressures in the control group were significantly higher than those before anesthesia (all P<0.05), while there were no significant intra-group differences in the observation group (all P>0.05), and the indicators were lower than those in the control group at the same time points (all P<0.05). Two hours, 12 h and 24 h after surgery, the serum β-EP levels in the observation group were significantly higher than those before anesthesia (all P<0.05), and significantly higher than those in the control group at the same time points (all P<0.05). Two hours, 12 h and 24 h after surgery, the serum ACTH levels in the control group were significantly higher than those before anesthesia (all P<0.05), and were significantly higher than those in the observation group at the same time points (all P<0.05). Conclusion: Electroacupuncture plus drug anesthesia can significantly relieve pain and stress response in patients after radical surgery for stomach cancer.

Normativity of overview report of the systematic review of acupuncture and moxibustion at home and abroad based on PRIO-harms scale / 中国针灸

OBJECTIVE@#To evaluate and compare the normativity of overview report of systematic review (Overviews) of acupuncture and moxibustion at home and abroad so as to further improve the report quality of Overviews of acupuncture and moxibustion in China and provide reliable evidences.@*METHODS@#The articles relevant with Overviews of acupuncture and moxibustion at home and abroad were retrieved by computer from the databases of CNKI, VIP, Wanfang, China BioMedical Literature database (SinoMed), PubMed, Embase and Conchrane Library, dated from the time of establishment to February 12, 2019. The preferred reporting items for Overviews (PRIO-harms) was adopted to evaluate their normativity and make the comparison of the articles between China and foreign countries.@*RESULTS@#A total of 13 articles of Overviews of acupuncture and moxibustion were included, 9 articles of them were of Chinese version and the rest were of English version. The results of PRIO-harms indicated that the proportions of the item numbers related to adequate, partial and inadequate adherence of Chinese version were 3.7%, 63.8% and 32.5%, and those of English version were 12.0%, 57.4% and 30.6% respectively. The reports on the item 10 "additional search for primary studies", the item 12 "data items" and the item 26 "Dual/(co-)authorship" were inadequate adherence by 100% in the articles of both Chinese and English version.@*CONCLUSION@#The overall information of English article report is better than Chinese one, but the reports of either Chinese or English articles are not so satisfactory. It is suggested that the Overviews report should be in reference to the specification in PRIO-harms and the Chinese researchers should study the advantages of English article report and improve the normalization and report quality so as to obtain the high-quality evidences in evidence-based medicine.

Ammonium Acetate Supplement Strategy for Enhancement of Chaetominine Production in Liquid Culture of Marine-Derived Aspergillus fumigatus CY018.

Pharmacological research on (CHA), a marine-derived quinazolinone alkaloid with significant cytotoxic activity, is restricted by low yields and is a problem that needs to be settled urgently. In this work, the selection of additional nitrogen sources and the optimization of additional concentrations and longer fermentation times using ammonium acetate, were investigated. CHA production was optimized to 62.1 mg/l with the addition of 50 mM ammonium acetate at 120 h of the fermentation in the shaker flask. This feeding strategy significantly increased 3- deoxy-arabino-heptulosonate-7-phosphate synthase activity and transcript levels of critical genes (laeA, dahp and trpC) in the shikimate pathway compared with the non-treatment group. In addition, the selection of the feeding rate (0.01 and 0.03 g/l/h) was investigated in a 5-L bioreactor. As a result, CHA production was increased by 57.9 mg/l with a 0.01 g/l/h ammonium acetate feeding rate. This work shows that the strategy of ammonium acetate supplementation had an effective role in improving CHA production by Aspergillus fumigatus CY018. It also shows that this strategy could serve as an important example of large-scale fermentation of a marine fungus in submerged culture.

[Effect of Acupuncture Intervention on Depression Behavior and Expression of ERK 1/2 and BDNF in Prefrontal Cortex in Chronic Unpredictable Mild Stress Induced Depression Rats].

OBJECTIVE: To investigate the effect of acupuncture intervention on the depression behavior and expression of extracellular signal-regulated protein kinases (ERK 1/2), p-ERK 1/2 and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of chronic unpredictable mild stress (CUMS) induced depression rats, so as to explore its antidepressant mechanism. METHODS: Sixty-four male SD rats were randomly divided into control, model, acupuncture, Fluoxetine, model ＋ Dimethyl sulfoxide (DMSO), model ＋ PD 98059(an ERK pathway inhibitor), acupuncture ＋ PD 98059 and Fluoxetine ＋ PD 98059 groups (n＝8 rats in each). The CUMS depression model was established by using chronic mild and unpredictable stress methods for 21 days. Manual acupuncture stimulation was applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 10 min before modeling, once daily for 21 days. Fluoxetine hydrochloride suspension (1.8 mg•kg－1•d－1) was given to rats of the Fluoxetine group and Fluo-xetine ＋ PD 98059 group by gavage 30 min before CUMS. PD 98059 (dissolved in DMSO, 10 µL) was administered to rats of model ＋ PD 98059 group, acupuncture ＋ PD 98059 and Fluoxetine ＋ PD 98059 group, and DMSO (10 µL) to rats of model ＋ DMSO group by intracerebroventricular injection 1 h before CUMS. Sucrose consumption test was carried out to evaluate the depressive behavior. Western blot was performed to detect the expression of ERK 1/2, p-ERK 1/2 and BDNF of prefrontal cortex. RESULTS: Compared with the control group, the sucrose consumption and the expression levels of p-ERK 1/2 and BDNF protein in the prefrontal cortex were significantly reduced in the model and model＋DMSO group (P<0. 01). After the intervention, modeling induced decrease of the sucrose consumption, and p-ERK 1/2 and BDNF expression was significantly up-regulated in both acupuncture and Fluoxetine groups (P<0.01, P<0.05), but not in the model＋PD 98059, Fluoxetine ＋PD 98059 and acupuncture＋PD 98059 groups (P>0.05). No significant differences were found among the model＋PD 98059, Fluoxetine ＋PD 98059 and acupuncture＋PD 98059 groups in the sucrose consumption, and ERK 1/2, p-ERK 1/2 and BDNF expression levels (P>0.05), and in the expression levels of ERK 1/2 protein among the 8 groups (P>0.05). CONCLUSION: Acupuncture intervention has an anti-depressive role in CUMS induced depression rats, which may be related to its effects in up-regulating the expression of p-ERK 1/2 and BDNF in the prefrontal cortex tissue.