Investigation of the enhancement for Echinocandin B fermentation with methyl oleate from transcription level.

Echinocandin B (ECB) is the key precursor compound of the antifungal drug Anidulafungin. The effects of the five precursor amino acids on ECB biosynthesis were firstly investigated. It showed that although L-threonine was a main compound of the hexapeptide scaffold of ECB, exogenous addition of L-threonine had no significant effect on the increase of ECB fermentation titer. Meanwhile, the ECB fermentation titer with methyl oleate showed two times higher than that of the other carbon sources. Transcription level analysis of the key genes for ECB biosynthesis indicated that the gene an655543 related to L-threonine biosynthesis showed higher value during the fermentation process, therefore, the exogenous addition of L-threonine had no obvious affection. Furthermore, it indicated that the transcription level of gene ecdA might be the main restriction factor for the ECB biosynthesis. The study provided the research foundation for the modification of the ECB producing strains in the following work.

[Vitiligo Combined With Annular Lichen Planus: A Rare Case Report].

A 36-year-old female patient came to our hospital with the chief complaint of having white patches on her waist for 10-plus years and having new annular plaques appearing on the white patches for 6-plus months. Wood's lamp examination done in the hospital showed a positive result. Histopathology of skin tissue from the edge of the annular swelling on the right waist revealed epidermal hyperkeratosis, wedge-shaped thickening of the granular layer, liquefactive degeneration of the basal cells, and a band-like infiltration of lymphocytes in the superficial dermis. The patient was diagnosed with vitiligo combined with annular lichen planus (ALP). The patient was treated with topical halometasone cream administered twice a day. The purplish-red annular plagues subsided and disappeared almost completely one month after the treatment was started and no signs of recurrence were observed duringn the 2-month follow-up. ALP is a rare variant of lichen planus. There has been no reported case of vitiligo combined with ALP so far.

Moxibustion regulates the polarization of macrophages through the IL-4/STAT6 pathway in rheumatoid arthritis.

OBJECTIVE: To observe the effects of moxibustion on "Shenshu" and "Zusanli" on macrophage polarization and IL-4/STAT6 signaling pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. METHODS: The rats' right hind paws were injected with freund's complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The researchers measured the thickness of the foot pad. ELISA and Histological Analysis were performed to observe the anti-inflammatory effect of moxibustion. Then researchers detected the expression of macrophage phenotype and the expression of IL-4/STAT6 signaling pathway related molecules. RESULTS: It was observed that after the injection of FCA, the rats' feet showed obvious symptoms of redness and swelling. But the symptoms were significantly improved when moxibustion was employed. The study found lower IL-23 and higher IL-4 level in the serum of FCA-injected rats after moxibustion treatment. HE staining showed that the synovium of the RA group was hyperemia and edema, with a large number of inflammatory cells infiltration and vascular dilatation. In the moxibustion group, the degree of synovial hyperemia and edema was improved, and the infiltration of inflammatory cells and vascular dilation were reduced. The study also found that there wer differences among the expressions of macrophage phenotypes in RA, and this was shown by the high expression of CD86 and low expression of CD206. However, the polarization of macrophages in the moxibustion group changed, and that was manifested by enhanced M2-polarized Mφs and inhibited M1-polarized Mφs. Meanwhile, moxibustion suppressed the activation of JAK1, JAK3 and STAT6 in the IL-4/STAT6 signaling pathway, which contributed to the polarization of M2 . CONCLUSION: The results demonstrate that moxibustion not only suppresses the polarization of M1, but also promotes the polarization of M1. The anti-inflammatory effect of moxibustion may be related to the regulation of macrophage polarization through IL-4/STAT6 signaling pathway.

Sulforaphane alleviates LPS-induced inflammatory injury in ARPE-19 cells by repressing the PWRN2/NF-kB pathway.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population and its pathogenesis has been associated with inflammatory damage to retinal pigment epithelial (RPE) cells. Here, we explored the ability of sulforaphane to protect ARPE-19 cells from lipopolysaccharide (LPS)-induced inflammatory injury and elucidated the underlying molecular mechanism. METHODS: Cell viability, apoptosis, inflammation, PWRN2 expression, nuclear transcription factor-kappa B (NF-kB) activity, and the interaction between PWRN2 and the IkBa protein were assessed in RPE cells under- or over-expressing PWRN2 that had been treated with LPS and sulforaphane. RESULTS: Overexpression of PWRN2 in LPS-treated cells promoted NF-kB activation by interacting with IkBa, thus reducing cell viability. In contrast, PWRN2 downregulation repressed LPS-induced NF-kB activation and apoptosis in RPE cells. Similarly, sulforaphane downregulated PWRN2 and inhibited NF-kB activation in a concentration-dependent manner. Conversely, PWRN2 overexpression or NF-kB upregulation weakened the anti-inflammatory effects of sulforaphane. CONCLUSION: Our results suggest that sulforaphane protects RPE cells from LPS-induced inflammatory injury by suppressing the PWRN2/NF-kB pathway.

Bacterial dynamics and functions driven by bulking agents to enhance organic degradation in food waste in-situ rapid biological reduction (IRBR).

This study investigated the effects of different bulking agents (i.e., sawdust, wheat straw, rice straw, and corncob) on bacterial structure and functions for organic degradation during food waste in-situ rapid biological reduction (IRBR) inoculated with microbial agent. Results showed that the highest organic degradation (409.5 g/kg total solid) and volatile solids removal efficiency (41.0%) were achieved when wheat straw was used, largely because the degradation of readily degradable substrates and cellulose was promoted by this bulking agent. Compared with other three bulking agents, the utilization of wheat straw was conducive to construct a more suitable environmental condition (moisture content of 18.0-28.2%, pH of 4.91-5.87) for organic degradation during IRBR process, by virtue of its excellent structural and physiochemical properties. Microbial community analysis suggested that the high-moisture environment in rice straw treatment promoted the growth of Staphylococcus and inhibited the activity of the inoculum. By contrast, lowest bacterial richness was observed in corncob treatment due to the faster water loss. Compared with these two bulking agents, sawdust and wheat straw treatment led to a more stable bacterial community structure, and the inoculated Bacillus gradually became the dominant genus (36.6-57.8%) in wheat straw treatment. Predicted metagenomics analysis showed that wheat straw treatment exhibited the highest carbohydrate metabolism activity which improved the pyruvate, amino sugar and nucleotide sugar metabolism, and thereby promoted the organic degradation and humic substrate production. These results indicated that wheat straw was a more desirable bulking agent, and revealed the potential microbial organics degradation mechanism in IRBR process.

Research progress of L-aspartate-α-decarboxylase and its isoenzyme in the ß-alanine synthesis.

Driven by the massive demand in recent years, the production of ß-alanine has significantly progressed in chemical and biological ways. Although the chemical method is relatively mature compared to biological synthesis, its high cost of waste disposal and environmental pollution does not meet the environmental protection standard. Hence, the biological method has become more prevalent as a potential alternative to the chemical synthesis of ß-alanine in recent years. As a result, the aspartate pathway from L-aspartate to ß-alanine (the most significant rate-limiting step in the ß-alanine synthesis) catalyzed by L-aspartate-α-decarboxylase (ADC) has become a research hotspot in recent years. Therefore, it is vital to comprehensively understand the different enzymes that possess a similar catalytic ability to ADC. This review will investigate the exploratory process of unique synthesis features and catalytic properties of ADC/ADC-like enzymes in particular creatures with similar catalytic capacity or high sequence homology. At the same time, we will discuss the different ß-alanine production methods which can apply to future industrialization.

Sex effects on clinical features in LRRK2 G2385R carriers and non-carriers in Parkinson's disease.

BACKGROUND: Differences of genotypes between male and female have been studied in Parkinson's disease (PD), but limited research has focused on the comparison between sexes with LRRK2 G2385 variant. OBJECTIVE: The aim of this study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex in PD. METHODS: 613 PD patients were recruited from the Movement Disorders Clinic in Ruijin Hospital. We did not include healthy controls in this study. The data collected includes demographic information, disease history, scores of motor and non-motor symptoms scales, midbrain transcranial sonography and DNA. Binary logistic regression analysis was performed to evaluate the association between clinical features and sex in LRRK2 G2385R carriers and non-carriers, as well as the association between the clinical features and LRRK2 G2385R variants in male and female sex. RESULTS: Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135-0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167-0.960). In LRRK2 G2385R non-carriers, female sex showed lower risk of impairment in activity of daily living (OR = 0.610, p = 0.021, 95%CI 0.400-0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361-0.853), substantia nigra hyperechogenicity (OR = 0.448, p = 0.019, 95%CI 0.228-0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428-0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI 1.078-2.654) compared with male. In LRRK2 G2385R carriers, female sex showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102-0.849) compared with male. CONCLUSION: In contrast to male PD patients, a more benign disease course was observed in female in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 G2385R variants.

The sequential activation of H2 and N2 mediated by the gas-phase Sc3N+ clusters: Formation of amido unit.

The activation and hydrogenation of nitrogen are central in industry and in nature. Through a combination of mass spectrometry and quantum chemical calculations, this work reports an interesting result that scandium nitride cations Sc3N+ can activate sequentially H2 and N2, and an amido unit (NH2) is formed based on density functional theory calculations, which is one of the inevitable intermediates in the N2 reduction reactions. If the activation step is reversed, i.e., sequential activation of first N2 and then H2, the reactivity decreases dramatically. An association mechanism, prevalent in some homogeneous catalysis and enzymatic mechanisms, is adopted in these gas-phase H2 and N2 activation reactions mediated by Sc3N+ cations. The mechanistic insights are important to understand the mechanism of the conversion of H2 and N2 to NH3 synthesis under ambient conditions.

Heterologous expression and biochemical characterization of a thermostable endo-ß-1,4-glucanase from Colletotrichum orchidophilum.

To develop new cellulases for efficient utilization of the lignocellulose, an endoglucanase (CoCel5A) gene from Colletotrichum orchidophilum was synthesized and a recombinant Pichia pastoris GS115/pPIC9K/cocel5A was constructed for secretory expression of CoCel5A. After purification, the protein CoCel5A was biochemically characterized. The endoglucanase CoCel5A exhibited the optimal activity at 55-75 °C and high thermostability (about 85% residual activity) at the temperature of 55 °C after incubation for 3 h. The highest activity of CoCel5A was detected when 100 mM citric acid buffer (pH 4.0-5.0) was used and excellent pH stability (up to 95% residual activity) was observed after incubation in 100 mM citric acid buffer (pH 3.0-6.0) at 4 °C for 24 h. Carboxymethyl cellulose sodium salt (n = approx. 500) (CMC) and ß-D-glucan were the best substrates for CoCel5A among the tested substrates. The kinetic parameters Vmax, Km, and Kcat/Km values against CMC were 290.70 U/mg, 2.65 mg/mL, and 75.67 mL/mg/s, respectively; and 228.31 U/mg, 2.06 mg/mL, and 76.45 mL/mg/s against ß-D-glucan, respectively, suggesting that CoCel5A has high affinity and catalytic efficiency. These properties supported the potential application of CoCel5A in biotechnological and environmental fields.

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

Midbrain/pons area ratio and clinical features predict the prognosis of progressive Supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare movement disorder with poor prognosis. This retrospective study aimed to characterize the natural history of PSP and to find predictors of shorter survival and faster decline of activity of daily living. METHOD: All patients recruited fulfilled the movement disorder society (MDS) clinical diagnostic criteria for PSP (MDS-PSP criteria) for probable and possible PSP with median 12 years. Data were obtained including age, sex, date of onset, age at onset (AAO), symptoms reported at first visit and follow-up, date of death and date of institutionalization. Magnetic resonance imaging was collected at the first visit. Endpoints were death and institutionalization. Kaplan-Meier method and Cox proportional hazard model were used to explore factors associated with early death and institutionalization. RESULTS: Fifty-nine patients fulfilling MDS-PSP criteria were enrolled in our study. Nineteen patients (32.2%) had died and 31 patients (52.5%) were institutionalized by the end of the follow-up. Predictors associated with poorer survival were late-onset PSP and decreased M/P area ratio. Predictors associated with earlier institutionalization were older AAO and decreased M/P area ratio. CONCLUSION: Older AAO and decreased M/P area ratio were predictors for earlier dearth and institutionalization in PSP. The neuroimaging biomarker M/P area ratio was a predictor for prognosis in PSP.

Oxidation of isoprene by titanium oxide cluster cations in the gas phase.

The heterogeneous oxidation of isoprene (C5H8) by metal-oxide particles, such as the typical mineral aerosols TiO2, plays an important role in the isoprene atmospheric chemistry. However, the underlying mechanism of C5H8 oxidation remains elusive owing to the complexities of aerosol surfaces and reaction channels. Herein, we report the gas-phase reactions of TixOy+ (x = 1-7, y = 1-14) cations with isoprene by using mass spectrometry and density functional theory (DFT) calculations. Five types of reaction channels were observed: association, hydrogen atom transfer (HAT), C-C bond cleavage, combined oxygen atom transfer (OAT) and HAT and combined OAT and C-C bond cleavage. It is noteworthy that formaldehyde is known as the major oxidation product of isoprene/hydroxyl radicals in the atmosphere. In addition, CO has not been observed in the reactions of isoprene with gas-phase ions. Therefore, the reaction mechanisms of CH2O and CO generation observed in Ti2O5+/C5H8 and Ti4O8+/C5H8 systems were further investigated by DFT calculations, and the calculated results are in agreement with the experimental observations. In these two reactions, both Ti and O atoms can be the adsorption sites for C5H8. The reaction channels and mechanistic information gained in these gas-phase model reactions may offer fundamental insights relevant to the corresponding oxidation processes over titanium oxide aerosols in the atmosphere.

Improvement of R-2-(4-hydroxyphenoxy) propionic acid biosynthesis of Beauveria bassiana by combined mutagenesis.

R-2-(4-hydroxyphenoxy)propionicacid (HPOPA) is a valuable intermediate for the synthesis of enantiomerically pure aryloxyphenoxypropionic acid herbicides. In this work, to improve the HPOPA biosynthesis by Beauveria bassiana ZJB16002 from the substrate R-2-phenoxypropionic acid (POPA), the original HPOPA producer B. bassiana ZJB16002 was subjected to physical mutagenesis with 137 Cs-γ irradiation and chemical mutagen N-methyl-N'-nitro-N-nitrasoguanidine (NTG) induced mutagenesis. The effects of different treatment doses of the mutagens on the lethal rate and positive mutation rate were investigated, and the results showed that the optimal 137 Cs-γirradiation dose and NTG concentration was 850 Gy and 500 µg/mL, respectively. Under these conditions, a mutant strain CCN-7 with the highest HPOPA production capacity was obtained through two rounds of 137 Cs-γ irradiation treatment followed by one round of NTG mutagenesis. At the substrate (POPA) concentration of 50 g/L, HPOPA titer of CCN-7 reached 36.88 g/L, which was 9.73-fold higher than the parental strain. The morphology of the wild-type and mutant strain was compared and the results might provide helpful information in exploration of the correlation of morphology and biochemical features of B. bassiana.

Effect of dissolved oxygen on L-methionine production from glycerol by Escherichia coli W3110BL using metabolic flux analysis method.

L-Methionine is an essential amino acid in humans, which plays an important role in the synthesis of some important amino acids and proteins. In this work, metabolic flux of batch fermentation of L-methionine with recombinant Escherichia coli W3110BL was analyzed using the flux balance analysis method, which estimated the intracellular flux distributions under different dissolved oxygen conditions. The results revealed the producing L-methionine flux of 4.8 mmol/(g cell·h) [based on the glycerol uptake flux of 100 mmol/(g cell·h)] was obtained at 30% dissolved oxygen level which was higher than that of other dissolved oxygen levels. The carbon fluxes for synthesizing L-methionine were mainly obtained from the pathway of phosphoenolpyruvate to oxaloacetic acid [15.6 mmol/(g cell·h)] but not from the TCA cycle. Hence, increasing the flow from phosphoenolpyruvate to oxaloacetic acid by enhancing the enzyme activity of phosphoenolpyruvate carboxylase might be conducive to the production of L-methionine. Additionally, pentose phosphate pathway could provide a large amount of reducing power NADPH for the synthesis of amino acids and the flux could increase from 41 mmol/(g cell·h) to 51 mmol/(g cell·h) when changing the dissolved oxygen levels, thus meeting the requirement of NADPH for L-methionine production and biomass synthesis. Therefore, the following modification of the strains should based on the improvement of the key pathway and the NAD(P)/NAD(P)H metabolism.

Acupuncture versus sham acupuncture for simple obesity: a systematic review and meta-analysis.

Obesity is a growing chronic health problem worldwide. Studies about acupuncture for obesity treatment are many. But there are some doubts about the effectiveness of acupuncture versus sham acupuncture in treating obesity due to its lack of medical evidence. Therefore, the aim of this study is to assess the efficacy of acupuncture for obesity treatment and provide clinic evidence. Four English databases (PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials) and four Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Database, Chinese Scientific Journal Database and Wan-Fang Data) were searched from their receptions to August 2019. Randomized controlled trials (RCTs) using the comparison between acupuncture and sham acupuncture to treat simple obesity were included. The primary outcome of body mass index (BMI) would be used to measure the effect of acupuncture on obesity. According to the trial data extraction form based on the Cochrane Handbook, two reviewers separately extracted the data. Risk of bias of the RCTs was assessed by the Cochrane Risk of Bias Tool. The study included 8 RCTs with 403 patients. When compared with sham acupuncture, acupuncture showed obviously effect in BMI reduction (MD=1.0kg/m2, 95% CI=0.6 to 1.4, P<0.001). There was also significant reduction in body weight (MD=1.85kg, 95%CI=0.82 to 2.88, p<0.001), WC (MD=0.97cm, 95%CI=0.24 to 1.71, p=0.01) and body fat mass percentage (MD=1.01, 95%CI=0.25 to 1.77, p<0.05). However, WHR (MD=0.01, 95%CI=0 to 0.03, p>0.05) was not statistically and significantly different between the acupuncture and control groups. Adverse effects were reported in 3 studies. The review suggests that acupuncture is an effective therapy for simple obesity rather than a placebo effect. This potential benefit needs to be further evaluated by longer-term and more rigorous RCTs.

Production of (R)-2-(4-hydroxyphenoxy) propionic acid by Beauveria bassiana ZJB16007 in solid state fermentation using rice bran.

R-2-(4-hydroxyphenoxy)propionic acid (R-HPPA) is a key chiral intermediate for phenoxypropionic acid herbicide synthesis. In this study, to improve the production of R-HPPA with B. bassiana ZJB16007, the cultivation conditions in solid-state fermentation (SSF) were investigated. The effects of various substrates on R-HPPA production were evaluated and the process parameters were also optimized. The results showed that rice bran was the optimal substrate for R-HPPA production. The optimal medium components and cultivation conditions were: rice bran: silkworm chrysalis powder = 5.25: 2.25 (g: g), nutrient salts solution 12 mL which contained 50 g/L R-PPA, pH 5.0, and cultivated at 28 °C for 11 days. Under the optimized conditions, the transformation of R-HPPA was significantly improved and the yield of R-HPPA reached 77.78%, which was 15.14% higher than that of the control (67.55%). Therefore, SSF may serve as an alternative for R-HPPA production by B. bassiana ZJB16007.

A high-throughput screening method for improved R-2-(4-hydroxyphenoxy)propionic acid biosynthesis.

R-2-(4-hydroxyphenoxy)propionic acid (R-HPPA) is a key intermediate of the enantiomerically pure phenoxypropionic acid herbicides. R-HPPA could be biosynthesized through selective introduction of a hydroxyl group (-OH) into the substrate R-2-phenoxypropionic acid (R-PPA) at C-4 position, facilitated by microorganisms with hydroxylases. In this study, an efficient high-throughput screening method for improved R-HPPA biosynthesis through microbial hydroxylation was developed. As a hydroxylated aromatic product, R-HPPA could be oxidized by oxidant potassium dichromate to form brown-colored quinone-type compound. The concentration of R-HPPA can be quantified according to the absorbance of the colored compound at a suitable wavelength of 570 nm; and the R-HPPA biosynthetic capability of microorganism strains could also be rapidly evaluated. After optimization of the assay conditions, the high-throughput screening method was successfully used in identification of Beauveria bassiana mutants with enhanced R-HPPA biosynthesis capacity. A positive mutant C-7 with high tolerance to 20 g/L R-PPA was rapidly selected from 1920 mutants. The biomass and R-HPPA titer were 12.5- and 38.19-fold higher compared with the original strain at 20 g/L R-PPA. This high-throughput screening method developed in this work could also be a potential tool for screening strains producing other important phenolic compounds.

[Discussion and research progress in standard decoction of medicinal slices].

Standard decoction of medicinal slices has gradually acquired the height of researcher,government and enterprise for approval. And much consensus are increasingly reached. But there are lots of problem needing further discussing.This article summaries the published literature about standard decoction of medicinal slices in recent 3 years. And clarifies the origin of standard decoction of medicinal slices,explain the definition. The study status of standard decoction was reviewed and further analyzed in detail. And then the application fields of standard decoction of medicinal slices are listed. Combined with the research examples of groups,the problem in the study of standard decoction of medicinal slices was discussed. And relevant suggestions are put forward. All this is expected to provide reference in standard decoction research,the quality criterion o of formula granule and study of classical traditional Chinese medicine( TCM) excellent prescriptions.

Isoalantolactone protects LPS-induced acute lung injury through Nrf2 activation.

Isoalantolactone (ISO), a sesquiterpene lactone isolated from Inula helenium, is known to have anti-inflammatory activity. Here, using a mouse model of acute lung injury, we investigated the effects of ISO on lung inflammation in vivo. ISO (2.5, 5, 10 mg/kg) was administered 1 h before LPS treatment. Histopathological changes suggested that ISO attenuated the injury of lung tissues induced by LPS. ISO also inhibited LPS-induced MPO activity, MDA content, lung W/D ratio, and the production of inflammatory cytokines TNF-α and IL-1ß. LPS decreased the activities of the antioxidant enzymes SOD, GPX, and CAT and the decreases were inhibited by ISO. Further studies were performed to detect the Nrf2 and NF-κB signaling pathway. The results showed that ISO significantly suppressed LPS-induced NF-κB activation, as well as PI3K and AKT phosphorylation. Additionally, the expression of Nrf2 and HO-1 were dose-dependently up-regulated by the treatment of ISO. Taken together, the results indicate the protective action of ISO against LPS-induced ALI were through activation of the Nrf2 signaling pathway.