MF Treatment Research Articles

Bone morphogenetic protein-9 maybe an important factor which improves insulin resistance in PCOS

Background Polycystic ovary syndrome (PCOS) is closely related to insulin resistance (IR). Bone morphogenetic protein-9 (BMP-9) plays an important role in maintaining glucose homeostasis, but an association between BMP-9 and PCOS has not been reported. Here, we report the changes in BMP-9 and the influence of this protein on IR in PCOS. Methods 57 PCOS patients were selected (among them 25 received interventional treatment with exenatide (EX) for 3 months, and 32 received no treatment). 22 normal control individuals and 30 IR patients were also recruited. We evaluated IR with the euglycaemic-hyperinsulinaemic clamp (EHC) technique. IR and the glucose metabolism rate were assessed by EHC and [3-3H]glucose tracer experiments. We determined the protein expression levels of BMP-9, p-AKT (protein kinase B) and androgen receptor in the ovaries and liver by Western blotting. Results We found that circulating BMP-9 levels were significantly decreased in PCOS with IR patients. Circulating BMP-9 levels and p-AKT levels were decreased in HFD and PCOS rats and increased after MF and EX treatment. The glucose infusion rate, glucose disappearance rate and suppression of hepatic glucose production decreased in the HFD and PCOS groups, the opposite results were found for HGP. AR protein expression levels increased in the HFD and PCOS groups and decreased in the MF and EX groups. Conclusions Our study results suggest that BMP-9 is an independent factor that influences IR in PCOS patients. The decrease in BMP-9 levels in the liver and ovaries may be involved in IR through the PI3K/AKT signaling pathway in PCOS rats.

Effects of long-term organic matter application on soil carbon accumulation and nitrogen use efficiency in a double-cropping rice field

Increasing soil carbon (C) sequestration in paddy field and improving rice nitrogen use efficiency (NUE) are vital for sustainable agriculture and environmental protection. It was a benefit practice for achieving these goals by taken rice straw and organic manure managements. However, there is still need to further investigate the effects of different long-term fertilizer managements on soil C sequestration and NUE under the double-cropping rice system in southern of China. Therefore, the effects of different long-term (36-years) fertilizer practices on soil C sequestration and NUE under the double-cropping rice system in southern of China were investigated in the present paper. The field experiment was included four different fertilizer treatments: chemical fertilizer alone (MF), rice straw residue and chemical fertilizer (RF), 30% organic manure and 70% chemical fertilizer (OM), and without fertilizer input as a control (CK). This result indicated that soil C content at plough layer in paddy field with RF and OM treatments were increased, compared with MF and CK treatments. Besides input C directly into paddy field, soil original organic C accumulation with RF and OM treatments were increased by 1.54% and 3.01%, compared with MF treatment. This result indicated that soil TOC content increase rate and annual topsoil organic C sequestration rate in paddy field with RF and OM treatments increased by 55.56%, 88.89% and 48.05%, 76.62%, compared with MF treatment, respectively. Compared with MF treatment, NUE with RF and OM treatments increased by 10.43% and 22.61%, respectively, mainly due to increasing soil organic C. Grain yield of double-cropping rice with RF and OM treatments increased by 1009.5 and 1166.5 kg ha−1, compared with MF treatment, respectively. This result indicated that there was significantly correlation between NUE/NUENPK and TOC content with RF and OM treatments, at early rice and late rice growth seasons. Therefore, it was benefit practice for increasing soil carbon sequestration and improving rice NUE in the double-cropping rice system with long-term application of rice straw and organic manure managements.

Reducing cherry rain-cracking: Development and characterization of cold-water fish gelatin films reinforced by dual rod-spherical nanoscale structures formed under magnetic fields

In order to solve the problem of cherry rain-cracking, cold-water fish gelatin (CFG)-based edible films (CFG, CFG-CNC [cellulose nanocrystals], CFG-CA [chitosan hydrochloride-sodium alginate nanoparticles], CFG–CNC–CA, and their magnetic field [MF] films) were prepared with reinforcement by rod-spherical dual-nanoscale structures. Here, the spherical nanoparticles CA were formed based on static electricity interaction between chitosan hydrochloride and sodium alginate according to pre-gel method, whereas the rods consisted of CNC extracted from sugarcane bagasse. Studies were conducted in laboratory to determine the coating-ductility, hydrophobic, water-vapor barrier, mechanical, and retention properties, and in the field to determine cracking index (CI) and cracking ratio (CR). MF treatment was found to induce the rod-spherical dual-nanoparticles to arrange into C–O–C linkages. Compared to the other films, the CFG–CNC–CA (MF) film showed superior coating-ductility properties (surface tension: 61.8 mN m−1), hydrophobicity (water contact angle: 111.6°), and water-vapor barrier (water-vapor permeability: 7.43 × 10−10 gm−1Pa−1s−1), as well as superior mechanical (Young's modulus: 351 MPa; tensile strength: 30.1 MPa) and retention properties on cherry (water solubility: 38.4%; swelling degree: 876%). Compared with the experimental control, the total CI of cherries treated with CFG–CNC–CA (MF) was reduced from 43.3% to 11.8%, and the total CR was reduced from 34.8% to 11.1%, type Ⅰ’ cracking in particular experienced a greater reduction (from 26.7% to 9.16%) than did type Ⅱ’ (13.7%–4.96%) or Ⅲ’ (8.90%–3.48%). Thus, this study successfully provided a reference for edible CFG–CNC–CA (MF) coatings that prevent and control cherry rain-cracking disasters worldwide in a timely, safe, and efficient manner.

Mangiferin exert protective effects on joints of adjuvant-induced arthritis rats by regulating the MAPKs/NF-κB pathway of fibroblast-like synoviocytes

BackgroundMangiferin (MF) is a bioactive ingredient predominantly isolated from the mango tree, that has been reported to have antioxidant, anti-inflammatory, and immunomodulatory effects. This study was aimed to investigate the protective effect of MF on the joints of arthritic rats and explore the underlying mechanisms of this function. MethodsAdjuvant-induced arthritis (AA) rat model was established and clinical severity of AA was evaluated by arthritis index, paw edema, plasma, and synovium homogenate parameters. The severity of joint destruction was assessed by radiological and histopathological. Immunohistochemical analysis was employed to detect the protein expression of MMP-3, MMP-13 in synovium and cartilage tissues. The vitro effects of MF on proliferation, migration, apoptosis, and production of inflammatory mediators in RA- FLSs were determined by the CCK8 assay, transwell assay, flow cytometry, and real-time PCR, respectively. ResultsThe results demonstrated that MF treatment significantly alleviated arthritis index, paw swelling and decreased the secretion of inflammatory cytokines in plasma and synovium. Meanwhile, MF inhibited synovial inflammation, pannus formation, and bone erosion in AA rats. It also ameliorated the oxidative stress state of arthritic rats via modulating the level of MDA, SOD, CAT, GSH, NO. In addition, MF effectively attenuated the destructive behavior of RA-FLSs by inhibiting proliferation, migration, and secretion of inflammatory mediators, and promoting apoptosis. The further mechanistic analysis demonstrated that MF might exert an antiarthritic effect via inhibiting the pathway of MAPKs (ERK2 and p38) and NF-κ B. ConclusionTaken together, our results demonstrated that MF would be a promising anti-arthritic agent candidate for further research.

Quantitative Testing of the Myelofibrosis Symptom Assessment Form Version 4.0, a Harmonized Patient-Reported Outcome Measure for Collecting Key Secondary Endpoint Data in Myelofibrosis Clinical Trials

Background: The original 20-item Myelofibrosis Symptom Assessment Form (MFSAF) was developed to assess patient-reported symptom improvement in MF treatment trials (Mesa et al, 2009). The MFSAF was expanded to 27 items for use in myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET) and polycythemia vera (PV; MPN-SAF, Scherber et al, 2011), and later reduced to a 10-item version called the MPN-10 (Emanuel et al, 2012; scale 0-100). At the same time, investigators developed a modified version of the MFSAF called the MFSAF v2.0 diary (6 items, scale 0-60) for use in an MF treatment trial (Falcone and Levy, 2012). As part of next generation JAK1/2 inhibitor trials, various pharma companies collaborated with the US FDA to develop other versions (e.g., MFSAF-revised; 7 items, scale 0-70). Variability across versions (e.g., item wording, recall periods, response scales) increases uncertainty when selecting a measure for use in trials and when comparing findings across trials. To mitigate this uncertainty, the 7-item MFSAF v4.0 (scale 0-70) was recently developed through a harmonization process including stakeholders and the developers of the legacy measures (Gwaltney et al, 2017).Methods: To compare the MFSAF v4.0 to previous versions, an online REDCap survey was developed to assess symptoms (four symptom measures using 24-hour recall), physical functioning (PROMIS® Physical Function-Short Form 10a [PROMIS-PF]), and preference-based health status (EQ-5D-5L Index). Subjects were randomized to complete the (1) MFSAF v4.0 twice (for test-retest reliability) and MFSAF v2.0; or the (2) MFSAF v4.0, MFSAF v2.0, and MPN-10+MFSAF-revised. The three measures in each arm were administered in random order. PROMIS-PF and EQ-5D-5L were used as distractors between the 1st/2nd and 2nd/3rd symptom measures, respectively. The survey was promoted via multiple MPN-related websites and their affiliated Facebook pages June-July 2017. Differences between groups were assessed by ANOVA F-tests and within subjects by paired t-tests. Pearson correlations were computed for the entire sample and then within MF patients only. Cronbach's alphas assessed internal consistency and intraclass correlation coefficients assessed test-retest reliability.Results: 636 subjects accessed the survey of which 513 (81%) were eligible, consented, and attempted at least one of the symptom measures. Respondents with ET (37%), PV (41%), or MF (22%) were 81% female, 95% white, 68% residing in US, and 14% high school education or less with median age 59 (range 27-90). Among 511 with spleen information, 10/511 (2%) reported a prior splenectomy and 175/511 (34%) reported an enlarged spleen (91 [18%] unsure). Similar to other versions, MFSAF v4.0 Total Symptom Score (TSS; overall mean 20.4, SD 14.5, range 0-69) did not significantly differ across disease groups (ET mean 21.1, SD 15.4; PV mean 20.6, SD 14.4; MF mean 18.8, SD 12.9; p=.43) but did significantly differ between subjects with (mean 23.9, SD 14.8) and without enlarged spleen (mean 15.7, SD 12.1; p<.001). MFSAF v4.0 TSS was significantly correlated with the MFSAF v2.0 TSS (overall r=.96, MF r=.97), MPN-10 TSS (overall r=.92, MF r=.85), MFSAF-revised TSS (overall r=.97, MF r=.96), EQ-5D-5L Index (overall r=-.63, MF r=-.61), and PROMIS-PF (overall r=-.60, MF r=-.65; all p<.001). For individual symptoms, correlation among symptoms within the MFSAF v4.0 ranged from .40-.54 (MF .36-.63). Correlations between corresponding items on the different versions were similarly high (.84-.97). Three items of the MPN-10 and 1 item of the MFSAF v2.0 have higher mean scores, and 1 item of each of the MFSAF v2.0 and MFSAF-revised have a lower mean score relative to the MFSAF v4.0 (all p<.05). Internal consistency (overall .86, MF .84) and test-retest reliability (overall .98, 95% CI .97-.98; MF .98, .97-.99) of the MFSAF v4.0 TSS were high.Conclusions: The content validity of the MFSAF v4.0 was established through the harmonization process. Results of this study demonstrate favorable reliability and cross-sectional validity of the MFSAF v4.0 and a high level of comparability to the previous versions, both overall and for individual symptoms. The uniform use of this harmonized version in clinical trials may reduce the uncertainty of assessing symptom improvement and enable comparison across trials. The MFSAF v4.0 is now publicly available for use through the Critical Path Institute. DisclosuresPierson:Janssen: Employment. Trudeau:Janssen Global Services, LLC: Employment, Equity Ownership. Mesa:Ariad: Consultancy; Promedico: Research Funding; Celgene Corporation: Research Funding; CTI BioPharma Corp.: Research Funding; Galena Biopharma, Inc.: Consultancy; Incyte Corporation: Research Funding; Gilead Sciences, Inc.: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy.

Do magnetic field applications affect in vitro regeneration, growth, phenolic profiles, antioxidant potential and defense enzyme activities (SOD, CAT and PAL) in lemon balm (Melissa officinalis L.)?

Melissa officinalis L. (lemon balm) is a valuable medicinal plant used in the treatment of nervousness, cardiac failure, hypersensitivities, depression, insomnia, indigestion and colic.Objective of the first part of the study was to determine the effect of 3 different magnetic fields (MF-50 mT, 100 mT and 150 mT) with 5 different exposure times (5 min, 15 min, 30 min, 1 h and 3 h) on in vitro regeneration of explants containing preexisting meristem (axillary, shoot tip and hypocotyl buds). Regenerated shoots were also compared in terms of shoot length, root length, fresh-dry weight and % water content. In the second stage, regenerated shoots obtained from 3 different MF treatments for 1 h and no MF-treated shoots (control) were compared according to their phenolic profile, total phenol-flavonoid content, free radical scavenging activity, superoxide dismutase (SOD), catalase (CAT) and phenylalanine ammonium lyase (PAL) activities. The best regeneration was obtained with axillary buds exposed to 100 mT for 1 h (15.8 shoots at 100 % shoot frequency). Furthermore, 50 mT and 100 mT MF treatments improved the growth parameter and water contents of regenerated shoots. Comparison of 4 different sources (3 MF exposure and no exposure-control) found out that 50 mT MF treatment was the most effective for the enhancement of rosmarinic acid quantity, total phenol-flavonoid content, non-enzymatic antioxidant activity (IC50), stress related enzymatic antioxidant activity (SOD and CAT) and phenol production related PAL enzyme activity. Although 100 mT MF for 1 h treatment was found to be the most potent in regard to number of shoot formation, the most productive shoot length and fresh-dry weight was obtained with 50 mT MF exposure for 1 h. Considering the all results about growth parameters, medicinal quality (rosmarinic acid amount, total phenol-flavonoid content and antioxidant activity) and endurance capacity against stress (SOD, CAT and PAL activities), it can be concluded that exposure to 50 mT MF was the most effective treatment for in vitro culture of M. officinalis.

Chemical fertilizer reduction with organic fertilizer effectively improve soil fertility and microbial community from newly cultivated land in the Loess Plateau of China

Improving the soil quality of cultivated land generated by the Gully Land Consolidation Project could promote sustainable economic and ecological development in the hilly gully area of the Loess Plateau, China. A pot experiment with maize crop was conducted to assess the effects of different organic amendments and chemical fertilizer reduction on soil fertility and the microbial community in newly cultivated land, of which the amount of chemical fertilizer applied was half of the local conventional maize field (90 kg ha−1 of CO(NH2)2, 45 kg ha−1 of P2O5, and 60 kg ha−1 of K2O). The experiment involved six treatments: bare soil (CK), only maize (M), maize + chemical fertilizer (MF), maize + chemical fertilizer + organic fertilizer (MFO), maize + chemical fertilizer + biochar (MFB), and maize + chemical fertilizer + polyacrylamide (MFP). The results are as follows: (1) compared with the MF treatment, the MFO treatment exhibited the best effect on improving soil physicochemical properties, such as electrical conductivity (EC), soil organic carbon (SOC), nitrate nitrogen (NO3−-N), total nitrogen (TN), available phosphorus (AP) and available potassium (AK), followed by MFB and MFP. (2) The MFO treatment significantly (P < 0.05) improved the Species richness and Shannon indices of the bacteria, but its effects on fungal diversity index are not significant. (3) The MFO treatment increased the relative abundance of Betaproteobacteria, Alphaproteobacteria, Gammaproteobacteria and Gemmatimonadetes and decreased the relative abundance of Sordariomycetes and Agaricomycetes, and it also increased the functional abundance of Amino acid metabolism, Membrane transport, Xenobiotics biodegradation and metabolism, Undefined Saprotrophs and Arbuscular Mycorrhizal Fungi. (4) The TN and EC were the main driving factors of bacterial community structural variation, while TN and NO3−-N were the main factors for variation of fungal community structure. (5) The fresh weight and dry weight of maize increased significantly (P < 0.05) under all amendment treatments, among which the MFO treatment had the greatest effect. In conclusion, organic fertilizer application is the most effective measure for rapidly improving soil fertility and microbial community structure. Our findings have valuable implications for agricultural land productivity, food security and long-term sustainability of the environment.

Effects of long-term fertilizer management on soil labile organic carbon fractions and hydrolytic enzyme activity under a double-cropping rice system of southern China.

Fertilization is an effective way to improve soil quality, increase soil fertility and soil microbial diversity in paddy soil. To explore the changes of soil labile organic carbon (C) fractions and hydrolytic enzyme activity after 34 years fertilization treatments in a field experiment in double-cropping rice system of southern China. There were four treatments, including chemical fertilizer alone (MF), rice residue and chemical fertilizer (RF), 30% organic matter and 70% chemical fertilizer (OM), and the control without fertilizer input (CK). We measured soil organic carbon (SOC) content, soil labile organic C fractions, SOC related hydrolytic enzyme activity, correlation coefficients of soil enzyme activity with SOC content and its labile organic C fractions. The results showed that MF, RF and OM increased SOC content by 4.5%, 22.4% and 53.5%, respectively. Compared with MF and CK, RF and OM increased soil labile organic C fractions [cumulative C mineralization (Cmin), permanganate oxidizable C (KMnO4-C), particulate organic C (POC), dissolved organic C (DOC), light fraction organic C (LFOC), microbial biomass C (MBC)] and the proportion of each labile organic C fractions to total organic C. The contents of Cmin, KMnO4-C, POC, DOC, LFOC and MBC under OM treatment were 3.5, 3.1, 3.7, 1.9, 1.2 and 1.9 times higher than CK treatment, respectively. The proportion of labile organic C fractions to total organic C of RF and OM treatments was significantly higher than that in CK. The order of soil hydrolytic enzyme activity [α-glucosidase (αG), β-glucosidase (βG), β-xylosidase (βX), cellobiohydrolase (GBH), and N-acetyl-β-glucosaminidase (NAG)] was OM&gt;RF&gt;MF&gt;CK. The soil hydrolytic enzyme activity under OM treatment increased by 111.8%, 14.1%, 127.3%, 285.6% and 91.4% compared with CK, respectively. Furthermore, RF and OM treatments were beneficial to soil peroxidase (POD) activity. MF treatment was beneficial to soil polyphenol oxidase (PPO) activity. There was a significant positive correlation between soil hydrolytic enzyme activity and SOC content and its labile organic C fractions. In conclusion, the combined application of organic manure, rice straw returning and chemical fertilizer is an effective method to improve soil labile organic C fractions and hydrolytic enzyme activity in a double-cropping rice paddy field of southern China.

Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations. Additional disease features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival. Bone marrow morphology is the primary basis for diagnosis. Presence of JAK2, CALR, or MPL mutation, expected in around 90% of the patients, is supportive but not essential for diagnosis; these mutations are also prevalent in the closely related MPNs, namely polycythemia vera (PV) and essential thrombocythemia (ET). The 2016 World Health Organization classification system distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic ET in its presentation. Furthermore, approximately 15% of patients with ET or PV might progress into a PMF-like phenotype (post-ET/PV MF) during their clinical course. SRSF2, ASXL1, and U2AF1-Q157 mutations predict inferior survival in PMF, independent of each other and other risk factors. RAS/CBL mutations predicted resistance to ruxolitinib therapy. Very high risk abnormalities include -7, inv (3), i(17q), +21, +19, 12p-, and 11q-. Two new prognostic systems for PMF have recently been introduced: GIPSS (genetically-inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation- and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSSv2 includes, in addition, clinical risk factors. GIPSS features four and MIPSSv2 five risk categories. Observation alone is advised for MIPSSv2 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment for "very high" and "high" risk disease (estimated 10-year survival 0%-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. In non-transplant candidates, conventional treatment for anemia includes androgens, prednisone, thalidomide, and danazol; for symptomatic splenomegaly, hydroxyurea and ruxolitinib; and for constitutional symptoms, ruxolitinib. Fedratinib, another JAK2 inhibitor, has now been FDA-approved for use in ruxolitinib failures. Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for non-hepatosplenic EMH and extremity bone pain. A number of new agents, alone or in combination with ruxolitinib, are currently under investigation for MF treatment (ClinicalTrials.gov); preliminary results from some of these clinical trials were presented at the 2020 ASH annual meeting and highlighted in the current document.

Mallotus furetianus extract protects against ethanol-induced liver injury via the activation of the cAMP-PKA pathway.

The protective effects of Mallotus furetianus extract (MF) on liver fibrosis induced with ethanol were examined using in vivo and in vitro model. MF treatment suppressed plasma alanine aminotransferase and aspartate aminotransferase activities in ethanol plus carbon tetrachloride (CCl4)‐induced cirrhosis rat model. MF also suppressed the increase in type l collagen and α‐smooth muscle actin expression in the livers of ethanol plus CCl4‐induced rat by the maintenance of intracellular glutathione levels. Furthermore, we evaluated the effect of MF on the alcohol‐induced activation of hepatic stellate cells (HSCs), which are responsible for the increased production and deposition of the extracellular matrix in liver injury. Here, we observed the enhancement of the intracellular reactive oxygen species (ROS) levels and the increase in type I collagen and a‐SMA expression in HSCs activated with ethanol. However, the enhanced ROS levels were suppressed with the treatments of MF or diphenyleneiodonium (DPI). Furthermore, the treatment of MF or DPI suppressed the increase in type I collagen and a‐SMA expression activated with ethanol. We also observed that the treatment of MF or LY194002 suppressed the increase in type I collagen expression in HSCs activated with ethanol, suggesting that ethanol induced type I collagen expression via the PI3K‐Akt signaling pathway. On the other hand, the suppression of the synthesis of type I collagen in ethanol and MF‐treated HSCs was inhibited by H‐89. From these results, MF may suppress the increase in the activity of NADPH oxidase in HSCs activated with ethanol through the cAMP‐PKA pathway.

The impact of chronic exposure to a magnetic field on energy metabolism and locomotion of Blaptica dubia

Purpose: This study deals with a comparative analysis of the effects of chronic exposure to a static magnetic field (SMF) and an extremely low frequency magnetic field (ELF MF) in Blaptica dubia nymphs. The outcome of such treatment on insect and fat body mass, glycogen and total lipid content in the fat body and locomotion, as an energy demanding process, were examined.Materials and methods: One-month-old nymphs of B. dubia were exposed to an SMF (110 mT) or ELF MF (50 Hz, 10 mT) for 5 months. Their locomotion was monitored in the ‘open-field’ test for 10 min and expressed as travel distance, time in movement and average speed while in motion. After that, fat body mass and content of its main components (glycogen and total lipids) were determined. Nymph body mass was also estimated after 1 and 5 months of MF treatment.Results: Chronic exposure to the SMF and ELF MF decreased nymph body mass and glycogen content in the fat body but increased all examined parameters of locomotion. In addition, chronic SMF treatment elevated total lipid content in the fat body, while chronic ELF MF treatment reduced fat body mass and total lipid content.Conclusions: These findings indicate that B. dubia nymphs are sensitive to the applied MFs and possess different strategies for fuel usage in response to the SMF and ELF MF in order to satisfy increased energy demands and to overcome stressful conditions.

PINK1–PRKN mitophagy suppression by mangiferin promotes a brown-fat-phenotype via PKA-p38 MAPK signalling in murine C3H10T1/2 mesenchymal stem cells

ObjectiveMangiferin (MF), a xanthonoid derived from Mangifera indica, has shown therapeutic effects on various human diseases including cancer, diabetes, and obesity. Nonetheless, the influence of MF on non-shivering thermogenesis and its underlying mechanism in browning remains unclear. Here, our aim was to investigate the effects of MF on browning and its molecular mechanisms in murine C3H10T1/2 mesenchymal stem cells (MSCs). Materials/methodsTo determine the function of MF on browning, murine C3H10T1/2 MSCs were treated with MF in an adipogenic differentiation cocktail and the thermogenic and correlated metabolic responses were assessed using MF-mediated signalling. Human adipose-derived MSCs were differentiated and treated with MF to confirm its role in thermogenic induction. ResultsMF treatment induced the expression of a brown-fat signature, UCP1, and reduced triglyceride (TG) in C3H10T1/2 MSCs. MF also induced the expression of major thermogenesis regulators: PGC1α, PRDM16, and PPARγ and up-regulated the expression of beiging markers CD137, HSPB7, TBX1, and COX2 in both murine C3H10T1/2 MSCs and human adipose-derived mesenchymal stem cells (hADMSC). We also observed that MF treatment increased the mitochondrial DNA and improved mitochondrial homeostasis by regulating mitofission–fusion plasticity via suppressing PINK1–PRKN-mediated mitophagy. Furthermore, MF treatment improved mitochondrial respiratory function by increasing mitochondrial oxygen consumption and expression of oxidative-phosphorylation (OXPHOS)-related proteins. Chemical-inhibition and gene knockdown experiments revealed that β3-AR-dependent PKA-p38 MAPK-CREB signalling is crucial for MF-mediated brown-fat formation via suppression of mitophagy in C3H10T1/2 MSCs. ConclusionsMF promotes the brown adipocyte phenotype by suppressing mitophagy, which is regulated by PKA-p38MAPK-CREB signalling in C3H10T1/2 MSCs. Thus, we propose that MF may be a good browning inducer that can ameliorate obesity.

Fungal community composition change and heavy metal accumulation in response to the long-term application of anaerobically digested slurry in a paddy soil.

Anaerobically digested slurry (ADS) has been widely used as a liquid fertilizer in agroecosystems. However, there is scant information on the effects of successive ADS applications on heavy metals (HMs) accumulation and fungal community composition in paddy soils. In this study, we conducted a field experiment over 10 years to assess the changes in soil HMs and fungal community composition under the long-term application of ADS in a paddy field. The four treatments were (1) no fertilizer (CK); (2) mineral fertilizer and 270kgN ha-1 from urea (MF); (3) 270kgN ha-1 from ADS (ADS1); and (4) 540kgN ha-1 from ADS (ADS2). The results revealed that ADS application improved paddy soil fertility compared to that under the MF treatment by increasing soil organic C (SOC), total N (TN) and available potassium (AK). Long-term application of ADS significantly increased soil total and available Zn (TZn and AZn) concentrations as compared to those under the MF treatment. However, there were no significant differences in the total and available Cu concentrations or the total Pb concentration between the ADS and MF treatments. Sequence analysis showed that application of ADS increased the fungal richness indexes (Chao1 and ACE) compared to MF treatment. Principal coordinate analysis (PCoA) showed that the soil fungal community compositions were significantly separated by high levels of ADS application. Long-term application of ADS increased the relative abundance of classes Sordariomycetes, Dothideomycetes and Agaricomycetes by 20.8-29.0%, 107.3-141.4% and 289.5-387.5%, respectively, but decreased that of Pezizomycetes by 14.0-33.0% compared to that under the MF treatment. At the genus level, compared to those under the MF treatment, the relative abundances of Pyrenochaetopsis and Myrothecium were significantly increased by the application of ADS, but those of Mrakia and Tetracladium were significantly decreased. Redundancy analysis (RDA) revealed that SOC, AZn and AP were the three most important factors affecting the fungal community composition of the paddy soil. Our findings suggested that fungal community composition could be affected by changes in the chemical properties and heavy metal contents of paddy soil under high application of ADS in the long term.

Mangiferin Relieves Lipopolysaccharide-Induced Injury by Up-Regulating miR-181a via Targeting PTEN in ATDC5 Cells.

BackgroundMangiferin (MF) was reported to possess anti-inflammatory activity. This investigation tried to probe into the underlying mechanism of MF in osteoarthritis.MethodsATDC5 cells were pretreated with series concentrations of MF (0.1, 1, 5, 10, 15, 20 μM) for 2 h and then were exposed to lipopolysaccharide (LPS) (5 μg/ml) for 12 h to construct the inflammatory injury model. The cell viability, productions of pro-inflammatory cytokines and enzymes were respectively measured by employing CCK-8 assay, western blot, ELISA, and quantitative reverse-transcription (qRT)-PCR. miR-181a expression was altered by employing cell transfection. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) method was employed for detection of reactive oxygen species (ROS) generation. Dual luciferase activity assay was conducted for analyzing the relationship between miR-181a and PTEN. The underlying mechanism was determined by employing western blot.ResultsHigh doses of MF treatment (15 and 20 μM) noticeably induced inflammatory injury exhibiting as increased the productions of pro-inflammatory cytokines, enzymes and ROS, activated NF-κB pathway and deactivated PTEN/PI3K/AKT pathway in ATDC5 cells. Besides, MF treatment notably remitted LPS-induced inflammatory injury through deactivation of NF-κB pathway and activation of PTEN/PI3K/AKT pathway. PTEN was a target of miR-181a. Inhibition of miR-181a remarkably reversed MF-triggered impacts on ATDC5 cells.ConclusionMF attenuated LPS-induced inflammatory damage through miR-181a/PTEN axis and thereby inhibiting NF-κB pathway and activating PI3K/AKT pathway.

Partial substitution of mineral fertilizer with biofertilizer enhances cauliflower nutritional quality, yield, and soil characteristics

AbstractCauliflower (Brassica oleracea L. var. botrytis L.) is as an important ingredient in many healthy diets worldwide, but there is a lack of scientific knowledge about fertilizer management during cauliflower production. We conducted field experiments in Yuzhong, China, in 2015 and 2016 to determine the effects of the integrated use of biofertilizer and a reduced rate of mineral fertilizers on cauliflower growth, quality, and yield and on soil characteristics. Three different rates of mineral fertilizer (60, 80, and 100% of the mineral fertilizers; 100% rate = 400 N kg ha−1, 225 kg P2O5 ha−1, 125 kg K2O ha−1) and 500 kg ha−1 biofertilizer were applied to the crop with three replicates. The results showed that the use of the mineral fertilizer at 80% in combination with biofertilizer (80% BF) increased the vitamin C content of cauliflower heads by 39.5% in 2015 and 43.6% in 2016 compared with the 100% mineral fertilization treatment (100% MF). The 80% BF treatment decreased the nitrate content by 27.1% in 2015 and 27.6% in 2016 and improved the soluble sugar contents by 19.1% in 2015 and 29.5% in 2016 compared with the 100% MF treatment. However, the effect of the 80% BF treatment on marketable yield was found to be nonsignificant. Biofertilization also improved the soil organic matter, available N, P, and K, and enzyme activities. We observed that conjugative use of biofertilizer and a reduction in mineral N–P–K fertilizer can be used successfully in cauliflower production without compromising marketable yields.

The decreased permittivity of zebrafish embryos culture medium by magnetic fields did not affect early development of zebrafish embryos.

Epidemiological studies have shown associations between exposure to environmental extremely low frequency magnetic fields (ELF-MF) and health effects, but the mechanisms of ELF-MF induced biological effects remain unclear. We hypothesized that ELF-MF may regulate functions of tissues or cells via its effects on surrounding environment, e.g., culture medium. To test this hypothesis, we investigated the effects of 50HzMF on the relative permittivity of zebrafish embryos culture medium as well as of MF-exposed medium on zebrafish embryos development. The responses of medium to 50HzMF exposure were evaluated by a phase-sensitive surface plasmon resonance (SPR) system. The results demonstrated that MF treatment decreased relative permittivity of zebrafish embryos medium in a dose and time-dependent way. Interestingly, the decreased permittivity induced by MF exposure gradually recovered and approached to the base level when the exposure was removed off. However, MF-exposed medium did not trigger adverse consequences of embryos during zebrafish embryonic development, including mortality, malformation, hatching and heart rate when the MF pre-exposed medium was subjected to one cell-stage embryos. Moreover, the MF-exposed medium did not induce apoptosis of zebrafish embryos at 48 and 72h post fertilization. Our data demonstrated that the relative permittivity of zebrafish embryos medium was decreased by MF exposure, whereas this decrease failed to result in abnormal development of zebrafish embryos.

Comparing the effects of proactive treatment with tacrolimus ointment and mometasone furoate on the epidermal barrier structure and ceramide levels of patients with atopic dermatitis

Background The epidermal skin barrier and lipids that are integral to its structure are impaired in atopic dermatitis (AD). Current treatment guidelines include proactive therapy. Objective This study assessed the effect of 12 weeks of proactive treatment with tacrolimus ointment 0.1% (TAC) compared with mometasone furoate cream (MF) on specific skin barrier lipids in patients with AD who previously received 10 days of reactive treatment with either agent. Methods This was an open-label, non-interventional study. In the reactive phase, forearm lesions in 20 patients were treated with either TAC or MF twice daily for 10 days. In the subsequent proactive phase, patients applied TAC or MF twice weekly for 12 weeks (n = 16 patients). Results Over the 12-week proactive treatment period, the mean local SCORAD significantly decreased in the TAC and MF treatment group. Levels of total and individual ceramides increased in both groups. Normalized intercellular lipid lamellae values were significantly higher with proactive TAC treatment than MF and undistinguishable from healthy skin. Conclusion The results show that proactive treatment with TAC is superior in restoring the skin barrier.

Effect of bypass fat on growth and body condition score of male Beetal goats during summer

The objective of the present study was to investigate the effect of feeding rumen bypass fat on the growth of male Beetal goats. Twenty-seven male kids with an average bodyweight of 34 ± 1.8 kg (mean ± SD) and aged 12 to 15 months were randomly divided into three treatment groups under a completely randomized design. The treatments consisted of : i) CON, basal diet without added fat (basal diet of chopped sorghum with 0.75 kg concentrate per animal); ii) MF, basal diet with added fat at 2.5% of dry matter in concentrate (Energizer-RP10, Scothorn Nutrition, Malaysia); and iii) HF, basal diet with added fat at 5% of dry matter in concentrate. Dry matter intake (DMI) and faecal score were recorded daily. Live bodyweight was recorded fortnightly. Linear body measurements, which included wither height (WH), heart girth (HG), body length (BL), and body condition scores (BCS), were recorded monthly. The results indicated that the addition of bypass fat in concentrate did not affect DMI linearly. However, a quadratic trend of DMI was observed in response to fat addition (P &lt;0.1). The average daily gain was similar for CON, MF, and HF treatment groups (P &gt;0.05). Moreover, the addition of bypass fat did not affect the BCS, WH, HG, and BL. The HF group had a higher faecal score than the CON and MF groups (P &lt;0.05). The current findings conclude that the addition of bypass fat in diets did not improve the growth performance of yearling Beetal male goats.Keywords: average daily gain, body measurements, supplemental fat

PSI-11 Anti-inflammatory treatment modifies epigenetics changes to muscle tissue caused by altered nutrient demand in early lactation dairy cows

Abstract Short-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to alter whole-lactation milk yield; perhaps because epigenetic modifications are responsible for long-term effects, although mechanisms are unclear. Altered nutrient demand due to fasting or exercise in other species has been shown to affect DNA methylation in muscle tissue. Our objective was to determine if NSAID treatment or alterations to nutrient demand have epigenetic effects on muscle tissue in early lactation. In this study, 33 multiparous Holstein cows were enrolled at parturition and randomly assigned to milking frequency (MF; 1× or 3×/day), and either sodium salicylate (SS; 2.3 g/L administered via drinking water) or control (CTL; molasses carrier alone) treatment in a 2×2 factorial design, beginning ~24 h postpartum. Milking frequency treatments were designed to alter nutrient demand, and 3× milked increased milk yield by 24%. After 5 days of treatment, tissue biopsies were collected from the Longissimus dorsi muscle and snap-frozen. DNA was isolated and global methylation (GM) was assessed with a 5-methylcytosine enzyme-linked immunosorbent assay. An interaction between MF and SS treatment was detected (P = 0.02), with GM of muscle tissue decreased by more frequent milking only in the CTL cows (4.9 and 1.4 ± 1.0% of DNA methylated for 1× and 3×, respectively; P &lt; 0.001). No effect of MF was detected in SS-treated cows (2.9 and 2.4 ± 1.0% of DNA methylated for 1× and 3×, respectively; P &gt; 0.1). Observed changes to DNA methylation in muscle tissue due to altered nutrient supply are consistent with results reported after fasting and exercise. Additionally, increased demand for milk component precursors in 3×-milked cows may alter the availability of methyl donors for DNA methylation. Our data support a link between SS and epigenetic changes, but further research is needed to determine how SS may have altered the muscle DNA methylation response to nutrient demand.

Assessment of induced genomic instability in rat primary astrocytes exposed to intermediate frequency magnetic fields

We investigated whether exposure to intermediate frequency magnetic fields (IF MFs) could induce or enhance genomic instability in primary astrocytes. Rat primary astrocytes were exposed to vertical or horizontal 7.5 kHz, 300 μT MF for 24 h. To study possible combined effects with known genotoxic agents, the cells were exposed for 3 h to menadione or methyl methanesulfonate after the MF treatment. Induced genomic instability was evaluated 36 days after exposures using the Comet assay and flow cytometric scoring of micronuclei. Exposure to 7.5 kHz, 300 μT MF did not induce genomic instability alone or in combination with chemicals in measurements performed several cell generations after exposure.