[Metabolomic study on urine of chronic inflammation rats treated with Buyang Huanwu Decoction based on UPLC-Q-TOF-MS].

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 µg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

The influence of spermidine on the build-up of fucoxanthin in Isochrysis sp. Acclimated to varying light intensities.

Spermidine is a type of important growth regulator, which involved in the biosynthesis of photosynthetic pigments, and has the function of promoting cell proliferation. In this study, Isochrysis sp. was selected as the research object to explore the effects of spermidine supplementation on the growth of algal cells and fucoxanthin synthesis under different light intensities. The results showed that the cell density (5.40 × 106 cells/mL) of algae were the highest at 11 days under the light intensity of 200 µmol·m-2·s-1 and spermidine content of 150 µM. The contents of diadinoxanthin (1.09 mg/g) and fucoxanthin (6.11 mg/g) were the highest when spermidine was added under low light intensity, and the growth of algal cells and fucoxanthin metabolism were the most significant. In the carotenoid synthesis pathway, PDS (phytoene desaturase) was up-regulated by 1.96 times and VDE (violaxanthin de-epoxidase) was down-regulated by 0.95 times, which may promote fucoxanthin accumulation.

Fucoxanthin, a marine derived carotenoid, attenuates surgery-induced cognitive impairments via activating Akt and ERK pathways in aged mice.

BACKGROUND: Fucoxanthin is the most abundant marine carotenoid derived from brown seaweeds, possesses antioxidant, anti-inflammatory, and neuroprotective properties, and might be benefit for the treatment of neurological disorders. Post-operative cognitive dysfunction (POCD) is a neurological symptom with learning and memory impairments, mainly affecting the elderly after surgery. However, there is no effective treatments for this symptom. PURPOSES: In this study, we evaluated the neuroprotective effects of fucoxanthin against POCD in aged mice after surgery. STUDY DESIGN AND METHODS: The animal model of POCD was established in 12 - 14 month aged mice with a laparotomy. Curcumin was used as a positive control. The beneficial effects of fucoxanthin on POCD was analyzed by behavioral tests. Pro-inflammatory cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA). And the expressions of key proteins in the Akt and ERK signaling pathways were analyzed by Western blotting analysis. The morphology of microglial cells and astrocytes was explored by immunohistochemical staining. The activity of antioxidant superoxide dismutase (SOD) and catalase (CAT) were measured by anti-oxidative enzyme activity assays. RESULTS: Fucoxanthin at 100 - 200 mg/kg significantly attenuated cognitive dysfunction, with a similar potency as curcumin, in aged mice after surgery. In addition, fucoxanthin and curcumin significantly increased the expression of pAkt, prevented the activation of microglial cells and astrocytes, and inhibited the secretion of pro-inflammatory interleukin-1ß (IL - 1ß) and tumor necrosis factor-α (TNF-α). Furthermore, fucoxanthin and curcumin elevated the ERK pathway and potently increased the activity of antioxidant enzymes. Most importantly, U0126, an inhibitor of the ERK pathway, and wortmannin, an inhibitor of the Akt pathway, significantly abolished the cognitive-enhancing effects, as well as the inhibition of neuroinflammation and the reduction of oxidative stress, induced by fucoxanthin in aged mice after surgery. CONCLUSION: Fucoxanthin might be developed as a functional food or drug for the treatment of POCD by inhibiting neuroinflammation and enhancing antioxidant capacity via the activation of the Akt and ERK signaling pathways.

Fertilization as the most critical factor affecting yield response and agronomic efficiency of phosphorus in Chinese rice production: evidence from multi-location field trials.

BACKGROUND: Efficient utilization of phosphorus (P) has been a major challenge for sustainable agriculture. However, the responses of fertilizer rate, region, soil properties, cropping systems and genotypes to P have not been investigated comprehensively and systematically. RESULTS: A comprehensive analysis of 9863 fertilizer-P experiments on rice cultivation in China showed that rice yield  increased first and then fell down with the addition of P fertilizer, and the highest yield of 7963 kg ha-1 was observed under 100% P treatment. Under 100% P treatment, the yield response of applied P (YRP ) and agronomic efficiency of applied P (AEP ) were 12.8% and 30.1 kg ha-1 , respectively. Lower soil pH (< 5.5) and organic matter (< 30.0 g kg-1 ) were associated with lower YRP and AEP . By contrast, soil available P < 25.0 mg kg-1 resulted in decreased YRP (15.3 to 11.4%) and AEP (32.3 kg kg-1 to 26.2 kg kg-1 ), whereas soil available P > 25.0 mg kg-1 maintained the relatively stable YRP and AEP . Also, the YRP and AEP were significantly higher for single-cropping rice compared to other cropping systems. Moreover, the rice genotypes such as 'Longdun', 'Kendao' and 'Jigeng' had higher YRP and AEP than the average value. Overall, the fertilizer-P rate was the primary factor affecting YRP and AEP , and the recommended P fertilizer rate can be reduced by 9-21 kg P ha-1 compared to existing expert recommendations. CONCLUSION: The present study highlights the role of fertilizer-P rate in maximizing the YRP and AEP , thereby providing a strong basis for future fertilizer management in rice cultivation systems. © 2023 Society of Chemical Industry.

Proteomics and phosphoproteomics analysis identifies liver immune protein markers in large yellow croakers (Larimichthys crocea) fed a soybean oil-based diet.

Dietary fish oil (FO) replacement has led to an inflammatory response in fish species. This study aimed to identify immune-related proteins in the liver tissue of fish fed a FO-based or soybean oil (SO)-based diet. By conducting proteomics and phosphoproteomics analyses, a total of 1601 differentially expressed proteins (DEPs) and 460 differentially abundant phosphorylated proteins (DAPs) were identified, respectively. Enrichment analysis revealed immune-related proteins involved in bacterial infection, pathogen identification, cytokine production, and cell chemotaxis. The mitogen-activated protein kinase (MAPK) pathway exhibited significant alterations in both protein and phosphorylation levels, with several hub DEPs and DAPs associated with MAPK pathway and leukocyte transendothelial migration being notable. In vitro experiments indicated that linolenic acid (LNA), derived from SO, inhibited the expression of NF-E2-related factor 2 (Nrf2), but increased the expression of signaling proteins linked to nuclear factor κB (NF-κB) and MAPK pathways. Transwell assays indicated that treatment of liver cells with LNA promoted macrophage migration. Collectively, the results showed that the SO-based diet upregulated the expression of NF-κB signaling-related proteins and activated the MAPK pathway, promoting immune cell migration. These findings provide novel insights for developing effective solutions to alleviate health problems caused by dietary high levels of SO inclusion.

Acupotomy in the treatment of tenosynovitis of hand flexor tendons: A systematic review and meta-analysis.

BACKGROUND: Acupotomy was used to treat tenosynovitis of hand flexor tendons (THFT) in China. But it's uncertain about the efficacy of acupotomy for THFT. We plan to evaluate the efficacy and safety about acupotomy therapy in the treatment of THFT through this review. METHODS: The protocol about this review was registered in PROSPERO (registration number: CRD42022330568). We searched 6 databases from their respective inception dates to January 11, 2022. Studies searched was screened by our reviewers, and then the raw data was filtered out. We used RevMan 5.3 software to perform statistical analysis. RESULTS: 11 studies involving 828 patients were shortlisted. The experimental group showed obvious advantages compared with the control group, such as effective rate (odds ratio [OR] = 6.77, 95% CI [confidence intervals] = [3.89, 11.77], P < .00001), cure rate (OR = 3.32, 95% CI = [1.81, 6.11], P = .0001) and Vas score (MD = -1.21, 95% CI = [-2.00, -0.42], Z = 3.01, P < .003). CONCLUSIONS: According to the above results, Acupotomy is an effective and safe treatment for THFT. So it should be recommended for the treatment of THFT patients.

The phytochemical constituents and protective effect of Fritillaria hupehensis on acute lung injury.

Acute lung injury (ALI), a severe respiratory disorder, frequently develops into acute respiratory distress syndrome (ARDS) without timely treatment and scores highly in terms of morbidity and mortality rates. Fritillaria hupehensis is a famous traditional Chinese medicine with antitussive, expectorant and anti-asthmatic effect. Here, the effects of F. hupehensis extracts on lipopolysaccharide (LPS)-induced ALI mice were evaluated for the first time. We showed ethyl acetate fraction (EAF) significantly reduced the leukocytes and neutrophils of bronchoalveolar lavage fluid (BALF) and the lung index as well as pro-inflammatory cytokines (TNF-α and IL-6) of lung homogenates but increasing the anti-inflammatory cytokines (IL-4 and IL-10). Additionally, the alleviation of EAF treatment on lung injury was verified through histopathological observations. Subsequent phytochemical investigation on bioactive fraction led to isolation of 17 compounds including two new, in which compounds 2, 5 and 6 exhibited better anti-inflammatory effect on LPS-induced 16 human airway epithelial (16HBE) cells model by inhibiting the production of CRP and PCT. Furthermore, compound 2 suppressed the LPS-induced upregulation of proteins containing p-p65, COX-2, Caspase-1 and IL-18. In summary, F. hupehensis alleviating LPS-induced ALI in mice may be associated with the anti-inflammatory activity of steroidal alkaloids by suppressing the NF-κB-regulated pro-inflammatory proteins.

The Protective Effect of Sweet Potato Root Tuber on Chemotherapy-Induced Thrombocytopenia.

SCOPE: Sweet potato (Ipomoea batatas L.) is one of the leading crops worldwide, containing high nutritional components such as fiber and polyphenols. Root tuber of Simon 1 (SIMON), a cultivar of sweet potato, is a folk food in China with a hemostasis function but lacking experimental data support. METHODS AND RESULTS: Now the protective effect of SIMON on chemotherapy-induced thrombocytopenia (CIT), a serious complication of cancer treatment, is investigated for the first time by a CIT mouse model induced by intraperitoneal injection of carboplatin. As a result, SIMON raises the number of peripheral platelets, white blood cells, and bone marrow nucleated cells in CIT mice significantly. Besides, carboplatin-induced atrophy of the thymus, spleen, and disordered metabolism of the inflammatory immune system and glycerophospholipids are also reversed by SIMON. Phytochemical analysis of SIMON indicates 16 compounds including eight phenolic derivatives, which might be associated with its anti-CIT bioactivity. CONCLUSION: Sweet potato (SIMON) may be an efficient function food in the prevention of bleeding disorders.

Exploring the Mechanism of Yiqi Qingre Ziyin Method in Regulating Neuropeptide Expression for the Treatment of Atrophic Rhinitis.

Atrophic rhinitis (AR) is a chronic disease that causes severe structural changes to the nasal mucosa leading to squamous epithelial metaplasia. However, treatment regarding AR remains a major challenge. We used network pharmacology and molecular docking methods to explore the potential mechanisms of the Yiqi Qingre Ziyin method to modulate neuropeptides in the treatment of AR. The active ingredients of the Yiqi Qingre Ziyin method and their targets of action were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database Analysis Platform (TCMSP). Disease targets for AR were obtained from four databases: GeneCards, PharmGKB, DrugBank, and Online Mendelian Inheritance in Man (OMIM). A total of 59 active ingredients, 39 potential targets, and 76 relevant neuropeptides were obtained after deduplication. We constructed target interaction networks with the STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the 14 potential target proteins. We used Cytoscape software to construct the "drug-active ingredient-potential target" and "ingredient-target-pathway" networks of the Yiqi Qingre Ziyin method for treating AR. Molecular docking results suggest that dipeptidyl peptidase 4 (DPP4), opioid receptor gene d1 (OPRD1), and opioid receptor m1 (OPRM1) are key targets for the Yiqi Qingre Ziyin method. Therefore, this study proposed a potential mechanism for the treatment of AR by affecting the expression of neuropeptide-related genes (including DPP4, OPRD1, and OPRM1), which may potentially improve the immune microenvironment of the nasal mucosa.

Alteration of Growth Performance, Antioxidant Capacity, Tissue Fatty Acid Profiles, and Lipid Metabolism of Mud Crab (Scylla paramamosain) Juvenile in Response to Different Dietary Arachidonic Acid Levels.

An eight-week feeding trail was carried out to investigate the impacts of different dietary arachidonic acid (ARA) supplementations on growth performance, antioxidant capacity, tissue fatty acid profiles, and lipid metabolism of mud crab (Scylla paramamosain) juvenile. Six isonitrogenous (480 g kg-1 crude protein) and isolipidic (80 g kg-1 crude lipid) diets were formulated to contain 0.40, 2.50, 4.60, 8.90, 12.50, and 15.70 g ARA kg-1 (dry matter), respectively. Each experimental treatment included 24 mud crab juveniles (initial weight 11.29 ± 0.09 g) and was assigned to triplicate groups (n = 3). Crabs fed diets with 2.50, 4.60, and 8.90 g kg-1 ARA presented significantly higher percent weight gain (PWG) and specific growth rate (SGR) than those fed the other diets. Based on two-slope broken-line and quadratic curve regression analysis of PWG against dietary ARA levels, optimal dietary ARA levels were determined to be 5.20 g kg-1 and 6.20 g kg-1, respectively. Crabs fed with 4.60 g kg-1 ARA diet showed the lowest activities of alanine aminotransferase (ALT) as well as aspartate aminotransferase (AST) in hemolymph among all treatments. In hemolymph and hepatopancreas, total antioxidant capacity (T-AOC), the activities of total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) as well as the contents of reduced glutathione (GSH) rose first and then dropped with the increase of dietary ARA levels, while the concentration of malondialdehyde (MDA) showed an opposite trend. Tissue fatty acid profiles reflected diets fatty acid compositions. The ARA contents in hepatopancreas and muscle significantly increased with the increase of dietary ARA levels. Furthermore, the areas of blasenzellen (B) cells and restzellen (R) cells were significantly downregulated with the increase of dietary ARA levels. Crabs fed with 0.40 g kg-1 ARA diet showed significantly higher gene expression levels of fatty acid synthase (fas) as well as acetyl-CoA carboxylase (acc) among all treatments. Relative gene expression levels of 6-phosphogluconate dehydrogenase (6pgd) as well as glucose-6-phosphate dehydrogenase (g6pd) have been significantly upregulated in 0.40 and 2.50 g kg-1 ARA groups. Relative gene expression level of fatty acid binding protein 1 (fabp1) significantly increased in 4.60, 8.90, 12.50, and 15.70 g kg-1 ARA groups. However, the gene expression levels of fatty acid binding protein 4 (fabp4) as well as scavenger receptor class 2 (srb2) have not been influenced by dietary ARA levels. What is more, crabs fed diets with 4.60, 8.90, 12.50, and 15.70 g kg-1 ARA had a significantly higher expression level of carnitine palmitoyltransferase 1 (cpt1) than those fed diets with 0.40 and 2.50 g kg-1 ARA. In summary, optimum dietary ARA can promote growth, enhance antioxidant capacity, and improve health of mud crab juveniles. It also demonstrated that lipogenesis has been restrained with the increasing dietary ARA levels. These findings could provide theoretical guidance and reference for the lipid nutrition research as well as the development of the commercial diet in mud crab.

Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets.

Fucoxanthin, one of the most abundant carotenoids from edible brown seaweeds, for years has been used as a bioactive dietary supplement and functional food ingredient. Recently, fucoxanthin was reported to penetrate the blood-brain barrier, and was superior to other carotenoids to exert anti-neurodegenerative disorder effects via acting on multiple targets, including amyloid protein aggregation, oxidative stress, neuroinflammation, neuronal loss, neurotransmission dysregulation and gut microbiota disorder. However, the concentration of fucoxanthin required for in vivo neuroprotective effects is somewhat high, and the poor bioavailability of this molecule might prevent its clinical use. As such, new strategies have been introduced to overcome these obstacles, and may help to develop fucoxanthin as a novel lead for neurodegenerative disorders. Moreover, it has been shown that some metabolites of fucoxanthin may produce potent in vivo neuroprotective effects. Altogether, these studies suggest the possibility for future development of fucoxanthin as a one-compound-multiple-target or pro-drug type pharmaceutical or nutraceutical treatment for neurodegenerative disorders.Trial registration: ClinicalTrials.gov identifier: NCT03625284.Trial registration: ClinicalTrials.gov identifier: NCT02875392.Trial registration: ClinicalTrials.gov identifier: NCT03613740.Trial registration: ClinicalTrials.gov identifier: NCT04761406.

A new antibacterial chromone from a marine sponge-associated fungus Aspergillus sp. LS57.

Chemical investigation for the secondary metabolite of marine-derived fungus Aspergillus sp. LS57 resulted in the isolation of one new chromone named aspergilluone A (1) containing a chromone skeleton fused with an unusual hydrogenation cyclopentanoid ring, along with three known compounds 2-4. The structure of 1 was elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric analyses. Its absolute configuration was established by combining NMR quantum chemical calculations and comparison between the experimental and calculated circular dichroism (CD) curves. Additionally, the antibacterial assay of compound 1 was performed. As a result, compound 1 showed in vitro anti-Mycobacterium tuberculosis with MIC value of 32 µg/mL, together with moderate antibacterial activity against Staphylococcus aureus (MIC values = 64 µg/mL), and exhibited feeble activity against gram-positive Bacillus subtilis and gram-negative pathogen Escherichia coli (both MICs = 128 µg/mL).

Soil Phosphorus Pools, Bioavailability and Environmental Risk in Response to the Phosphorus Supply in the Red Soil of Southern China.

Excess phosphorus (P) accumulation in the soil can change the bioavailability of P and increase the leaching risks, but the quantitative evaluation of these responses in acidic red soil is lacking. This study aimed to investigate the composition of soil P fractions under different phosphorus apparent balances (PAB) in acidic red soil and the bioavailability and the leaching change-points of different P fractions. Five phosphorus (P) fertilization rates were applied (0, 16.38, 32.75, 65.50, 131.00 kg P·ha-1) in every sweet corn cultivation from the field experiment, and the treatments were marked as P0, P1, P2, P3, and P4, respectively. The PAB showed negative values in P0 and P1 which were -49.0 and -15.0 kg P·ha-1 in two years, respectively. In contrast, PAB in P2 as well as in P3 and P4 were positive, the content ranging from 40.2 to 424.3 kg P·ha-1 in two years. Per 100 kg ha-1 P accumulate in the soil, the total P increased by 44.36 and 10.41 mg kg-1 in the surface (0-20 cm) and subsurface (20-40 cm) soil, respectively. The content of inorganic P fractions, including solution phosphate (Sol-P), aluminum phosphate (Al-P), iron phosphate (Fe-P), reduction phosphate (Red-P), and calcium phosphate (Ca-P), significantly increased by 0.25, 16.22, 22.08, 2.04, and 5.08 mg kg-1, respectively, in surface soil per 100 kg ha-1 P accumulated in the soil. Path analysis showed that the most important soil P fractions contributing to Olsen-P were Sol-P and Al-P, which can directly affect Olsen-P, and their coefficients were 0.24 and 0.73, respectively. Furthermore, the incubation experiments were conducted in the laboratory to investigate the leaching risk of different P fractions, and they showed Sol-P was a potential source of leaching, and the leaching change-points of Al-P and Fe-P were 74.70 and 78.34 mg·kg-1, respectively. Continuous P that accumulated in soil changed the composition of P fractions, and the bioavailability as well as the leaching risks increased. This is important in optimizing soil P fertilization management in agricultural ecosystems based on the bioavailability and critical levels for leaching of P fractions.

[Molecular mechanism analysis of Erzhi Wan in treatment of aging based on network pharmacology].

This present study aimed to explore the molecular mechanism of Erzhi Wan(a prescription of nourishing Yin and toni-fying liver and kidney) in treatment of aging by network pharmacology. The active constituents and target proteins of Erzhi Wan were searched from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and PubChem databases respectively. Aging-related genes were searched from Gene and HAGR databases. Based on the Ingenuity Pathway Analysis(IPA), we analyzed the common molecular network, biological pathway and interaction sites between these two parts, and verified some of them by Western blot. Twelve active constituents of Erzhi Wan were screened by TCMSP databases, 69 protein targets were predicted through PubChem, and 148 aging-related genes were found in Gene and HAGR databases. IPA comparison showed that the molecular networks of these two were complex, with diversity of biological functions. The common pathways involved 292 pathways, mainly related to tumors. They acted on hypoxia inducible factor-1α gene(HIF1α), nuclear factor-E2 related factor(Nrf2/NFE2 L2), tumor necrosis factor(TNF) and other sites. Western blot results suggested that Erzhi Wan could down-regulate the expression of HIF1α, with statistical difference(P<0.05). It was concluded that, Erzhi Wan could intervene aging through improving pseudo-hypoxic microenvironment and inflammation. The molecular mechanism of Erzhi Wan in delaying aging was preliminarily revealed, which laid a foundation for further stu-dying the anti-aging mechanism of Erzhi Wan, and also provided a reference for the compatibility mechanism and extended application of Chinese medicine compounds.

Gegen Qinlian Decoction Coordinately Regulates PPARγ and PPARα to Improve Glucose and Lipid Homeostasis in Diabetic Rats and Insulin Resistance 3T3-L1 Adipocytes.

Gegen Qinlian Decoction (GQD), a well-documented traditional Chinese Medicine (TCM) formula, was reported with convincing anti-diabetic effects in clinical practice. However, the precise antidiabetic mechanism of GQD remains unknown. In this study, the anti-hyperglycemic and/or lipid lowering effects of GQD were demonstrated in high-fat diet with a low dose of streptozotocin induced diabetic Sprague-Dawley rats and insulin resistance (IR)-3T3-L1 adipocytes. GQD treatment increased expression and activity levels of both PPARγ and PPARα in adipocytes, which transcriptionally affected an ensemble of glucose and lipid metabolic genes in vivo and in vitro. The results clearly indicated that GQD treatment intervened with multiple pathways controlled by concomitantly downstream effects of adipocytic PPARγ and PPARα, to influence two opposite lipid pathways: fatty acid oxidation and lipid synthesis. Antagonist GW9662 decreased the mRNA expression of Pparγ and target genes Adpn and Glut4 whereas GW6471 decreased the mRNA expression of Pparα and target genes Cpt-1α, Lpl, Mcad, Lcad, Acox1, etc. Nuclear location and activity experiments showed that more PPARγ and PPARα shuttled into nuclear to increase its binding activities with target genes. GQD decreased the phosphorylation level of ERK1/2 and/or CDK5 to elevate PPARγ and PPARα activities in IR-3T3-L1 adipocytes through post-translational modification. The increase in p-p38MAPK and SIRT1 under GQD treatment may be attributed to partially reduce PPARγ adipogenesis activity and/or activate PPARα activity. Compared with the rosiglitazone-treated group, GQD elevated Cpt-1α expression, decreased diabetic biomarker Fabp4 expression, which produced an encouraging lipid profile with triglyceride decrease partially from combined effects on upregulated adipocytic PPARγ and PPARα activities. These results suggested that GQD improved diabetes by intervening a diverse array of PPARγ and PPARα upstream and downstream signaling transduction cascades, which jointly optimized the expression of target gene profiles to promote fatty acid oxidation and accelerate glucose uptake and utilization than PPARγ full agonist rosiglitazone without stimulating PPARα activity. Thus, GQD showed anti-diabetic/or antihyperglycemic effects, partially through regulating adipocytic PPARα and PPARγ signaling systems to maintaining balanced glucose and lipid metabolisms. This study provides a new insight into the anti-diabetic effect of GQD as a PPARα/γ dual agonist to accelerate the clinical use.

New antifungal tetrahydrofuran derivatives from a marine sponge-associated fungus Aspergillus sp. LS78.

Two new tetrahydrofuran derivatives named aspericacids A and B (1 and 2) were isolated from the metabolites produced by the sponge-associated Aspergillus sp. LS78. They represented an unusual type of tetrahydrofuran derivatives, possessing 2,5-disubstituted tetrahydrofuran ring coupled with a chain unsaturated fatty acid. The planar structures of 1 and 2 were determined by HRESIMS, 1D and 2D NMR spectroscopy. The absolute configuration of 1 was assigned using both experimental and computational electronic circular dichroism (ECD). In addition, aspericacid A (1) exhibited in vitro antifungal activity (MIC = 50 µg/mL), but 2 showed not significantly activity against any of the tested strains with the MIC values of 128 µg/mL.

Kelp cultivation effectively improves water quality and regulates phytoplankton community in a turbid, highly eutrophic bay.

Coastal eutrophication and its associated harmful algal blooms have emerged as one of the most severe environmental problems worldwide. Seaweed cultivation has been widely encouraged to control eutrophication and algal blooms. Among them, cultivated kelp (Saccharina japonica) dominates primarily by production and area. However, the responses of water quality and phytoplankton community to kelp farming remain unclear. Here, thirteen cruises were conducted in the kelp farms and control areas in the turbid, highly eutrophic Xiangshan Bay of the East China Sea from 2008 to 2015. Results indicated that kelp cultivation slightly increased dissolved oxygen and pH, but reduced dissolved inorganic nitrogen and phosphorus. We estimated that kelp harvesting would remove 297 t of nitrogen and 42 t of phosphorus from this bay annually. Because of decreased flow velocity, turbulence, and sediment resuspension, kelp farming greatly reduced suspended solids and increased transparency, resulting in increases in phytoplankton chlorophyll a and abundance. Additionally, kelp farming appreciably increased phytoplankton species number, Marglef richness, and Shannon-Wiener diversity indices by 51.6%, 40.1%, and 13.1%, respectively. Analysis of similarity and similarity percentages demonstrated that phytoplankton community composition differed significantly between the farm and control area, which was mostly attributed to long-chained diatoms and single-celled dinoflagellates. However, after the kelp harvesting, all measurements of water quality and phytoplankton biomass, diversity, and community composition exhibited no significant difference. Our study highlights that kelp cultivation alleviates eutrophication and acidification and enhances phytoplankton diversity, thus providing guidance for macroalgal aquaculture and remediation in eutrophic waters.

A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors.

Protein kinases are validated drug targets for a number of therapeutic areas, as kinase deregulation is known to play an essential role in many disease states. Many investigated protein kinase inhibitors are natural product small molecules or their derivatives. Many marine-derived natural products from various marine sources, such as bacteria and cyanobacteria, fungi, animals, algae, soft corals, sponges, etc. have been found to have potent kinase inhibitory activity, or desirable pharmacophores for further development. This review covers the new compounds reported from the beginning of 2014 through the middle of 2019 as having been isolated from marine organisms and having potential therapeutic applications due to kinase inhibitory and associated bioactivities. Moreover, some existing clinical drugs based on marine-derived natural product scaffolds are also discussed.

Acupuncture for Chronic Pain-Related Insomnia: A Systematic Review and Meta-Analysis.

Objectives. Acupuncture has been widely used to relieve chronic pain-related insomnia (CPRI). However, the efficacy of acupuncture for CPRI is uncertain. The purpose of this study was to evaluate the efficacy of acupuncture for CPRI. Methods. Seven electronic databases were searched from inception to December 2018. Randomized controlled trials (RCTs) were included if acupuncture was compared to sham acupuncture or conventional drug therapies for treating CPRI. Two reviewers screened each study and extracted data independently. Statistical analyses were conducted by RevMan 5.3 software. Results. A total of nine studies involving 944 patients were enrolled. The pooled analysis indicated that acupuncture treatment was significantly better than control group in improving effective rate (OR = 8.09, 95%CI = [4.75, 13.79], P < 0.00001) and cure rate (OR = 3.17, 95%CI = [2.35, 4.29], P < 0.00001), but subgroup analysis showed that there was no statistically significant difference between acupuncture and sham acupuncture in improving cure rate (OR =10.36, 95% CI [0.53, 201.45], P=0.12) based on one included study. In addition, meta-analysis demonstrated that acupuncture group was superior to control group in debasing PSQI score (MD = -2.65, 95%CI = [-4.00, -1.30], P = 0.0001) and VAS score (MD = -1.44, 95%CI = [-1.58, -1.29], P < 0.00001). And there was no significant difference in adverse events (OR =1.73, 95%CI = [0.92, 3.25], P =0.09) between the two groups. Conclusions. Acupuncture therapy is an effective and safe treatment for CPRI, and this treatment can be recommended for the management of patients with CPRI. Due to the low quality and small sample size of the included studies, more rigorously designed RCTs with high quality and large sample size are recommended in future.

High-Dose Astaxanthin Supplementation Suppresses Antioxidant Enzyme Activity during Moderate-Intensity Swimming Training in Mice.

Exercise-induced reactive oxygen and nitrogen species are increasingly considered as beneficial health promotion. Astaxanthin (ASX) has been recognized as a potent antioxidant suitable for human ingestion. We investigated whether ASX administration suppressed antioxidant enzyme activity in moderate-intensity exercise. Seven-week-old male C57BL/6 mice (n = 8/group) were treated with ASX (5, 15, and 30 mg/kg BW) combined with 45 min/day moderate-intensity swimming training for four weeks. Results showed that the mice administrated with 15 and 30 mg/kg of ASX decreased glutathione peroxidase, catalase, malondialdehyde, and creatine kinase levels in plasma or muscle, compared with the swimming control group. Beyond that, these two (15 and 30 mg/kg BW) dosages of ASX downregulated gastrocnemius muscle erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Meanwhile, mRNA of Nrf2 and Nrf2-dependent enzymes in mice heart were also downregulated in the ASX-treated groups. However, the mice treated with 15 or 30 mg/kg ASX had increased constitutive nitric oxidase synthase and superoxide dismutase activity, compared with the swimming and sedentary control groups. Our findings indicate that high-dose administration of astaxanthin can blunt antioxidant enzyme activity and downregulate transcription of Nrf2 and Nrf2-dependent enzymes along with attenuating plasma and muscle MDA.