Chelativorans salis sp. nov., a slightly halophilic bacterium isolated from an enrichment system with saline lake sediment.

A Gram-stain-negative, non-motile, and slightly halophilic alphaproteobacterium, designated strain EGI FJ00035T, was isolated from enrichment sediment samples of a saline lake in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using the polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain EGI FJ00035T formed a distinct clade with 'Chelativorans alearense' UJN715 and 'Chelativorans xinjiangense' lm93 with sequence similarities of 98.44 and 98.22 %, respectively, while sharing less than 96.7 % with other valid type strains. The novel isolate could be distinguished from other species of the genus Chelativorans by its distinct phenotypic, physiological, and genotypic characteristics. Optimal growth of strain EGI FJ00035T occurred on marine agar 2216 at pH 7.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>5 %) were C19 : 0 cyclo ω8c, summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c), C16 : 0, C18 : 0, and iso-C17 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipids, unidentified glycolipids, and an unidentified lipid. Based on its genome sequence, the G+C content of strain EGI FJ00035T was 63.2 mol%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values of strain EGI FJ00035T against related members of the genus Chelativorans were below the thresholds for delineation of a novel species. According our polyphasic taxonomic data, strain EGI FJ00035T represents a new species of the genus Chelativorans, for which the name Chelativorans salis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI FJ00035T (=KCTC 92251T=CGMCC 1.19480T).

Cytotoxic phenazine and antiallergic phenoxazine alkaloids from an arctic Nocardiopsis dassonvillei SCSIO 502F.

Microbes well-adapted to the Arctic Ocean are promising for producing novel compounds, due to their fancy strategies for adaptation and being under-investigated. Two new phenazine alkaloids (1 and 2) and one new phenoxazine (3) were isolated from Nocardiopsis dassonvillei 502F, a strain originally isolated from Arctic deep-sea sediments. AntiSMASH analysis of the genome of Nocardiopsis dassonvillei 502F revealed the presence of 16 putative biosynthetic gene clusters (BGCs), including a phenazine BGC. Most of the isolated compounds were evaluated for their antibacterial, antiallergic, and cytotoxic activities. Among them, compounds 4 and 5 exhibited potent in vitro cytotoxic activities against osteosarcoma cell line 143B with IC50 values 0.16 and 20.0 µM, respectively. Besides, the results of antiallergic activities of compounds 6-8 exhibited inhibitory activities with IC50 values of 10.88 ± 3.05, 38.88 ± 3.29, and 2.44 ± 0.17 µg/mL, respectively (IC50 91.6 µM for the positive control loratadine).

Indole diketopiperazine alkaloids and aromatic polyketides from the Antarctic fungus Penicillium sp. SCSIO 05705.

A new indole diketopiperazine alkaloid, named penilline D (1), together with five known indole alkaloid analogues (2-5, 11), two meroterpenoids (6 and 12), and four butenolide derivatives (7-10), were isolated from the Antarctic fungus Penicillium sp. SCSIO 05705. Extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation were used to elucidate the structure of penilline D (1), including its absolute configuration. All isolated compounds (1-12) were evaluated for their cytotoxic, antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among them, compound 5 exhibited moderate in vitro cytotoxic activity against the 143B cell line with IC50 value of 12.64 ± 0.78 µM. Compound 6 showed strong inhibitory activity against AChE with IC50 value of 0.36 nM (IC50 18.7 nM for Tacrine), while compounds 6 and 11 showed weak PL enzyme inhibitory activity. Furthermore, an in silico molecular docking study was also performed between 6 and AChE.

A glyoxylate-containing benzene derivative and butenolides from a marine algicolous fungus Aspergillus sp. SCSIO 41304.

A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3'-methyl-2'-butenyl)phenyl)-2-oxoacetate (1), together with ten known compounds (2-11), were isolated from the marine algicolous fungus, Aspergillus sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data. Compound 1 was isolated as a new fungal secondary metabolite, possessing a methyl glyoxylate moiety R-CO-CO-OCH3, which is rare in natural sources. All the isolated compounds (1-11) were tested for their antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among these compounds, aspulvinone H (4) showed moderate inhibition against AChE and PL with IC50 values of 25.95 and 47.06 µM, respectively. Further molecular docking simulation exhibited that compound 4 could well bind to the catalytic pockets of the AChE and PL.

Pseudalkalibacillus salsuginis sp. nov., a novel salt-tolerant bacterium isolated from a saline lake sediment.

A salt-tolerant bacterium, designated strain EGI L200015T, was isolated from saline lake sediment in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using polyphasic taxonomic analysis and phylogenomic analysis. Phylogenetic analysis and 16S rRNA gene sequence similarities indicated that EGI L200015T formed a distinct clade with Pseudalkalibacillus berkeleyi KCTC 12718T with sequence identity of 98.3%. The novel isolate could be distinguished from species of the genus Pseudalkalibacillus by its distinct phenotypic, physiological and genotypic characteristics. Cells of EGI L200015T were aerobic, Gram-stain-positive, non-motile and rod-shaped. Optimal growth conditions for EGI L200015T occurred on marine agar 2216 at pH 8.0 at 30 °C. The major respiratory quinone was MK-7, while the major fatty acids (> 10 %) were anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The detected polar lipids of included diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. On the basis of the genome sequence data, the DNA G+C content of EGI L200015T was 41.6 %. On the basis of the phenotypic, physiological, genotypic and phylogenetic data, strain EGI L200015T represents a novel species of the genus Pseudalkalibacillus, for which the name Pseudalkalibacillus salsuginis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI L200015T (= KCTC 43363T = CGMCC 1.19260T).

Penicixanthene E, a new xanthene isolated from a mangrove-derived fungus Penicillium sp.

One new xanthene derivative, named penicixanthene E (1), together with one known compound 2, was isolated from the EtOAc extract of the endophytic fungus Penicillium sp. GXIMD 03101, which was identified from the mangrove Acanthus ilicifolius L. collected in the South China Sea. The structure of 1 was elucidated by 1D and 2D NMR spectral interpretation and HREISMS data. The absolute configurations of C-9 and C-11 in 1 were proposed based on electronic circular dichroism (ECD), but the configuration at C-3 in 1 was unassigned. Compound 1 represents a xanthene derivative that was first reported, in which carbon-carbon double bond has been reduced. The cytotoxic activities of all compounds were evaluated, the result showed that compound 1 has weak activity against pancreatic cancer SW1990.

Paracoccus salsus sp. nov., a novel slightly halophilic bacterium isolated from saline lake sediment.

A Gram-stain-negative, non-motile, slightly halophilic and non-endospore-forming alphaproteobacterium, designated strain EGI L200073T, was isolated from saline lake sediment sampled in Xinjiang Uygur Autonomous Region, China. The taxonomic position of the isolate was determined using the polyphasic taxonomic analysis and phylogenomic analysis. Phylogenetic analysis based on 16S rRNA gene sequence similarities indicated that strain EGI L200073T formed a distinct clade with Paracoccus seriniphilus DSM 14827T and shared sequence identity of 98.56 %. The novel isolate could be distinguished from other species of the genus Paracoccus by its distinct phenotypic, physiological and genotypic characteristics. Optimal growth of strain EGI L200073T occurred on marine agar 2216 at pH 8.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>10%) were summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c) and C18 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine and phosphatidylglycerol. Based on the genome sequence of strain EGI L200073T, the G+C content of the novel isolate was 65.7 mol%. The average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values of strain EGI L200073T against related members in the genus Paracoccus were below the cut-off points proposed for delineation of a novel species. According our polyphasic taxonomic data, strain EGI L200073T represents a new species of the genus Paracoccus, for which the name Paracoccus salsus sp. nov. is proposed. The type strain of the proposed novel isolate is EGI L200073T (=KCTC 92045T=CGMCC 1.19242T).

Agromyces cavernae sp. nov., a novel member of the genus Agromyces isolated from a karstic cave in Shaoguan.

A novel actinobacterial strain, designated SYSU K20354T, was isolated from a soil sample collected from a karst cave in Shaoguan city, Guangdong province, southern China. The taxonomic position of the strain was investigated using a polyphasic approach. Cells of the strain were aerobic, Gram-stain-positive and non-motile. On the basis of 16S rRNA gene sequence similarities and phylogenetic analysis, strain SYSU K20354T was most closely related to Agromyces humatus JCM 14319T, and shared the highest sequence identity of 98.3 % based on NCBI database. In addition, 2,4-diaminobutyric acid was the diagnostic diamino acid in cell-wall peptidoglycan. The whole-cell sugars were galactose, glucose, mannose and ribose. The major isoprenoid quinone was MK-12, while the major fatty acids (>10 %) were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, three unknown glycolipids, three unknown phospholipids and two unknown lipids. The draft genome size of strain SYSU K20354T was 3.96 Mbp with G+C content of 69.7 mol%. Furthermore, the average nucleotide identity and digital DNA-DNA hybridization values between strain SYSU K20354T and A. humatus JCM 14319T were 90.3 and 55.6 %, respectively. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU K20354T represents a novel species of the genus Agromyces, for which the name Agromyces cavernae sp. nov. is proposed. The type strain is SYSU K20354T (=KCTC 49499T= CGMCC 4.7691T).

Rhabdothermincola salaria sp. nov., a novel actinobacterium isolated from a saline lake sediment.

An actinobacterium, designated strain EGI L10124T, was isolated from saline lake sediment collected in Xinjiang province, PR China. The taxonomic position of the isolate was determined based on polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis and 16S rRNA gene sequence similarities indicated that strain EGI L10124T formed a distinct clade with Rhabdothermincola sediminis SYSU G02662T, with a shared sequence identity of 95.2 %. The novel isolate could be distinguished from species in the genus Rhabdothermincola by its distinct phenotypic, physiological and genotypic characteristics. The cells of strain EGI L10124T were aerobic, Gram-stain-positive and short rod-shaped. Optimal growth conditions of strain EGI L10124T on marine agar 2216 were registered at pH 8.0 at 37 °C. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major respiratory quinone was MK-9 (H8), while the major fatty acids were iso-C16 : 0, C17 : 0 and C16 : 0. The polar lipids included diphosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. Based on the genome sequence of strain EGI L10124T, it appears that the G+C content of the novel isolate was 71.8 mol%. According to our data, strain EGI L10124T represents a new species of the genus Rhabdothermincola, for which the name Rhabdothermincola salaria sp. nov. is proposed. The type strain of the proposed novel isolate is EGI L10124T (=CGMCC 1.19113T=KCTC 49679T).

Ornithinimicrobium sediminis sp. nov., a novel actinobacterium isolated from a saline lake sediment.

An actinobacterium, designated strain EGI L100131T, was isolated from saline lake sediment in Xinjiang Province, China. The taxonomic position of the isolate was determined using analysis based on the polyphasic taxonomy and phylogenomics. Phylogenetic analysis and 16S rRNA gene sequence similarities indicated that strain EGI L100131T formed a distinct clade with Ornithinimicrobium murale DSM 22056T and Ornithinimicrobium cavernae CFH 30183T, and shared sequence identities of 97.8% and 97.0%, respectively. The novel isolate could be distinguished from other species of the genus Ornithinimicrobium by its distinct phenotypic, physiological, and genotypic characteristics. Cells of strain EGI L100131T were aerobic, Gram-staining positive, and coccoid to rod-shaped. Optimal growing conditions of strain EGI L100131T occurred at pH 8.0 and 28 ºC. Ornithine was the diagnostic diamino acid in the cell-wall peptidoglycan. The respiratory quinone was MK-8 (H4), while the major fatty acids (> 10%) were C17:1 ω8c, C17:0, iso-C16:0, and iso-C15:0. The detected polar lipids included diphosphatidylglycerol, phosphatidylinositol, phosphatidylglycerol, and a glycophospholipid. The G + C content based on genomic DNA was 71.5%. According to the phenotypic, physiological, genotypic, and phylogenetic data, strain EGI L100131T represents a new species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium sediminis sp. nov. is proposed. The type strain is EGI L100131T (= KCTC 49716 T = CGMCC 1.19241T).

Machine learning-based random forest for predicting decreased quality of life in thyroid cancer patients after thyroidectomy.

OBJECTIVE: Decreased quality of life (QoL) in thyroid cancer patients after thyroidectomy is a common, but there is a lack of predictive methods for decreased QoL. This study aimed to construct a machine learning-based random forest for predicting decreased QoL in thyroid cancer patients 3 months after thyroidectomy. MATERIALS AND METHODS: Two hundred and eighty-six thyroid cancer patients after thyroidectomy were enrolled in this prospective cross-sectional study from November 2018 to June 2019, and were randomly assigned to training and validation cohorts at a ratio of 7:3. The European Organization for Research and Treatment of Cancer quality of life questionnaire version 3 (EORTC QLQ-C30) questionnaire was used to assess the QoL 3 months after thyroidectomy, and decreased QoL was defined as EORTC QLQ-C30 < 60 points. The random forest model was constructed for predicting decreased QoL in thyroid cancer patients after thyroidectomy. RESULTS: The mean QoL 3 months after thyroidectomy was 65.93 ± 9.00 with 21.33% (61/286) decreased QoL. The main manifestation is fatigue in symptom scales and social functioning dysfunction in functional scales. The top seven most important indices affecting QoL were clinical stage, marital status, histological type, age, nerve injury symptom, economic income and surgery type. For random forest prediction model, the areas under the curve in the training and validation courts were 0.834 and 0.897, respectively. CONCLUSION: The present study demonstrated that random forest model for predicting decreased QoL in thyroid cancer patients 3 months after thyroidectomy displayed relatively high accuracy. These findings should be applied clinically to optimise health care.

Diagnostic Performance of Strain and Shear Wave Elastography for the Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: Systematic Review and Meta-Analysis.

OBJECTIVES: To investigate the diagnostic performance of strain and shear wave elastography for the response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Relevant studies were searched in the databases of PubMed, Web of Science and Cochrane Library until October 2021. The diagnostic performance of ultrasonic elastography for the response to NAC were estimated by calculating the area under the curve (AUC) with sensitivity and specificity using Stata 14.0. RESULTS: A total of 15 studies that comprise 1147 breast cancer patients were included in this meta-analysis. The pooled AUC of strain elastography in diagnosing responses were 0.89 (95% CI = 0.86-0.91) with 87% (95% CI = 75-94%) of sensitivity and 80% (95% CI = 72-84%) of specificity. The pooled AUC of shear wave elastography in diagnosing response were 0.82 (95% CI = 0.78-0.85) with 79% (95% CI = 72-84%) of sensitivity and 81% (95% CI = 71-88%). No publication bias was observed across the studies using Deek's funnel plot. CONCLUSIONS: Based on current evidence, this meta-analysis confirmed that strain and shear wave elastography exhibited favorable performance for predicting responses to NAC. Strain and shear wave elastography may be a useful, noninvasive method for the assessment of response to NAC in breast cancer patients.

Appearance characteristics of incision, satisfaction with the aesthetic effect, and quality of life in of thyroid cancer patients after thyroidectomy.

OBJECTIVE: This study aimed to assess the correlation between satisfaction with aesthetic effect (SAE) and quality of life (QoL) in thyroid cancer patients after thyroidectomy and identify the impact of appearance characteristics of scars on SAE. METHODS: This prospective, single-centre, cross-sectional study from November 2018 to June 2019 enrolled 285 thyroid cancer patients three months after their thyroidectomy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 was used to assess QoL 3 months after thyroidectomy, while the Patient Scar Assessment Scale (PSAS) was used to assess the SAE of patients. RESULTS: The mean PSAS score was 35.00, and the mean QoL score was 69.96. Correlation analysis demonstrated that PSAS was negatively correlated with QoL score. Multivariate logistic regression analysis demonstrated that age, marital status, radiotherapy, surgery type, neurological deficits, and PSAS were independent risk factors with decreased QoL. Furthermore, correlation analysis showed that scar colour, stiffness, thickness, irregularity and length were positively correlated with poor PSAS. Scar irregularity and length were independent risk factors with poor PSAS. CONCLUSION: This study demonstrated that scar irregularity and length were independent risk factors with SAE, and poor SAE was correlated with decreased QoL in thyroid cancer patients after thyroidectomy.

Cytotoxic benzopyranone and xanthone derivatives from a coral symbiotic fungus Cladosporium halotolerans GXIMD 02502.

Coral-derived microorganisms have been historically proven to be prolific sources of bioactive secondary metabolites. Twelve benzopyranone and/or xanthone derivatives, including a new benzopyranone with an uncommon carboxyl group at C-8, coniochaetone K (1), were obtained from the Beibu Gulf-derived coral symbiotic fungus Cladosporium halotolerans GXIMD 02502. Their structures were determined by extensive spectroscopic data interpretation and comparison with literature values. The absolute configuration of 1 was accomplished by comparison of specific optical rotation as well as quantum chemical ECD calculations. The in vitro cytotoxicity of compounds 1-12 against two human prostatic cancer cell lines, C4-2B and 22RV1, were evaluated. And compounds 1, 3, 6-8, and 10-11 demonstrated significant cytotoxicity with inhibitions ranging from 55.8% to 82.1% at the concentration of 10 µM.

Two new bioactive polyphenols from the soft coral-derived fungus Talaromyces sp. SCSIO 041201.

Two new polyphenols, talaversatilis A (1) and B (2), together with fifteen known compounds (3-17) were isolated from the extract of the culture broth of a soft coral-derived fungus Talaromyces sp. SCSIO 041201. The structures of these compounds were elucidated by the extensive analyses of spectroscopic data and by comparison with the reported literature. Antifouling and antibacterial activities of all purified compounds were tested and evaluated. Compounds 5 and 6 showed antifouling activity towards Bugula neritina larva, with LC50 values of 3.86 µg/mL and 3.05 µg/mL, respectively. Compounds 7, 8, 10 and 13 exhibited significant antibacterial activities against E. coli, MRSA, S. aureus and E. faecalis, with MIC values ranging from 0.45 to 15.6 µg/mL.

Antioxidant CPA-type indole alkaloids produced from the deep-sea derived fungus Aspergillus sp. SCSIO 41024.

Twelve indole alkaloids, including α-cyclopiazonic acid (CPA) (1), nine 2-oxo indole CPA derivatives (2-10), and two open-ring indole CPA derivatives (11 and 12), were isolated from the fermentation broth of a deep-sea derived fungus Aspergillus sp. SCSIO 41024. Their structures and absolute configurations were elucidated mainly by using extensive NMR spectroscopic, mass spectrometric and single crystal X-ray diffraction analysis. To the best of our knowledge, the crystallographic data of 3 and 7 were firstly reported, and the absolute configuration of 3 was confirmed for the first time by the single crystal X-ray diffraction analysis. Most isolated compounds were tested for their antimicrobial, antitumor and radical scavenging activities. In addition, compounds 1, 2 and 11 showed moderate antioxidative activity against DPPH with IC50 values of 190.1, 31.9, 228.4 µg/mL, respectively.

Four new steroids from the marine soft coral-derived fungus Penicillium sp. SCSIO41201.

Penicildiones A-D (1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy (5), stachybotrylactone B (6) and stachybotrin (7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 µmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 µmol·L-1.

Cyclobacterium salsum sp. nov. and Cyclobacterium roseum sp. nov., isolated from a saline lake.

Two novel strains, designated SYSU L10167T and SYSU L10180T, were isolated from sediment sampled at Dabancheng saline lake in Xinjiang, PR China. A polyphasic approach was used to clarify the taxonomic positions of the two strains. Cells of the isolates were curved ring-like, horseshoe-shaped or rod-shaped, non-motile and non-spore-forming. Cells were Gram-stain-negative, aerobic, heterotrophic and rose-pigmented. The phylogenetic trees based on 16S rRNA gene sequences showed that strains SYSU L10167T and SYSU L10180T formed a distinct lineage within the genus Cyclobacterium. Strains SYSU L10167T and SYSU L10180T showed highest similarities to Cyclobacterium jeungdonense KCTC 23150T (98.0 and 97.4%, respectively). Results of genomic analyses (including average nucleotide identity, digital DNA-DNA hybridization and the marker gene tree) and pan-genome analysis further confirmed that strains SYSU L10167T and SYSU L10180T were separate from each other and other species of the genus Cyclobacterium. The draft genomes of the isolates had sizes of 5.5-5.7 Mb and reflected their major physiological capabilities. Based on phenotypic, physiological, chemotaxonomic and genotypic characterization, we propose that the isolates represent two novel species, for which the names Cyclobacterium salsum sp. nov. and Cyclobacterium roseum sp. nov. are proposed. The type strains of the species are SYSU L10167T (=KCTC 72390T=CGMCC 1.17521T) and SYSU L10180T (=KCTC 72391T=CGMCC 1.17278T).

HPLC-DAD-Guided Isolation of Diversified Chaetoglobosins from the Coral-Associated Fungus Chaetomium globosum C2F17.

Cytochalasans have continuously aroused considerable attention among the chemistry and pharmacology communities due to their structural complexities and pharmacological significances. Sixteen structurally diverse chaetoglobosins, 10-(indol-3-yl)-[13]cytochalasans, including a new one, 6-O-methyl-chaetoglobosin Q (1), were isolated from the coral-associated fungus Chaetomium globosum C2F17. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations. Meanwhile, the structures and absolute configurations of the previously reported compounds 6, 12, and 13 were confirmed by single-crystal X-ray analysis for the first time. Chaetoglobosins E (6) and Fex (11) showed significant cytotoxicity against a panel of cancer cell lines, K562, A549, Huh7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4, with the IC50 values ranging from 1.4 µM to 9.2 µM.

The marine-derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα.

Recent studies have demonstrated that commercially available lipid-lowering drugs cause various side effects; therefore, searching for anti-hyperlipidaemic compounds with lower toxicity is a research hotspot. This study was designed to investigate whether the marine-derived compound, 5-hydroxy-3-methoxy-5-methyl-4-butylfuran-2(5H)-one, has an anti-hyperlipidaemic activity, and the potential underlying mechanism in vitro. Results showed that the furanone had weaker cytotoxicity compared to positive control drugs. In RAW 264.7 cells, the furanone significantly lowered ox-LDL-induced lipid accumulation (~50%), and its triglyceride (TG)-lowering effect was greater than that of liver X receptor (LXR) agonist T0901317. In addition, it significantly elevated the protein levels of peroxisome proliferator-activated receptors (PPARα) and ATP-binding cassette (ABC) transporters, which could be partially inhibited by LXR antagonists, GSK2033 and SR9243. In HepG2 cells, it significantly decreased oleic acid-induced lipid accumulation, enhanced the protein levels of low-density lipoprotein receptor (LDLR), ABCG5, ABCG8 and PPARα, and reduced the expression of sterol regulatory element-binding protein 2 (~32%). PPARα antagonists, GW6471 and MK886, could significantly inhibit the furanone-induced lipid-lowering effect. Furthermore, the furanone showed a significantly lower activity on the activation of the expression of lipogenic genes compared to T0901317. Taken together, the furanone exhibited a weak cytotoxicity but had powerful TC- and TG-lowering effects most likely through targeting LXRα and PPARα, respectively. These findings indicate that the furanone has a potential application for the treatment of dyslipidaemia.