Novosphingobium beihaiensis sp. nov., a novel pesticide-tolerant bacterium isolated from mangrove sediments.

A novel Novosphingobium species, designated strain B2638T, was isolated from mangrove sediments which was collected from Beibu Gulf, Beihai, P. R. China. The isolate could grow in the presence of chlorpyrifos. Phylogenetic analysis based on 16S rRNA gene sequence revealed that the isolate belonged to the genus Novosphingobium, showing 99.9% sequence similarity with N. decloroationis 502str22T and less than 98% similarity with other type strain of species of this genus. Molecular typing by BOX-PCR divided strain B2638T and N. declorationis 502str22T into two clusters and indicated that they were not identical. Genomic comparison referenced by values of the DNA-DNA hybridization (dDDH) and the average nucleotide identity (ANI) between strain B2638T and its close phylogenetic neighbors were 20.0-29.5% and 75.3-85.3%, respectively, that were lower than proposed thresholds for bacterial species delineation. The major fatty acids (> 10%) were identified as C18:1 ω7c, C17:1 iso ω9c and C16:0. The main polar lipids contained diphosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid, phosphatidyl glycerol, unidentified lipid and unidentified aminolipid. Results from phenotypic, chemotaxonomic and genotypic analyses proposed that strain B2638T (= MCCC 1K07406T = KCTC 72968 T) is represented a novel species in the genus Novosphingobium, for which the names Novosphingobium beihaiensis sp. nov. is proposed.

Taxonomy and anticancer potential of Streptomyces niphimycinicus sp. nov. against nasopharyngeal carcinoma cells.

Streptomyces species are ubiquitous, Gram-positive, spore-forming bacteria with the ability to produce various clinically relevant compounds. The strain 4503 T was isolated from mangrove sediments, showing morphological and chemical properties which were consistent with those of members of the genus Streptomyces. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate was primarily identified as members of the genus Streptomyces, sharing more than 99% sequence identity to Streptomyces yatensis DSM 41771 T, S. antimycoticus NBRC 12839 T, and S. melanosporofaciens NBRC 13061 T. Average nucleotide identities (ANI) and digital DNA-DNA hybridization (dDDH) values between strain 4503 T and its close relatives were all below 95-96% and 75% of the novel species threshold, respectively. Results from phylogenetic, genomic, phenotypic, and chemotaxonomic characteristics analyses confirmed that the isolate represented a novel species of the genus Streptomyces, for which the name Streptomyces niphimycinicus sp. nov. 4503 T (= MCCC 1K04557T = JCM 34996 T) is proposed. The bioassay-guided fractionation of the extract of strain 4503 T resulted in the isolation of a known compound niphimycin C, which showed cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines TW03 and 5-8F with half maximal inhibitory concentration (IC50) values of 12.24 µg/mL and 9.44 µg/mL, respectively. Further experiments revealed that niphimycin C not only exhibited the capacity of anti-proliferation, anti-metastasis, induction of cell cycle arrest, and apoptosis, but was also able to increase the reactive oxygen species (ROS) production and regulate several signaling pathways in NPC cells. KEY POINTS: • Strain 4503 T was classified as a novel species of Streptomyces. • Niphimycin C correlates with the cytotoxic effect of strain 4503 T against NPC cells. • Niphimycin C induces apoptosis, autophagic flux disruption and cell cycle arrest.

Novosphingobium album sp. nov., Novosphingobium organovorum sp. nov. and Novosphingobium mangrovi sp. nov. with the organophosphorus pesticides degrading ability isolated from mangrove sediments.

Members of the genus Novosphingobium were frequently isolated from polluted environments and possess great bioremediation potential. Here, three species, designated B2637T, B2580T and B1949T, were isolated from mangrove sediments and might represent novel species in the genus Novosphingobium based on a polyphasic taxonomy study. Phylogenomic analysis revealed that strains B2580T, B1949T and B2637T clustered with Novosphingobium naphthalenivorans NBRC 102051T, 'N. profundi' F72 and N. decolorationis 502str22T, respectively. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between isolates and their closely related species were less than 94 and 54 %, respectively, all below the threshold of species discrimination. The sizes of the genomes of isolates B2580T, B2637T and B1949T ranged from 4.4 to 4.6 Mb, containing 63.3-66.4 % G+C content. Analysis of their genomic sequences identified genes related to pesticide degradation, heavy-metal resistance, nitrogen fixation, antibiotic resistance and sulphur metabolism, revealing the biotechnology potential of these isolates. Except for B2637T, B1949T and B2580T were able to grow in the presence of quinalphos. Results from these polyphasic taxonomic analyses support the affiliation of these strains to three novel species within the genus Novosphingobium, for which we propose the name Novosphingobium album sp. nov. B2580T (=KCTC 72967T=MCCC 1K04555T), Novosphingobium organovorum sp. nov. B1949T (=KCTC 92158T=MCCC 1K03763T) and Novosphingobium mangrovi sp. nov. B2637T (KCTC 72969T=MCCC 1K04460T).

Parvularcula maris sp. nov., an algicidal bacterium isolated from seawater.

A taxonomic study was carried out on strain BGMRC 0090T, which was isolated from seawater. The isolate was a Gram-negative, aerobic, flagellated, rod-shaped bacterium with algicidal activity. Optimal growth was observed at 30 °C, pH 6.0 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain BGMRC 0090T belonged to the genus Parvularcula, with highest sequence similarity to Parvularcula lutaonensis CC-MMS-1T (98.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain BGMRC 0090T and five strains of the genus Parvularcula with publicly available genomes were below 84.0, 69.2 and 21.4 %, respectively. The genome of strain BGMRC 0090T was 3.2 Mb with 64.8 mol% DNA G+C content and encoded 2905 predicted proteins, three rRNA, 42 tRNA and four ncRNA genes. Some algicidal biosynthesis-associated genes were detected in the genome. Strain BGMRC 0090T contained Q-10 as the major quinone. The predominant fatty acids were identified as summed feature 8 (C18 : 1ω7c/ω6c) and C16 : 0. Based on the polyphasic evidence presented in this paper, strain BGMRC 0090T is concluded to represent a novel species of the genus Parvularcula, for which the name Parvularcula maris sp. nov. is proposed. The type strain is BGMRC 0090T (= KCTC 92591T=MCCC 1K08100T).

Dietary precursors and cardiovascular disease: A Mendelian randomization study.

Background: The Dietary precursor has been identified as a contributor in the development of cardiovascular disease. However, it is inconsistent if dietary precursors could affect the process of cardiovascular disease. Methods: Here we performed Mendelian randomization (MR) analysis of the data from genome-wide association study of European ancestry to evaluate the independent effects of three dietary precursors on cardiovascular disease (CVD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and valvular disease (VHD). Inverse variance weighting method was used for the MR estimation. Sensitivity was determined by MR-PRESSO analysis, weighted median analysis, MR-Egger analysis, and Leave-one-out analysis. Results: We found that elevated choline level had a causal relationship with VHD [odds ratio (OR) = 1.087, 95% confidence interval (CI), 1.003-1.178, P = 0.041] and MI (OR = 1.250, 95% CI, 1.041-1.501, P = 0.017) by single-variable MR analysis. Furthermore, elevated carnitine level was associated with MI (OR = 5.007, 95% CI, 1.693-14.808, P = 0.004) and HF (OR = 2.176, 95% CI, 1.252-3.780, P = 0.006) risk. In addition, elevated phosphatidylcholine level can increase the risk of MI (OR = 1.197, 95% CI, 1.026-1.397, P = 0.022). Conclusion: Our data show that choline increases VHD or MI risk, carnitine increases the risk of MI or HF, and phosphatidylcholine increases HF risk. These findings suggest the possibility that decrease in choline level in circulation may be able to reduce overall VHD or MI risk, reduce in carnitine level could be decrease MI and HF risks as well as decrease in phosphatidylcholine could reduce MI risk.

Allorhizobium sonneratiae sp. nov., an endophytic bacterium isolated from the root of Sonneratia apetala.

A novel endophytic bacterium, designated strain BGMRC 0089T, was isolated from a surface-sterilized root of Sonneratia apetala. Cells were observed to be Gram-negative, rod-shaped and motile with polar flagella. Strain BGMRC 0089T was found to grow optimally at 28-30 °C, pH 7.0-8.0 and in the presence of 1 % (w/v) NaCl. Strain BGMRC 0089T contained ubiquinone Q-10 and the predominant fatty acid was summed feature 8. The polar lipid profile of strain BGMRC 0089T was found to contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine and phosphatidylethanolamine. Based on the results of 16S rRNA gene analysis, this isolate has the closest phylogenetic relationships with Rhizobium lemnae L6-16T (96.5 %) and Allorhizobium oryziradicis N19T (96.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values of the isolate with the type strains of the genera Rhizobium and Allorhizobium were below 84.6, 73.9 and 22.1  %, respectively. Analysis the 4.55 Mb draft genome of strain BGMRC 0089T revealed several plant-associated genes, which may play important roles for the plant in the adaptation to the mangrove habitat. Based on its distinct phylogenetic, phenotypic and chemotaxonomic characteristics, strain BGMRC 0089T is proposed to represent a novel Allorhizobium species, for which the name Allorhizobium sonneratiae sp. nov. is proposed (type strain BGMRC 0089T=DSM 100171T=MCCC 1K04805T).

Liquid hot water pretreatment combined with high-solids enzymatic hydrolysis and fed-batch fermentation for succinic acid sustainable processed from sugarcane bagasse.

In order to sustainable process of bio-succinic acid (SA), response surface methodology (RSM) was applied to optimize liquid hot water pretreatment pretreatment of sugarcane bagasse (SCB), followed by high-solids enzymatic hydrolysis of pretreated residual that without washing, then the hydrolysates and partial pretreatment liquid were used as carbon sources for SA fermentation. Results showed that the highest sugars yield could be achieved at pretreatment conditions of temperature 186 °C, time 25 min and solid-to-liquid ratio 0.08; enzymatic digestion the pretreated residuals at 20 % (w/v) solid content via enzymes reconstruction and fed-batch strategy, the obtained sugars reached to 121 g/L; by controlling the nutrition and conditions of the fermentation process, most of the C5 and C6 sugars in the hydrolysate and pretreatment liquid were converted into SA with a conversion rate high to 280 mg/g SCB. This study can provide a novel clue for clean and efficient biorefining of chemicals.

Mechanism of norfloxacin transformation by horseradish peroxidase and various redox mediated by humic acid and microplastics.

The catalysis of HRP coupling with redox mediator was a feasible technology for the transformation of antibiotics. This work screened three effective redox mediators syringaldehyde (SYR), acetosyringone (AS) and p-coumaric acid (PCA) for the norfloxacin (NOR) transformation in HRP/redox mediator system. Then, compared their transformation characteristics under varying conditions. The molecular docking results indicated HRP catalytic mediator was spontaneous, and the absolute value order of free energy between three redox mediators and HRP was consistent with the order of NOR removal in experiment. The presence of humic acid (HA) and polystyrene (PS) microplastics could block the removal of NOR, and the inhibition effect was proportional to the level of HA and PS particles. Seven and six possible intermediate products were identified by using SYR/AS and PCA as redox mediators, respectively, and potential NOR transformation pathways were proposed. SYR and AS treatment had the same transformation products and pathways due to their similar structure, including defluorination, oxidation, cross-coupled with mediator, demethylation and dehydrogenation. While for the PCA group, NOR not only performed the above action (except defluorination), but also underwent decarbonylation. These findings may expand our knowledge of the conversion and fate of fluoroquinolones through HRP coupled with redox mediator in the environment.

Mycolicibacterium aurantiacum sp. nov. and Mycolicibacterium xanthum sp. nov., two novel actinobacteria isolated from mangrove sediments.

Two novel actinobacteria with the ability to degrade kerosene, designated as B3033T and Y57T, were isolated from mangrove sediments in Tieshan Harbour, South China Sea. Both strains are Gram-staining-positive, non-spore forming, slow-growing, oxidase-positive, non-motile and aerobic. Their major cellular fatty acids were C16 : 0 and C18 : 1ω9c. Analysis of 16S rRNA gene sequences revealed the close relationship of strain B3033T to Mycobacterium kyogaense DSM 107316T (99.4 % nucleotide identity) and strain Y57T to Mycolicibacterium chubuense ATCC 27278T (98.7 %) and Mycolicibacterium rufum JS14T (98.7 %). Whole genome average nucleotide blast identity (ANI) and the digital DNA-DNA hybridization (dDDH) values between the two isolates and the type strains of species of the genus Mycolicibacterium were lower than 94 and 45 %, respectively, which were below the threshold values of 95 % (for ANI) and 70 % (for dDDH) recommended for bacterial species differentiation. The genome sequence of B3033T comprised a circular 11.0 Mb chromosome with a DNA G+C content of 68.1 mol%. Y57T had a genome size of 5.6 Mb and a DNA G+C content of 68.7 mol%. Genes involved in degradation of aromatic compounds and copper resistance were identified in the genomes of both strains that could improve their adaptive capacity to the mangrove environment. These results combined with those of chemotaxonomic analyses, MALDI-TOF MS profiles and phenotypic analyses support the affiliation of these strains to two novel species within the genus Mycolicibacterium, for which we propose the names Mycolicibacterium aurantiacum sp. nov. B3033T (=KCTC 49712T=MCCC 1K04526T) and Mycolicibacterium xanthum sp. nov. Y57T (=KCTC 49711T=MCCC 1K04875T) as type strains.

Environmental risks of polymer materials from disposable face masks linked to the COVID-19 pandemic.

The indispensable role of plastic products in our daily life is highlighted by the COVID-19 pandemic again. Disposable face masks, made of polymer materials, as effective and cheap personal protective equipment (PPE), have been extensively used by the public to slow down the viral transmission. The repercussions of this have generated million tons of plastic waste being littered into the environment because of the improper disposal and mismanagement amid. And plastic waste can release microplastics (MPs) with the help of physical, chemical and biological processes, which is placing a huge MPs contamination burden on the ecosystem. In this work, the knowledge regarding to the combined effects of MPs and pollutants from the release of face masks and the impacts of wasted face masks and MPs on the environment (terrestrial and aquatic ecosystem) was systematically discussed. In view of these, some green technologies were put forward to reduce the amounts of discarded face masks in the environment, therefore minimizing MPs pollution at its source. Moreover, some recommendations for future research directions were proposed based on the remaining knowledge gaps. In a word, MPs pollution linked to face masks should be a focus worldwide.

Alkaline hydrogen peroxide pretreatment combined with bio-additives to boost high-solids enzymatic hydrolysis of sugarcane bagasse for succinic acid processing.

Alkaline hydrogen peroxide (AHP) pretreatment of sugarcane bagasse (SCB) at mild conditions was optimized with response surface methodology (RSM), then enzymatic hydrolysis was performed at high-solids substrate loading (30 %, w/v), followed by fed-batch fermentation to convert the fermentable sugars into succinic acid (SA). Results showed the AHP pretreatment conditions of H2O2 concentration 5.5 % (v/v), solid-to-liquid ratio 0.08, pretreatment temperature 65 °C and time 5 h could achieve the highest sugar yield (74.3 %); both additives and fed-batch strategy were favored to boost enzymatic hydrolysis, the concentration and yield of total sugars reached to 195 g/L and 70 % with cellulase dosage of only 6 FPU/g dry biomass (DM); all glucose and xylose could be utilized after fed-batch fermentation, and the obtained concentration and yield of SA reached 41.4 g/L and 63.8 %. In summary, a SA conversion rate high to 0.29 g/g SCB raw material could be achieved via the developed process.

Acuticoccus mangrovi sp. nov., with an antibacterial property, isolated from mangrove sediment.

A Gram-stain-negative, aerobic, milky white bacterium, designated B2012T, was isolated from mangrove sediment collected at Beibu Gulf, South China Sea. Antimicrobial activity assay revealed that the isolate possesses the capability of producing antibacterial compounds. Strain B2012T shared the highest 16S rRNA gene sequence relatedness (96.9-95.5 %) with members of the genus Acuticoccus. The isolate and all known Acuticoccus species contain Q-10 as the main respiratory quinone and have the same polar lipid components (phosphatidylcholine, unidentified glycolipid, unidentified lipid, unidentified amino lipid and phosphatidylglycerol). However, genomic relatedness referred by values of average nucleotide identity, digital DNA-DNA hybridization, average amino acid identity and the percentage of conserved proteins between strain B2012T and other type strains of the genus Acuticoccus were below the proposed thresholds for species discrimination. The genome of strain B2012T was assembled into 65 scaffolds with an N50 size of 244239 bp, resulting in a 5.5 Mb genome size. Eight secondary metabolite biosynthetic gene clusters were detected in this genome, including three non-ribosomal peptide biosynthetic loci encoding yet unknown natural products. Strain B2012T displayed moderately halophilic and alkaliphilic properties, growing optimally at 2-3 % (w/v) NaCl concentration and at pH 8-9. The major cellular fatty acids (>10 %) were anteiso-C15 : 0, C16 : 0 dimethyl aldehyde (DMA) and C16 : 0. Combined data from phenotypic, genotypic and chemotaxonomic analyses suggested that strain B2012T represents a novel species of the genus Acuticoccus, for which the name Acuticoccus mangrovi sp. nov. is proposed. The type strain of the type species is B2012T (=MCCC 1K04418T=KCTC 72962T).

Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review.

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potential of marine natural products or their derivatives that were isolated from January 2019 to March 2020, in cancer cell lines, with a focus on the class and type of isolated compounds, source and location of isolation, cancer cell line type, and potency (IC50 values) of the isolated compounds that could be a guide for drug development.

Thermohalobaculum xanthum gen. nov., sp. nov., a moderately thermophilic bacterium isolated from mangrove sediment.

A novel moderately thermophilic and halophilic bacterium, designated strain M0105T, was isolated from mangrove sediment collected in the Beibu Gulf, south China. The isolate is Gram-negative, non-motile and rod-shaped bacterium with smooth colonies of pale-yellow appearance. Growth occurs at 15-46 °C (optimum 37-40 °C) and pH range of 6.0-10.0 (optimum pH 8.0-9.0). It required 1-7% NaCl (optimum 3-5%) for growth. Strain M0105T was affiliated to the family 'Rhodobacteraceae', sharing the highest 16S rRNA gene sequence similarity with Limibaculum halophilum CAU 1123T (96.8%). The major menaquinone Q-10 and the dominant unsaturated fatty acid (C18:1ω7) in this family were also detected in the strain M0105T. The genome sequence possesses a circular 4.1 Mb chromosome with a G + C content of 67.9%. Strain M0105T encoded many genes for cellular stress resistance and nutrient utilization, which could improve its adaptive capacity to the mangrove environment. Values of conserved proteins (POCP), average nucleotide identity, average amino acid identity (AAI) and DNA-DNA hybridization (dDDH) between the isolate and closely related species were below the proposed threshold for species discrimination. Information from phenotypic, chemotaxonomic and phylogenetic analyses proposed that strain M0105T should be assigned to a novel genus within the family 'Rhodobacteraceae'. Thus, we suggested that the strain M0105T represents a novel species in a new genus, for which the name Thermohalobaculum xanthum gen. nov., sp. nov. is proposed. The type strain of the type species is M0105T (= BGMRC 2019T = KCTC 52118T = MCCC 1K03767T = NBRC 112057T).

Co-fermentation of succinic acid and ethanol from sugarcane bagasse based on full hexose and pentose utilization and carbon dioxide reduction.

The full utilization of carbohydrates in lignocellulosic biomass is essential for an efficient biorefining process. In this study, co-fermentation was performed for processing ethanol and succinic from sugarcane bagasse. By optimizing the co-fermentation conditions, nutrition and feeding strategies, a novel process was developed to make full utilization of the glucose and xylose in the hydrolysate of sugarcane bagasse. The achieved concentrations of succinic acid and ethanol reached to 22.1 and 22.0 g/L, respectively, and could realize the conversion of 100 g SCB raw material into 8.6 g ethanol and 8.7 g succinic acid. It is worth mentioning that the CO2 released from S. cerevisiae in co-fermentation system was recycled by A. succinogenes to synthesize succinic acid, realized CO2 emission reduction in the process of lignocellulosic biomass biorefinery. This study provided a clue for efficient biorefinery of lignocellulosic biomass and reduction greenhouse gas emissions.

Mechanisms of bio-additives on boosting enzymatic hydrolysis of lignocellulosic biomass.

Expensive cellulase is one of the major obstacles hinders large-scale biorefining of lignocellulosic biomass. The cheap and biodegradable additives sophorolipid and whey protein were found to boost enzymatic hydrolysis, their mechanisms were clarified firstly in this study. Results showed that the effects of these additives on enhancing enzymatic hydrolysis were positively correlated with substrate content; when the solid dosage was 20% (w/v), the presence of sophorolipid and whey protein increased glucose yield by 17.8% and 11.9%, respectively; this could be attributed to sophorolipid favor to alleviate the non-productive adsorption between undesired substrates and enzymes caused by hydrophobic and electrostatic forces, and the ability of whey protein to block the site of enzyme adsorption of lignin; high shear and temperature conditions accelerate the inactivation of cellulase, and the addition of sophorolipid and whey protein reduced the inactivation rate by 7.8% and 13.6%, respectively, under enzymatic hydrolysis conditions.

Mesobaculum littorinae gen. nov., sp. nov., a novel bacterium isolated from a sea snail Littorina scabra.

Members within the family Rhodbacteraceae are morphologically and genetically highly diverse, and originate mostly from coastal marine environments. In this study, a novel species of this family, designated M0103T, was isolated from the surface of a sea snail Littorina scabra. Strain M0103T is Gram-stain-negative, halophilic, non-motile and non-Bacteriochlorophyll a-producing bacterium. Several phenotypic characteristics of the isolate were similar to other species within this family, such as the sole respiratory quinone Q-10 and major fatty acid components C18 : 1 ω7c, C18 : 0 and C16 : 0. Strain M0103T contains a diphosphatidylglycerol, a phosphatidylglycerol, a phosphatidylcholine, a phosphatidy ethanolamine, a phosphatidylinositol, five unidentified phospholipids and four unidentified polar lipids. Based on the 16S rRNA gene sequence analysis, this isolate showed the closest phylogenetic relationship with 'Palleronia pontilimi' GH1-23T (95.1 %). Values of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) of genome sequences were of 70.1-76.4 % and 18.3-20.9 % between the isolate and 24 closely related type strains. Analysis the 4.0 Mb genome of strain M0103T revealed several putative genes associated with cellular stress resistance, which may play protective roles for the isolate in the adaptation to a marine environment. Phylogenetic, phenotypic and chemotaxonomic analyses suggested that strain M0103T represents a novel genus and novel species of the family Rhodobacteraceae, for which the name Mesobaculum littorinae gen. nov., sp. nov. is proposed. The type strain is M0103T (=MCCC 1K03619T=KCTC 62358T).

Inhibition of CDK9 attenuates atherosclerosis by inhibiting inflammation and phenotypic switching of vascular smooth muscle cells.

BACKGROUND: Recent studies have demonstrated a key role of vascular smooth muscle cell (VSMC) dysfunction in atherosclerosis. Cyclin-dependent kinases 9 (CDK9), a potential biomarker of atherosclerosis, was significantly increased in coronary artery disease patient serum and played an important role in inflammatory diseases. This study was to explore the pharmacological role of CDK9 inhibition in attenuating atherosclerosis. METHODS: A small-molecule CDK9 inhibitor, LDC000067, was utilized to treat the high fat diet (HFD)-fed ApoE-/- mice and human VSMCs. RESULTS: The results showed that inflammation and phenotypic switching of VSMCs were observed in HFD-induced atherosclerosis in ApoE-/- mice, which were accompanied with increased CDK9 in the serum and atherosclerotic lesions where it colocalized with VSMCs. LDC000067 treatment significantly suppressed HFD-induced inflammation, proliferation and phenotypic switching of VSMCs, resulting in reduced atherosclerosis in the ApoE-/- mice, while had no effect on plasma lipids. Further in vitro studies confirmed that LDC000067 and siRNA-mediated CDK9 knockdown reversed ox-LDL-induced inflammation and phenotypic switching of VSMCs from a contractile phenotype to a synthetic phenotype via inhibiting NF-κB signaling pathway in human VSMCs. CONCLUSION: These results indicate that inhibition of CDK9 may be a novel therapeutic target for the prevention of atherosclerosis.

Myeloid differentiation 2 deficiency attenuates AngII-induced arterial vascular oxidative stress, inflammation, and remodeling.

Vascular remodeling is a pertinent target for cardiovascular therapy. Vascular smooth muscle cell (VSMC) dysfunction plays a key role in vascular remodeling. Myeloid differentiation 2 (MD2), a cofactor of toll-like receptor 4 (TLR4), is involved in atherosclerotic progress and cardiac remodeling via activation of chronic inflammation. In this study, we explored the role of MD2 in vascular remodeling using an Ang II-induced mouse model and cultured human aortic VSMCs. MD2 deficiency suppressed Ang II-induced vascular fibrosis and phenotypic switching of VSMCs without affecting blood pressure in mice. Mechanistically, MD2 deficiency prevented Ang II-induced expression of inflammatory cytokines and oxidative stress in mice and cultured VSMCs. Furthermore, MD2 deficiency reversed Ang II-activated MAPK signaling and Ang II-downregulated SIRT1 expression. Taken together, MD2 plays a significant role in Ang II-induced vascular oxidative stress, inflammation, and remodeling, indicating that MD2 is a potential therapeutic target for the treatment of vascular remodeling-related cardiovascular diseases.