Inhibition of EphA2 protects against atherosclerosis by synergizing with statins to mitigate macrophage inflammation.

Statins are highly prevalent in patients with coronary artery disease. Statins exert their anti-inflammatory effects on the vascular wall and circulating levels of pro-inflammatory cytokines. However, increasing attention revealed the exacerbation of macrophage inflammation induced by statins, and a clear mechanistic explanation of whether the detrimental effects of statins on macrophage inflammatory phenotypes outweigh the beneficial effects is has not yet been established. Here, RNA-sequencing and RT-qPCR analyses demonstrated that statins significantly upregulated EphA2, Nlrp3, IL-1ß and TNF-α expression in macrophages. Mechanistically, we found that atorvastatin reduced KLF4 binding to the EphA2 promoter using KLF4-chromatin immunoprecipitation, suppressed HDAC11-mediated deacetylation and subsequently led to enhanced EphA2 transcription. The 4D-label-free proteomics analysis further confirmed the upregulated EphA2 and inflammatory signals. Furthermore, the proinflammatory effect of atorvastatin was neutralized by an addition of recombinant Fc-ephrinA1, a selective Eph receptor tyrosine kinase inhibitor (ALW-II-41-27) or EphA2-silencing adenovirus (siEphA2). In vivo, EphA2 was identified a proatherogenic factor and apoE-/- mice placed on a high-fat diet following gastric gavage with atorvastatin exhibited a consistent elevation in EphA2 expression. We further observed that the transfection with siEphA2 in atorvastatin-treated mice significantly attenuated atherosclerotic plaque formation and abrogated statin-orchestrated macrophages proinflammatory genes expression as compared to that in atorvastatin alone. Increased plaque stability index was also observed following the addition of siEphA2, as evidenced by increased collagen and smooth muscle content and diminished lipid accumulation and macrophage infiltration. The data suggest that blockage of EphA2 provides an additional therapeutic benefit for further improving the anti-atherogenic effects of statins.

Ca2+-responsive phospholipid-binding BONZAI genes confer a novel role for cotton resistance to Verticillium wilt.

Verticillium wilt which produced by the soil-borne fungus Verticillium dahliae is an important biotic threat that limits cotton (Gossypium hirsutum) growth and agricultural productivity. It is very essential to explore new genes for the generation of V. dahliae resistance or tolerance cotton varieties. Ca2+ signaling as a secondary messenger is involved in pathogen stress response. Despite Ca2+-responsive phospholipid-binding BONZAI (BON) genes have intensively been investigated in Arabidopsis, their function has not still been characterized in cotton. Here, we showed that three copies of GhBON1, two copies of GhBON2 and GhBON3 were found from the genome sequences of upland cotton. The expression of GhBON1 was inducible to V. dahliae. Knocking down of GhBON1, GhBON2 and GhBON3 using virus induced gene silencing (VIGS) each increased up-regulation of defense responses in cotton. These GhBON1, GhBON2 and GhBON3-silenced plants enhanced resistance to V. dahliae accompanied by higher burst of hydrogen peroxide and decreased cell death and had more effect on the up-regulation of defense response genes. Further analysis revealed that GhBON1 could interacts with BAK1-interacting receptor-like kinase 1 (GhBIR1) and pathogen-associated molecular pattern (PAMP) receptor regulator BAK1 (GhBAK1) at plasma membrane. Our study further reveals that plant Ca2+ -responsive phospholipid-binding BONZAI genes negatively regulate Verticillium wilt with the conserved function in response to disease resistance or plant immunity.

Associated congenital anomalies and genetic anomalies in fetuses with isolated and non-isolated aberrant right subclavian artery.

OBJECTIVE: This study's aim was to determine the prevalence of chromosomal anomalies in fetuses with isolated and non-isolated aberrant right subclavian artery (ARSA) and to evaluate its association with other congenital anomalies. METHODS: From September 2018 to October 2021, 668 ARSA cases were diagnosed by prenatal ultrasound in our hospital; cases with missed visits and a lack of chromosomal findings were excluded and 363 cases were eligible for enrollment. General information, ultrasound presentation, chromosomal findings and pregnancy outcomes were retrospectively analyzed. RESULTS: Among the 363 cases, 296 were isolated, and 67 were associated with structural abnormalities or soft marker abnormalities. The proportion of fetuses with chromosomal abnormalities in the isolated ARSA group was significantly lower than that in the non-isolated ARSA group (p < .001). In the non-isolated ARSA group, 22 cases were combined with other soft marker abnormalities and 45 cases were combined with structural abnormalities. The most frequent structural abnormality coexisting with ARSA was cardiac malformations (38.81%). CONCLUSION: The most common combined malformation in ARSA is intracardiac malformation. Isolated ARSA has a low risk of chromosomal abnormalities, so invasive chromosomal testing is not recommended. Non-isolated ARSA has a high incidence of chromosomal abnormalities, so early karyotyping should be recommended.

High temporal waveform fidelity stimulated Brillouin scattering phase conjugate mirror using Novec-7500.

A high temporal waveform fidelity stimulated Brillouin scattering phase conjugate mirror (SBS-PCM) with high energy efficiency, based on a novel medium, Novec-7500, is proposed and practically achieved in this study. A theoretical analysis reveals that the temporal-domain waveform distortion is caused by the inherent pulse duration compression effect of the SBS, and this undesirable phenomenon can be significantly suppressed by decreasing the compression coefficient (CC afterwards), which is defined as the gain coefficient divided by the phonon lifetime, which coefficient and is identified as the key parameter for high waveform-fidelity in SBS-PCM. The feasibility of this approach was demonstrated experimentally, in which a reflected pulse with waveform symmetry equals to the pump and an average pulse duration of 0.974 τp (τp is the duration of pump) with an energy efficiency of over 90% was achieved using Novec-7500.

Three New Selaginellin Derivatives from Selaginella pulvinata and Their α-Glucosidase Inhibitory Activity.

Three new selaginellin derivatives, selaginpulvilins V-X (1-3), together with seven known analogs (4-10) were isolated from whole plants of Selaginella pulvinata. Their structures were determined by extensive spectroscopic methods including 1D and 2D NMR, HR-ESI-MS and chemical derivatization method. Compound 1 represents a rare example of naturally occurring selaginellin with an alkynylphenol-trimmed skeleton. Biological evaluation showed that compounds 2, 6 and 8 displayed moderate inhibition against α-glucosidase with IC50 values of 3.71, 2.04 and 4.00 µM, respectively.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior.

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.

Composition-Controllable Syntheses and Property Modulations from 2D Ferromagnetic Fe5 Se8 to Metallic Fe3 Se4 Nanosheets.

Exploring new-type 2D magnetic materials with high magnetic transition temperature and robust air stability has attracted wide attention for developing innovative spintronic devices. Recently, intercalation of native metal atoms into the van der Waals gaps of 2D layered transition metal dichalcogenides (TMDs) has been developed to form 2D non-layered magnetic TMDs, while only succeeded in limited systems (e.g., Cr2 S3 , Cr5 Te8 ). Herein, composition-controllable syntheses of 2D non-layered iron selenide nanosheets (25% Fe-intercalated triclinic Fe5 Se8 and 50% Fe-intercalated monoclinic Fe3 Se4 ) are firstly reported, via a robust chemical vapor deposition strategy. Specifically, the 2D Fe5 Se8 exhibits intrinsic room-temperature ferromagnetic property, which is explained by the change of electron spin states from layered 1T'-FeSe2 to non-layered Fe-intercalated Fe5 Se8 based on density functional theory calculations. In contrast, the ultrathin Fe3 Se4 presents novel metallic features comparable with that of metallic TMDs. This work hereby sheds light on the composition-controllable synthesis and fundamental property exploration of 2D self-intercalation induced novel TMDs compounds, by propelling their application explorations in nanoelectronics and spintronics-related fields.

Implications for long COVID: A systematic review and meta-aggregation of experience of patients diagnosed with COVID-19.

AIMS AND OBJECTIVES: This review aims to synthesize the available evidence of what patients experience when infected with COVID-19, both in hospital and post-discharge settings. DESIGN: This review was conducted using the Joanna Briggs Institute (JBI) methodology for qualitative systematic reviews and evidence synthesis. Reporting of results was presented according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist. BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a public health crisis worldwide. Many patients diagnosed with COVID-19 have varied levels of persisting mental disorders. Previous studies have reported the degree, prevalence and outcome of psychological problems. Minimal research explored the experience of patients with long COVID. The real-life experience of patients with COVID-19 from diagnosis to post-discharge can deepen the understanding of nurses, physicians and policymakers. METHODS: All studies describing the experience of patients were included. Two authors independently appraised the methodological quality of the included studies using the JBI Critical Appraisal Checklist for Qualitative Research 2020. RESULTS: This systematic review aggregated patients' experience of being diagnosed with COVID-19 in both hospitalized and post-discharge settings. Finally, 17 studies met inclusion criteria and quality appraisal guidelines. The selected studies in the meta-synthesis resulted in 12 categories, and further were concluded as five synthesized findings: physical symptoms caused by the virus, positive and negative emotional responses to the virus, positive coping strategies as facilitators of epidemic prevention and control, negative coping strategies as obstacles of epidemic prevention and control, and unmet needs for medical resource. CONCLUSIONS: The psychological burden of patients diagnosed with COVID-19 is heavy and persistent. Social support is essential in the control and prevention of the epidemic. Nurses and other staff should pay more attention to the mental health of the infected patients both in and after hospitalization. RELEVANCE TO CLINICAL PRACTICE: Nurses should care about the persistent mental trauma of COVID-19 survivors and provide appropriate psychological interventions to mitigate the negative psychological consequences of them. Besides, nurses, as healthcare professionals who may have the most touch with patients, should evaluate the level of social support and deploy it for them. It is also needed for nurses to listen to patient's needs and treat them with carefulness and adequate patience in order to decrease the unmet needs of patients.

Sinensiols H-J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring.

One new lignan sinensiol H (1) and two new bisnorlignans, sinensiols I and J (2 and 3), along with three known compounds were isolated from the whole plants of Selaginella sinensis. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy as well as high-resolution mass spectrometry. The absolute configuration of 1 was established by ECD calculation. Compounds 2 and 3 represent rare examples of naturally occurring 9,9'-bisnorlignans. All the isolated compounds were assayed for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages.

A temperature-regulated circuit for feeding behavior.

Both rodents and primates have evolved to orchestrate food intake to maintain thermal homeostasis in coping with ambient temperature challenges. However, the mechanisms underlying temperature-coordinated feeding behavior are rarely reported. Here we find that a non-canonical feeding center, the anteroventral and periventricular portions of medial preoptic area (apMPOA) respond to altered dietary states in mice. Two neighboring but distinct neuronal populations in apMPOA mediate feeding behavior by receiving anatomical inputs from external and dorsal subnuclei of lateral parabrachial nucleus. While both populations are glutamatergic, the arcuate nucleus-projecting neurons in apMPOA can sense low temperature and promote food intake. The other type, the paraventricular hypothalamic nucleus (PVH)-projecting neurons in apMPOA are primarily sensitive to high temperature and suppress food intake. Caspase ablation or chemogenetic inhibition of the apMPOA→PVH pathway can eliminate the temperature dependence of feeding. Further projection-specific RNA sequencing and fluorescence in situ hybridization identify that the two neuronal populations are molecularly marked by galanin receptor and apelin receptor. These findings reveal unrecognized cell populations and circuits of apMPOA that orchestrates feeding behavior against thermal challenges.

Deficiency of proline/serine-rich coiled-coil protein 1 (PSRC1) accelerates trimethylamine N-oxide-induced atherosclerosis in ApoE-/- mice.

AIMS: The main therapeutic strategies for coronary artery disease (CAD) are mainly based on the correction of abnormal cholesterol levels; however, residual risks remain. The newly proven gut microbial metabolite trimethylamine N-oxide (TMAO) linked with CAD has broadened our horizons. In this study, we determined the role of proline/serine-rich coiled-coil protein 1 (PSRC1) in TMAO-driven atherosclerosis. METHODS AND RESULTS: We first analyzed the levels of TMAO and PSRC1 in patients with or without atherosclerosis with a target LDL-C < 1.8 mmol/L. Plasma TMAO levels were increased and negatively associated with decreased PSRC1 in peripheral blood mononuclear cells. Animals and in vitro studies showed that TMAO inhibited macrophage PSRC1 expression due to DNA hypermethylation of CpG islands. ApoE-/- mice fed a choline-supplemented diet exhibited reduced PSRC1 expression accompanied by increased atherosclerotic lesions and plasma TMAO levels. We further deleted PSRC1 in apoE-/- mice and PSRC1 deficiency significantly accelerated choline-induced atherogenesis, characterized by increased macrophage infiltration, foam cell formation and M1 macrophage polarization. Mechanistically, we overexpressed and knocked out PSRC1 in cultured macrophages to explore the mechanisms underlying TMAO-induced cholesterol accumulation and inflammation. PSRC1 deletion impaired reverse cholesterol transport and enhanced cholesterol uptake and inflammation, while PSRC1 overexpression rescued the proatherogenic phenotype observed in TMAO-stimulated macrophages, which was partially attributed to sulfotransferase 2B1b (SULT2B1b) inhibition. CONCLUSIONS: Herein, clinical data provide evidence that TMAO may participate in the development of CAD beyond well-controlled LDL-C levels. Our work also suggests that PSRC1 is a negative regulator mediating the unfavorable effects of TMAO-containing diets. Therefore, PSRC1 overexpression and reduced choline consumption may further alleviate atherosclerosis.

Deficiency of PSRC1 accelerates atherosclerosis by increasing TMAO production via manipulating gut microbiota and flavin monooxygenase 3.

Maladaptive inflammatory and immune responses are responsible for intestinal barrier integrity and function dysregulation. Proline/serine-rich coiled-coil protein 1 (PSRC1) critically contributes to the immune system, but direct data on the gut microbiota and the microbial metabolite trimethylamine N-oxide (TMAO) are lacking. Here, we investigated the impact of PSRC1 deletion on TMAO generation and atherosclerosis. We first found that PSRC1 deletion in apoE-/- mice accelerated atherosclerotic plaque formation, and then the gut microbiota and metabolites were detected using metagenomics and untargeted metabolomics. Our results showed that PSRC1 deficiency enriched trimethylamine (TMA)-producing bacteria and functional potential for TMA synthesis and accordingly enhanced plasma betaine and TMAO production. Furthermore, PSRC1 deficiency resulted in a proinflammatory colonic phenotype that was significantly associated with the dysregulated bacteria. Unexpectedly, hepatic RNA-seq indicated upregulated flavin monooxygenase 3 (FMO3) expression following PSRC1 knockout. Mechanistically, PSRC1 overexpression inhibited FMO3 expression in vitro, while an ERα inhibitor rescued the downregulation. Consistently, PSRC1-knockout mice exhibited higher plasma TMAO levels with a choline-supplemented diet, which was gut microbiota dependent, as evidenced by antibiotic treatment. To investigate the role of dysbiosis induced by PSRC1 deletion in atherogenesis, apoE-/- mice were transplanted with the fecal microbiota from either apoE-/- or PSRC1-/-apoE-/- donor mice. Mice that received PSRC1-knockout mouse feces showed an elevation in TMAO levels, as well as plaque lipid deposition and macrophage accumulation, which were accompanied by increased plasma lipid levels and impaired hepatic cholesterol transport. Overall, we identified PSRC1 as an atherosclerosis-protective factor, at least in part, attributable to its regulation of TMAO generation via a multistep pathway. Thus, PSRC1 holds great potential for manipulating the gut microbiome and alleviating atherosclerosis.

Quarter acoustic period pulse compression using stimulated Brillouin scattering in PF-5060.

The pulse duration of the near quarter-acoustic period (τa) is demonstrated in transient stimulated Brillouin scattering (SBS) pulse compression by the suppressing Stokes trailing-edge broadening at high intensities. A theoretical analysis reveals that the difficulty in attaining the transient compression limit is caused by the broadening of the Stokes trailing edge owing to insufficient pump depletion, and this undesirable phenomenon can be significantly suppressed by a high SBS gain coefficient. An average pulse duration of ∼1.05 τa was experimentally achieved in transient compression with a high-energy efficiency of over 30%. Benefiting from energy back conversion, compression below the transient SBS limit (< τa) also occurred when the pump peak power was increased to 150 MW.

Fabrication of Tß4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization.

Currently, stem cell transplantations in cardiac repair are limited owing to disadvantages, such as immunological rejection and poor cell viability. Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation, high clearance hinders its application in clinical practice. Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia. In this study, to mimic the paracrine and biological activity of stem cells, we developed artificial stem cells that can continuously release Tß4-exosomes (Tß4-ASCs) by encapsulating specific exosomes within microspheres using microfluidics technology. The results show that Tß4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area, and its therapeutic effect is superior to that of directly injecting the exosomes. In addition, to better understand how it works, we demonstrated that the Tß4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells (CAECs) via the miR-17-5p/PHD3/Hif-1α pathway. In brief, as artificial stem cells, Tß4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction, providing a feasible and alternative method for clinical revascularization.

New Insight into a Fenton-like Reaction Mechanism over Sulfidated ß-FeOOH: Key Role of Sulfidation in Efficient Iron(III) Reduction and Sulfate Radical Generation.

Sulfidation can greatly improve the efficiency of utilization of reducing equivalents for contaminant removal; however, whether this method benefits Fenton-like reactions or not and the possible mechanism are not well understood. In this study, we revealed that surface sulfidation can greatly promote the heterogeneous Fenton activity of ß-FeOOH (Fe3S4@ß-FeOOH) by 40 times, in which not only the •OH formation was enhanced but also SO4•- as a new oxidation species was generated. Moreover, their contribution to metronidazole (MTZ) degradation was 52.5 and 37.1%, respectively. In comparison, almost no HO2•/O2•- was detected in the Fe3S4@ß-FeOOH/H2O2 system. These results were different from some previously reported Fenton counterparts. Based on the characterization and probe experiments, sulfur species, including S2-, S0, and Sn2-, as an electron donor and electron shuttle were responsible for efficient conversion of Fe(III) into Fe(II) other than via the Haber-Weiss mechanism, leading to excellent •OH generation via a Fenton-like mechanism. Most importantly, HSO5- can be generated from SO32- oxidized by •OH, and its scission into SO4•- was not dependent on the extra electric potential or Fe-O2-S(IV) intermediate. These findings provided new insight for utilizing sulfidation to improve the activity of iron-based Fenton catalysts.

C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats.

Activation of microglia and astrocytes following germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) plays a detrimental role in posthemorrhagic hydrocephalus (PHH). It is still unclear whether or how an interaction occurs between microglia and astrocytes in PHH. Here, we investigated the role of the C3/C3aR pathway in microglia and astrocyte interactions and whether C3/C3aR-targeted inhibition could alleviate PHH following GMH-IVH. A total of 152 Sprague-Dawley rats at postnatal day seven (P7) were enrolled in the study, and collagenase VII was used to induce GMH-IVH. Minocycline (45 mg/kg) was administered to inhibit microglial activation. Complement C3a peptide and C3aR antagonist (SB 290157, 10 mg/kg) were used to regulate the C3/C3aR pathway. As a result, the data demonstrated that periventricular C3aR+/Iba-1+ microglia and C3+/GFAP+ astrocytes were significantly increased in GMH-IVH pups at 28 days after surgery. Intranasal C3a peptide upregulated C3aR expression in microglia. Inhibition of microglia by minocycline decreased both C3+/GFAP+ astrocytes and the colocalization volume of Iba-1 and GFAP. In addition, intraperitoneally injected C3aRA alleviated the periventricular colocalization volume of microglia and astrocytes. Compared with vehicle-treated pups, the protein level of IL-1ß, IL-6 and TNF-α in cerebral spinal fluid and brain tissue at 28 days following GMH-IVH were reduced in C3aRA-treated pups. Moreover, hydrocephalus was alleviated, and long-term cognitive ability were improved in the C3aRA-treated group. Our data presented simultaneous periventricular astrogliosis and microgliosis of pups following GMH-IVH and proved their potential interaction through the C3/C3aR pathway, indicating C3aRA as a potential pharmacological treatment of PHH in neonates.

Linear Mixed-Effects Model to Quantify the Association between Somatic Cell Count and Milk Production in Italian Dairy Herds.

Milk production loss due to mastitis in dairy herds is economically important. Before estimating the economic impacts of mastitis, it is crucial to quantify the association between mastitis and milk production. The objective of this study was to estimate the association between somatic cell count (SCC, as an indicator of intramammary infection due to mastitis) and milk production for dairy cows in Lombardy, Italy. The test-day (TD) records data of 3816 dairy herds located in three different geographical areas of Lombardy from January 2016 to December 2018 were used. After data editing, the final dataset comprised 10,445,464 TD records from 2970 farms and 826,831 cows. The analysis was carried out by using a mixed-effects model with six fixed effects (geographical Area, Breed, Days in Milk, Parity, Season and Year) and nested random effects for each cow and herd. The results confirmed that the SCC had a negative association with milk production. On average, this study found that any two-fold increase of SCC resulted in a milk production loss of 0.830 (95% CI: -0.832, -0.828) kg/cow/day in the whole of Lombardy. These results can be used for economic calculations on the costs of mastitis.

ROS and Oxidative Response Systems in Plants Under Biotic and Abiotic Stresses: Revisiting the Crucial Role of Phosphite Triggered Plants Defense Response.

Phosphite (Phi) is a chemical analog of orthophosphate [HPO4 3-]. It is a systemic pesticide generally known to control the prevalence of oomycetes and soil-borne diseases such as Phytophthora, Pythium, and Plasmopora species. Phi can also control disease symptoms and the spread of pathogenic bacteria, fungi, and nematodes. Phi plays critical roles as a fungicide, pesticide, fertilizer, or biostimulator. Overall, Phi can alleviate the severity of the disease caused by oomycete, fungi, pathogenic bacteria, and nematodes (leave, stem, fruit, tuber, and root) in various plants (vegetables, fruits, crops, root/tuber crops, ornamental plants, and forests). Advance research in molecular, physiological, and biochemical approaches has approved the key role of Phi in enhancing crop growth, quantity, and quality of several plant species. Phi is chemically similar to orthophosphate, and inside the cells, it is likely to get involved in different features of phosphate metabolism in both plants and pathogens. In plants, a range of physiobiochemical alterations are induced by plant pathogen stress, which causes lowered photosynthesis activities, enzymatic activities, increased accumulation of reactive oxygen species (ROS), and modification in a large group of genes. To date, several attempts have been made to study plant-pathogen interactions with the intent to minimize the loss of crop productivity. Phi's emerging function as a biostimulant in plants has boost plant yield and tolerance against various stress factors. This review discusses Phi-mediated biostimulant effects against biotic and abiotic stresses.

Reduced SULT2B1b expression alleviates ox-LDL-induced inflammation by upregulating miR-148-3P via inhibiting the IKKß/NF-κB pathway in macrophages.

Atherosclerosis is a lipid-driven chronic inflammatory disease in which lipid-laden macrophage foam cells lead to inflamed lesions in arteries. Previous studies have proven that sulfotransferase 2B1b (SULT2B1b) has several roles in the regulation of lipid metabolism and the inflammatory response. However, little is known about the functions of SULT2B1b in ox-LDL-induced inflammation in macrophages. In this study, after treatment with either ox-LDL alone or combined with transfection of siRNAs targeting SULT2B1b, IL-6, TNF-α, NF-κB, IKKß and IκB mRNA and protein expression were determined in Raw264.7 cells by real-time PCR and Western blot, respectively. The proliferative capacity was determined by EdU staining and Cell Counting Kit-8. Our data demonstrated that SULT2B1b knockdown could reduce phosphorylated NF-κB levels and downregulate IKKß protein levels. Additionally, IκB levels were increased and the proliferation of ox-LDL stimulated cells was inhibited after SULT2B1b silencing. Downregulation of SULT2B1b expression was found to upregulate miR-148a-3p expression by microarray assay, while IKKß was a miR-148a-3p target gene. Our study suggests that SULT2B1b knockdown could promote miR148a-3p expression and inhibit activation of the IKKß/NF-κB signalling pathway, which suppressed the inflammatory response in macrophages. Therefore, targeting the SULT2B1b gene might be potentially beneficial for atherosclerosis prevention by decreasing the inflammatory response.