Surf4 (Surfeit Locus Protein 4) Deficiency Reduces Intestinal Lipid Absorption and Secretion and Decreases Metabolism in Mice.

BACKGROUND: Postprandial dyslipidemia is a causative risk factor for cardiovascular disease. The majority of absorbed dietary lipids are packaged into chylomicron and then delivered to circulation. Previous studies showed that Surf4 (surfeit locus protein 4) mediates very low-density lipoprotein secretion from hepatocytes. Silencing hepatic Surf4 markedly reduces the development of atherosclerosis in different mouse models of atherosclerosis without causing hepatic steatosis. However, the role of Surf4 in chylomicron secretion is unknown. METHODS: We developed inducible intestinal-specific Surf4 knockdown mice (Surf4IKO) using Vil1Cre-ERT2 and Surf4flox mice. Metabolic cages were used to monitor mouse metabolism. Enzymatic kits were employed to measure serum and tissue lipid levels. The expression of target genes was detected by qRT-PCR and Western Blot. Transmission electron microscopy and radiolabeled oleic acid were used to assess the structure of enterocytes and intestinal lipid absorption and secretion, respectively. Proteomics was performed to determine changes in protein expression in serum and jejunum. RESULTS: Surf4IKO mice, especially male Surf4IKO mice, displayed significant body weight loss, increased mortality, and reduced metabolism. Surf4IKO mice exhibited lipid accumulation in enterocytes and impaired fat absorption and secretion. Lipid droplets and small lipid vacuoles were accumulated in the cytosol and the endoplasmic reticulum lumen of the enterocytes of Surf4IKO mice, respectively. Surf4 colocalized with apoB and co-immunoprecipitated with apoB48 in differentiated Caco-2 cells. Intestinal Surf4 deficiency also significantly reduced serum triglyceride, cholesterol, and free fatty acid levels in mice. Proteomics data revealed that diverse pathways were altered in Surf4IKO mice. In addition, Surf4IKO mice had mild liver damage, decreased liver size and weight, and reduced hepatic triglyceride levels. CONCLUSIONS: Our findings demonstrate that intestinal Surf4 plays an essential role in lipid absorption and chylomicron secretion and suggest that the therapeutic use of Surf4 inhibition requires highly cell/tissue-specific targeting.

RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice.

Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated.

Quantifying population-level conservation impacts for a perpetual conservation program on private land.

Area-based targets, such as percentages of regions protected, are popular metrics of success in the protection of nature. While easily quantified, these targets can be uninformative about the effectiveness of conservation interventions and should be complemented by program impact evaluations. However, most impact evaluations have examined the effect of protected areas on deforestation. Studies that have extended these evaluations to more dynamic systems or different outcomes are less common, largely due to data availability. In these cases, simulations might prove to be a valuable tool for gaining an understanding of the potential range of program effect sizes. Here, we employ simulations of wetland drainage to estimate the impact of the United States Fish and Wildlife Service Small Wetlands Acquisition Program (SWAP) across a ten-year period in terms of wetland area, and breeding waterfowl and brood abundance in the Prairie Pothole Region of North Dakota, South Dakota, and Montana. Using our simulation results, we estimate a plausible range of program impact for the SWAP as an avoided loss of between 0.00% and 0.02% of the carrying capacity for broods and breeding waterfowl from 2008-2017. Despite the low programmatic impact that these results suggest, the perpetual nature of SWAP governance provides promising potential for a higher cumulative conservation impact in the long term if future wetland drainage occurs.

[Effects of Qilan Prescription on the proliferation and apoptosis of human prostate cancer DU145 cells and its action mechanism].

OBJECTIVE: To investigate the effects of different concentrations of Qilan Prescription (QLP) on the proliferation and apoptosis of human PCa DU145 cells and its underlying mechanism. METHODS: We treated human PCa DU145 cells with QLP at 400, 200, 100, 50, 25, 12.5, 6.25, 3.125 or 1.56 µg/ml for 24, 48 and 72 hours respectively. Then we observed the morphological changes of the cells, examined their viability by CCK-8 assay, detected their cell cycle and apoptosis by flow cytometry, and determined the protein expressions of cyclin D1, Bax, Bcl-2 and cleaved-caspase 3 in the DU145 cells by Western blot, followed by comparison of the parameters with those obtained from the blank control group. RESULTS: QLP significantly inhibited the growth, reduced the contour clarity and adhesion ability of the DU145 cells at the concentrations of 100, 200 and 400 µg/ml, and markedly decreased the activity of the cells at 200 and 400 µg/ml, most significantly at 400 µg/ml. The number of the G2-phase DU145 cells was dramatically increased in all the concentration groups (P < 0.01), so was the total number of apoptotic DU145 cells (P < 0.01), while that of the S-phase cells remarkably decreased in the 400 µg/ml QLP (P < 0.01) and 200 µg/ml QLP (P < 0.05) groups. The expression of the cyclin D1 protein was significantly down-regulated in the 400 µg/ml QLP group (P < 0.01). That of Bcl-2 was also down-regulated (P < 0.01) while those of Bax and cleaved-caspase 3 up-regulated in the 400 and 200 µg/ml QLP groups (P < 0.01). CONCLUSION: QLP can inhibit the proliferation and promote the apoptosis of human PCa DU145 cells, which may be associated with its effects of down-regulating the expression of the cell cycle-related protein cyclin D1, disrupting the Bax-Bcl-2 balance, and up-regulating the expression of cleaved-caspase 3.

A BiVO4 Photoanode with a VOx Layer Bearing Oxygen Vacancies Offers Improved Charge Transfer and Oxygen Evolution Kinetics in Photoelectrochemical Water Splitting.

Sluggish oxygen evolution kinetics are one of the key limitations of bismuth vanadate (BiVO4 ) photoanodes for efficient photoelectrochemical (PEC) water splitting. To address this issue, we report a vanadium oxide (VOx ) with enriched oxygen vacancies conformally grown on BiVO4 photoanodes by a simple photo-assisted electrodeposition process. The optimized BiVO4 /VOx photoanode exhibits a photocurrent density of 6.29 mA cm-2 at 1.23 V versus the reversible hydrogen electrode under AM 1.5 G illumination, which is ca. 385 % as high as that of its pristine counterpart. A high charge-transfer efficiency of 96 % is achieved and stable PEC water splitting is realized, with a photocurrent retention rate of 88.3 % upon 40 h of testing. The excellent PEC performance is attributed to the presence of oxygen vacancies in VOx that forms undercoordinated sites, which strengthen the adsorption of water molecules onto the active sites and promote charge transfer during the oxygen evolution reaction. This work demonstrates the potential of vanadium-based catalysts for PEC water oxidation.

Genome assembly of the Chinese maize elite inbred line RP125 and its EMS mutant collection provide new resources for maize genetics research and crop improvement.

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: "missing a small part" in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis-like cell death were detected in qk1 endosperm. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.

Identification and Fine Mapping of the Recessive Gene BK-5, Which Affects Cell Wall Biosynthesis and Plant Brittleness in Maize.

The cellulose of the plant cell wall indirectly affects the cell shape and straw stiffness of the plant. Here, the novel brittleness mutant brittle stalk-5 (bk-5) of the maize inbred line RP125 was characterized. We found that the mutant displayed brittleness of the stalk and even the whole plant, and that the brittleness phenotype existed during the whole growth period from germination to senescence. The compressive strength was reduced, the cell wall was thinner, and the cellulose content was decreased compared to that of the wild type. Genetic analysis and map-based cloning indicated that bk-5 was controlled by a single recessive nuclear gene and that it was located in a 90.2-Kb region on chromosome 3 that covers three open reading frames (ORFs). Sequence analysis revealed a single non-synonymous missense mutation, T-to-A, in the last exon of Zm00001d043477 (B73: version 4, named BK-5) that caused the 951th amino acid to go from leucine to histidine. BK-5 encodes a cellulose synthase catalytic subunit (CesA), which is involved with cellulose synthesis. We found that BK-5 was constitutively expressed in all tissues of the germinating stage and silking stage, and highly expressed in the leaf, auricula, and root of the silking stage and the 2-cm root and bud of the germinating stage. We found that BK-5 mainly localized to the Golgi apparatus, suggesting that the protein might move to the plasma membrane with the aid of Golgi in maize. According to RNA-seq data, bk-5 had more downregulated genes than upregulated genes, and many of the downregulated genes were enzymes and transcription factors related to cellulose, hemicellulose, and lignin biosynthesis of the secondary cell wall. The other differentially expressed genes were related to metabolic and cellular processes, and were significantly enriched in hormone signal transduction, starch and sucrose metabolism, and the plant-pathogen interaction pathway. Taken together, we propose that the mutation of gene BK-5 causes the brittle stalk phenotype and provides important insights into the regulatory mechanism of cellulose biosynthesis and cell wall development in maize.

Atherosclerosis-associated hepatic secretion of VLDL but not PCSK9 is dependent on cargo receptor protein Surf4.

Plasma LDL is produced from catabolism of VLDL and cleared from circulation mainly via the hepatic LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDLR degradation, increasing plasma LDL-C levels. Circulating PCSK9 is mainly secreted by the liver, whereas VLDL is exclusively secreted by hepatocytes. However, the mechanism regulating their secretion is not completely understood. Surfeit 4 (Surf4) is a cargo receptor localized in the ER membrane. It recruits cargos into coat protein complex II vesicles to facilitate their secretion. Here, we investigated the role of Surf4 in VLDL and PCSK9 secretion. We generated Surf4 liver-specific knockout mice and found that knockout of Surf4 did not affect PCSK9 secretion, whereas it significantly reduced plasma levels of cholesterol, triglyceride, and lipid-binding protein apolipoprotein B (apoB). In cultured human hepatocytes, Surf4 coimmunoprecipitated and colocalized with apolipoprotein B100, and Surf4 silencing reduced secretion of apolipoprotein B100. Furthermore, knockdown of Surf4 in LDLR knockout (Ldlr-/-) mice significantly reduced triglyceride secretion, plasma levels of apoB and non-HDL-C, and the development of atherosclerosis. However, Surf4 liver-specific knockout mice and Surf4 knockdown in Ldlr-/- mice displayed similar levels of liver lipids and plasma alanine aminotransferase activity as control mice, indicating that inhibition of Surf4 does not cause notable liver damage. Expression of stearoyl-CoA desaturase-1 was also reduced in the liver of these mice, suggesting a reduction in de novo lipogenesis. In summary, hepatic deficiency of Surf4 reduced VLDL secretion and the development of atherosclerosis but did not cause significant hepatic lipid accumulation or liver damage.

Macrophage membrane camouflaged reactive oxygen species responsive nanomedicine for efficiently inhibiting the vascular intimal hyperplasia.

BACKGROUND: Intimal hyperplasia caused by vascular injury is an important pathological process of many vascular diseases, especially occlusive vascular disease. In recent years, Nano-drug delivery system has attracted a wide attention as a novel treatment strategy, but there are still some challenges such as high clearance rate and insufficient targeting. RESULTS: In this study, we report a biomimetic ROS-responsive MM@PCM/RAP nanoparticle coated with macrophage membrane. The macrophage membrane with the innate "homing" capacity can superiorly regulate the recruitment of MM@PCM/RAP to inflammatory lesion to enhance target efficacy, and can also disguise MM@PCM/RAP nanoparticle as the autologous cell to avoid clearance by the immune system. In addition, MM@PCM/RAP can effectively improve the solubility of rapamycin and respond to the high concentration level of ROS accumulated in pathological lesion for controlling local cargo release, thereby increasing drug availability and reducing toxic side effects. CONCLUSIONS: Our findings validate that the rational design, biomimetic nanoparticles MM@PCM/RAP, can effectively inhibit the pathological process of intimal injury with excellent biocompatibility.

Analysis of risk factors and prognosis of 253 lymph node metastasis in colorectal cancer patients.

BACKGROUND: This study aimed to explore potential risk factors for 253 lymph node metastasis, and to identify the prognostic impact of 253 lymph node metastasis in colorectal cancer patients. METHODS: A retrospective study was conducted of 391 colorectal cancer patients who underwent surgical treatments that included 253 lymph node dissection. Clinicopathological features, molecular indexes and 1-year overall survival rates were analyzed. RESULTS: Univariate analyses revealed the following risk factors for 253 lymph node metastasis: high preoperative levels of CEA, large tumour max diameters, and numbers of harvested lymph nodes, presence of vessel carcinoma emboli, low level of MSH6 and MLH1 immunohistochemical staining intensity. Multivariate analysis showed that elevated MLH1 immunohistochemical staining intensity was an independent protective factor for 253 lymph node metastasis (OR: 0.969, 95% CI 0.945, 0.994, P = 0.015). A significant difference was found in 1-year overall survival rate between 253 lymph node-positive and lymph node-negative colorectal cancer patients (88.9% vs.75.0%, P < 0.001). CONCLUSIONS: 253 lymph node-positive colorectal cancer patients had a worse prognosis than the 253 lymph node-negative patients. 253 lymph node dissection may improve the prognosis of colorectal cancer patients with high risk factors for 253 lymph node metastasis.

Flexible Multiscale Pore Hybrid Self-Powered Sensor for Heart Sound Detection.

This research introduces an idea of producing both nanoscale and microscale pores in piezoelectric material, and combining the properties of the molecular ß-phase dipoles in ferroelectric material and the space charge dipoles in order to increase the sensitivity of the sensor and modulate the response frequency bandwidth of the material. Based on this idea, a bi-nano-micro porous dual ferro-electret hybrid self-powered flexible heart sound detection sensor is proposed. Acid etching and electrospinning were the fabrication processes used to produce a piezoelectric film with nanoscale and microscale pores, and corona poling was used for air ionization to produce an electret effect. In this paper, the manufacturing process of the sensor is introduced, and the effect of the porous structure and corona poling on improving the performance of the sensor is discussed. The proposed flexible sensor has an equivalent piezoelectric coefficient d33 of 3312 pC/N, which is much larger than the piezoelectric coefficient of the common piezoelectric materials. Experiments were carried out to verify the function of the flexible sensor together with the SS17L heart sound sensor (BIOPAC, Goleta, CA, USA) as a reference. The test results demonstrated its practical application for wearable heart sound detection and the potential for heart disease detection. The proposed flexible sensor in this paper could realize batch production, and has the advantages of flexibility, low production cost and a short processing time compared with the existing heart sound detection sensors.

[Oxidized phospholipids and atherosclerosis].

Phospholipids are important components of biomembrane and lipoproteins. Phospholipids can be oxidized by free radicals/nonradicals and enzymes to form oxidized phospholipids (OxPLs), which can lead to further generation of oxidation products with different biological activities. Clinical evidence shows that OxPLs are constantly generated and transformed during the pathogenesis of atherosclerosis and accumulated at the lesion sites. OxPLs are highly heterogeneous mixtures that can influence the progress of atherosclerosis through a variety of related receptors or signaling pathways. This review summarizes the process of phospholipid oxidation, the related products, the interaction of OxPLs with endothelial cells, monocytes/macrophages, smooth muscle cells, platelets and lipoproteins involved in the pathological process of atherosclerosis, and the progress of the researches using OxPLs as a target to inhibit atherosclerosis in recent years.

Repair of Bone Defects With Endothelial Progenitor Cells and Bone Marrow-Derived Mesenchymal Stem Cells With Tissue-Engineered Bone in Rabbits.

PURPOSE: This study aimed to investigate the repair of bone defects in rabbits with tissue-engineered bones using cocultured endothelial progenitor cells (EPCs) and bone marrow mesenchymal stem cells (BMSCs) as seeding cells. METHODS: Endothelial progenitor cells and BMSCs were isolated and purified from the peripheral blood and bone marrow, respectively, of New Zealand rabbits. The third passage of BMSCs was cultured alone or with EPCs. Cells were characterized using specific markers and then seeded on partially deproteinized biologic bones from pigs as a scaffold. The engineered bones were used to repair bone defects in rabbits. Hematoxylin and eosin and Masson staining were performed to examine vascularization and osteogenesis in the engineered bone. RESULTS: The cocultured EPCs and BMSCs grew well on the surface of the scaffold. Compared with monocultured BMSCs, cocultured EPCs and BMSCs promoted the formation of blood vessels and bone on the scaffold, in addition to accelerating the repair of bone defects. The collagen content was significantly increased in the scaffold with cocultured EPCs and BMSCs, compared with the scaffold seeded with mono-cultured BMSCs. CONCLUSIONS: Tissue-engineered bones seeded with cocultured EPCs and BMSCs may be used effectively for the repair of bone defects.

[Different types of molecular hydrogen donors and their pharmacokinetics in vivo].

Molecular hydrogen (H2) has been shown to have diverse biomedical effects. As a small molecular gas, hydrogen can be diffused to the target without hindrance. A variety of related hydrogen products used in medical research and public health have been developed. There are various methods of administration of H2, mainly including inhaling hydrogen gas, drinking hydrogen water, injecting hydrogen-saline, orally taking solid-state H2 sustained-release agents, and stimulating intestinal microbiomes to produce hydrogen. Pharmacokinetics of H2 in vivo vary with methods of administration and thus influence its biomedical effects. This review summarizes the types of H2 donors and their pharmacokinetics in vivo.

Preparation, Phytochemical Investigation, and Safety Evaluation of Chlorogenic Acid Products from Eupatorium adenophorum.

Eupatorium adenophorum is widely distributed throughout the world's tropical and temperate regions. It has become a harmful weed of crops and natural environments. Its leaves contain bioactive compounds such as chlorogenic acid and may be used as feed additives. In this study, chlorogenic acid was extracted and separated from leaves of E. adenophorum. Three chlorogenic acid products were prepared with different purities of 6.11%, 22.17%, and 96.03%. Phytochemical analysis demonstrated that the main toxins of sesquiterpenes were almost completely removed in sample preparation procedure. The three products were evaluated for safety via in vitro and in vivo toxicological studies. All the products exhibited no cytotoxic effects at a dose of 400 µg/mL in an in vitro cell viability assay. When administered in vivo at a single dose up to 1.5 g/kg bw, all three products caused no signs or symptoms of toxicity in mice. These results encourage further exploration of extracts from E. adenophorum in feed additive application.

Ultrasound-assisted aqueous two-phase extraction of phenylethanoid glycosides from Cistanche deserticola Y. C. Ma stems.

An efficient ultrasound-assisted aqueous two-phase extraction and enrichment process for phenylethanoid glycosides from Cistanche deserticola Y. C. Ma stems was developed in this work. An ethanol/ammonium sulfate system was chosen for the aqueous two-phase system due to its fine partitioning and recycling behaviors. Single-factor experiments and response surface methodology were used to optimize the process parameters of the ultrasound-assisted aqueous two-phase extraction. The optimal conditions were as follows: a salt concentration of 23.5%, an ethanol concentration of 20%, an extraction time of 37 min, an extraction temperature of 30°C, a liquid/solid ratio of 30:1 w/w, and an ultrasound power of 300 W. Under the above conditions, the extraction yields of echinacoside and acteoside (the main components of phenylethanoid glycosides) reached 5.35 and 6.22 mg/g dry material weight, respectively. The contents of echinacoside and acteoside in the extracts reached 27.56 and 30.23 mg/g, respectively, which were 2.46- and 2.58-fold higher than the amounts obtained in ultrasound-assisted extraction. In conclusion, ultrasound-assisted aqueous two-phase extraction was an efficient, ecofriendly, and economical method, and it may be a promising technique for extracting and enriching bioactive components from plants.

Failure Mechanism Analysis and Emerging Strategies for Enhancing the Photoelectrochemical Stability of Photoanodes.

The development of efficient and stable photoanode materials is essential for driving the possible practical application of photoelectrochemical water splitting. This article begins with a basic understanding of the fundamentals of photoelectrochemical devices and photoanodes. State-of-the-art strategies for designing photoanodes with long-term stability are highlighted, including insertion of hole transport layers, construction of protective/passivation layers, loading of co-catalysts, construction of heterojunctions, and modification of the electrolyte. Based on the insights gained from these effective strategies, we present an outlook for addressing key aspects of the challenges of stabilizing photoanodes development in the future work. Widespread adoption of stability assessment criteria will facilitate reliable comparisons of results from different laboratories. In addition, deactivation of photoanode is defined as a 50 % reduction in productivity. An in-depth understanding of the deactivation mechanism is essential for the design and development of efficient and stable photoanodes. This work will provide insights into the stability assessment of photoanode and facilitate the production of practical solar fuels.

Directional regulation of reactive oxygen species in titanium dioxide boosting the photocatalytic degradation performance of azo dyes.

It has been widely accepted that the generation of reactive oxygen species such as superoxide radical, hydroxyl radical, and hydrogen peroxide during photocatalysis is responsible for the degradation of azo dyes. However, it is unclear which reactive oxygen species primarily contributes to the degradation efficiency of azo dyes. Here, we demonstrate that the directional regulation of reactive oxygen species in titanium dioxide (TiO2) to form superoxide radicals by ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) can significantly improve the degradation performance of methyl orange. The optimized addition of EDTA-2Na can completely degrade azo dyes such as methyl orange, acid orange and alkaline orange at a concentration of 10 mg/L in about 20 min, which is not only higher than that achieved by pristine TiO2 under Xe lamp light but also far superior to the reported degradation efficiency of modified TiO2. Even under natural sunlight, this strategy can also effectively decompose azo dyes, demonstrating the great potential for practical water treatment using low-cost TiO2 photocatalysts.

Potential impact of ezetimibe on patients with NAFLD/NASH: a meta-analysis of randomized controlled trials.

Background: Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease. Studies have found that ezetimibe may be utilized as a supplemental treatment for NAFLD. Additionally, many clinical trials reported the potential impacts of ezetimibe on patients with NAFLD, although some conclusions remain controversial. Therefore, this study aimed to evaluate the effects of ezetimibe on patients with NAFLD. Method: Online search was conducted across databases including PubMed, Embase, Scopus, Web of Science, Cochrane Library, Wanfang, VIP, and CNKI to retrieve all relevant controlled studies on the treatment of NAFLD with ezetimibe from the inception of the databases until April 2024. This meta-analysis comprised 10 randomized controlled trials (RCTs). Statistical analysis was conducted using the Meta package in R v4.3.2. Results: A total of ten RCTs were included in this study, encompassing 578 patients (290 in the ezetimibe group and 288 in the control group) diagnosed with NAFLD/non-alcoholic steatohepatitis (NASH). The results indicated that ezetimibe significantly reduced levels of aspartate aminotransferase (P < 0.01), glutamyl transferase (γ-GT) (P < 0.01), total cholesterol (P < 0.01), low-density lipoprotein cholesterol (P < 0.01), high-sensitivity C-reactive protein (P < 0.01), and interleukin-6 (P < 0.01), and markedly increased levels of glycated hemoglobin (P = 0.02). Conclusions: Ezetimibe may partially improve transaminase levels and positively impact liver function in patients with NAFLD/NASH. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023461467.

H3K27ac-activated LncRNA NUTM2A-AS1 Facilitated the Progression of Colorectal Cancer Cells via MicroRNA-126-5p/FAM3C Axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are of great importance in the process of colorectal cancer (CRC) tumorigenesis and progression. However, the functions and underlying molecular mechanisms of the majority of lncRNAs in CRC still lack clarity. METHODS: A Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect lncRNA NUTM2A-AS1 expression in CRC cell lines. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to examine the biological functions of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of CRC cells. RT-qPCR and western blot were implemented for the detection of cell proliferation-, apoptosis-related proteins, and FAM3C. Bioinformatics analysis and dual- luciferase reporter assays were utilized to identify the mutual regulatory mechanism of ceRNAs. RESULTS: lncRNA NUTM2A-AS1 notably elevated in CRC cell lines and the silenced of NUTM2A- AS1 declined proliferation and facilitated apoptosis. Mechanistically, NUTM2A-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) enriched at its promoter region, and NUTM2A-AS1 acted as a sponge for miR-126-5p, leading to the upregulation of FAM3C expression in CRC cell lines. CONCLUSION: Our research proposed NUTM2A-AS1 as an oncogenic lncRNA that facilitates CRC malignancy by upregulating FAM3C expression, which might provide new insight and a promising therapeutic target for the diagnosis and treatment of CRC.