Multi-omics analysis identifies potential mechanisms by which high glucose accelerates macrophage foaming.

Atherosclerotic morbidity is significantly higher in the diabetic population. Hyperglycemia, a typical feature of diabetes, has been proven to accelerate foam cell formation. However, the molecular mechanisms behind this process remain unclear. In this study, LPS and IFN-γ were used to convert THP-1-derived macrophages into M1 macrophages, which were then activated with ox-LDL in either high glucose or normal condition. We identified lipids within macrophages by Oil red O staining and total cholesterol detection. The genes involved in lipid absorption, efflux, inflammation, and metabolism were analyzed using qRT-PCR. The mechanisms of high glucose-induced foam cell formation were further investigated through metabolomics and transcriptomics analysis. We discovered that high glucose speed up lipid accumulation in macrophages (both lipid droplets and total cholesterol increased), diminished lipid efflux (ABCG1 down-regulation), and aggravated inflammation (IL1B and TNF up-regulation). Following multi-omics analysis, it was determined that glucose altered the metabolic and transcriptional profiles of macrophages, identifying 392 differently expressed metabolites and 293 differentially expressed genes, respectively. Joint pathway analysis suggested that glucose predominantly disrupted the glycerolipid, glycerophospholipid, and arachidonic acid metabolic pathways in macrophages. High glucose in the glyceride metabolic pathway, for instance, suppressed the transcription of triglyceride hydrolase (LIPG and LPL), causing cells to deposit excess triglycerides into lipid droplets and encouraging foam cell formation. More importantly, high glucose triggered the accumulation of pro-atherosclerotic lipids (7-ketocholesterol, lysophosphatidylcholine, and glycerophosphatidylcholine). In conclusion, this work elucidated mechanisms of glucose-induced foam cell formation via a multi-omics approach.

Volar locking plate versus external fixation for unstable distal radius fractures: a systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: The outcomes for volar locking plate (VLP) and external fixation (EF) in distal radius fracture cases remain controversial. The current study of randomized controlled trials (RCTs) aimed to assess VLP and EF, which might benefit distal radius fracture cases. METHODS: RCTs comparing VLP and EF in distal radius fracture cases, until 18 March 2020, were systematically reviewed and summarized. The functional and radiographic outcomes, together with complications, for distal radius fracture cases, were evaluated. RESULTS: In total, 12 studies comprising 1205 distal radius fracture cases were included. The VLP group had observed lower disability in the arm shoulder and hand score (DASH) at 3rd, 6th, and 12th -month post-operation, with the mean differences (MDs) of - 10.43 (95 % CI = - 15.77 to - 5.08, P < 0.01), - 3.48 (95 % CI = - 6.37 to - 0.59, P = 0.02), and - 4.13 (95 % CI = - 6.94 to - 1.33, P < 0.01), respectively. The VLP group also had lower visual analog scale scores (VAS) compared to the EF group, with MDs of - 0.10 (95 % CI = - 0.18 to - 0.03, P < 0.01) for the former at 6th -month post-operation. Also, the EF group exhibited better grip strength than that in the VLP group, with MD of 12.48 (95 % CI = 7.00-17.95, P < 0.01) at the 3rd month and 4.54 (95 % CI = 0.31-8.76, P = 0.04) at 6th month. No significant differences in radiographic outcomes were observed between the VLP and EF groups (P > 0.05). The VLP group had a lower complication rate than that in the EF group. CONCLUSIONS: VLP had a lower DASH score and VAS score but with lower grip strength. No significant differences in radiographic outcomes were observed. VLP had a lower complication rate than that of EF.

[Downregulation of 53BP1 by short hairpin RNA enhances radiosensitivity in laryngeal carcinoma cells].

OBJECTIVE: To determine the effect of downregulation of 53BP1 expression on cell growth and radiosensitivity in laryngeal carcinoma Hep-2 cells. METHODS: HEP-2 cell lines were established with a stable knockdown of 53BP1 with short hairpin RNA (shRNA). The level of expressed protein of negative control group (NC),wild type Hep-2 and downregulation of 53BP1 (P6) group was determined by Western blotting. Proliferation on normal conditions was detected by MTT. Radiosensitivity and growth of cells were detected by flow cytometry. RESULTS: A stable 53BP1 downregulated cell line P6 was established. Similar cell growth was observed between the 53BP1 downregulated cells and the control cells. The downregulation of 53BP1 reduced the number of clonogenic cells exposed to radiation. Compared with wild type Hep-2 group and NC group, Western blot results showed a decrease in 53BP1 protein level in P6 group (P < 0.05), reducing the ratio of arrest of G2/M with radiation dose increased (P < 0.05). MTT results revealed the lower 53BP1 protein level did not affect the cell proliferation. After exposure to 0, 2, 6, 10 Gy ionizing radiation (IR), P6 cells had lower, radiosensitivity parameters (D0, SF2, Dq, N) than controls and wild type Hep-2 (P < 0.05). CONCLUSION: RNA interference could effectively down-regulate the expression of 53BP1 and reduce arrest of G2/M phase, thus enhancing the radiosensitivity of Hep-2 cell line.

Effect of ligninolytic axenic and coculture white-rot fungi on rice straw chemical composition and in vitro fermentation characteristics.

The study sought to investigate the potentials of axenic cultures of Pleurotus ostreatus, Phanerochaete chrysosporium and their coculture (P. chrysosporium and P. ostreatus) to break down lignin and to enhance the rumen fermentability of rice straw. Rice straw was fermented by two lignin-degrading fungi, namely, P. ostreatus, P. chrysosporium and its coculture (P. ostreatus and P. chrysosporium) with uninoculated straw as control under solid-state fermentation employing a completely randomized research design. The coculture exhibited a mutual intermingling plus inhibition interaction. The fungi treatment increased the crude protein from (5.1%) in the control to (6.5%, 6.6%, and 6.7%) in the P. ostreatus, P. chrysosporium and coculture respectively. The coculture treated straw had a lower lignin content (5.3%) compared to the P. chrysosporium (6.2%) with the P. ostreatus recording the least (3.3%) lignin fraction. Treatment of rice straw with coculture improved the in vitro dry matter digestibility (68.1%), total volatile fatty acids (35.3 mM), and total gas (57.4 ml/200 mg) compared to P. chrysosporium (45.1%, 32.2 mM, 44.4 ml/200 mg) but was second to P. ostreatus (75.3%, 38.3 mM, 65.6 ml/200 mg). Instead of an anticipated synergistic effect from the coculture, a competitive antagonistic effect was rather observed at the end of the study, a condition that can be attributed to the coculture behavior.

Hydrogen sulfide ameliorated preeclampsia via suppression of toll-like receptor 4-activated inflammation in the rostral ventrolateral medulla of rats.

This study aims to determine whether toll-like receptor 4 (TLR4)-mediated inflammation in rostral ventrolateral medulla (RVLM) causes sympathetic overactivity leading to preeclampsia (PE) and if TLR4 inhibition with hydrogen sulfide (H2S) would reduce PE severity. Thirty patients with PE and 30 pregnant controls were involved. PE in rats was induced through deoxycorticosterone acetate and normal saline. NaHS (donor of H2S), lipopolysaccharide (LPS) (TLR4 agonist), and TAK-242 (TLR4 inhibitor) were injected in lateral cerebral ventricle to investigate their effect on microglia-mediated inflammation in RVLM, sympathetic activation, and PE symptoms. In patients with PE, plasma levels of NE, TNF-α, and interleukin-1ß were high compared with those of controls, whereas levels of H2S were low. Rats with PE showed an increased amount of renal sympathetic nerve activity and plasma levels of NE, with decreased H2S levels in RVLM. Microglia-mediated inflammation was observed in the RVLM of PE rats. Central infusion of LPS in pregnant rats induced microglia-mediated inflammation, sympathetic nervous tension, and PE-like symptoms, whereas TAK-242 reduced PE symptoms. NaHS treatment lessened microglia-mediated inflammation in the RVLM, sympathetic tension, and symptoms of PE both in PE rats and LPS-treating pregnant rats.These results suggest that inflammation in the RVLM caused by microglial activation might contribute to the progression of PE via an overactive sympathetic system. H2S could reduce PE via inhibiting inflammation in the RVLM. These results might provide a new target for the treatment of PE.

Case report of a rare giant bone island in a vertebral body combined with hemangioma.

This case report describes a rare giant bone island combined with hemangioma diagnosed in a patient with osteolytic vertebral metastases. The bone island's greatest diameter was 3.15 cm, and bone islands of this size are rare in the literature. This article aims to provide clinicians with information about the diagnosis and relevant literature of bone islands.