Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by stimulating the release of neutrophil extracellular traps in the tumor immune microenvironment.

BACKGROUND: The aim of this study was to investigate the impact of Porphyromonas gingivalis (P. gingivalis) on the progression of oral squamous cell carcinoma (OSCC) through neutrophil extracellular traps (NETs) in the tumor immune microenvironment. METHODS: The expression of NETs-related markers was identified through immunohistochemistry, immunofluorescence, and Western blotting in different clinical stages of OSCC samples. The relationship between NETs-related markers and clinicopathological characteristics in 180 samples was analyzed using immunohistochemistry data. Furthermore, the ability to predict the prognosis of OSCC patients was determined by ROC curve analysis and survival analysis. The effect of P. gingivalis on the release of NETs was identified through immunofluorescence and immunohistochemistry, both in vitro and in vivo. CAL27 and SCC25 cell lines were subjected to NETs stimulation to elucidate the influence of NETs on various cellular processes, including cell proliferation, migration, invasion, and metastasis in vitro. Furthermore, the impact of NETs on the growth and metastatic potential of OSCC was assessed using in vivo models involving tumor-bearing mice and tumor metastasis mouse models. RESULTS: Immunochemistry analysis revealed a significant correlation between the NETs-related markers and clinical stage, living status as well as TN stage. P. gingivalis has demonstrated its ability to effectively induce the release of NETs both in vivo and in vitro. NETs have the potential to facilitate cell migration, invasion, and colony formation. Moreover, in vivo experiments have demonstrated that NETs play a pivotal role in promoting tumor metastasis. CONCLUSION: High expression of NETs-related markers demonstrates a strong correlation with the progression of OSCC. Inhibition of the NETs release process stimulated by P. gingivalis and targeted NETs could potentially open up a novel avenue in the field of immunotherapy for patients afflicted with OSCC.

Chronic vascular pathogenesis results in the reduced serum Metrnl levels in ischemic stroke patients.

Metrnl is a secreted protein involved in neurite outgrowth, insulin sensitivity, immunoinflammatory responses, blood lipids and endothelial protection. In this study, we investigated the role of Metrnl in ischemic stroke. Fifty-eight ischemic stroke patients (28 inpatient patients within 2 weeks of onset and 30 emergency patients within 24 h of onset) and 20 healthy controls were enrolled. Serum Metrnl was measured by enzyme-linked immunosorbent assay. We showed that serum Metrnl levels were significantly reduced in both inpatient and emergency patient groups compared with the controls. Different pathological causes for ischemic stroke such as large artery atherosclerosis and small artery occlusion exhibited similar reduced serum Metrnl levels. Transient ischemic attack caused by large artery atherosclerosis without brain infarction also had lower serum Metrnl levels. Metrnl was correlated with some metabolic, inflammatory and clotting parameters. Reduced serum Metrnl was associated with the severity of intracranial arterial stenosis and the presence of ischemic stroke. In order to elucidate the mechanisms underlying the reduced serum Metrnl levels, we established animal models of ischemic stroke in normal mice, atherosclerotic apolipoprotein E-knockout mice and Metrnl-knockout mice by middle cerebral artery occlusion (MCAO) using intraluminal filament or electrocoagulation. We demonstrated that serum Metrnl levels were significantly lower in atherosclerosis mice than normal mice, whereas acute ischemic stroke injury in normal mice and atherosclerosis mice did not alter serum Metrnl levels. Metrnl knockout did not affect acute ischemic stroke injury and death. We conclude that reduced serum Metrnl levels are attributed to the chronic vascular pathogenesis before the onset of ischemic stroke. Metrnl is a potential target for prevention of ischemic stroke.

Melatonin activates Nrf2/HO-1 signalling pathway to antagonizes oxidative stress-induced injury via melatonin receptor 1 (MT1) in cryopreserved mice ovarian tissue.

Our previous research has shown that melatonin (MLT) can reduce cryopreserved ovarian damage in mice. Yet, the molecular mechanism of MLT protection is still unclear. Some studies have shown that melatonin receptor 1 (MT1) is very important for animal reproductive system. To evaluate whether MLT exerts its protective effect on cryopreserved mice ovarian tissue via MT1, we added antagonist of MT1/MT2 (Luzindor) or antagonist of MT2 (4P-PDOT) to the freezing solution, followed by cryopreservation and thawing of ovarian tissue. The levels of total superoxide dismutase (T-SOD), catalase (CAT), nitric oxide (NO) and malondialdehyde (MDA) were detected. Besides, by using RT-PCR and Western blotting, the expression of Bcl-2, Bax and Nrf2/HO-1 signalling pathway-related proteins was detected. These findings demonstrated that compared with the melatonin group, the addition of Luzindor increased apoptosis, NO and MDA activities, decreased CAT and T-SOD activities and inhibited Nrf2/HO-1 signalling pathway. In conclusion, melatonin can play a protective role in cryopreserved ovarian tissue of mice through MT1 receptor.

Effectiveness of near-infrared light devices for peripheral intravenous cannulation in children and adolescents: A meta-analysis of randomized controlled trials.

OBJECTIVES: To examine the effectiveness of near-infrared light devices (NIR) on procedure time of successful cannulation, success rate at the first attempt, and pain scores among pediatric patients and explore potential covariates on the intervention effect. BACKGROUND: Pediatric patients have encountered a high failure rate as compared with adult patients using traditional cannulation. NIR devices might help to access veins with an optimum viewing area and eliminate the number of attempts. However, methodological limitations and inconsistent results from previous reviews were found. METHODS: A three-step comprehensive search was performed in nine databases. Meta-analysis, subgroup, and meta-regression analyses were conducted. Individual quality assessment and certainty of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations, Assessments, Development, and Evaluation criteria, respectively. RESULTS: We included 18 randomized controlled trials (RCTs) with 5298 children and adolescents across nine countries. NIR light devices significantly reduce -29.43 s of procedure time and -0.47 attempts of peripheral intravenous cannulation compared with traditional methods. Subgroup analysis observed a significantly large effect size on procedure time using AccuVein with pre-procedure training at the clinics. However, NIR light devices do not significantly decrease the procedure time, first attempt success rate, and pain scores. Meta-regression identified sample size as a significant covariate that had an impact on the success rate at the first attempt. CONCLUSIONS: The near-infrared light device can statistically significantly reduce the procedure time and the number of attempts. Given the low or very low certainty of the evidence, future well-designed RCTs are necessary.

A randomized controlled clinical trial of concentrated growth factor combined with sodium hyaluronate in the treatment of temporomandibular joint osteoarthritis.

OBJECTIVE: To investigate the effect of concentrated growth factor (CGF) combined with sodium hyaluronate (SH) on temporomandibular joint osteoarthritis (TMJOA). METHODS: Sixty patients with TMJOA who were diagnosed by cone-beam computed tomography (CBCT) between March 2020 and March 2023 at the Stomatological Hospital of Xi'an Jiaotong University were randomly divided into a control group (n = 30) and an experimental group (n = 30). The patients in the experimental group were treated with CGF + SH, and those in the control group were treated with SH only. The visual analogue scale (VAS) score indicating pain in the temporomandibular joint (TMJ) area; the Helkimo Clinical Dysfunction Index (Di); and changes in condylar CBCT at the first visit and 2 weeks, 3 months and 6 months after treatment were recorded. The CBCT data of the patients in the experimental and control groups were collected, and the three-dimensional CBCT image sequences were imported into Mimics Medical 19.0 software in DICOM format for condylar reconstruction. RESULTS: The VAS scores at 2 weeks, 3 months and 6 months after treatment were significantly lower in the experimental group than in the control group (P < 0.05), and the pain in the experimental group was significantly relieved. The Di was significantly lower in the experimental group than in the control group (P < 0.05), and the clinical function of the TMJ improved. After treatment, the CBCT score was significantly lower in the experimental group than in the control group (P < 0.05), and the condylar bone cortex was obviously repaired. Observation of the condylar bone cortex by three-dimensional reconstruction showed the same results as those obtained by CBCT. CONCLUSION: CGF combined with SH is effective in the treatment of TMJOA and can improve muscle pain, TMJ pain, Impaired TMJ function, Impaired range of movement, Pain on movement of the mandible and promote bone repair. THE REGISTRATION NUMBER (TRN): ChiCTR2400082712. THE DATE OF REGISTRATION: April 5, 2024.

Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Brønsted Acid-Catalyzed Isomerization of BCBs.

Chiral cyclobutene units are commonly found in natural products and biologically active molecules. Transition-metal-catalysis has been extensively used in asymmetric synthesis of such structures, while organocatalytic approaches remain elusive. In this study, bicyclo[1.1.0]butanes are involved in enantioselective transformation for the first time to offer a highly efficient route toward cyclobutenes with good regio- and enantiocontrol. The utilization of N-triflyl phosphoramide as a chiral Brønsted acid promoter enables this isomerization process to proceed under mild conditions with low catalyst loading as well as good functional group compatibility. The resulting chiral cyclobutenes could serve as platform molecules for downstream manipulations with excellent reservation of stereochemical integrity, demonstrating the synthetic practicality of the developed method. Control experiments have also been performed to verify the formation of a key carbocation intermediate at the benzylic position.

Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by activating the neutrophil chemotaxis in the tumour microenvironment.

BACKGROUND: We aimed to determine the significance of Porphyromonas gingivalis (P. gingivalis) in promoting tumour progression in the tumour microenvironment (TME) of oral squamous cell carcinoma (OSCC). METHODS: The Gene Expression Omnibus (GEO) was used to screen out the differentially expressed genes from the two datasets of GEO138206 and GSE87539. Immunohistochemistry and immunofluorescence analysis of samples, cell biological behaviour experiments, and tumour-bearing animal experiments were used to verify the results in vivo and in vitro. The mechanism was revealed at the molecular level, and rescue experiments were carried out by using inhibitors and lentiviruses. RESULTS: CXCL2 was selected by bioinformatics analysis and was found to be related to a poor prognosis in OSCC patients. Samples with P. gingivalis infection in the TME of OSCC had the strongest cell invasion and proliferation and the largest tumour volume in tumour-bearing animal experiments and exhibited JAK1/STAT3 signalling pathway activation and epithelial-mesenchymal transition (EMT). The expression of P. gingivalis, CXCL2 and TANs were independent risk factors for poor prognosis in OSCC patients. A CXCL2/CXCR2 signalling axis inhibitor significantly decreased the invasion and proliferation ability of cells and the tumour volume in mice. When lentivirus was used to block the CXCL2/CXCR2 signalling axis, the activity of the JAK1/STAT3 signalling pathway was decreased, and the phenotype of EMT was reversed. CONCLUSION: Porphyromonas gingivalis promotes OSCC progression by recruiting TANs via activation of the CXCL2/CXCR2 axis in the TME of OSCC.

Noncovalent composites of meso-substituted A2B2-porphyrins and carbon nanotubes for enhanced electrocatalytic oxygen reduction.

Exploring highly active oxygen reduction electrocatalysts with low precious metals content is imperative but remains a considerable challenge. Herein, a series of heterobimetallic multi-walled carbon nanotubes (MWCNTs) electrocatalysts based on metal complexes are presented. These electrocatalysts feature diverse transition metals (M=Mn, Fe, Co, Ni) 5,15-bromophenyl-10, 20-methoxyphenyl porphyrin (MBMP) and tetrakis(triphenylphosphine)palladium (0) (Pd[P(Ph3)4]) anchored non-covalently on its surface. The resulting NiBMP-based MWCNTs with Pd[P(Ph3)4] (PdNiN4/MWCNTs) display outstanding electrocatalytic oxygen reduction activity (onset potential, 0.941 V; half wave potential, 0.830 V) and robust long-term durability in alkaline electrolyte. While in neutral condition, the MnBMP-based MWCNTs with Pd[P(Ph3)4] (PdMnN4/MWCNTs) are the most active heterobimetallic ORR catalyst and produce ultra-low concentration hydrogen peroxide (H2O2yield, 1.2%-1.3%). Synergistically tuning the ORR electrocatalytic activity and electron transfer pathway is achieved by the formation of NiBMP/MnBMP-Pd[P(Ph3)4] active sites. This work indicates such metalloporphyrin-Pd[P(Ph3)4] active sites on MWCNTs have significantly positive influence on electrocatalytic ORR systems and provides facile and mild strategy for designing highly efficient ORR electrocatalysts with ultra-low loading precious metal.

The impact of the chalcogen-substitution element and initial spectroscopic state on excited-state relaxation pathways in nucleobase photosensitizers: a combination of static and dynamic studies.

The substitution of oxygen with chalcogen in carbonyl group(s) of canonical nucleobases gives an impressive triplet generation, enabling their promising applications in medicine and other emerging techniques. The excited-state relaxation S2(ππ*) → S1(nπ*) → T1(ππ*) has been considered the preferred path for triplet generation in these nucleobase derivatives. Here, we demonstrate enhanced quantum efficiency of direct intersystem crossing from S2 to triplet manifold upon substitution with heavier chalcogen elements. The excited-state relaxation dynamics of sulfur/selenium substituted guanines in a vacuum is investigated using a combination of static quantum chemical calculations and on-the-fly excited-state molecular dynamics simulations. We find that in sulfur-substitution the S2 state predominantly decays to the S1 state, while upon selenium-substitution the S2 state deactivation leads to simultaneous population of the S1 and T2,3 states in the same time scale and multi-state quasi-degeneracy region S2/S1/T2,3. Interestingly, the ultrafast deactivation of the spectroscopic S3 state of both studied molecules to the S1 state occurs through a successive S3 → S2 → S1 path involving a multi-state quasi-degeneracy S3/S2/S1. The populated S1 and T2 states will cross the lowest triplet state, and the S1 → T intersystem crossing happens in a multi-state quasi-degeneracy region S1/T2,3/T1 and is accelerated by selenium-substitution. The present study reveals the influence of both the chalcogen substitution element and initial spectroscopic state on the excited-state relaxation mechanism of nucleobase photosensitizers and also highlights the important role of multi-state quasi-degeneracy in mediating the complex relaxation process. These theoretical results provide additional insights into the intrinsic photophysics of nucleobase-based photosensitizers and are helpful for designing novel photo-sensitizers for real applications.

Metrnl regulates cognitive dysfunction and hippocampal BDNF levels in D-galactose-induced aging mice.

Aging is one of the main risk factors for cognitive dysfunction. During aging process, the decrease of brain-derived neurotrophic factor (BDNF) and the impairment of astrocyte function contribute to the cognitive impairment. Metrnl, a neurotrophic factor, promotes neural growth, migration and survival, and supports neural function. In this study, we investigated the role of Metrnl in cognitive functions. D-galactose (D-gal)-induced aging model was used to simulate the process of aging. Cognitive impairment was assessed by the Morris water maze test. We showed that Metrnl expression levels were significantly increased in the hippocampus of D-gal-induced aging mice. Metrnl knockout did not affect the cognitive functions in the baseline state, but aggravated the cognitive impairment in the D-gal-induced aging mice. Furthermore, Metrnl knockout significantly reduced hippocampal BDNF, TrkB, and glial fibrillary acidic protein (GFAP) levels in the D-gal-induced aging mice. In the D-gal-induced aging cell model in vitro, Metrnl levels in the hippocampal astrocytes were significantly increased, and Metrnl knockdown and overexpression regulated the BDNF levels in primary hippocampal astrocytes rather than in neurons. We conclude that Metrnl regulates cognitive functions and hippocampal BDNF levels during aging process. As a neurotrophic factor and an endogenous protein, Metrnl is expected to become a new candidate for the treatment or alleviation of aging-related cognitive dysfunction.

Metrnl deficiency retards skin wound healing in mice by inhibiting AKT/eNOS signaling and angiogenesis.

Meteorin-like (Metrnl) is a novel secreted protein with various biological activities. In this study, we investigated whether and how Metrnl regulated skin wound healing in mice. Global Metrnl gene knockout mice (Metrnl-/-) and endothelial cell-specific Metrnl gene knockout mice (EC-Metrnl-/-) were generated. Eight-mm-diameter full-thickness excisional wound was made on the dorsum of each mouse. The skin wounds were photographed and analyzed. In C57BL/6 mice, we observed that Metrnl expression levels were markedly increased in skin wound tissues. We found that both global and endothelial cell-specific Metrnl gene knockout significantly retarded mouse skin wound healing, and endothelial Metrnl was the key factor affecting wound healing and angiogenesis. The proliferation, migration and tube formation ability of primary human umbilical vein endothelial cells (HUVECs) were inhibited by Metrnl knockdown, but significantly promoted by addition of recombinant Metrnl (10 ng/mL). Metrnl knockdown abolished the proliferation of endothelial cells stimulated by recombinant VEGFA (10 ng/mL) but not by recombinant bFGF (10 ng/mL). We further revealed that Metrnl deficiency impaired VEGFA downstream AKT/eNOS activation in vitro and in vivo. The damaged angiogenetic activity in Metrnl knockdown HUVECs was partly rescued by addition of AKT activator SC79 (10 µM). In conclusion, Metrnl deficiency retards skin wound healing in mice, which is related to impaired endothelial Metrnl-mediated angiogenesis. Metrnl deficiency impairs angiogenesis by inhibiting AKT/eNOS signaling pathway.

Altered functional activity in the right superior temporal gyrus in patients with definite vestibular migraine.

BACKGROUND: Vestibular migraine (VM) is one of the most common causes of episodic central vestibular disorders; it is worth investigating whether VM belongs to the migraine subtype or is a separate disorder. The study is aimed at investigating resting-state functional brain activity alterations in patients with definite VM (dVM). METHODS: Seventeen patients with dVM, 8 patients with migraine, and 17 health controls (HCs) were recruited. The amplitude of low frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were calculated to observe the changes in spontaneous brain activity. RESULTS: Compared with HCs, VM patients showed significantly increased ALFF values in the right temporal lobe (P = 0.002) and increased ReHo values in the right superior, middle, and inferior temporal gyrus (STG, MTG, and ITG, P = 0.013); patients with migraine showed significantly increased ALFF values in the right limbic lobe (P = 0.04), left ITG (P = 0.024), and right frontal lobe (P < 0.001), significantly decreased ALFF values in the pons and brainstem (P = 0.013), and significantly decreased ReHo values in the frontal cortex (P < 0.001). Compared with patients with migraine, VM patients showed significantly increased fALFF values in the right parietal lobe (P = 0.011) and right frontal lobe (P = 0.026) and significantly increased ReHo values in the right thalamus (P = 0.043). CONCLUSIONS: Patients with VM and migraine both had altered brain function, but the regions involved are different.

Overground Robotic Exoskeleton Training for Patients With Stroke on Walking-Related Outcomes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This review aims to evaluate the effectiveness of solely overground robotic exoskeleton (RE) training or overground RE training with conventional rehabilitation in improving walking ability, speed, and endurance among patients with stroke. DATA SOURCES: Nine databases, 5 trial registries, gray literature, specified journals, and reference lists from inception until December 27, 2021. STUDY SELECTION: Randomized controlled trials adopting overground robotic exoskeleton training for patients with any phases of stroke on walking-related outcomes were included. DATA EXTRACTION: Two independent reviewers extracted items and performed risk of bias using the Cochrane Risk of Bias tool 1 and certainty of evidence using the Grades of Recommendation Assessment, Development, and Evaluation. DATA SYNTHESIS: Twenty trials involving 758 participants across 11 countries were included in this review. The overall effect of overground robotic exoskeletons on walking ability at postintervention (d=0.21; 95% confidence interval [CI], 0.01, 0.42; Z=2.02; P=.04) and follow-up (d=0.37; 95% CI, 0.03, 0.71; Z=2.12; P=.03) and walking speed at postintervention (d=0.23; 95% CI, 0.01, 0.46; Z=2.01; P=.04) showed significant improvement compared with conventional rehabilitation. Subgroup analyses suggested that RE training should combine with conventional rehabilitation. A preferable gait training regime is <4 times per week over ≥6 weeks for ≤30 minutes per session among patients with chronic stroke and ambulatory status of independent walkers before training. Meta-regression did not identify any effect of the covariates on the treatment effect. The majority of randomized controlled trials had small sample sizes, and the certainty of the evidence was very low. CONCLUSION: Overground RE training may have a beneficial effect on walking ability and walking speed to complement conventional rehabilitation. Further large-scale and long-term, high-quality trials are recommended to enhance the quality of overground RE training and confirm its sustainability.

Effects of sericin on oxidative stress and PI3K/AKT/mTOR signal pathway in cryopreserved mice ovarian tissue.

Ovarian tissue cryopreservation is an effective fertility protective strategy for preadolescent female cancer patients, whose tumor treatment cannot be delayed. In the present study, the effects of sericin, as an antioxidant, on mice ovarian tissue freezing and thawing were investigated. Mice ovarian tissues were cryopreserved and thawed in medium containing 0.5% or 1%sericin (w/v), and 0.1 mM melatonin. Then, the follicular morphology was observed. The levels of antioxidant enzymes were determined, including glutathione (GSH), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT). Moreover, the levels of nitric oxide (NO), malondialdehyde (MDA) and lactate dehydrogenase (LDH) were also tested. Besides, apoptosis-related proteins Bcl-2 and Bax were determined. Our results showed that 1% sericin maintained follicular morphology, inhibited apoptosis, decreased MDA and NO levels, and boosted endogenous antioxidant enzyme levels, while had no significant effect on LDH levels. Furthermore, these effects may be related with the activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of Rapamycin (mTOR) signaling pathway, as demonstrated by increased PI3K, p-AKT and mTOR levels. These findings demonstrate that 1% sericin may reduce oxidative stress and protect ovarian tissues during freezing and thawing via PI3K/AKT/mTOR signaling pathway.

[Comparison of distribution of eight components from Liangxue Tuizi Mixture between normal and Henoch-Schonlein purpura rats].

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.

CircAHNAK upregulates EIF2B5 expression to inhibit the progression of ovarian cancer by modulating the JAK2/STAT3 signaling pathway.

Recent studies highlighted non-coding RNAs as potential therapeutic targets in ovarian cancer. We aimed to investigate the roles of circAHNAK in ovarian cancer pathogenesis. Here, RNA immunoprecipitation, dual-luciferase reporter assay and RNA fluorescence in situ hybridization were adopted to determine circAHNAK, miR-28 or EIF2B5 interaction. CCK-8 assay was used to detect cell proliferation. Wound healing and Transwell assays were employed to assess cell migration and invasion, respectively. Flow cytometry was performed to measure cell apoptosis. The roles of circAHNAK on tumor growth in vivo were evaluated using subcutaneous xenograft model. The expression levels of circAHNAK, miR-28, EIF2B5, markers of EMT and JAK2/STAT3 pathway were measured by qRT-PCR, western blotting or immunohistochemistry staining. We reported that circAHNAK was decreased in ovarian cancer tissues. Forced expression of circAHNAK promoted apoptosis and inhibited cell proliferation, migration, invasion, EMT and JAK2/STAT3 signaling pathway. Mechanistically, circAHNAK acted as a miR-28 sponge. CircAHNAK deficiency resulted in the amassing of miR-28, which was elevated in ovarian cancer and promoted cancer cell malignancy. MiR-28 in turn inhibited EIF2B5 expression. Silence of EIF2B5 abolished the anticancer effects of miR-28 inhibitor. CircAHNAK overexpression retarded tumor growth in vivo, along with the decreased miR-28 and increased EIF2B, as well as EMT inhibition. In conclusion, circAHNAK targets miR-28 to upregulate EIF2B5 expression, thus inhibits progression of ovarian cancer by suppressing JAK2/STAT3 signaling pathway.

LncRNA KCNQ1OT1 promotes the metastasis of ovarian cancer by increasing the methylation of EIF2B5 promoter.

BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as regulators of human malignancies, including ovarian cancer (OC). LncRNA KCNQ1OT1 could promote OC progression, and EIF2B5 was associated with development of several tumors. This project was aimed to explore the role of lncRNA KCNQ1OT1 in OC development, as well as the involving action mechanism. METHODS: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) or Western blotting was employed to determine the expression levels of KCNQ1OT1 and EIF2B5. OC cell proliferation was evaluated by MTT and colony formation assays, and wound healing and Transwell assays were implemented to monitor cell migration and invasion, respectively. The methylation status of EIF2B5 promoter was examined by MS-PCR, to clarify whether the expression of EIF2B5 was decreased. The binding activity of KCNQ1OT1 to methyltransferases DNMT1, DNMT3A and DNMT3B was determined by dual luciferase reporter assay or RIP assay, to explore the potential of KCNQ1OT1 alters the expression of its downstream gene. ChIP assay was carried out to verify the combination between EIF2B5 promoter and above three methyltransferases. RESULTS: Expression of lncRNA KCNQ1OT1 was increased in OC tissues and cells. EIF2B5 expression was downregulated in OC, which was inversely correlated with KCNQ1OT1. Knockdown of KCNQ1OT1 inhibited OC cell proliferation and metastasis. KCNQ1OT1 could downregulate EIF2B5 expression by recruiting DNA methyltransferases into EIF2B5 promoter. Furthermore, interference of EIF2B5 expression rescued KCNQ1OT1 depletion-induced inhibitory impact on OC cell proliferation and metastasis. CONCLUSION: Our findings evidenced that lncRNA KCNQ1OT1 aggravated ovarian cancer metastasis by decreasing EIF2B5 expression level, and provided a novel therapeutic strategy for OC.

Morphology analysis of unlabeled red blood cells based on quantitative differential phase contrast microscopy.

The current classical blood smear technique to observe the morphology of single red blood cells (RBCs) for classification is a laborious and error-prone process. To objectively evaluate the morphology of blood cells, we established a method of computational imaging based on a programmable light emitting diode array. By using quantitative differential phase contrast (qDPC), we characterized the morphology of unlabeled RBCs as well as blood smears. By focusing on comparing the difference of imaging between unlabeled RBCs and stained RBCs under multimode microscopic imaging technology, we demonstrated that qDPC could clearly differentiate discocytes and spherocytes in both unlabeled RBCs and blood smears. The phase map provided by quantitative phase imaging further enhanced the classification accuracy. According to statistical analysis from morphological indexes, the qDPC imaging has a significantly improvement in non-circularity, texture inhomogeneity and equivalent diameters of cells. Thus, this method has a significant superiority in the capability to analyze the morphology of RBCs and could be applied to clinical assays for determining morphological, functional, and structural deterioration of RBCs.

Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway.

RATIONALE: SNX10 (sorting nexin 10) has been reported to play a critical role in regulating macrophage function and lipid metabolism. OBJECTIVE: To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms. METHODS AND RESULTS: SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE-/- (apolipoprotein E) background and atherogenesis (high-cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE-/- mice. Myeloid cell-specific SNX10 deficiency (Δ knockout [KO]) attenuated atherosclerosis progression in APOE-/- mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of ΔKO mice. In vitro experiments showed that SNX10 deficiency-inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT (protein kinase B). The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB (transcription factor EB), thereby enhanced lysosomal biogenesis and LAL (lysosomal acid lipase) activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype. CONCLUSIONS: Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.

Effects of long-term PM2.5 exposure on metabolic syndrome among adults and elderly in Guangdong, China.

BACKGROUND: We aimed to explore the association between long-term exposure to particulate matter ≤ 2.5 µm (PM2.5) and metabolic syndrome (MetS) and its components including fasting blood glucose (FBG), blood pressure, triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and waist circumference among adults and elderly in south China. METHODS: We surveyed 6628 participants in the chronic disease and risk factors surveillance conducted in 14 districts of Guangdong province in 2015. MetS was defined based on the recommendation by the Joint Interim Societies' criteria. We used the spatiotemporal land-use regression (LUR) model to estimate the two-year average exposure of ambient air pollutants (PM2.5, PM10, SO2, NO2, and O3) at individual levels. We recorded other covariates by using a structured questionnaire. Generalized linear mixed model was used for analysis. RESULTS: A 10-µg/m3 increase in the two-year mean PM2.5 exposure was associated with a higher risk of developing MetS [odd ratio (OR): 1.17, 95% confidence interval (CI): 1.01, 1.35], increased risk of fasting blood glucose level. (OR: 1.18, 95% CI: 1.02, 1.36), and hypertriglyceridemia (OR: 1.36, 95% CI: 1.18, 1.58) in the adjusted/unadjusted models (all P < 0.05). We found significant interaction between PM2.5 and the region, exercise on the high TG levels, and an interaction with the region, age, exercise and grain consumption on FBG (P interaction < 0.05). CONCLUSIONS: Long-term exposure to PM2.5 was associated with MetS, dyslipidemia and FBG impairment. Efforts should be made for environment improvement to reduce the burden of MetS-associated non-communicable disease.