Asia Pacific Academy of Science Pte. Ltd.
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CLOCK Stabilizes Vulnerable Plaques by Regulating Vascular Smooth Muscle Cell Phenotype Switching via RhoA/ROCK Signaling in Atherosclerosis
No full textBackground: It has been known that circadian locomotor output cycles kaput protein (CLOCK) can not only regulate circadian rhythm but also participates in various biological processes. However, the association between CLOCK expression and plaque stability has not been well examined. This study aims to explore the role of CLOCK in the stability of atherosclerotic plaque and its potential molecular mechanism. Methods: The expression of CLOCK in stable plaque and ruptured plaque in the GSE41571 dataset was analyzed. The qRT-PCR (quantitative real-time polymerase chain reaction) and western blot were used to analyze the mRNA (messenger ribonucleic acid) and protein expression levels of CLOCK and phenotypic transformation markers of vascular smooth muscle cells (VSMCs) in human carotid atherosclerotic plaque samples or HAVSMCs (Human aortic vascular smooth muscle cells) cells, respectively. Cell Counting Kit-8 (CCK-8) and Transwell® assays were used to evaluate the cell proliferation and migration ability, respectively. Results: This study revealed that the CLOCK mRNA levels were reduced in unstable plaques (USP), following a similar pattern as the expression of vascular smooth muscle cells contractile markers such as calponin, α-smooth muscle actin (α-SMA), and smooth muscle protein 22α (SM22-α). Meanwhile, vascular smooth muscle cell synthetic phenotypic marker osteopontin (OPN) was increased. In addition, we found that oxidized low-density lipoprotein (ox-LDL) exposure accelerated phenotypic switching in VSMCs, a process promoted by knocking down the expression of CLOCK and inhibited by CLOCK overexpression. Further mechanisms studies showed that the Y-27632-mediated suppression of the RhoA/ROCK (Rho-Rho kinase) pathway rescued the phenotype induced by CLOCK deletion in VSMCs. Conclusions: Our results showed that decreased expression of CLOCK could contribute to phenotype switching of VSMCs and could be associated with atherosclerotic plaque instability
High-Metastatic Triple-Negative Breast Cancers Cell-Derived Exosomal miR-525-5p Inhibits Anoikis and Promotes Metastasis of Low-Metastatic TNBC Cells via Downregulating Bax
No full textBackground: Exosomes play crucial roles in cell-to-cell communication and metastatic progression in triple-negative breast cancers (TNBC). However, the intercellular communication between different metastatic potential cancer cells is not fully understood in TNBC. Thus, we aimed to evaluate miR-525-5p mechanism in the communication between different metastatic potential TNBC cells. Methods: Exosomes were collected from high-metastatic (HM)- and low-metastatic (LM)-TNBC cells and then identified by nanoparticle tracking analysis (NTA) and transmission electronic microscopy (TEM), and miR-525-5p level was evaluated by real-time quantitative-polymerase chain reaction (RT-qPCR). Additionally, in vitro assays were used to clarify the role of exosomal miR-525-5p to regulate the crosstalk between HM- and LM-TNBC cells. Moreover, dual-luciferase reporter assay was used to identify the relationship between miR-525-5p and its target gene Bcl-2 associated X (Bax). Western blot assay was performed to determine Bax, Bcl-2 and cleaved caspase 3 levels in TNBC cells. Results: MiR-525-5p level in HM-TNBC cells exosomes significantly increased compared to LM-TNBC cells exosomes. Additionally, HM-TNBC cells exosomes can deliver miR-525-5p to LM-TNBC cells. Moreover, exosomal miR-525-5p derived from HM-TNBC cells enhanced the migration of LM-TNBC cells. Furthermore, Bax was found as a potential target of miR-525-5p. Exosomal miR-525-5p inhibited anoikis of recipient cancer cells via downregulation of Bax and cleaved caspase 3 and upregula-tion of Bcl-2. Conclusions: Our results show that exosomal miR-525-5p could suppress anoikis and facilitate LM-TNBC cells metastasis via Bax downregulation
Analysis of Allergen Detection Results and the Pattern of Allergic Disease Visits in Patients with Suspected Allergic Diseases
No full textObjective: With the development of social material civilization, the change of living environment and diet structure, the number of allergic disease visits is increasing gradually. Seeking patient of medical treatment for allergen disease visits is necessary. To analyze the pattern of allergy-related hospital visits and the characteristics of allergen distribution in patients with suspected allergic diseases. Methods: A total of 1584 patients with suspected allergic diseases who underwent allergen testing in the outpatient clinic of the Third Medical Center of Chinese People’s Liberation Army (PLA) General Hospital between January 2018 and December 2020 were enrolled. Serum-specific immunoglobulin E (sIgE) antibodies to multiple allergens and total immunoglobulin E (TIgE) were determined in each patient’s serum using a domestic chemiluminescence instrument. Results: The number of allergic disease visits indicated a bimodal pattern for three consecutive years, with the highest number of visits being between March and May and between August and October. The results of the allergen tests were ranked as follows: Artemisia pollen was the most common seasonal inhalant allergen, dust mites were the most common perennial inhalant allergen, and the three most common food allergens were sea fish/sea crab, milk, and sea shrimp. Conclusions: Based on the distribution characteristics of allergens in this study, most of the allergic disease visits are currently in passive medical mode. It is planned to adjust the patient’s treatment mode to active treatment before the occurrence of allergic symptoms give preventive measures and medication guidance to reduce patients’ allergic symptoms
Treadmill and Wheel Exercise Protect against Knee Osteoarthritis in Monosodium Iodoacetate-Induced Knee Osteoarthritis by Inhibiting the ROS-Mediated Apoptosis Pathway in Mice
No full textPurpose: The current study evaluated treadmill and wheel exercise as potential treatments for osteoarthritis (OA) in an animal model, and investigated the reactive oxygen species (ROS)-mediated apoptosis pathway in knee osteoarthritis (KOA) models. Methods: We used male BALB/c mice to establish a KOA model, and divided the mice into four groups: (1) Control (normal saline);(2) KOA (monosodium iodoacetate (MIA) induced);(3) KOA with treadmill exercise (treadmill + KOA);And (4) KOA with wheel exercise (wheel + KOA). Safranin O staining, Tartrate-resistant acid phosphatase staining, western blot, and ELISA assays were utilized to explore the influence of treadmill and wheel exercise in KOA. Results: Our results revealed that, compared with the control group, the KOA groups showed severe damage to joint cartilage and enhanced numbers of osteoclasts as well as chondrocyte apoptosis-related protein levels of caspase-3 and Bcl-2-associated X protein (BAX), but downregulated the Bcl-2 protein expression. However, treatment with treadmill or wheel exercise alleviated chondrocyte apoptosis and decreased ROS production in mice with KOA. Conclusions: Our data showed that treadmill and wheel exercise protects against chondrocyte apoptosis by regulating the ROS-mediated apoptosis pathway in knee osteoarthritis (KOA) models
Effect of Combined Probiotics on the Intestinal Ecosystem during Triple Therapy for Eradication of Helicobacter Pylori
No full textBackground: China has a high incidence of Helicobacter pylori (Hp)-positive peptic ulcers and triple therapy is widely used to eradicate Hp. However, the antibiotics and proton pump inhibitors used in the standard triple therapy can potentially disrupt the equilibrium of the intestinal flora, resulting in adverse reactions such as loss of appetite, abdominal pain, and diarrhea. Aim: To explore the effect of combined probiotics on the intestinal ecosystem during triple therapy. Methods: A total of 120 patients with a diagnosis of duodenal ulcer and confirmed Hp infection, admitted to the Third Hospital of Hebei Medical University between January 2018 and January 2019, were selected for a prospective randomized clinical study. They were divided into two groups. A joint group (n = 60) and a control group (n = 60) using a simple randomized method. The control group was treated with standard triple therapy, specifically a proton pump inhibitor + clarithromycin + amoxicillin, while the joint group received triple therapy plus Bacillus subtilis and Enterococcus faecium enteric-soluble capsules. Ulcer healing rate, clinical efficacy, Hp eradication rate, changes in the primary intestinal flora, and incidence of adverse reactions were compared between the two groups. Results: After treatment, there was no significant difference in the overall healing effect, clinical efficacy, and Hp-negative conversion rate between the two groups (p > 0.05). During treatment, the incidence of adverse reactions in the combined treatment group was 5.00% lower than 20.00% in the control group, and the difference was statistically significant (p < 0.05). After treatment, the numbers of Enterococcus and Enterobacter in the joint group were lower than those of the control group (p < 0.05), while the numbers of Lactobacillus, Bifidobacterium, Bacteroidetes, Clostridium, and total bacteria in the joint group were higher than those of the control group (p < 0.05). Conclusions: Combined probiotics used as an adjuvant to standard triple therapy have no beneficial or disadvantageous effects on ulcer healing and Hp eradication. But they can reduce adverse reactions for the duration of the treatment process and maintain the equilibrium of the intestinal flora
Fibulin-5 Gene Attenuates Inflammation via the Calcitonin Gene-Related Peptide (CGRP)
No full textBackground: This study determined the function and the underlying mechanism of fibulin-5 in patients with lung infections. Methods: Serum was collected from patients with lung infections and healthy volunteers. Mice underwent cecal ligation and puncture surgery as served as a lung infection model. Serum expression of fibulin-5 was downregulated in patients and mice with lung infections. Results: Fibulin-5 attenuated inflammation and prevented lung injury in mice with lung infections via suppression of the calcitonin gene-related peptide (CGRP) pathway. Upregulation of fibulin-5 attenuated inflammation and suppressed the CREB/CGRP pathway in an in vitro model. Upregulation of the CREB/CGRP pathway weakened the anti-inflammation effects of fibulin-5 in an infection—induced lung injury model. These data demonstrated, for the first time, that serum fibulin-5 gene expression may be a clinical indicator in patients with lung infections. Conclusions: Furthermore, fibulin-t attenuated inflammation via the CREB/CGRP pathway
Trimetazidine Protects against Hypoxia/Reoxygenation Injury in Cardiomyocytes by Modulating miR-125b-5p/ATG4D Axis
No full textBackground: Trimetazidine (TMZ) has been shown to have a protective effect against myocardial ischemia/reperfusion (I/R) injury (MIRI) by modulating the levels of microRNA (miRNA). The aim of this study was to investigate whether TMZ could prevent myocardial I/R injury by regulating miR-125b-5p. Methods: A cardiomyocyte injury model was established using hypoxia/reoxygenation (H/R) processing. Cellular function assays were used to determine the viability, apoptosis, miR-125b-5p expression, apoptosis- and autophagy-related protein levels as well as Adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/unc-51-like kinase 1 (ULK1) pathway level in cardiomyocytes under H/R treatment or co-treatment of miR-125b-5p inhibitor and TMZ. A dual-luciferase reporter assay was used to verify the predicted targeting relationship between autophagy-related 4D (ATG4D) and miR-125b-5p. The possible involvement of target genes and the AMPK/mTOR/ULK1 pathway in miR-125b-5p-mediated effects was also analyzed. Results: H/R reduced miR-125b-5p messenger RNA (mRNA) expression and cell viability, while promoting the apoptosis and the protein levels of markers relevant to autophagy and apoptosis (p < 0.01). These effects of H/R were reversed by TMZ, while the reversing effect of TMZ was largely diminished by miR-125b-5p inhibitor (p < 0.01). The targeting relationship between miR-125b-5p and ATG4D has been confirmed. ATG4D overexpression or knockdown rescued the impact of miR-125b-5p mimic/inhibitor upon H/R-treated cells (p < 0.01). H/R facilitated phosphorylated (p)-AMPK and p-ULK1 protein levels yet reduced that of p-mTOR, and this effect was offset by miR-125b-5p mimic but was potentiated by the inhibitor (p < 0.01). The impacts of miR-125b-5p mimic or inhibitor upon the AMPK/mTOR/ULK1 pathway were reversed following the overexpression or knockdown of ATG4D, respectively (p < 0.01). Besides, the impacts of miR-125b-5p mimic or inhibitor upon H/R-treated cells were confirmed to be counteracted in the presence of AMPK/mTOR/ULK1 pathway agonist or inhibitor. Conclusions: Trimetazidine protects cardiomyocytes from H/R injury by modulating miR-125b-5p/ATG4D axis
Efficacy of Roxadustat in the Treatment of Hemodialysis in Patients with Renal Anemia
No full textObjective: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). This study retrospectively analyzed the clinical data of 30 renal anemia patients undergoing maintenance hemodialysis treated with Roxadustat to confirm its efficacy and safety. Methods: Patients who regularly underwent hemodialysis at the Blood Purification Center of the Third Hospital of Shanxi Medical University were screened from December 2019 to December 2020. All the included patients had failed to meet the hemoglobin standard after 12 weeks of erythropoiesis stimulants (ESAs) treatment. The starting dose of Roxadustat was determined according to body weight. The hemoglobin levels were monitored for 12 weeks, with 110–130 g/L as the target. Hemoglobin, hematocrits, iron metabolism indexes, C-reactive protein (CRP), blood lipids, electrolytes, blood pressure, and adverse reactions were recorded. Results: A total of 30 renal anemia patients who received maintenance hemodialysis were included. After 12 weeks, their hemoglobin levels significantly increased from 87.73 ± 14.52 g/L to 105.27 ± 14.27 g/L (p < 0.001). After Roxadustat treatment, triglycerides, total cholesterol, CRP and ferritin decreased, and the total iron-binding ability increased, showing a significant difference from the baseline values (p < 0.05). There were no significant changes in electrolytes, platelets, and blood pressure before and after treatment. No serious adverse reactions occurred in any of the patients during treatment. Conclusions: Roxadustat is effective in patients with renal anemia who have a poor response to erythropoietin therapy
Regenerative Potential of Platelet—Rich Fibrin in Maxillary Sinus Floor Lift Techniques: A Systematic Review
No full textBackground: Platelet-rich Fibrin (PRF) represents a type of autologous biomaterial investigated through the years by in vitro and in vivo studies to assess the real inductivity properties, presumed due to the growth factors presence. This systematic review aims to evaluate the efficacy of PRF in sinus lift procedures, compared and/or in addition to Deproteinized Bovine Bone Materials (DBBM) according to emerging scientific evidence. Materials and Methods: Selected databases were PubMed, Scopus, and Cochrane Library. The search strategy included the following terms: “PRF”, “platelet concentrate”, “autologous platelet concentrate”, “platelet-rich fibrin”, “bone grafts” or “DBBM”, “xenografts” or “Bio-Oss”, “maxillary sinus lift”, “maxillary sinus elevation”, “maxillary sinus augmentation”. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Results: Four studies were included in the systematic review, evaluating clinical, histological, histomorphometric, and radiological data. Three of four studies reported no statistically significant differences between the test and control groups. In one study, the presence of Leukocyte-Platelet Rich Fibrin (L-PRF) could allow earlier implant placement, achieving the same clinical, histological, histomorphometric, and radiological results of bone regeneration at an earlier time, compared to the DBBM used alone. Conclusions: The regenerative potential of PRF associated with DBBM resulted in a valid alternative in the bone regeneration procedure to DBBM grafts. Further new studies are needed, with more rigid protocols, to investigate the potential of platelet concentrates in sinus lift techniques and to evaluate the real inductivity properties of DBBM
NEUROD1 Promotes Apoptosis and Inflammation Response of Retinal Pigment Epithelial Cells and Participates in the Development of Diabetic Retinopathy
No full textBackground: Diabetic retinopathy (DR) is a commonly encountered microvascular complication in diabetic patients. It is a serious public health issue because it threatens human vision. To delve deeper into the molecular regulation mechanisms underlying DR, the present study screened differentially expressed genes (DEGs) in DR using a bioinformatic approach, and then investigated the regulatory effects on DR of candidate genes in cultured retinal epithelial cells and DR model mice. Methods: We first searched the Gene Expression Omnibus (GEO) database using diabetic retinopathy as the keyword and selected the GSE102485 data set for analysis. In retinal pigment epithelial (RPE) cells, lentiviruses were employed to overexpress and interfere with the gene NEUROD1. Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability. DR mice were injected with overexpressed lentivirus and interfering lentivirus of NEUROD1. Finally, NEUROD1 was overexpressed and interfered with vascular endothelial cells (VECs) cultured in vitro. Quantitative polymerase chain reaction (qPCR) and western blot were applied to test the expressions of BCL2-associated X protein (BAX), BCL-2 homologous antagonist/killer (BAK), B-cell lymphoma 2 (BCL-2), Transforming growth factor beta (TGF-β), Tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1β), and Interleukin 6 (IL-6). An immunofluorescence assay was applied to test NEUROD1 protein expression levels and cell apoptosis. Hematoxylin and eosin (HE) staining was applied to detect the condition of the retina in DR mice. An enzyme linked immunosorbent assay (ELISA) was used to detect the expressions of TNF-α, IL-1β, IL-6 and TGF-β in mouse serum. Results: The analysis revealed that the NEUROD1 gene was highly expressed in the DR group. When NEUROD1 was overexpressed, RPE cell viability was markedly reduced (p < 0.01) and apoptosis of RPE cells was increased. In contrast, after interference with NEUROD1, the viability of RPE cells was substantially increased (p < 0.05) and RPE cell apoptosis was decreased. After overexpression of NEUROD1, the expressions of BAX, BAK, TNF-α, IL-1β, and IL-6 increased markedly, whereas the expressions of the anti-apoptotic proteins BCL-2 and TGF-β decreased greatly. After overexpression of NEUROD1, the levels of blood glucose, total cholesterol, and triglyceride of mice were further increased. Interference of NEUROD1 aggravated the morphology of retinal blood vessels and the infiltration of inflammatory cells. Interference of NEUROD1 impaired the ability of VECs to adhere to the wall, causing cell aggregation and floating, thereby affecting cell viability. In the control group and the NEUROD1 overexpression group, VECs could grow and adhere to the wall and form primary blood vessels. Conclusions: The current study demonstrated that NEUROD1 inhibited the proliferation of RPE cells, promoted apoptosis and inflammation in RPE cells, promoted blood vessel formation, and exacerbated the development of DR. This research may establish a foundation for diagnosing and treating DR in a clinical setting