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Background. Neutrophils play an important role in maintaining periodontal status in conditions of healthy homeostasis. They achieve their surveillance function by continuously migrating to the gingival sulcus and eradicating periodontal pathogens. In addition, neutrophils are considered an integral element in the pathogenesis of periodontal diseases. Among several neutrophil subsets, low‐density neutrophils (LDN) have recently received attention and are linked with cancer, immunological, inflammatory, and infectious diseases. However, the presence, phenotypes, and potential role of LDN in the pathogenesis of periodontitis have not yet been investigated. Objectives. To investigate the presence, subsets (normal, band, suppressive, and active), and phenotypes via marker expression surface protein known as the cluster of differentiation (CD) (CD16b, CD14, CD15, and CD62L) of LDN in patients with periodontitis. Materials and Methods. The observational case‐control study was conducted to estimate the potential role of LDNs in periodontitis. Venous blood and periodontal indices were obtained from 40 healthy control individuals and 60 periodontitis patients. Subsequently, CD16b, CD62L, CD14, and CD15 expression on the surface of LDN was examined by multicolor flow cytometry, and their subsets were classified as "normal" (CD16brightCD62Lbright), "bands" (CD16dimCD62Lbright), "suppressive" (CD16brightCD62Ldim), and "active" (CD16brightCD62Lnegative). Results. There was a significant difference in the expression of LDN markers for active and suppressive phenotypes, respectively, favoring periodontitis over the control group. In contrast, there were significantly higher levels of CD16b, CD62L, and CD15 ("normal") in the control group when compared with the periodontitis group. Conclusion. LDN was associated with periodontitis as it was significantly increased in the periodontitis group in comparison with the control group and was positively correlated with all periodontal parameters. Cells from both groups of patients (periodontitis and control) expressed a normal mature phenotype (CD16b + High, CD62L + High, CD15+, and CD14‐). Regarding subsets, the normal LDN (CD16brightCD62Lbright) was the most predominant phenotype in both periodontitis and control groups. However, the active subset increased in periodontitis compared to normal, indicating their destructive role in periodontitis. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most prevalent type of brain tumour; although advancements in treatment have been made, the median survival time for GBM patients has persisted at 15 months. This study is aimed at investigating the genetic alterations and clinical features of GBM patients to find predictors of survival. GBM patients' methylation and gene expression data along with clinical information from TCGA were retrieved. The most overrepresented pathways were identified independently for each omics dataset. From the genes found in at least 30% of these pathways, one gene that was identified in both sets was further examined using the Kaplan-Meier method for survival analysis. Additionally, three groups of patients who started radio and chemotherapy at different times were identified, and the influence of these variations in treatment modality on patient survival was evaluated. Four pathways that seemed to negatively impact survival and two with the opposite effect were identified. The methylation status of PRKCB was highlighted as a potential novel biomarker for patient survival. The study also found that treatment with chemotherapy prior to radiotherapy can have a significant impact on patient survival, which could lead to improvements in clinical management and therapeutic approaches for GBM patients. [ABSTRACT FROM AUTHOR]

Background. Though most people with COVID-19 disease show asymptomatic to mild illness, a substantial number of patients are at high risk of developing severe disease and adverse outcomes with long COVID-19 and death. Even though some studies showed that previously existing infections with parasites amend the host's body defenses to increase resistance to infection with SARS-CoV-2, there is limited data in Ethiopia. Objectives. This study is aimed at determining the COVID-19 disease severity and its association with intestinal parasite coinfection and urine biochemical parameters among COVID-19-confirmed patients admitted at Debre Markos University COVID-19 Center, 2021. Methods. A prospective cohort study was conducted on 136 RT-qPCR-confirmed COVID-19 patients admitted at Debre Markos University COVID-19 Center from January 1 to March 30, 2021. Sociodemographic and clinical data were collected by using standardized data collection forms. A urine biochemical test was performed using a dry urine dipstick kit and stool examination using direct wet mount microscopic examination and formalin-ether concentration method. The chi-square test, Fisher exact test, and ordinal logistic regression analysis were computed to assess association with outcome variables using Statistical Package for Social Science software (version 24). Result. A total of 136 COVID-19-confirmed patients participated in this study. The median age of the participants was 48 years. The majority (86 (62.5%)) of them were male in sex. Of the 136 cases, 39 (28.7%) had died. Among the 136 patients, 22 (16.2%) were coinfected with intestinal parasites. COVID-19 patients who have intestinal parasite coinfection had lower odds of developing clinically severe COVID-19 compared to noninfected (AOR = 0.37 ; 95% CI = 0.147 ‐ 0.944 ; P = 0.037). The majority (104 (76.5%)) of them have abnormal urine biochemical results. From the abnormal urine biochemical tests observed, the urine blood, glucose, and ketone tests were positive for 54 (39.7%), 36 (26.5%), and 30 (21.1%) patients, respectively. Among the 31 critical COVID-19 patients, 25 (80.6%) showed abnormal urine biochemical parameters. Age and comorbidity were significantly associated with COVID-19 severity (P < 0.05). Conclusion. Patients with old age and comorbidity had an increased risk of developing severe COVID-19 disease. Patients having SARS-CoV-2 and intestinal parasitic coinfections demonstrated mild COVID-19 disease severity. Abnormal urine biochemical results were common among critical COVID-19 patients. Thus, advanced study on the effect of the interaction among intestinal parasites on COVID-19 clinical severity and its mechanisms is essential. [ABSTRACT FROM AUTHOR]

Background. It is well known that laboratory markers could help in identifying risk factors of severe illness and predicting outcomes of diseases. Here, we performed a retrospective modeling study of severity and mortality predictors of hematological and biochemical laboratory parameters in Iranian COVID-19 patients. Methods. Data were obtained retrospectively from medical records of 564 confirmed Iranian COVID-19 cases. According to the disease severity, the patients were categorized into two groups (severe or nonsevere), and based on the outcome of the disease, patients were divided into two groups (recovered or deceased). Demographic and laboratory data were compared between groups, and statistical analyses were performed to define predictors of disease severity and mortality in the patients. Results. The study identified a panel of hematological and biochemical markers associated with the severe outcome of COVID-19 and constructed different predictive models for severity and mortality. The disease severity and mortality rate were significantly higher in elderly inpatients, whereas gender was not a determining factor of the clinical outcome. Age-adjusted white blood cells (WBC), platelet cells (PLT), neutrophil-to-lymphocyte ratio (NLR), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), erythrocyte sedimentation rate (ESR), mean corpuscular hemoglobin (MCHC), blood urea nitrogen (BUN), and creatinine (Cr) also showed high accuracy in predicting severe cases at the time of hospitalization, and logistic regression analysis suggested grouped hematological parameters (age, WBC, NLR, PLT, HGB, and international normalized ratio (INR)) and biochemical markers (age, BUN, and lactate dehydrogenase (LDH)) as the best models of combined laboratory predictors for severity and mortality. Conclusion. The findings suggest that a panel of several routine laboratory parameters recorded on admission could be helpful for clinicians to predict and evaluate the risk of disease severity and mortality in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have appeared lately as a new class of genes that may control and mediate cellular processes. It plays a critical role in many diseases, including neurodegenerative disorders. HOTAIR and MKRN2-42:1 are two lncRNAs that have been seen upregulated in various diseases including in the peripheral blood of the patients suffering from Parkinson's disease (PD) in different countries. It has also been seen that Meg3v1 and NEAT1 lncRNAs are expressed highly in patients suffering from motor neuron disease (MND) from various countries, though the association between the reason for the onset of this disease and the expression of these specific lncRNAs is not clear. The primary aim of this study was to observe expression variations for specific lncRNAs in the peripheral blood of PD and MND patients compared with healthy individuals and to look for lncRNAs that might be related to the pathogenesis of PD and MND. The aim of this study was also to investigate the association of lncRNA sequence as biomarkers with the risk of having neurodegenerative disorders (PD and MND) in the population of Bangladesh. The purpose of this research also included the possibility of prediction of these neurodegenerative disorders by analyzing and comparing the data which was acquainted from the study where 20 PD patients and 20 healthy subjects and 25 MND patients and 25 healthy subjects of Bangladesh were examined. Their peripheral blood was taken, and plasma was separated. Later, RT-PCR was performed to observe the changes in the expression of specific lncRNAs. Results showed that expression of HOTAIR and MKRN2-42:1 was positively correlated (p < 0.05) with the symptoms (5) of Parkinson's suspects in comparison to the healthy subjects. Similarly, Meg3v1 and NEAT1 lncRNAs were expressed significantly (p < 0.05) in MND patients rather than that in healthy controls. Data were analyzed using GraphPad Prism 7.0, where p < 0.05 was considered statistically significant. Successful prediction of the possibility of neurodegenerative disorder by analyzing data regarding the expression of lncRNAs as biomarkers may help in advance clinicians to stratify high-risk patients and prepare for appropriate medical intervention. [ABSTRACT FROM AUTHOR]

Purpose. ITP is the most prevalent autoimmune blood disorder. The lack of predictive biomarkers for therapeutic response is a major challenge for physicians caring of chronic ITP patients. This study is aimed at identifying predictive biomarkers for drug therapy responses. Methods. 2D gel electrophoresis (2-DE) was performed to find differentially expressed proteins. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis was performed to identify protein spots. The Cytoscape software was employed to visualize and analyze the protein-protein interaction (PPI) network. Then, enzyme-linked immunosorbent assays (ELISA) were used to confirm the results of the proteins detected in the blood. The DAVID online software was used to explore the Gene Ontology and pathways involved in the disease. Results. Three proteins, including APOA1, GC, and TF, were identified as hub-bottlenecks and confirmed by ELISA. Enrichment analysis results showed the importance of several biological processes and pathway, such as the PPAR signaling pathway, complement and coagulation cascades, platelet activation, vitamin digestion and absorption, fat digestion and absorption, cell adhesion molecule binding, and receptor binding. Conclusion and Clinical Relevance. Our results indicate that plasma proteins (APOA1, GC, and TF) can be suitable biomarkers for the prognosis of the response to drug therapy in ITP patients. [ABSTRACT FROM AUTHOR]

Background. A major issue is finding a valid biomarker able to diagnose periodontal disease with the presence and absence of risk factors. Indeed, the association between smoking and periodontal diseases and its impact on the manifestation of antimicrobial peptides has been delineated in clinical and epidemiological investigations. The antimicrobial peptide cathelicidin (LL-37) is pivotal in preserving periodontal health. Objectives. This investigation examines and contrasts the levels of cathelicidin in the saliva of smokers and nonsmokers of periodontitis. The study also seeks to establish this biomarker's diagnostic ability to differentiate between periodontal health and disease. Materials and Methods. The study involved the collection of unstimulated saliva samples from 160 participants, comprising 80 patients diagnosed with periodontitis (40 of whom were smokers and 40 were nonsmokers) and 80 periodontitis-free individuals (40 smokers and 40 nonsmokers). The clinical periodontal parameters were assessed, including recording the probing pocket depth, the level of clinical attachment, and the percentage of bleeding on probing. Subsequently, enzyme-linked immunosorbent assays were conducted to quantify the protein levels of LL-37 in the saliva samples obtained from the subjects mentioned above. Results. The highest level of salivary LL-37 was found in the nonsmoker periodontitis (NSP) patients, followed by the group of smoker periodontitis (SP) and then nonsmoker healthy (NSH) group, while the lowest level was found in the healthy smoker (HS) group. At the same time, the LL-37 seems to be a very good biomarker in differentiating periodontal health from disease with the presence and absence of smoking. Conclusion. Periodontitis results in a significant elevation of salivary LL-37 levels in smoker and nonsmoker patients compared to healthy individuals. These levels are positively correlated with the periodontal parameter and can serve as a valuable diagnostic tool to predict periodontitis, whereas smoking significantly reduces these levels. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a blood cancer caused by the abnormal proliferation and differentiation of hematopoietic stem cells in the bone marrow. The actual genetic markers and molecular mechanisms of AML prognosis are unclear till today. This study used bioinformatics approaches for identifying hub genes and pathways associated with AML development to uncover potential molecular mechanisms. The expression profiles of RNA-Seq datasets, GSE68925 and GSE183817, were retrieved from the Gene Expression Omnibus (GEO) database. These two datasets were analyzed by GREIN to obtain differentially expressed genes (DEGs), which were used for performing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), and survival analysis. The molecular docking and dynamic simulation were performed to identify the most effective drug/s for AML from the drug list approved by the Food and Drug Administration (FDA). By integrating the two datasets, 238 DEGs were identified as likely to be affected by AML progression. GO enrichment analyses exhibited that the upregulated genes were mainly associated with inflammatory response (BP) and extracellular region (CC). The downregulated DEGs were involved in the T-cell receptor signalling pathway (BP), an integral component of the lumenal side of the endoplasmic reticulum membrane (CC) and peptide antigen binding (MF). The pathway enrichment analysis showed that the upregulated DEGs were mainly associated with the T-cell receptor signalling pathway. Among the top 15 hub genes, the expression levels of ALDH1A1 and CFD were associated with the prognosis of AML. Four FDA-approved drugs were selected, and a top-ranked drug was identified for each biomarker through molecular docking studies. The top-ranked drugs were further confirmed by molecular dynamic simulation that revealed their binding stability and confirmed their stable performance. Therefore, the drug compounds, enasidenib and gilteritinib, can be recommended as the most effective drugs against the ALDH1A1 and CFD proteins, respectively. [ABSTRACT FROM AUTHOR]

Purpose. As a scientific field, bioinformatics has drawn remarkable attention from various fields, such as information technology, mathematics, and modern biological sciences, in recent years. The topic models originating from the field of natural language processing have become the focus of attention with the rapid accumulation of biological datasets. Thus, this research is aimed at modeling the topic content of the bioinformatics literature presented by Iranian researchers in the Scopus Citation Database. Methodology. This research was a descriptive-exploratory study, and the studied population included 3899 papers indexed in the Scopus database, which had been indexed in this database until March 9, 2022. The topic modeling was then performed on the abstracts and titles of the papers. A combination of LDA and TF-IDF was utilized for topic modeling. Findings. The data analysis with topic modeling resulted in identifying seven main topics "Molecular Modeling," "Gene Expression," "Biomarker," "Coronavirus," "Immunoinformatics," "Cancer Bioinformatics," and "Systems Biology." Moreover, "Systems Biology" and "Coronavirus" had the largest and smallest clusters, respectively. Conclusion. The present investigation demonstrated an acceptable performance for the LDA algorithm in classifying the topics included in this field. The extracted topic clusters indicated excellent consistency and topic connection with each other. [ABSTRACT FROM AUTHOR]

Trypanosomiasis is an important but neglected tropical diseases which continues to cause morbidity and mortality on a large scale in sub-Saharan Africa. In the present study, the aqueous leaf extract, flavonoid fraction, and subfractions of the flavonoid from A. senegalensis leaves were evaluated for their antitrypanosomal activities, effects on some hematological parameters, and some liver-based enzymes in mice infected with Trypanosoma brucei brucei. Mice treated with aqueous extract at a concentration range of 100–400 mg kg bw exhibited parasite inhibition range between 66.08 and 73.09% while mice treated with the flavonoid fraction (50-200 mg/kg bw) exhibited higher parasite inhibition (83.37-86.38%). Mice treated with subfractions of the flavonoids showed a significant decrease in parasite count (p < 0.05), with subfraction 3 completely clearing parasites in the circulation after twenty-one days of treatment. Biochemical analysis revealed that the subfraction 3 restored the alterations in the serum aspartate transaminase (AST), alanine transaminase (ALT), and total protein concentrations that were observed in the infected nontreated mice. The subfraction 3 was subsequently characterized by HPLC analysis which revealed the presence of rutin (RT: 22.26, 65.34 ppm) as the most abundant bioactive compound that could be attributed to the bioactivity of the subfraction 3. Other polyphenolic compounds identified included gallic acid (RT: 4.39, 0.578 ppm), quercetin (RT: 37.27, 0.729 ppm), kaempferol (RT: 38.33, 1.52 ppm), and luteolin (RT; 39.173, 32.77 ppm). Taken together, subfraction 3 of the flavonoid fraction from of A. senegalensis demonstrated potent antitrypanosomal activities and therefore represents a reserve of bioactive metabolite worthy of further exploration for the treatment of trypanosomiasis. [ABSTRACT FROM AUTHOR]

Introduction. Helicobacter pylori is a prevalent pathogenic bacterium that resides in the human stomach. Outer membrane vesicles (OMVs) are known as nanosized cargos released by H. pylori, which have been proposed to have a key role in disease progression, pathogenesis, and modulation of the immune system. There are multiple evidences for the role of H. pylori in extragastroduodenal illnesses especially liver-related disorders. However, the precise mechanism of H. pylori extragastroduodenal pathogenesis still remains unclear. In the current study, we aimed to determine the impact of H. pylori-isolated OMVs on hepatic stellate cell (HSC) activation and expression of liver fibrosis markers. Materials and Methods. Five H. pylori clinical strains with different genotype profiles were used. Helicobacter pylori OMVs were isolated using ultracentrifugation and were analyzed by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis was applied to determine protein components of H. pylori-derived OMVs. Cell viability of LX-2 human hepatic stellate cell line exposed to OMVs was measured by MTT assay. LX-2 cells were treated with OMVs for 24 h. The gene expression of α-SMA, E-cadherin, vimentin, snail, and β-catenin was analyzed using quantitative real-time PCR. The protein expression of α-SMA, as a well-studied profibrotic marker, was evaluated with immunocytochemistry. Results. Our results showed that H. pylori strains released round shape nanovesicles ranging from 50 to 500 nm. Totally, 112 various proteins were identified in OMVs by proteomic analysis. The isolated OMVs were negative for both CagA and VacA virulence factors. Treatment of HSCs with H. pylori-derived OMVs significantly increased the expression of fibrosis markers. Conclusions. In conclusion, the present study demonstrated that H. pylori-derived OMVs could promote HSC activation and induce the expression of hepatic fibrosis markers. Further research is required to elucidate the definite role of H. pylori-derived OMVs in liver fibrosis and liver-associated disorders. [ABSTRACT FROM AUTHOR]

Cigarette smoking is a significant risk factor for chronic and atherosclerotic vascular disease that causes preventable considerable morbidity and mortality worldwide. This study is aimed at comparing inflammation and the levels of oxidative stress biomarkers in elderly subjects. The authors recruited the participants (1281 older adults) from the Birjand Longitudinal of Aging study. They measured oxidative stress and inflammatory biomarkers serum levels in the 101 cigarettes and 1180 nonsmokers. The mean age of smokers was 69.3 ± 7.95 years, and most were male. The most percentage of male cigarette smokers have lower body mass index (BMI) (≤19 kg/m2). Females have higher BMI categories than males (P ≤ 0.001). The percentage of diseases and defects was different between cigarette and non-cigarette smoker adults (P ≤ 0.01 to P ≤ 0.001). The total white blood cells, neutrophils, and eosinophils were significantly higher in cigarettes compared to non-cigarette smokers (P ≤ 0.001). Besides, cigarette consumers' percentage of hemoglobin and hematocrit compared to other aged people was significantly different (P ≤ 0.001). However, biomarkers of oxidative stress and antioxidant levels were not significant differences between the two senior groups. Cigarette smoking in older adults was associated with increased inflammatory biomarkers and cells, but it did not find a significant difference in oxidative stress markers. Longitudinal prospective studies may help illuminate the mechanisms inducing oxidative stress and inflammation due to cigarette smoking in each gender. [ABSTRACT FROM AUTHOR]

Objective. Hyperandrogenaemia and insulin resistance (IR) are the main characteristics of polycystic ovary syndrome (PCOS). Here, we study to find appropriate markers predicting IR and hyperandrogenaemia of women with PCOS in northwest China. Methods. According to body mass index (BMI), 953 patients with PCOS were divided into two groups. All the patients underwent physical examination and ultrasonography and collected elbow vein blood. Their BMI, waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), LAP, VAI, homeostasis model assessment index of insulin resistance (HOMA-IR), and free androgen index (FAI) were calculated. Each group (normal weight and obesity/overweight) was further divided into two subgroups according to their HOMA-IR and FAI: the IR+ subgroup/IR- subgroup and FAI+ subgroup/FAI- subgroup. Furthermore, we compared the clinical indices, hormone levels, and metabolic makers separately between these groups. The correlations between these parameters and HOMA-IR or FAI were tested; sensitivity, specificity, and receiver-operating characteristic (ROC) curves were calculated. Results. In the obesity/overweight group, the VAI (best cut-off value: 2.27, area under the curve AUC = 0.699) and LAP (best cut-off value: 45.54, AUC = 0.680) were sensitive predictors of IR (sensitivity = 72 % and sensitivity = 67 %). Additionally, the VAI (best cut-off value: 2.13, AUC = 0.624) and LAP (best cut-off value: 51.18, AUC = 0.582) were sensitive predictors of FAI (sensitivity = 87 % and sensitivity = 64 %). In the normal weight group, BMI could preferably predict HOMA-IR (AUC = 0.717 , best cut-off value: 21.62) and HOMA-IR could preferably predict FAI (best cut-off value: 2.11, AUC = 0.648). Conclusion. Our data indicated that the VAI and LAP may contribute to the early identification of IR and hyperandrogenaemia in the obesity/overweight patients of PCOS. In normal weight PCOS, BMI was a better predictor to IR, and HOWA-IR was a better predictor to FAI. [ABSTRACT FROM AUTHOR]

Objective. Hyperuricemia (HUA) is a common metabolic disease caused by disordered purine metabolism. We aim to reveal the mechanisms underlying the anti-HUA function of Simiao pill and provide therapeutic targets. Methods. Simiao pill-related targets were obtained using Herbal Ingredients' Targets (HIT), Traditional Chinese Medicine Systems Pharmacology (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID). HUA-associated targets were retrieved from GeneCards, DisGeNET, and Therapeutic Targets Database (TTD). Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, ggraph and igraph R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfiler. The top 10 core targets were identified through cytoHubba. Molecular docking was conducted using PyMOL and AutoDock high-performance liquid chromatograph (HPLC) analysis was performed to identify effective compounds of Simiao pill. Results. Simiao pill-HUA target network contained 80 targets. The key targets were mainly involved in inflammatory responses. Insulin (INS), tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin 1 beta (IL1B), vascular endothelial growth factor A (VEGFA), leptin (LEP), signal transducer and activator of transcription 3 (STAT3), C-C motif chemokine ligand 2 (CCL2), interleukin-10 (IL10), and toll like receptor 4 (TLR4) were the top 10 targets in the PPI network. GO analysis demonstrated the main implication of the targets in molecular responses, production, and metabolism. KEGG analysis revealed that Simiao pill might mitigate HUA through advanced glycation end-product- (AGE-) receptor for AGE- (RAGE-) and hypoxia-inducible factor-1- (HIF-1-) associated pathways. IL1B, IL6, IL10, TLR4, and TNF were finally determined as the promising targets of Simiao pill treating HUA. Through molecular docking and HPLC analysis, luteolin, quercetin, rutaecarpine, baicalin, and atractylenolide I were the main active compounds. Conclusions. Simiao pill can mitigate HUA by restraining inflammation, mediating AGE-RAGE- and HIF-1-related pathways, and targeting IL1B, IL6, IL10, TLR4, and TNF. [ABSTRACT FROM AUTHOR]

Background. Renal ischemia-reperfusion injury (RIRI) plays an important role in the poor prognosis of patients with renal transplants. However, the potential targets and mechanism of IRI are still unclear. Method. Differential gene expression (DEG) analysis and weighted correlation network analysis (WGCNA) were performed on the GSE27274 dataset. Pathway enrichment analysis on the DEGs was performed. To identify the hub DEGs, we constructed a protein-protein interaction (PPI) network. Finally, the hub genes were verified, and candidate drugs were screened from the DsigDB database. Results. A hundred DEGs and four hub genes (Atf3, Psmb6, Psmb8, and Psmb10) were screened out. Pathway enrichment analysis revealed that 100 DEGs were mainly enriched in apoptosis and the TNF signaling pathway. The four hub genes were verified in animal models and another dataset (GSE148420). Thereafter, a PPI network was used to identify the four hub genes (Atf3, Psmb6, Psmb8, and Psmb10). Finally, eight candidate drugs were identified as potential drugs. Conclusion. Three hub genes (Psmb6, Psmb8, and Psmb10) were associated with RIRI and could be potential novel biomarkers for RIRI. [ABSTRACT FROM AUTHOR]

Background. Celiac disease (CD) is an autoimmune genetic disorder in which gluten protein causes inflammation of the intestinal enterocytes. CD diagnosis in most cases is delayed or mistreated due to its varied clinical features. We aimed to evaluate the protein profile imbalance in different CD groups of children, which could help aid in the diagnosis and proper management of the disease. Methodology. This was a cross-sectional study with a nonrandom purposive sampling technique. All samples were taken from tertiary care hospitals of Hyderabad, Pakistan. In total, there were 175 children (age 3-15 years) divided into five equal groups (n = 35), namely, group A (control), group B (celiac diagnosed), group C (celiac-like symptoms), group D (celiac with type 1 diabetes mellitus), and group E (type 1 diabetes mellitus only). Clinical symptoms and laboratory parameters were analyzed among all the groups. Sera proteins, albumin, globulins, and transferrin levels were evaluated and compared with healthy individuals. Results. The albumin in serum of celiac groups B and C was 3.0 g/dl and 2.8 g/dl, respectively. While in diabetic patients with CD, it is 2.7 g/dl. The globulin levels were raised among all the celiac groups with typical GIT symptoms. The highest transferrin was observed in group B, celiac patients with severe anemia. Patients were not on GFD, hence had no or less recovery and had chronic symptoms of celiac. Conclusion. The misdiagnosis and poor management of celiac leads to chronic villous atrophy with imbalance in metabolic profile. Serum analysis of albumin, globulins, and transferrin may help in the diagnosis and proper management of the disease to recover the celiac symptoms. [ABSTRACT FROM AUTHOR]

Objective. ETS1 and ETS2, the main ETS family of transcription factors, have been found to act as downstream effectors of the RAS/MAPK pathway. This study explores the expression and prognostic values of ETS1 and ETS2 across cancers. We also aimed to explore the significance of ETS1 and ETS2 expression in normal immune cells with relation to tumorigenesis. Methods. The expression of ETS1 and ETS2 was examined in the HPA and GEPIA2 databases. The KM plotter was applied to examine prognostic value of ETS1 and ETS2. Correlation between ETS1/ETS2 and infiltrating immune cells and immune checkpoints was assessed using TIMER2.0. The mutation landscape of ETS1/ETS2 was explored using the cBioPortal. STRING and GEPIA2 were used to screen ETS1/ETS2 binding and correlated genes. Enrichr was applied to perform GO and KEGG enrichment analyses. Results. ETS1 showed enhanced expression in lymphoid tissue, while ETS2 showed low tissue specificity. ETS1 was increased in 12 and decreased in 6 cancers, while ETS2 was increased in 4 and decreased in 13 cancers. Both ETS1 and ETS2 were favorable prognostic markers in LIHC and KIRC, while they showed different prognostic roles in more cancers. ETS1 showed stronger correlation with several infiltrating immune cells and immune checkpoints compared with ETS2. Both ETS1 and ETS2 harbored low mutation ratio. ETS1 interacting and correlated genes were enriched in GO terms in response to cadmium ion and response to oxidative stress, while those of ETS2 were enriched in transcription regulation. Conclusion. ETS1 and ETS2 showed different patterns in expression, prognostic values, correlation with immune infiltrating, and immune checkpoints. ETS1 and ETS2 play distinct roles across cancer. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is commonly encountered, which is a kind of systemic injury of bone mass and microstructure, leading to brittle fractures. With the aging of the population, this disease will pose a more serious impact on medical, social, and economic aspects, especially postmenopausal osteoporosis (PMOP). This study is aimed at figuring out potential therapeutic targets and new biomarkers in OP via bioinformatics tools. After differentially expressed gene (DEG) analysis, we successfully identified 97 upregulated and 172 downregulated DEGs. They are mainly concentrated in actin binding, regulation of cytokine production, muscle cell promotion, chemokine signaling pathway, and cytokine-cytokine receiver interaction. According to the diagram of protein-protein interaction (PPI), we obtained 10 hub genes: CCL5, CXCL10, EGFR, HMOX1, IL12B, CCL7, TBX21, XCL1, PGR, and ITGA1. Expression analysis showed that Egfr, Hmox1, and Pgr were significantly upregulated in estrogen-treated osteoporotic patients, while Ccl5, Cxcl10, Il12b, Ccl7, Tbx21, Xcl1, and Itga1 were significantly downregulated. In addition, the analysis results of Pearson's correlation revealed that CCL7 has a strong positive association with IL12b, TBX21, and CCL5 and so was CCL5 with IL12b. Conversely, EGFR has a strong negative association with XCL1 and CXCL10. In conclusion, this study screened 10 hub genes related to OP based on the GEO database, laying a biological foundation for further research on new biomarkers and potential therapeutic targets in OP. [ABSTRACT FROM AUTHOR]

Background. This study is aimed at constructing a nomogram to predict the risk of clinically significant prostate cancer (csPCa) based on the aggregate index of systemic inflammation (AISI) and prostate imaging-reporting and data system version (PIRADS) score. Methods. Clinical data on patients who had undergone initial prostate biopsy from January 2019 to December 2021 were collected. Patients were randomized in a 7 : 3 ratio to the training cohort and the validation cohort. Potential risk factors for csPCa were identified by univariable and multivariate logistic regression. Nomogram was conducted with these independent risk factors, and calibration curves, the receiver operating characteristic (ROC), and decision curve analysis (DCA) were employed to assess the nomogram's ability for prediction. Results. A total of 1219 patients were enrolled in this study. Multivariate logistic regression identified that age, AISI, total prostatic specific-antigen (tPSA), free to total PSA (f/tPSA), prostate volume (PV), and PIRADS score were potential risk predictors of csPCa, and the nomogram was developed based on these factors. The area under the curve (AUC) of the training cohort and validation cohort was 0.884 (95% CI: 0.862-0.906) and 0.899 (95% CI: 0.867-0.931). The calibration curves showed that the apparent curves were closer to the ideal curves. The DCA results revealed that the nomogram model seemed to have clinical application value per DCA. Conclusion. The nomogram model can efficiently predict the risk of csPCa and may assist clinicians in determining if a prostate biopsy is necessary. [ABSTRACT FROM AUTHOR]

Cang-ai volatile oil (CAVO) is an aromatic Chinese medicine and is widely used to treat upper respiratory tract infections in children. However, the mechanism of CAVO in asthma treatment is unclear. In this study, we investigated the effects of CAVO on airway inflammation and the mechanism of inhibiting Group-2 innate lymphoid cells (ILC2s) in asthmatic mice, which was induced with Ovalbumin (OVA). CAVO improved AHR and airway inflammation in asthmatic mice. CAVO reduced the production of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) in the bronchoalveolar lavage fluid (BALF), while increased the production of IL-10, significantly. CAVO also inhibited the suppressor of tumorigenicity 2 (ST2) and IL-33 expressions in the lung tissue. Moreover, flow analyses demonstrated that CAVO inhibited ILC2s activation by reducing the sedimentation of its upstream cytokines, thus alleviating downstream cytokines. This could be because of the downregulated microRNA-155 and upregulated microRNA-146a. CAVO inhibits ILC2s activation, thus further attenuating airway inflammation and AHR in asthmatic mice. These effects may be related to the downregulation of microRNA-155 and upregulation of microRNA-146a. [ABSTRACT FROM AUTHOR]

Several studies have been done to identify comorbidities of COVID-19. In this work, we developed an analytical bioinformatics framework to reveal COVID-19 comorbidities, their genomic associations, and molecular mechanisms accomplishing transcriptomic analyses of the RNA-seq datasets provided by the Gene Expression Omnibus (GEO) database, where normal and infected tissues were evaluated. Using the framework, we identified 27 COVID-19 correlated diseases out of 7,092 collected diseases. Analyzing clinical and epidemiological research, we noticed that our identified 27 diseases are associated with COVID-19, where hypertension, diabetes, obesity, and lung cancer are observed several times in COVID-19 patients. Therefore, we selected the above four diseases and performed assorted analyses to demonstrate the association between COVID-19 and hypertension, diabetes, obesity, and lung cancer as comorbidities. We investigated genomic associations with the cross-comparative analysis and Jaccard's similarity index, identifying shared differentially expressed genes (DEGs) and linking DEGs of COVID-19 and the comorbidities, in which we identified hypertension as the most associated illness. We also revealed molecular mechanisms by identifying statistically significant ten pathways and ten ontologies. Moreover, to understand cellular physiology, we did protein-protein interaction (PPI) analyses among the comorbidities and COVID-19. We also used the degree centrality method and identified ten biomarker hub proteins (IL1B, CXCL8, FN1, MMP9, CXCL10, IL1A, IRF7, VWF, CXCL9, and ISG15) that associate COVID-19 with the comorbidities. Finally, we validated our findings by searching the published literature. Thus, our analytical approach elicited interconnections between COVID-19 and the aforementioned comorbidities in terms of remarkable DEGs, pathways, ontologies, PPI, and biomarker hub proteins. [ABSTRACT FROM AUTHOR]

Object. L6 cells were cultured to explore the possible mechanism underlying the improvement of insulin resistance by Liraglutide (LR). Methods. Cells were divided into 5 groups—control, high-fat, 10 nmol/L LR + 0.6 mmol/L palmitic acid (PA) (10LR), 100 nmol/L LR + 0.6 mmol/L PA (100LR), and 1000 nmol/L LR + 0.6 mmol/L PA (1000LR). CCK-8 method to detect cell viability, GPO-PAP enzymatic method to detect intracellular triglyceride content, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting methods to detect fatty acid translocase CD36 (FAT/CD36) and fatty acid binding protein 4 (FABP4) in L6 cells, glucose-regulated protein 78 (GRP78), glucose transporter 4 (GLUT4) expression at the mRNA and protein levels, respectively, were performed. Results. We found that after PA intervention for 24 h, the cell viability decreased significantly; the cell viability of the LR group was higher than that of the high-fat group (P < 0.01). After PA intervention, compared with those in the high-fat group, GRP-78, FAT/CD36, FABP4 mRNA ((4.36 ± 0.32 vs. 8.15 ± 0.35); (1.00 ± 0.04 vs. 2.46 ± 0.08); (2.88 ± 0.55 vs. 8.29 ± 0.52), P < 0.01) and protein ((3338.13 ± 333.15 vs. 4963.98 ± 277.29); (1978.85 ± 124.24 vs. 2676.07 ± 100.64); (3372.00 ± 219.84 vs. 6083.20 ± 284.70), both P < 0.01) expression decreased in the LR group. The expression levels of GLUT4 mRNA ((0.75 ± 0.04 vs. 0.34 ± 0.03), P < 0.01) and protein ((3443.71 ± 191.89 vs. 2137.79 ± 118.75), P < 0.01) increased. Conclusion. Therefore, we conclude that LR can reverse PA-induced cell inactivation and lipid deposition, which may be related to the change in GRP-78, FAT/CD36, FABP4, GLUT4, and other factors. [ABSTRACT FROM AUTHOR]

Sarcoma, the second common type of solid tumor in children and adolescents, has a wide variety of subtypes that are often not properly diagnosed at an early stage, leading to late metastases and causing serious loss of life and property to patients and families. It exhibits a high degree of heterogeneity at the cellular, molecular, and epigenetic levels, where DNA methylation has been proposed to play a role in the diagnosis of sarcoma subtypes. Thus, this study is aimed at finding potential biomarkers at the DNA methylation level to distinguish different sarcoma subtypes. A machine learning process was designed to analyse sarcoma samples, each of which was represented by lots of methylation sites. Irrelevant sites were removed using the Boruta method, and remaining sites related to the target variables were kept for further analyses. Afterward, three feature ranking methods (LASSO, LightGBM, and MCFS) were adopted to rank these features, and six classification models were constructed by combining incremental feature selection and two classification algorithms (decision tree and random forest). Among these models, the performance of RF model was higher than that of DT model under all three ranking conditions. The specific expression of genes obtained from the annotation of highly correlated methylation site features, such as PRKAR1B, INPP5A, and GLI3, was proven to be associated with sarcoma by publications. Moreover, the quantitative rules obtained by decision tree algorithm helped us to understand the essential differences between various sarcoma types and classify sarcoma subtypes, providing a new means of clinical identification and determining new therapeutic targets. [ABSTRACT FROM AUTHOR]

Background. A plethora of inflammatory, angiogenic, and tissue remodeling factors has been reported in idiopathic epiretinal membranes (ERMs). Herein we focused on the expression of a few mediators (oxidative, inflammatory, and angiogenic/vascular factors) by means of short-term vitreal cell cultures and biomolecular analysis. Methods. Thirty-nine (39) ERMs and vitreal samples were collected at the time of vitreoretinal surgery and biomolecular analyses were performed in clear vitreous, vitreal cell pellets, and ERMs. ROS products and iNOS were investigated in adherent vitreal cells and/or ERMs, and iNOS, VEGF, Ang-2, IFNγ, IL18, and IL22 were quantified in vitreous (ELISA/Ella, IF/WB); transcripts specific for iNOS, p65NFkB, KEAP1, NRF2, and NOX1/NOX4 were detected in ERMs (PCR). Biomolecular changes were analyzed and correlated with disease severity. Results. The higher ROS production was observed in vitreal cells at stage 4, and iNOS was found in ERMs and increased in the vitreous as early as at stage 3. Both iNOS and NOX4 were upregulated at all stages, while p65NFkB was increased at stage 3. iNOS and NOX1 were positively and inversely related with p65NFkB. While NOX4 transcripts were always upregulated, NRF2 was upregulated at stage 3 and inverted at stage 4. No significant changes occurred in the release of angiogenic (VEGF, Ang-2) and proinflammatory (IL18, IL22 and IFNγ) mediators between all stages investigated. Conclusions. ROS production was strictly associated with iNOS and NOX4 overexpression and increased depending on ERM stadiation. The higher iNOS expression occurred as early as stage 3, with respect to p65NFkB and NRF2. These last mediators might have potential prognostic values in ERMs as representative of an underneath retinal damage. [ABSTRACT FROM AUTHOR]

Objective. To explore the relationship between vascular overload index (VOI) and cardiovascular disease (CVD) in rural population and find effective ways to prevent cardiovascular disease in rural low-income populations. Methods. The data for this study was obtained from a large cohort study called the Northeast China Rural Cardiovascular Health Study (NCRCHS) conducted in 2013 and followed up during 2015-2018. 10,174 subjects completed at least one follow-up visit. Cox regression equation was used to explore whether VOI and cardiovascular disease were independently related. The Kaplan-Meier curves were used to calculate the cumulative incidence of any adverse outcome, and the log-rank test and restrict mean survival analysis were used to compare group differences. Reclassification and discrimination statistics were used to determine whether VOI could strengthen the ability of the model to predict CVD events. Results. The prevalence of CVD in the VOI quartiles was 1.92%, 3.96%, 5.42%, and 11.34% for Q1–Q4, respectively (P for trend <0.001). After adjusting for multiple confounders, there was a 2.466-fold increased risk of CVD when comparing the highest and lowest groups. Besides, this study found that for every standard deviation increase, the results still exist. The risk of cardiovascular disease increased by 1.358-fold in this model. The restrict mean survival analysis results show that with the increase of VOI, the restrict mean survival time (RMST) within 5 years gradually became shorter. Reclassification and discrimination statistics indicated that VOI significantly enhanced the ability to estimate CVD events within 4 years. Conclusion. Analyses showed that VOI was significantly associated with CVD. VOI is a simple and accurate prognostic marker of CVD risk, which has the potential ability to improve the risk stratification of CVD. [ABSTRACT FROM AUTHOR]

In recent studies, stem cell-based therapy is a potential new approach in the treatment of stroke. The mechanism of human umbilical cord mesenchymal stem cell (hUMSC) transplantation as one of the new approaches in the treatment of ischemic stroke is still unclear. The aim of this study was to determine the traits of immune responses during stroke progression after treatment with human umbilical cord blood MSCs by bioinformatics, to predict potential prognostic biomarkers that could lead to sex differences, and to reveal potential therapeutic targets. The microarray dataset GSE78731 (mRNA profile) of middle cerebral artery occlusion (MCAO) rats was obtained from the Gene Expression Omnibus (GEO) database. First, two potentially expressed genes (DEGs) were screened using the Bioconductor R package. Ultimately, 30 specific DEGs were obtained (22 upregulated and 353 downregulated). Next, bioinformatic analysis was performed on these specific DEGs. We performed a comparison for the differentially expressed genes screened from between the hUMSC and MCAO groups. Gene Ontology enrichment and pathway enrichment analyses were then performed for annotation and visualization. Gene Ontology (GO) functional annotation analysis shows that DEGs are mainly enriched in leukocyte migration, neutrophil activation, neutrophil degranulation, the external side of plasma membrane, cytokine receptor binding, and carbohydrate binding. KEGG pathway enrichment analysis showed that the first 5 enrichment pathways were cytokine-cytokine receptor interaction, chemokine signal pathway, viral protein interaction with cytokine and cytokine receptor, cell adhesion molecules (CAMs), and phagosome. The top 10 key genes of the constructed PPI network were screened, including Cybb, Ccl2, Cd68, Ptprc, C5ar1, Il-1b, Tlr2, Itgb2, Itgax, and Cd44. In summary, hUMSC is likely to be a promising means of treating IS by immunomodulation. [ABSTRACT FROM AUTHOR]

Background. Baichanting (BCT),a traditional Chinese medicine prescription, is a combination of Acanthopanax senticosus, Paeonia lactiflora, and Uncaria three herbs, which has the effect of benefiting the kidney and calming the liver. The study was aimed at investigating the protective effect of BCT against Parkinson's disease using an integrated strategy of network pharmacology and brain metabolomics. Materials and Methods. By integrating network pharmacology with metabolomic research, the protective effect of BCT against PD was investigated using a transgenic mouse model for α-synuclein. The metabolite level and gene level components of BCT that might be anti-PD were separated out. Indicators of behavior and pharmacodynamics were employed to gauge the effectiveness of BCT on PD in the preliminary stages. Network pharmacology, which may be the target of BCT, screened the active substances and target genes. The use of metabolomics to identify potential biomarkers of PD, and then through network pharmacology and metabolic pathways to determine their regulatory enzymes and regulatory genes, improve the pathway mechanism of the disease, has important guiding significance for the in-depth study of the pathogenesis of PD. Results. 101 putative target genes were identified by the network pharmacology analysis in relation to the treatment of PD with BCT. According to the functional enrichment analysis, the proposed mechanism was primarily related to the transport of neurotransmitters, the metabolism of arachidonic acid, dopamine, and alpha-amino acids, as well as the transport of dopamine and the negative regulation of amino acid transport. 25 distinct endogenous metabolites were shown to be potential biomarkers for the BCT for treating PD based on metabolomics. These metabolites were mostly implicated in the important methionine and cysteine, tyrosine, histidine, and arginine and proline metabolic pathways. These results somewhat agreed with those of the network pharmacology analysis. Conclusions. In conclusion, this study showed that BCT could delay the occurrence and development of PD by improving the brain metabolic disorder of α-Syn mice, which revealed the mechanism of BCT through multitarget and multipathway treatment, and provided a new explanation for the mechanism of anti-PD action. Our research, on the other hand, demonstrated that the network pharmacology-integrated metabolomics approach was a potent tool for discovering the active ingredients and mechanisms underlying the pharmacological effects of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Background. Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is an integral membrane protein overexpressed in various cancers and may function as a prognostic tumor marker. The present study is aimed at understanding the clinical significance of serum LAPTM4B in breast cancer (BC). Methods. Serum LAPTM4B level was evaluated in 426 BC patients, 40 benign breast disease, and 80 healthy controls by ELISA. We used the receiver operator characteristic (ROC) curve to assess the diagnostic significance. 46 BC patients were recruited to monitor the dynamic change of serum LAPTM4B during adjuvant therapy (AT). In addition, sera from a subset of 330 patients undergoing AT, including anti-HER2 treatment, were collected to evaluate the association between LAPTM4B levels and AT efficacy. Descriptive and explorative statistical analyses were used to assess LAPTM4 B's potential as a diagnostic and prognostic marker in BC. Results. Serum LAPTM4B level was significantly increased in BC patients than benign group and controls. It could well discriminate BC from healthy controls with diagnostic accuracy with an AUC of 0.912, a sensitivity of 85.9%, and a specificity of 83.8%. Compared with pre-AT, serum LAPTM4B concentration remarkably decreased after AT. In addition, patients in the invalid response group (PD + SD) showed higher LAPTM4B levels than the valid response group (PR + CR). Conclusion. Our results proposed that serum LAPTM4B had a high diagnostic and prognostic impact as a circulating biomarker in BC. [ABSTRACT FROM AUTHOR]

Background. Neonatal sepsis is a leading cause of morbidity and mortality in low-and middle-income countries (LMICs). There are several sophisticated biomarkers; however, they are still insufficient in precision. In this perspective, our study aims to search for a pragmatic diagnostic biomarker in the age category. Methods. A cross-sectional study was conducted over six months(April-September 2018). All neonates with a diagnosis of probable sepsis were included. Logistic regression analysis of demographic variables was done to elucidate any association with confirmed sepsis cases. The median with interquartile range (IQR)] and mean with standard deviation (SD) were calculated, and then compared. The area under the receiver operating characteristic curve (AUROC) of the commonly opted biomarker tests [distribution width of red blood cells (RDW) and platelets(PDW), mean platelet volume(MPV), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] was compared to the culture-confirmed case. Results. Of the 171 suspected sepsis subjects, we discovered a significant burden of newborn sepsis, with 18.7% of cases being culture-confirmed. 66 Early-onset sepsis(EOS) and 105 Late-onset sepsis(LOS) probable sepsis cases were enrolled. A higher incidence was revealed among male infants 24(14%) compared to females 8(4.7%). On logistic regression analysis, preterm birth [odds ratio (OR): 10.9, 95% confidence interval (CI): 4.5-26.9] and low birth weight (OR: 6.5, 95% CI: 2.4-17.9) were significantly associated. Coagulase-negative Staphylococcus aureus (CoNS) (n =6) among gram-positive, and Pseudomonas aeruginosa (n =6) was among gram-negative, were the leading etiologies. Escherichia coli (n =3) was the predominant bacteria in EOS subjects, while Pseudomonas aeruginosa (n =6) among LOS. Median interquartile range(IQR): platelet count 144.5(99-192), red cell distribution width 18(16.9-20), CRP 6(3-18.3); and mean ± SD: MPV (11.7 ± 1.7); PDW (15.2 ± 3.5) were attained, among confirmed cases. The AUROC, of biomarker tests was attained in the order: PDW(0.86) > MPV(0.81) > RDW(0.76) > CRP(0.67) > ESR(0.59); similarly, the cut-off order was >11.2, >10.4, >16.8, >2.9, >4.5, respectively. Conclusions. Our finding shows an increment in the width and volume of RBCand platelet: RDW, MPV, and PDW have a diagnostic role in neonatal sepsis. [ABSTRACT FROM AUTHOR]

Background. To explore the normal changes in bone turnover markers (BTMs) and the correlations between the different BTMs after osteoporotic vertebral compression fracture (OVCF). Meanwhile, we explored the related differences that exist between sexes. Methods. A total of 130 OVCF patients were retrospectively reviewed. Using IBM SPSS 19.0 statistical software, the differences in the levels of BTMs and clinical parameters between sexes were assessed using Student's unpaired t test, and one-way ANOVA was used for the comparison of the three groups of samples. The correlations between P1NP, CTX, and clinical factors were assessed using Pearson's correlation coefficient. Results. P1NP was 52.15 ng/ml within two weeks in male patients, and the level increased to 96.33 ng/ml after 12 weeks; in female patients, the increase was not as obvious as in male patients. CTX in male patients reached as much as approximately twice the initial value after 12 weeks. However, the situation in female patients was diverse. CTX was 0.58 ng/ml within two weeks and increased to 0.61 ng/ml within 2-12 weeks after the onset of OVCF. Subsequently, CTX decreased suddenly after 12 weeks. The increase in P1NP levels within 2 weeks after OVCF was significantly correlated with the levels of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Changes in CTX within 2 weeks after OVCF were considerably related to phosphorus, 25 hydroxyvitamin D (25-OHD), OC, and BAP. Conclusion. The levels of P1NP and CTX increased differently in males and females after OVCF. The levels of OC and BAP were correlated with the levels of P1NP and CTX within 2 weeks of OVCF. [ABSTRACT FROM AUTHOR]

ADGRD1 (GPR133), an adhesion G protein-coupled receptor (GPCR), has been linked to cancer. However, the prognostic value and regulatory function within non-small-cell lung cancer (NSCLC) is still unclear. This work adopted various bioinformatics methods, including publicly available databases as well as real-time PCR (RT-PCR), for detecting ADGRD1 expression level and investigating the correlation between ADGRD1 expression level and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), immune infiltrating cells, immune-related genes, and targeted regulation mechanisms in NSCLC. According to the results, ADGRD1 expression decreased within NSCLC, which might be the factor predicting prognosis of NSCLC. Meanwhile, ADGRD1 showed significant correlation with TMB and MSI, respectively, as well as immune cell infiltrating levels in lung adenocarcinoma (LUAD), which were primarily linked to macrophage M1, mast cell resting, T cell CD4 memory activated, and T cell CD4 memory resting and were associated with mast cell activated and mast cell resting in lung squamous cell carcinoma (LUSC). The most promising upstream regulation pathways of ADGRD1 were likely miR-142-5p, miR-93-5p, and miR-17-5p, which were overexpressed and associated with poor prognosis in NSCLC. ADGRD1 and immune-related genes correlated with ADGRD1 were shown to be enriched in "positive regulation of leukocyte activation," "external side of plasma membrane," "receptor ligand activity," and "cytokine-cytokine receptor interaction" pathways. ADGRD1 expression and regulation may be critical in determining NSCLC prognosis. [ABSTRACT FROM AUTHOR]

Aluminum (Al) is an important factor in the environment as it is used in agriculture and several industries leading to hazardous effects via oxidative stress. Bromelain is a cheap extract from the byproduct waste of Ananas comosus stem. It has been used in several biological and therapeutic applications. So, this study was undertaken to assess the hepatoprotective potential of bromelain versus oxidative stress induced by aluminum chloride in rats. Results revealed that administration of AlCl3 reduced the body and liver weights and increased Al concentration in the blood and liver tissue. Also, AlCl3 caused valuable changes in hematological parameters and increased TBARS and H2O2 concentrations in rat liver. Enzymatic (SOD, CAT, GPx, GR, and GST) and nonenzymatic (GSH) antioxidants and protein content were significantly decreased. Furthermore, alterations in liver biomarkers such as bilirubin level and enzyme activities in both serum and liver homogenate (LDH, ALP, AST, and ALT) were detected. AlCl3 also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1β)], tumor necrosis factor-alpha (TNF-α), as well as matrix metalloproteinase (MMP9), and downregulation of nuclear factor erythroid 2 (Nrf2) expression. In addition, histopathological examination showed significant variations in the liver that confirms the biochemical results. Otherwise, bromelain intake alone slumped lipid peroxidation and gotten better antioxidant status significantly. Moreover, supplementation with bromelain before AlCl3 intoxication restores enzymatic and nonenzymatic antioxidants as well as biochemical indices and tissue architecture with respect to the AlCl3 group. In conclusion, bromelain proved its remarkable protective power to abolish AlCl3 toxicity. So, it might represent a new strategy in the therapy of metal toxicity by its antioxidant capacity. [ABSTRACT FROM AUTHOR]

In recent years, 2 major discoveries have modified the traditional understanding of the brain. First, meningeal lymphatic vessels (MLV) were found in the dural sinus, which may absorb and drain cerebrospinal fluid (CSF). Second, the glymphatic system was discovered, composed of para-arterial CSF influx channel, paravenous interstitial fluid (ISF) efflux channel, and the water channel aquaporin-4 (AQP4) in astrocytes connecting the 2 channels. Accumulating evidence demonstrates that the lymphatic system of the brain plays a vital role within the circulation of CSF and, therefore, in the removal of metabolites. Therefore, it is involved in the incidence and development of some central nervous system (CNS) diseases. The optic nerve and retina are the extension of the CNS in the orbit. Whether they have a lymphatic system and how they clear the metabolites of the optic nerve and retina are still unclear. Recent studies have found that the ocular lymphatic system has a crucial impact on bounding eye diseases, like disorders of the optic nerve and retina. Therefore, here we review the recent research progress concerning the structure and function of MLV and glymphatic system. We also discuss the biomarkers for identification of lymphatic vessels, the composition of ocular lymphatic systems, and the possible association with diseases. [ABSTRACT FROM AUTHOR]

Objective. We intend to identify differences in the clinicodemographic and laboratory findings of COVID-19 patients to predict disease severity and outcome on admission. Methods. This single-centred retrospective study retrieved laboratory and clinical data from 350 COVID-19 patients on admission, represented as frequency tables. A multivariate regression model was used to assess the statistically significant association between the explanatory variables and COVID-19 infection outcomes, where adjusted odds ratio (AOR), p value, and 95% CI were used for testing significance. Results. Among the 350 COVID-19 patients studied, there was a significant increase in the WBC count, neutrophils, aggregate index of systemic inflammation (AISI), neutrophil-to-lymphocyte ratio (dNLR), neutrophil-to-lymphocyte and platelet ratio (NLPR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), D-dimer, interleukin-6 (IL-6), ferritin, lactate dehydrogenase (LDH), prothrombin time (PT), glucose, urea, urea nitrogen, creatinine, alanine phosphatase (ALP), and aspartate aminotransferase (AST) and a significant decrease in lymphocytes, eosinophils, total protein, albumin, prealbumin serum, and albumin/globulin (A/G) ratio in the severe group when compared with the mild and moderate groups. However, after adjusting their age, gender, and comorbidities, WBC count (adjusted odds ratio AOR = 6.888 , 95% CI = 1.590 -29.839, p = 0.010), neutrophils (AOR = 5.912 , 95% CI = 2.131 -16.402, p = 0.001), and urea (AOR = 4.843 , 95% CI = 1.988 -11.755, p = 0.001) were strongly associated with disease severity. Interpretation and Conclusion. On admission, WBC count, neutrophils, and urea, with their cut of values, can identify at-risk COVID-19 patients who could develop severe COVID-19. [ABSTRACT FROM AUTHOR]

Objective. Tooth extraction causes a wound with hard and soft tissue defects in the alveolar ridge. Few studies have reported the function of microRNAs (miRNAs) in the healing of extraction sockets. This study used bioinformatics analysis to reveal the possible relevance and role of miRNAs during the early stages following tooth extraction. Materials and Methods. Socket tissues from beagle dogs (Canis familiaris; two males and two females) were collected 1 and 12 hours after extraction of premolars on both sides of the mandible. miRNA expression was profiled through miRNA sequencing, and hub miRNAs showing characteristic expression patterns were selected and subjected to target enrichment analysis. Alkaline phosphatase (ALP) activity analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to verify the effect of hub miRNA on osteoblast differentiation and bone regeneration in vivo. Results. Five miRNAs were identified to have consistently high expression levels, with cfa-miR-451 showing the highest expression. Additionally, 20 hub miRNAs were selected as candidates expected to play an important role in the healing process. Pathways, such as the MAPK, axon guidance, TGF-β, and Wnt signaling, were significantly enriched. Among hub miRNAs, miR-190a-5p increased ALP activity and mRNA expression of osteogenic markers and increased new bone formation in vivo. Conclusions. Our findings suggest that miRNAs may be involved in the earliest stages of socket healing after tooth extraction and can play an important role in moderating the entire socket healing mechanism in the extraction socket. [ABSTRACT FROM AUTHOR]

Lung cancer mortality and morbidity rates are the first among malignant tumors. It is extremely crucial to pay more attention to the early diagnosis and treatment of lung cancer and to grasp and judge the progress of the patient's condition promptly. In this study, lung cancer patients' early diagnosis with tumor markers and inflammatory variables is examined. The general surgery department of our hospital treated 98 patients with lung cancer and 100 patients with benign pulmonary hyperplasia from January 2017 to February 2018. Additionally, 100 healthy subjects who completed physical examinations during this time period were included. Based on the findings of the pathological examination, 100 patients with benign pulmonary hyperplasia were chosen as the benign group, 100 patients with lung cancer were chosen as the malignant group, and 100 healthy individuals were chosen as the healthy group. The tumor markers carbohydrate antigen 125 (CA125), CA153, and carcinoembryonic antigen (CEA), as well as inflammatory factors such as tumor necrosis factor- (TNF-) and high-sensitivity C-reactive protein, were measured in the venous blood of three groups of patients (hs-CRP). There was no discernible difference in tumor marker levels between the benign and healthy groups (P > 0.05). In comparison to the benign and healthy groups, the malignant group had higher serum levels of CA153, CA125, and CEA (P 0.05). Between the benign and healthy groups, there was no discernible difference in the levels of inflammatory factors (P > 0.05). TNF- and hs-CRP serum levels were observed to be higher in the malignant group compared to the benign and healthy groups (P 0.05). The combined detection of CA 153 + CA 125 + CEA + TNF − + hs − CRP showed the highest sensitivity and specificity, which were, respectively, 62.22 percent and 92.00 percent, when compared to single or mixed detection of tumor markers or inflammatory factors solely. Serum levels of inflammatory agents TNF- and hs-CRP may be related to the pathophysiology and other functions of patients with lung cancer, as well as to the development and metastasis of the disease. These markers include CA153, CA125, and CEA. For the early detection of lung cancer and the evaluation of the disease's severity, the detection of tumor markers in combination with inflammatory variables has a significant reference value. [ABSTRACT FROM AUTHOR]

The neutrophil to lymphocyte ratio (NLR) reflects a dynamic relationship between the innate (neutrophils) and adaptive (lymphocytes) cellular immune response. This systematic review and meta-analysis was conducted to critically evaluate the literature regarding the use of the NLR as a reliable means to detect several ocular disorders. Our study was registered with the PROSPERO (ID: CRD42022314850). Three databases, including PubMed, Embase, Scopus, and the Web of Science, were searched on September 9, 2022, with no restrictions on the article's language. Finally, 32 articles were recognized as eligible for our meta-analysis. We found that patients with eye diseases had significantly elevated levels of NLR in comparison to healthy controls (SMD =0.53, 95% CI =0.35-0.71, P < 0.001). In subgroup analysis, patients with keratoconus (SMD =0.69; 95% CI =0.33-1.05, P < 0.001), glaucoma (SMD =0.56, 95% CI =0.25-0.87, P < 0.001), pterygium (SMD =0.14; 95% CI =0.01-0.26, P < 0.001), and idiopathic epiretinal membrane (SMD =0.14; 95% CI =0.01-0.26, P < 0.001) had higher levels of NLR compared to healthy controls. However, NLR levels of patients with dry eye disease were similar to healthy controls (SMD =0.32, 95% CI = -0.49-1.13, P = 0.435). It can be said that NLR is a valuable marker of systemic inflammation, which is significantly increased in many eye disorders, suggesting that inflammation plays a key role in the pathophysiology of these diseases. [ABSTRACT FROM AUTHOR]

Objective. To investigate the risk of cardiovascular and neurodegenerative diseases induced by matrix metalloproteinases (MMPs) by meta-analysis. Methods. Relevant literature was searched from Wanfang Medical Center, CNQI, VIP, PubMed, and other domestic and foreign literature databases for the research direction, and the risk of cardiovascular and neurodegenerative diseases induced by MMPs was meta-analyzed using the fixed-effect model and random-effect model. Results. MMP-1 and MMP-9 were risk factors for cardiovascular diseases by fixed and random-effect model analysis, respectively, while MMP-2 and MMP-9 were risk factors for increased neurodegenerative diseases by random-effect model analysis. Conclusion. MMP-1 and MMP-9 are risk factors for cardiovascular diseases, and MMP-2 and MMP-9 are major factors for increased risk of neurodegenerative diseases. MMP-1, MMP-2, and MMP-9 can be used as new targets for clinical diagnosis, treatment, and research of subsequent cardiovascular and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Objective. This paper aims to explore novel ferroptosis-related biomarkers for acute kidney injury (AKI). Methods. Various bioinformatic methods, such as differential expression analysis, functional annotation analysis, machine learning, and chemical-gene network analysis, were used in this study. Furthermore, the expression and proferroptotic role of RPS7 were validated with further bioinformatics analysis and biochemical experiments. Results. GSE30718 dataset and GSE139061 dataset were used, and the differentially expressed genes (DEGs) were screened. The DEGs were overlapped with ferroptosis-related genes and genes associated with AKI, which led to the identification of four candidate genes. Machine learning and ROC curve analysis were conducted, and RPS7 and TRIB3 were selected for diagnostic model analysis and functional analysis. Finally, the upregulation of RSP7 in cisplatin-induced AKI was validated in cisplatin-induced AKI, and its proferroptotic role was confirmed in cisplatin-treated proximal tubular cells. Conclusion. Our results indicated that RPS7 might present as a novel ferroptosis-related biomarker for AKI, and it derived ferroptosis to accentuate cisplatin-induced AKI. [ABSTRACT FROM AUTHOR]

Myopia goes far beyond the inconvenience it brings. It is a prevailing and vision-threatening eye disease, especially in Asia. Aberrantly expressed miR-708a and miR-148 are critical for accurate diagnosis, good prognosis, and precise response prediction of myopia. In this paper, we aim to examine the potential contributions of miR-708a, miR-148a, and PAX6 to high myopia (HM). First, aqueous samples were taken from 25 exclusively HM eyes and 25 exclusively cataract eyes. For next-generation sequencing and bioinformatics analysis, RNA from sample 30one was used. Twenty more samples were used for RT-qPCR. 341 miRNAs in total were found in HM eyes; 249 mature miRNAs and 17 new miRNAs showed differential expression. The expression of hsa-miR-127-3p, hsa-let-7i-5p, and hsa-miR-98-5p was identified using RT-qPCR. MiR-708a and miR-148, which may be linked to the development of myopia and serve as possible biomarkers, are notably highly expressed in atrial tissues of HM patients. Our findings may help deepen the understanding of the mechanisms behind the high expression of miR-708a and miR-148 in atrial tissues of patients with HM. [ABSTRACT FROM AUTHOR]

This meta-analysis was conducted to determine the relationship between neutrophil to lymphocyte ratio (NLR) and febrile seizure (FS). Our study was registered with the PROSPERO (ID: CRD42021259944). Web of Science, Embase, PubMed, Scopus, and ProQuest Central were searched, and finally, 17 studies were included. Standardized mean difference (SMD) was reported with a 95% confidence interval (CI) for the NLR levels. Compared with the febrile control group, the FS patients' NLR levels were significantly higher (SMD = 0.49 ; 95 % CI = 0.26 to 0.72, P < 0.001). Furthermore, we conducted a comparison of NLR levels between febrile controls against simple and complex FS cases separately and found that NLR levels of children with either simple or complex FS were higher compared with those of febrile controls (SMD = 0.42 , 95 % CI = 0.14 to 0.69, P = 0.003 and SMD = 0.90 , 95 % CI = 0.71 to 1.09, P < 0.001 , respectively). Also, in comparison with the NLR levels of the simple FS group, the complex FS patients' NLR levels were significantly higher (SMD = 0.59 , 95 % CI = 0.34 to 0.85, P < 0.001). Our study indicated that NLR could be recommended as an inexpensive diagnostic biomarker for FS. In addition, it can be useful when distinguishing between simple FS and complex FS. [ABSTRACT FROM AUTHOR]

Neuroretinitis spectrum disorder (NMOSD) is generally regarded as an acute or subacute inflammatory demyelinating disease of the central nervous system, mainly involving the optic nerve and spinal cord, mediated by humoral immunity. To address these questions, this work established an immunomic library of the heavy chain complementarity determinant 3 (gHI-CDR3) of peripheral blood lymphocyte B cell receptors. The library was established in patients with a spectrum of neurosyphilis-retinitis disorders. Six NMOSD patients and six healthy volunteers were recruited, and the NMOSD group was divided into an early-onset group and a stable group according to treatment conditions. The IgH-CDR3 gene fragment cultured in vitro was amplified by multiplex PCR technology, and the gene was sequenced by the second-generation high-throughput sequencing technology, and the statistical analysis was carried out by the method without reference. The quantity, type, and diversity of IgH-CDR3 in peripheral blood B lymphocytes of NMOSD patients were significantly lower than those of normal group (P > 0.05); the variation of IgH-CDR3 sequence in the initial stage of treatment was higher than that in the stable stage (P > 0.05); the replication frequency of the characteristic gene "CASSICLGSGCGGYYYGMDVW" was significantly increased in patients at the initial stage of NMOSD treatment (P < 0.05). The conclusion was that the gene expression and gene expression analysis of NMOSD patients could accurately judge the condition of NMOSD patients, evaluate their efficacy, and provide new molecular targets and new theoretical basis for clinical application. [ABSTRACT FROM AUTHOR]

Chronic respiratory diseases (CRDs) like asthma and chronic obstructive pulmonary disease (COPD) are the leading causes of morbidity and mortality worldwide. Alveolar macrophages (AM) are immune cells that exist in different polarization states/phenotypes and have been shown to play a critical role during an inflammatory process. In this paper, differently polarized mouse bone marrow-derived macrophages (BMDM (M1-proinflammatory or M2-immunomodulator)) were radiolabeled with either 99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO), 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG), or 67Ga-citrate. Biocompatibility and in vivo biodistribution of radionuclide-labeled macrophages after intravenous injection were evaluated. Radioactivity measurements were performed using Packard Cobra Quantum 5002 Gamma Counter. Both M1 and M2 macrophages showed a higher uptake for 18F-FDG and 99mTc-HMPAO, than 67Ga-citrate. M2 macrophages showed a higher uptake of radionuclides than M1 macrophages. The used radionuclides were biocompatible for both M1 and M2 macrophages. At 2-hour postinjection, 18F-FDG-labeled M1 and M2 macrophages were found significantly higher in the lung of inflammatory animals (12.54 ± 1.58 % and 14.13 ± 1.03 % , respectively) than in control mice. Labeling macrophages with either 18F-FDG or 99mTc-HMPAO did not affect their biodistribution. The results from these initial experiments indicate that radionuclide-labeled macrophages may allow a higher sensitivity detection in nuclear imaging techniques such as PET and SPECT. Further confirmatory studies are needed to noninvasively image radiolabeled BMDM to understand their role in the inflammatory processes inherent to CRDs. [ABSTRACT FROM AUTHOR]

In order to solve the effect of orthodontics combined with implant repair on the aesthetic effect and gingival crevicular fluid factor of patients with dentition defect and periodontitis, 60 patients who met the diagnostic criteria of chronic periodontitis were proposed. They were randomly divided into treatment group (taking Bushen Huoxue Guchi recipe for 3 courses while basic periodontal treatment) and control group (only basic periodontal treatment without taking any drugs). The experimental method of 30 cases in each group showed that PD, Al, and GI in the treatment group and control group decreased to varying degrees compared with those before treatment. The treatment group decreased significantly compared with the control group (P < 0.01). Chronic periodontitis is a common clinical periodontal disease, accounting for up to 95%, local stimulation, a variety of anaerobic bacteria infection, and periodontal plaque, and other factors may cause the occurrence of diseases. Routine treatment mainly includes upper gingival cleaning, lower curettage treatment, and equal root surface treatment. Although the clinical symptoms can be alleviated to a certain extent, the cause cannot be fundamentally excluded, leading to the disease progression in some patients and the formation of aggressive periodontitis and necrotizing periodontal disease. [ABSTRACT FROM AUTHOR]

Objective. Neutrophil-lymphocyte ratio (NLR) and Platelet-lymphocyte ratio (PLR) have been proposed as prognostic biomarkers in multiple cancers. However, the implications of NLR and PLR in the responsiveness to neoadjuvant chemoradiotherapy (nCRT) remain to be clarified in locally advanced rectal cancer (LARC) patients. This retrospective study investigated the prognostic value of NLR and PLR in nCRT responsiveness of LARC patients. Methods. A total number of 86 patients diagnosed with LARC and treated with nCRT and total mesorectal excision were retrospectively followed from 2013 to 2016. Receiver operating characteristic (ROC) curve was used to determine the cutoff values of NLR and PLR, and the patients were divided into NLR elevation and NLR decrease groups, or PLR elevation and PLR decrease groups. The correlation between NLR and PLR changes, and clinicopathological factors were analyzed. The relationship between NLR and PLR changes and the curative responsiveness towards nCRT were further evaluated. Results. NLR and PLR changes after nCRT were significantly correlated with the distance of tumors to the anus and BMI (body mass index) (P < 0.05). The clinical remission rate of patients with NLR reduction was 72.09% (31/43), which was significantly higher than that in patients with NLR increment (22/43, 51.16%). There was no significant difference in the clinic remission rate between the patients with PLR reduction and those with PLR increment (P > 0.05). However, the pathological responsiveness rate was significantly higher in patients with PLR reduction (21/43, 48.84%) when compared to the ones with PLR increment (9/43, 20.9%) (P = 0.036). Conclusion. Our data indicate that in LARC patients with nCRT, the reduction of NLR and the reduction of PLR could serves as predictors for the clinic remission rate and pathological responsiveness rate, respectively. The combination of NLR and PLR changes may be employed as a simple and effective prognostic parameter to predict the treatment outcome of nCRT in LARC. [ABSTRACT FROM AUTHOR]

Background. Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease. Objective. (1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment. Materials and Methods. A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors' judgments were categorized as "low risk," "high risk," or "unclear risk" of bias. Results. Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be "low." 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice. Conclusions. The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background. Osteonecrosis of the femoral head (ONFH) is a disabling orthopedic disease, which is impacted by infiltration of immune cells. Thus, the aim of the current research was to determine the inflammation-related biomarkers in ONFH. Methods. GSE123568 dataset with control and steroid-induced osteonecrosis of the femoral head (SONFH) samples were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were detected by limma R package and weighted gene co-expression network analysis (WGCNA) was used to explore the co-expression genes and modules. We obtained inflammation-related genes (IRGs) from the Molecular Signatures Database (MSigDB). Then, the IRGs associated with SONFH (IRGs-SONFH) were screened out and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and hub genes were identified by the MCODE algorithm. Based on the hub genes, we constructed a lncRNA-miRNA-mRNA network. Results. We identified 535 DEGs between control and SONFH samples. The WGCNA clearly indicated that the brown module was most significantly associated with SONFH. We identified 25 IRGs-SONFH through WGCNA module genes, DEGs and IRGs. A total of 4 hub genes (CD14, CYBB, NOD2, and TLR1) were identified by Cytoscape. Receiver operating characteristic (ROC) curve analysis determined that the expressions of the four genes could distinguish SONFH from controls as evidenced by the area under the curve (AUC) greater than 0.7. Finally, we constructed a competitive endogenous RNA (ceRNA) network which included 67 lncRNAs, 1 miRNA (hsa-miR-320a), and 1 mRNA (NOD2). Conclusions. Our study identified 4 hub genes as potential inflammation-related biomarkers of SONFH. Moreover, we proposed a ceRNA network of lncRNAs targeting hsa-miR-320a, hsa-miR-320a, and NOD2 as a potential RNA regulatory pathway that controls disease progression in ONFH. [ABSTRACT FROM AUTHOR]

In this study, we have examined the anticancer effects of SH005S7 on MET-amplified and (HCC827GR) NSCLC cells and their primary HCC827 cells. In vitro, first of all, cell viability and colony formation assay confirmed the growth inhibitory effects of SH005S7 on both cells. Second, SH005S7 inactivated EGFR-related multiple cell signaling, which was associated with a marked decrease in the constitutive phosphorylation of EGFR, HER3, MET, AKT, and ERK. Third, SH005S7 attenuated the anchorage-independent cell growth. Fourth, SH005S7 blocked invasive and metastatic capability by downregulation of mesenchymal markers—vimentin, snail, and MMP-9. Fifth, BrdU assay confirmed the cell cycle arrest of SH005S7 on these cells. When administered orally to nude mice xenografically transplanted human NSCLC, SH005S7 inhibited the growth of tumor and did not cause hepatotoxicity and nephrotoxicity in animals. Immunohistochemical and Western blot analyses of tissue showed that the suppression of growth correlated with inhibition of proliferation (Ki-67, PCNA), invasiveness (vimentin, snail), and angiogenesis (CD31) marker and decrement in the constitutive and phosphorylation of EGFR, HER3, MET, AKT, and ERK. Additionally, SH005S7 had immune stimulatory effects by TNF-α cytokine release on macrophage, without cell cytotoxicity. Overall, our results suggest that SH005S7 can inhibit the growth of MET-amplified and gefitinib-resistant NSCLC cells through the suppression of EGFR-related multiple targets linked to overcome gefitinib resistance. [ABSTRACT FROM AUTHOR]

Background. The purpose of the present study was to investigate the impact of D-dimer-to-albumin ratio (DAR) on outcomes in patients with hepatitis B virus-associated decompensated cirrhosis (HBV-DeCi). Methods. A total of 172 HBV-DeCi patients were enrolled. Logistic regression was used to explore the association between DAR and 30-day mortality. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of DAR for predicting mortality. Results. The 30-day mortality was 19.8%. DAR was clearly higher in the nonsurvivors compared with the survivors, and increasing DAR was associated with an increasing risk of death. DAR was independently associated with mortality and its AUC for mortality was equivalent to that for Model for End-Stage Liver Disease score. Conclusions. DAR may be a potential prognostic marker for mortality in HBV-DeCi patients. [ABSTRACT FROM AUTHOR]