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Frontiers in Bioscience (Landmark... May 2024Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant...
BACKGROUND
Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis.
METHODS
The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB).
RESULTS
PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated.
CONCLUSION
PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.
Topics: Humans; Osteosarcoma; RNA, Long Noncoding; Ferroptosis; STAT3 Transcription Factor; Cell Line, Tumor; Bone Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase; Cell Proliferation; Reactive Oxygen Species; Signal Transduction; Cell Movement; Disease Progression; Apoptosis; Gene Expression Regulation, Neoplastic
PubMed: 38940027
DOI: 10.31083/j.fbl2906207 -
Frontiers in Bioscience (Landmark... Jun 2024Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved...
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an model.
METHODS
HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles.
RESULTS
Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways.
CONCLUSION
In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.
Topics: Humans; Thioctic Acid; Hep G2 Cells; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Oleic Acid; Palmitic Acid; Gene Expression Regulation; Fatty Acids; PPAR gamma; Lipid Droplets; PPAR alpha; Uncoupling Protein 2
PubMed: 38940024
DOI: 10.31083/j.fbl2906209 -
Frontiers in Bioscience (Landmark... Jun 2024The objective of this research was to identify differentially expressed genes (DEGs) related to ferroptosis in the annulus fibrosus (AF) during intervertebral disc...
BACKGROUND
The objective of this research was to identify differentially expressed genes (DEGs) related to ferroptosis in the annulus fibrosus (AF) during intervertebral disc degeneration (IDD).
METHODS
We analyzed gene data from degenerated and normal AF obtained from the GSE70362 and GSE147383 datasets. An analysis to determine the functional significance of the DEGs was conducted, followed by the creation of a network illustrating the interactions between proteins. We further analyzed the immune infiltration of the DEGs and determined the hub DEGs using LASSO regression analysis. Finally, we identified the hub ferroptosis-related DEGs (FRDEGs) and verified their expression levels using Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, Immunohistochemical Staining (IHC), and Immunofluorescence (IF).
RESULTS
By analyzing the GSE70362 and GSE147383 datasets, we identified 118 DEGs. In degenerative AF groups, we observed a significant increase in immune infiltration of resting memory CD4+ T cells. LASSO regression analysis revealed 9 hub DEGs. The construction of a Receiver Operating Characteristic (ROC) curve yielded an Area Under the Curve (AUC) value of 0.762. Furthermore, we found that is a hub gene related to ferroptosis. Our examination of immune infiltration indicated that primarily influences macrophage M0 in different immune cell expression groups. Finally, our observations revealed a marked upregulation of expression in the degenerated annulus fibrosus tissue.
CONCLUSION
Our findings indicate an upsurge in levels within degenerative AF, potentially playing a crucial role in the exacerbation of IDD. These findings provide a foundation for further exploration of the pathological mechanisms underlying IDD and offer potential drug targets for intervention.
Topics: Ferroptosis; Annulus Fibrosus; Humans; Intervertebral Disc Degeneration; Computational Biology; Intervertebral Disc; Gene Expression Profiling; Databases, Genetic; Protein Interaction Maps; Gene Regulatory Networks
PubMed: 38940022
DOI: 10.31083/j.fbl2906224 -
Frontiers in Bioscience (Scholar... Jun 2024Sickle cell disease (SCD) is a major heritable genetic disease in sub-Saharan Africa, including Mauritania. Fetal hemoglobin (HbF) can affect the pathophysiology,...
BACKGROUND
Sickle cell disease (SCD) is a major heritable genetic disease in sub-Saharan Africa, including Mauritania. Fetal hemoglobin (HbF) can affect the pathophysiology, moderate the clinical course, and offer prospects for curative treatment of SCD. This study aimed to investigate the influence of single nucleotide polymorphisms (SNPs) in the gene on the levels of HbF and hematological parameters in Mauritanian sickle cell () patients.
METHODS
Complete blood count was assessed in 565 patients suspected to have SCD. Polymerase chain reaction (PCR)-restriction fragment length polymorphism was performed to identify the , and sequencing was used for genotyping three SNPs: () and () in the intron 2 and () in the regions of the gene in 50 sickle cell patients.
RESULTS
The prevalence of HbSS among the study population was 8.8% (50/565), and the mean (± standard deviation) of HbF level was 15.0% (± 6.0%). Sequencing showed the presence of three genotypes: AA (13.6%), AG (46.6%), GG (39.6%) in rs4671393; CC (17.6%), CT (48.7%), and TT (33.6%) in . All samples from HbSS individuals displayed a wild-type genotype in the rs1052520 allele. The prevalence of minor alleles () and () were 37% and 39%, respectively. There was a statistically significant association ( = 0.034) between rs4671393 SNP and elevated HbF (mean 12.72 ± 6.26%).
CONCLUSIONS
The study of three SNPs in the locus in Mauritanian patients with SCD showed a significant association of allele with the HbF level. Further research is needed to explore additional SNPs in the locus and investigate other genetic markers reported to modulate HbF levels, such as and , to improve the management of this potentially life-threatening condition in Mauritania.
Topics: Humans; Fetal Hemoglobin; Anemia, Sickle Cell; Polymorphism, Single Nucleotide; Female; Male; Adult; Repressor Proteins; Mauritania; Genotype; Nuclear Proteins; Adolescent; Carrier Proteins; Young Adult; Child
PubMed: 38939975
DOI: 10.31083/j.fbs1602011 -
Journal of Parasitology Research 2024Human toxocariasis (HT) is a zoonotic disease with a global expansion. Contaminated soil with spp. eggs is the main source of human infection, which may lead to severe...
BACKGROUND
Human toxocariasis (HT) is a zoonotic disease with a global expansion. Contaminated soil with spp. eggs is the main source of human infection, which may lead to severe complications depending on the organs invaded by migrating larvae.
AIM
This study is aimed at eliciting the prevalence of spp. eggs in public parks in Zahedan, southeast Iran, and providing new insight into the soil contamination rate in this area using microscopic and molecular methods.
METHODS
Based on five municipal districts, 240 soil samples were collected from public parks and playgrounds in Zahedan. The modified Sheather's flotation technique was employed to isolate spp. eggs from the soil, followed by microscopic assessment and molecular evaluation of internal transcribed spacer 1 and 2 ribosomal deoxyribonucleic acid (ITS1 and 2 rDNA) using nested polymerase chain reaction (nested PCR) to identify the presence of spp. eggs. The Sanger sequence was used to differentiate the species. Subsequently, all the sequenced data were blasted and compared with other sequences available in the GenBank.
RESULTS
Out of 240 soil samples collected, 7 (2.9%) samples were identified to contain spp. eggs using Sheather's flotation and microscopic techniques. Meanwhile, 19 (7.9%) samples were positive using nested PCR. According to the Sanger sequencing analysis findings, all positive samples were contaminated with .
CONCLUSION
As evidenced by the obtained results, only species were detected in public parks and playgrounds in Zahedan; therefore, control and prevention programs against this species should be considered in human and animal communities.
PubMed: 38939904
DOI: 10.1155/2024/2132696 -
JACC. Advances Aug 2023Prior studies of COVID-19 cardiovascular sequelae include diagnoses made within 4 weeks, but the World Health Organization definition for "postacute phase" is >3 months.
BACKGROUND
Prior studies of COVID-19 cardiovascular sequelae include diagnoses made within 4 weeks, but the World Health Organization definition for "postacute phase" is >3 months.
OBJECTIVES
The purpose of this study was to determine which cardiovascular diagnoses in the postacute phase of COVID-19 are associated with SARS-CoV-2 infection.
METHODS
Retrospective cohort study of all adults in Alberta who had a positive SARS-CoV-2 reverse transcription polymerase chain reaction test between March 1, 2020 and June 30, 2021, matched (by age, sex, Charlson Comorbidity score, and test date) with controls who had a negative reverse transcription polymerase chain reaction test.
RESULTS
The 177,892 patients with laboratory confirmed SARS-CoV-2 infection (mean age 42.7 years, 49.7% female) were more likely to visit an emergency department (5.7% vs 3.3%), be hospitalized (3.4% vs 2.1%), or die (1.3% vs 0.4%) within 1 month than matched test-negative controls. After 3 months, cases were significantly more likely than controls to have an emergency department visit or hospitalization for diabetes mellitus (1.5% vs 0.7%), hypertension (0.6% vs 0.4%), heart failure (0.2% vs 0.1%), or kidney injury (0.3% vs 0.2%). In the 6,030 patients who had survived a hospitalization for COVID-19, postacute phase risks were substantially greater for diabetes mellitus (9.5% vs 3.0%, adjusted odds ratio [aOR]: 3.16 [95% CI: 2.43-4.12]), hypertension (3.5% vs 1.4%, aOR: 2.89 [95% CI: 1.97-4.23]), heart failure (2.1% vs 0.7%, aOR: 3.16 [95% CI: 1.88-5.29]), kidney injury (3.1% vs 0.8%, aOR: 2.70 [95% CI: 1.71-4.28]), bleeding (1.5% vs 0.5%, aOR: 3.40 [95% CI: 1.83-6.32]), and venous thromboembolism (0.8% vs 0.3%, aOR: 3.60 [95% CI: 1.59-8.13]).
CONCLUSIONS
Clinicians should screen COVID-19 survivors for diabetes mellitus, hypertension, heart failure, and kidney dysfunction in the postacute phase.
PubMed: 38939433
DOI: 10.1016/j.jacadv.2023.100391 -
Frontiers in Microbiology 2024This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics...
This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics as a therapeutic strategy for CRC patients with AIEC infections. Considering the pivotal role of integrons in bacterial antibiotic resistance, the frequency of class 1 and 2 integrons in AIEC isolated from CRC patients, in one of the referenced 3 gastroenterology clinics in Isfahan, Iran was examined. AIEC strains were isolated from the colorectal biopsies and their antimicrobial sensitivity was assessed using the disc diffusion method. Polymerase chain reaction (PCR) was employed to detect and . The multilocus sequence typing (MLST) method was utilized to type 10 selected isolates. Of the 150 samples, 24 were identified as AIEC, with the highest number isolated from CRC2 (33.4%) and CRC1 (29.16%), and the least from the FH group (8.3%) and control group (12.5%). in 79.2% and in 45.8% of AIEC strains were found and 41.6% of strains had both integrons. AIEC isolates with int1 exhibited the highest sensitivity to trimethoprim-sulfamethoxazole (57.9%), while those with int2 showed the highest sensitivity to ciprofloxacin (63.6%). A significant association between resistance to rifampin and integron 2 presence in AIEC isolates was observed. Furthermore, a significant correlation between integron 1 presence, invasion, survival, and replication within macrophages in AIEC strains was identified. MLST analysis revealed ST131 from CC131 with integron 1 as the most common sequence type (ST). The emergence of such strains in CRC populations poses a serious public health threat. The distribution pattern of STs varied among studied groups, with pandemic STs highlighting the importance of examining and treating patients infected with these isolates. Comprehensive prospective clinical investigations are warranted to assess the prognostic value of detecting this pathovar in CRC and to evaluate therapeutic techniques targeting drug-resistant AIECs, such as phage therapy, bacteriocins, and anti-adhesion compounds, for CRC prevention and treatment.
PubMed: 38939191
DOI: 10.3389/fmicb.2024.1366719 -
Frontiers in Microbiology 2024This study aimed to explore whether G423 could improve growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites. A total...
This study aimed to explore whether G423 could improve growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites. A total of 640 1-day-old AA broilers were randomly divided into 4 groups [Control (CON), Lac_L, Lac_H, and ABX]. Average daily gain (ADG), average daily feed intake (ADFI), feed conversion ratio (FCR), breast muscle, thigh muscle, and abdominal fat pad were removed and weighed at 42 days of age. Serum was obtained by centrifuging blood sample from jugular vein (10 mL) for determining high-density lipoprotein (HDL), total cholesterol (TC), low-density lipoprotein (LDL), and triglyceride (TG) using ELISA. The ileal contents were harvested and immediately frozen in liquid nitrogen for 16S rRNA and LC-MS analyses. Then, the results of 16S rRNA analysis were confirmed by quantitative polymerase chain reaction (qPCR). Compared with the CON group, FCR significantly decreased in the Lac_H group ( < 0.05) in 1-21 days; ADG significantly increased and FCR significantly decreased in the Lac_H group ( < 0.05) in 22-42 days. 42 days weight body and ADG significantly increased in the Lac_H group ( < 0.05) in 42 days. Abdominal fat percentage was significantly decreased by G423 ( < 0.05), the high dose of G423 significantly decreased the serum of TG, TC, and LDL level ( < 0.05), and the low dose of G423 significantly decreased the serum of TG and TC level ( < 0.05). A significant difference in microbial diversity was found among the four groups. Compared with the CON group, the abundance rates of in the Lac_H group were significantly increased ( 0.05). The global and overview maps and membrane transport in the Lac_L, Lac_H, and ABX groups significantly changed versus those in the CON group ( < 0.05). The results of LC-MS demonstrated that could significantly improve the levels of some metabolites (6-hydroxy-5-methoxyindole glucuronide, 9,10-DiHOME, -Acetyl-l-phenylalanine, and kynurenine), and these metabolites were involved in four metabolic pathways. Among them, the pathways of linoleic acid metabolism, phenylalanine metabolism, and pentose and glucuronate interconversions significantly changed ( < 0.05). G423 could ameliorate growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites.
PubMed: 38939183
DOI: 10.3389/fmicb.2024.1381756 -
Frontiers in Cellular and Infection... 2024Accurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the...
INTRODUCTION
Accurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the current study we explored the association of multiple bacterial pathogens with orthopedic infection.
METHODS
Hospitalized orthopedic patients were enrolled in a rural hospital in Qingdao, China. Wound or exudate swab samples were collected and tested for twelve bacterial pathogens with both culture and multiplex real time PCR.
RESULTS AND DISCUSSION
A total of 349 hospitalized orthopedic patients were enrolled including 193 cases presenting infection manifestations upon admission and 156 with no sign of infection. Orthopedic infection patients were mainly male (72.5%) with more lengthy hospital stay (median 15 days). At least one pathogen was detected in 42.5% (82/193) of patients with infection while 7.1% (11/156) in the patients without infection ( < 0.001). was the most prevalent causative pathogen (15.5%). Quantity dependent pathogen association with infection was observed, particularly for and , possibly indicating subclinical infection. Most of the patients with detected pathogens had a previous history of orthopedic surgery (odds ratio 2.8, = 0.038). Pathogen specific clinical manifestations were characterized. Multiplex qPCR, because of its high sensitivity, superior specificity, and powerful quantification could be utilized in combination with culture to guide antimicrobial therapy and track the progression of orthopedic infection during treatment.
Topics: Humans; Female; Male; Middle Aged; Aged; Multiplex Polymerase Chain Reaction; China; Adult; Bacteria; Bacterial Infections; Hospitalization; Aged, 80 and over; Real-Time Polymerase Chain Reaction; Hospitals, Rural
PubMed: 38938882
DOI: 10.3389/fcimb.2024.1394352 -
Frontiers in Cellular and Infection... 2024The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The...
The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The distribution and dynamics of Las within ACP are critical to understanding how the transmission, spread and infection of Las occurs within its host vector in nature. In this study, the distribution and titer changes of Las in various tissues of ACP 5 instar nymphs and adults were examined by (FISH) and real-time quantitative PCR (qPCR) techniques. Results demonstrated that 100% of ACP 5 instar nymphs and adults were infected with Las following feeding on infected plants, and that Las had widespread distribution in most of the tissues of ACP. The titers of Las within the midgut, salivary glands and hemolymph tissues were the highest in both 5 instar nymphs and adults. When compared with adults, the titers of Las in these three tissues of 5 instar nymphs were significantly higher, while in the mycetome, ovary and testes they were significantly lower than those of adults. FISH visualization further confirmed these findings. Dynamic analysis of Las demonstrated that it was present across all the developmental ages of ACP adults. There was a discernible upward trend in the presence of Las with advancing age in most tissues of ACP adults, including the midgut, hemolymph, salivary glands, foot, head, cuticula and muscle. Our findings have significant implications for the comprehensive understanding of the transmission, dissemination and infestation of Las, which is of much importance for developing novel strategies to halt the spread of Las, and therefore contribute to the efficient prevention and control of HLB.
Topics: Animals; Hemiptera; Insect Vectors; Plant Diseases; Nymph; Citrus; In Situ Hybridization, Fluorescence; Rhizobiaceae; Real-Time Polymerase Chain Reaction; Salivary Glands; Hemolymph
PubMed: 38938879
DOI: 10.3389/fcimb.2024.1408362