Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Objective: Anterior cervical discectomy and fusion (ACDF) with anterior plating is a commonly performed procedure for cervical disc diseases. While the clinical outcomes of most reported multilevel ACDF cases are excellent, symptomatic pseudarthrosis remains a challenge, often requiring revision surgeries. This study aims to present the radiological characteristics of multilevel ACDF constructs, which can be considered during intraoperative management to prevent pseudarthrosis. Methods: This retrospective cohort study included patients who underwent multilevel (3 or 4 levels) ACDF with anterior plating between June 2010 and August 2022. Patients were regularly followed at 4 months, 12 months, and then annually postoperation. Fusion rates and characteristic radiological patterns, such as the formation of bony buttresses underneath the anterior plate, were graded and evaluated. Results: A total of 163 patients were included in the study. Overall fusion rates were 26.38%, 64.34%, and 81.58% at 4-month, 1-year, and the final follow-up, respectively. Nonunions at 4-month follow-up with tightly engaged anterior plate with bony buttress formation were more likely to fuse in the later period (Buttress grade 0 vs. 1; p=0.01, odds ratio [OR], 5.70, Buttress grade 1 vs. >2; p<0.01, OR, 12.00). Conclusion This study emphasizes the significance of pseudarthrosis following multilevel ACDF. Pseudarthrosis predominantly occurs in the caudal-most segment of the construct, particularly when it terminates at C7. Constructs that are not tightly engaged and lack bony buttress formation in the caudal part of multilevel ACDF are more likely to develop pseudarthrosis.

Objective: Anterior cervical discectomy and fusion (ACDF) with anterior plating is a commonly performed procedure for cervical disc diseases. While the clinical outcomes of most reported multilevel ACDF cases are excellent, symptomatic pseudarthrosis remains a challenge, often requiring revision surgeries. This study aims to present the radiological characteristics of multilevel ACDF constructs, which can be considered during intraoperative management to prevent pseudarthrosis. Methods: This retrospective cohort study included patients who underwent multilevel (3 or 4 levels) ACDF with anterior plating between June 2010 and August 2022. Patients were regularly followed at 4 months, 12 months, and then annually postoperation. Fusion rates and characteristic radiological patterns, such as the formation of bony buttresses underneath the anterior plate, were graded and evaluated. Results: A total of 163 patients were included in the study. Overall fusion rates were 26.38%, 64.34%, and 81.58% at 4-month, 1-year, and the final follow-up, respectively. Nonunions at 4-month follow-up with tightly engaged anterior plate with bony buttress formation were more likely to fuse in the later period (Buttress grade 0 vs. 1; p=0.01, odds ratio [OR], 5.70, Buttress grade 1 vs. >2; p<0.01, OR, 12.00). Conclusion This study emphasizes the significance of pseudarthrosis following multilevel ACDF. Pseudarthrosis predominantly occurs in the caudal-most segment of the construct, particularly when it terminates at C7. Constructs that are not tightly engaged and lack bony buttress formation in the caudal part of multilevel ACDF are more likely to develop pseudarthrosis.

Objective: Anterior cervical discectomy and fusion (ACDF) with anterior plating is a commonly performed procedure for cervical disc diseases. While the clinical outcomes of most reported multilevel ACDF cases are excellent, symptomatic pseudarthrosis remains a challenge, often requiring revision surgeries. This study aims to present the radiological characteristics of multilevel ACDF constructs, which can be considered during intraoperative management to prevent pseudarthrosis. Methods: This retrospective cohort study included patients who underwent multilevel (3 or 4 levels) ACDF with anterior plating between June 2010 and August 2022. Patients were regularly followed at 4 months, 12 months, and then annually postoperation. Fusion rates and characteristic radiological patterns, such as the formation of bony buttresses underneath the anterior plate, were graded and evaluated. Results: A total of 163 patients were included in the study. Overall fusion rates were 26.38%, 64.34%, and 81.58% at 4-month, 1-year, and the final follow-up, respectively. Nonunions at 4-month follow-up with tightly engaged anterior plate with bony buttress formation were more likely to fuse in the later period (Buttress grade 0 vs. 1; p=0.01, odds ratio [OR], 5.70, Buttress grade 1 vs. >2; p<0.01, OR, 12.00). Conclusion This study emphasizes the significance of pseudarthrosis following multilevel ACDF. Pseudarthrosis predominantly occurs in the caudal-most segment of the construct, particularly when it terminates at C7. Constructs that are not tightly engaged and lack bony buttress formation in the caudal part of multilevel ACDF are more likely to develop pseudarthrosis.

Objective: Anterior cervical discectomy and fusion (ACDF) with anterior plating is a commonly performed procedure for cervical disc diseases. While the clinical outcomes of most reported multilevel ACDF cases are excellent, symptomatic pseudarthrosis remains a challenge, often requiring revision surgeries. This study aims to present the radiological characteristics of multilevel ACDF constructs, which can be considered during intraoperative management to prevent pseudarthrosis. Methods: This retrospective cohort study included patients who underwent multilevel (3 or 4 levels) ACDF with anterior plating between June 2010 and August 2022. Patients were regularly followed at 4 months, 12 months, and then annually postoperation. Fusion rates and characteristic radiological patterns, such as the formation of bony buttresses underneath the anterior plate, were graded and evaluated. Results: A total of 163 patients were included in the study. Overall fusion rates were 26.38%, 64.34%, and 81.58% at 4-month, 1-year, and the final follow-up, respectively. Nonunions at 4-month follow-up with tightly engaged anterior plate with bony buttress formation were more likely to fuse in the later period (Buttress grade 0 vs. 1; p=0.01, odds ratio [OR], 5.70, Buttress grade 1 vs. >2; p<0.01, OR, 12.00). Conclusion This study emphasizes the significance of pseudarthrosis following multilevel ACDF. Pseudarthrosis predominantly occurs in the caudal-most segment of the construct, particularly when it terminates at C7. Constructs that are not tightly engaged and lack bony buttress formation in the caudal part of multilevel ACDF are more likely to develop pseudarthrosis.

Objective: Anterior cervical discectomy and fusion (ACDF) with anterior plating is a commonly performed procedure for cervical disc diseases. While the clinical outcomes of most reported multilevel ACDF cases are excellent, symptomatic pseudarthrosis remains a challenge, often requiring revision surgeries. This study aims to present the radiological characteristics of multilevel ACDF constructs, which can be considered during intraoperative management to prevent pseudarthrosis. Methods: This retrospective cohort study included patients who underwent multilevel (3 or 4 levels) ACDF with anterior plating between June 2010 and August 2022. Patients were regularly followed at 4 months, 12 months, and then annually postoperation. Fusion rates and characteristic radiological patterns, such as the formation of bony buttresses underneath the anterior plate, were graded and evaluated. Results: A total of 163 patients were included in the study. Overall fusion rates were 26.38%, 64.34%, and 81.58% at 4-month, 1-year, and the final follow-up, respectively. Nonunions at 4-month follow-up with tightly engaged anterior plate with bony buttress formation were more likely to fuse in the later period (Buttress grade 0 vs. 1; p=0.01, odds ratio [OR], 5.70, Buttress grade 1 vs. >2; p<0.01, OR, 12.00). Conclusion This study emphasizes the significance of pseudarthrosis following multilevel ACDF. Pseudarthrosis predominantly occurs in the caudal-most segment of the construct, particularly when it terminates at C7. Constructs that are not tightly engaged and lack bony buttress formation in the caudal part of multilevel ACDF are more likely to develop pseudarthrosis.

Intervertebral disc (IVD) degeneration is the main source of intractable lower back pain, and symptomatic IVD degeneration could be due to different degeneration mechanisms. In this article, we describe the molecular basis of symptomatic IVD degenerative disc diseases (DDDs), emphasizing the role of degeneration, inflammation, angiogenesis, and extracellular matrix (ECM) regulation during this process. In symptomatic DDD, pro-inflammatory mediators modulate catabolic reactions, resulting in changes in ECM homeostasis and, finally, neural/vascular ingrowth-related chronic intractable discogenic pain. In ECM homeostasis, anabolic protein-regulating genes show reduced expression and changes in ECM production, while matrix metalloproteinase gene expression increases and results in aggressive ECM degradation. The resultant loss of normal IVD viscoelasticity and a concomitant change in ECM composition are key mechanisms in DDDs. During inflammation, a macrophage-related cascade is represented by the secretion of high levels of pro-inflammatory cytokines, which induce inflammation. Aberrant angiogenesis is considered a key initiative pathologic step in symptomatic DDD. In reflection of angiogenesis, vascular endothelial growth factor expression is regulated by hypoxia-inducible factor-1 in the hypoxic conditions of IVDs. Furthermore, IVD cells undergoing degeneration potentially enhance neovascularization by secreting large amounts of angiogenic cytokines, which penetrate the IVD from the outer annulus fibrosus, extending deep into the outer part of the nucleus pulposus. Based on current knowledge, a multi-disciplinary approach is needed in all aspects of spinal research, starting from basic research to clinical applications, as this will provide information regarding treatments for DDDs and discogenic pain.

Severe bacterial infections are frequently accompanied by depressed neutrophil functions. Thus, agents that increase the microbicidal activity of neutrophils could add to a direct antimicrobial therapy. Lysophosphatidylcholine augments neutrophil bactericidal activity via the glycine (Gly)/glycine receptor (GlyR) α2/ TRPM2/p38 mitogen-activated protein kinase (MAPK) pathway. However, the direct effect of glycine on neutrophil bactericidal activity was not reported. In this study, the effect of glycine on neutrophil bactericidal activity was examined. Glycine augmented bactericidal activity of human neutrophils (EC50 = 238 μM) in a strychnine (a GlyR antagonist)-sensitive manner. Glycine augmented bacterial clearance in mice, which was also blocked by strychnine (0.4 mg/kg, s.c.). Glycine enhanced NADPH oxidase-mediated reactive oxygen species (ROS) production and TRPM2-mediated [Ca2+ ]i increase in neutrophils that had taken up E. coli. Glycine augmented Lucifer yellow uptake (fluid-phase pinocytosis) and azurophil granule-phagosome fusion in neutrophils that had taken up E. coli in an SB203580 (a p38 MAPK inhibitor)-sensitive manner. These findings indicate that glycine augments neutrophil microbicidal activity by enhancing azurophil granule-phagosome fusion via the GlyRα2/ROS/calcium/ p38 MAPK pathway. We suggest that glycine could be a useful agent for increasing neutrophil bacterial clearance.