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International Journal of Medical... 2024The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions....
The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions. This study investigates the role of UPRmt in modulating the response of nasopharyngeal carcinoma cells to cisplatin-induced stress. We report that the inhibition of UPRmt via AEB5F exacerbates cisplatin cytotoxicity, as evidenced by increased lactate dehydrogenase (LDH) release and apoptosis, characterized by a surge in TUNEL-positive cells. Conversely, the activation of UPRmt with oligomycin attenuates these effects, preserving cell viability and reducing apoptotic markers. Immunofluorescence assays reveal that UPRmt activation maintains mitochondrial membrane potential and ATP production in the presence of cisplatin, countering the rise in reactive oxygen species (ROS) and inhibiting caspase-9 activation. These findings suggest that UPRmt serves as a cytoprotective mechanism in cancer cells, mitigating cisplatin-induced mitochondrial dysfunction and apoptosis. The data underscore the therapeutic potential of modulating UPRmt to improve the efficacy and reduce the side effects of cisplatin chemotherapy. This study provides a foundation for future research on the exploitation of UPRmt in cancer treatment, with the aim of enhancing patient outcomes by leveraging the cellular stress response pathways.
Topics: Humans; Unfolded Protein Response; Mitochondria; Cisplatin; Apoptosis; Cell Line, Tumor; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Antineoplastic Agents; Cell Survival
PubMed: 38818479
DOI: 10.7150/ijms.95624 -
Frontiers in Bioscience (Landmark... May 2024Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the... (Review)
Review
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.
Topics: Humans; PTEN Phosphohydrolase; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; MicroRNAs; Tumor Microenvironment; Cell Proliferation; Apoptosis; Gene Expression Regulation, Neoplastic; RNA, Long Noncoding; Autophagy; Cell Movement; RNA, Circular; Herpesvirus 4, Human; Signal Transduction
PubMed: 38812313
DOI: 10.31083/j.fbl2905179 -
BMC Infectious Diseases May 2024Human adenoviruses (HAdVs) are a diverse group of viruses associated with respiratory infections in humans worldwide. However, there is a lack of research on the genetic...
Human adenoviruses (HAdVs) are a diverse group of viruses associated with respiratory infections in humans worldwide. However, there is a lack of research on the genetic diversity and epidemiology of HAdVs in Pakistan. This study characterized HAdVs in pediatric patients with respiratory tract infections in Karachi, Pakistan, between 2022 and 2023. We analyzed 762 nasopharyngeal samples of children ≤ 5 years. DNA extraction, followed by PCR targeting E2B and hexon genes, was carried out. Data analysis was performed on SPSS 25.0, and phylogenetic analysis of hexon gene was performed on MEGA 11. HAdV was detected in 7.34% (56/762) of patients round the year, but at a significantly higher rate during the winter season. Age was insignificantly associated with HAdV incidence (p = 0.662), but more than 62.5% (35/56) of positive cases were younger than 10 months. The circulating HAdVs were identified as six different types from species B (78.57%) and C (21.42%), with the majority of isolates found to be like B3. HAdV was found to be co-infected with bocavirus (5.4%) and measles (7.14%). These findings revealed a high frequency and genetic diversity of respiratory HAdVs in Karachi, Pakistan. We conclude that periodic and continuous surveillance of adenoviruses and other respiratory pathogens is necessary to improve the prognosis and management of respiratory diseases, thereby reducing the child mortality rate in Pakistan.
Topics: Humans; Pakistan; Adenoviruses, Human; Respiratory Tract Infections; Child, Preschool; Infant; Phylogeny; Male; Female; Adenovirus Infections, Human; Nasopharynx; Genetic Variation; Infant, Newborn; Coinfection; DNA, Viral; Seasons; Genotype
PubMed: 38811902
DOI: 10.1186/s12879-024-09415-9 -
Technology in Cancer Research &... 2024Intensity-modulated radiotherapy (IMRT) is currently the most important treatment method for nasopharyngeal carcinoma (NPC). This study aimed to enhance prediction...
Deep Learning-Based Prediction of Radiation Therapy Dose Distributions in Nasopharyngeal Carcinomas: A Preliminary Study Incorporating Multiple Features Including Images, Structures, and Dosimetry.
Intensity-modulated radiotherapy (IMRT) is currently the most important treatment method for nasopharyngeal carcinoma (NPC). This study aimed to enhance prediction accuracy by incorporating dose information into a deep convolutional neural network (CNN) using a multichannel input method. A target conformal plan (TCP) was created based on the maximum planning target volume (PTV). Input data included TCP dose distribution, images, target structures, and organ-at-risk (OAR) information. The role of target conformal plan dose (TCPD) was assessed by comparing the TCPD-CNN (with dose information) and NonTCPD-CNN models (without dose information) using statistical analyses with the ranked Wilcoxon test ( < .05 considered significant). The TCPD-CNN model showed no statistical differences in predicted target indices, except for PTV60, where differences in the D98% indicator were < 0.5%. For OARs, there were no significant differences in predicted results, except for some small-volume or closely located OARs. On comparing TCPD-CNN and NonTCPD-CNN models, TCPD-CNN's dose-volume histograms closely resembled clinical plans with higher similarity index. Mean dose differences for target structures (predicted TCPD-CNN and NonTCPD-CNN results) were within 3% of the maximum prescription dose for both models. TCPD-CNN and NonTCPD-CNN outcomes were 67.9% and 54.2%, respectively. 3D gamma pass rates of the target structures and the entire body were higher in TCPD-CNN than in the NonTCPD-CNN models ( < .05). Additional evaluation on previously unseen volumetric modulated arc therapy plans revealed that average 3D gamma pass rates of the target structures were larger than 90%. This study presents a novel framework for dose distribution prediction using deep learning and multichannel input, specifically incorporating TCPD information, enhancing prediction accuracy for IMRT in NPC treatment.
Topics: Humans; Deep Learning; Nasopharyngeal Carcinoma; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Nasopharyngeal Neoplasms; Organs at Risk; Radiometry; Neural Networks, Computer
PubMed: 38808514
DOI: 10.1177/15330338241256594 -
BMC Infectious Diseases May 2024As SARS-CoV-2 continues to be relevant and cause illnesses, the effect of emerging virus variants on perinatal health remains to be elucidated. It was demonstrated that...
BACKGROUND
As SARS-CoV-2 continues to be relevant and cause illnesses, the effect of emerging virus variants on perinatal health remains to be elucidated. It was demonstrated that vertical transmission of SARS-CoV-2 is a relatively rare event in the original SARS-CoV-2 strain. However, very few reports describe vertical transmission related to the delta-variant.
CASE PRESENTATION
We report a case of a preterm male neonate born to a mother with positive SARS-CoV-2 and mild respiratory complications. The neonate was born by cesarean section due to fetal distress. The rupture of the amniotic membrane was at delivery. The neonate had expected prematurity-related complications. His nasopharyngeal swabs for RT-PCR were positive from birth till three weeks of age. RT-ddPCR of the Placenta showed a high load of the SARS-CoV-2 virus with subgenomic viral RNA. RNAscope technique demonstrated both the positive strand of the S gene and the orf1ab negative strand. Detection of subgenomic RNA and the orf1ab negative strand indicats active viral replication in the placenta.
CONCLUSIONS
Our report demonstrates active viral replication of the SARS-CoV-2 delta-variant in the placenta associated with vertical transmission in a preterm infant.
Topics: Humans; Infectious Disease Transmission, Vertical; COVID-19; Infant, Newborn; SARS-CoV-2; Female; Pregnancy; Male; Infant, Premature; Pregnancy Complications, Infectious; Placenta; Adult; RNA, Viral; Cesarean Section
PubMed: 38807052
DOI: 10.1186/s12879-024-09420-y -
Scientific Reports May 2024Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and...
Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.
Topics: Humans; Biomarkers, Tumor; Prognosis; Head and Neck Neoplasms; Immunotherapy; Procollagen-Proline Dioxygenase; Gene Expression Regulation, Neoplastic; Female; Male; Nasopharyngeal Carcinoma
PubMed: 38806556
DOI: 10.1038/s41598-024-62678-9 -
Cancer Science May 2024Because of the common physical condition, reduced organ function, and comorbidities, elderly patients with nasopharyngeal carcinoma (NPC) are often underrepresented in...
Because of the common physical condition, reduced organ function, and comorbidities, elderly patients with nasopharyngeal carcinoma (NPC) are often underrepresented in clinical trials. The optimal treatment of elderly patients with locally advanced NPC remains unclear. The purpose of this study was to evaluate the efficacy of concurrent nimotuzumab combined with intensity-modulated radiotherapy (IMRT) in elderly patients with locally advanced NPC. We conducted a single-arm, phase II trial for elderly patients with stage III-IVA NPC (according to UICC-American Joint Committee on Cancer TNM classification, 8th edition). All patients received concurrent nimotuzumab (200 mg/week, 1 week prior to IMRT) combined with IMRT. The primary end-point was complete response (CR) rate. The secondary end-points were survival, safety, and geriatric assessment. Between March 13, 2017 and November 12, 2018, 30 patients were enrolled. In total, 20 (66.7%) patients achieved CR, and objective response was observed in 30 (100.0%) patients 1 month after radiotherapy. The median follow-up time was 56.05 months (25th-75th percentile, 53.45-64.56 months). The 5-year locoregional relapse-free survival, distant metastasis-free survival, cancer-specific survival, disease-free survival, and overall survival were 89.4%, 86.4%, 85.9%, 76.5%, and 78.8%, respectively. Grade 3 mucositis occurred in 10 (33%) patients and grade 3 pneumonia in 3 (10%) patients. Concurrent nimotuzumab combined with IMRT is effective and well-tolerated for elderly patients with locally advanced NPC.
PubMed: 38806289
DOI: 10.1111/cas.16213 -
Journal of Ayurveda and Integrative... May 2024Shyonaka (Oroxylum indicum Vent) is widely used in Ayurveda and in ethnomedical practice for the treatment of inflammation, pain, diarrhea, non-healing ulcers, and...
BACKGROUND
Shyonaka (Oroxylum indicum Vent) is widely used in Ayurveda and in ethnomedical practice for the treatment of inflammation, pain, diarrhea, non-healing ulcers, and cancer. Owing to the high prevalence of Epstein-Barr virus (EBV) infection in Nasopharyngeal carcinoma (NPC) patients, simultaneous targeting of proteins involved in both EBV replication and NPC proliferation might help to manage the disease effectively.
OBJECTIVES
This study is designed to identify potential dual targeting inhibitors from Oroxylum indicum having the potential to inhibit both EBV and NPC. This study also attempted quantitative analysis of Shyonaka Bark Decoction (SBD) to confirm the presence of Baicalein and Chrysin which are predominant marker compounds of Shyonaka.
METHODOLOGY
The HPLC analysis of stem bark and root bark of Oroxylum indicum was done to estimate the presence of marker compounds Baicalein and Chrysalin. The in-silico analysis included ADMET analysis followed by molecular docking of known compounds from Oroxylum indicum (retrieved from IMPPAT database) onto the target proteins of EBV (BHRF1, NEC1, dUTPase, Uracil DNA glycosylase) and NPC (COX-2, EGFR, and MDM2) using DOCK6 tool. Further validations were done using the molecular dynamics simulations of top screened molecules onto the selected target proteins using AMBER20 package and their corresponding MMGBSA binding free-energy values were calculated.
RESULTS
The molecular docking revealed that the key molecules from the plant, scutellarein 7-rutinoside (S7R), scutellarin (SCU) and 6-hydroxyluteolin, Baicalein and 5,7-Dihydroxy-2-phenyl-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one (57D) are effectively intervening with the target proteins of EBV, one of the key causative factors of NPC and the NPC specific targets which have the potential to reduce tumor size and other consequences of NPC. The molecular dynamics simulations of S7R, Baicalein and 57D, Baicalein with MDM-2 protein and dUTPase protein, respectively, showed stable interactions between them which were further assessed by the binding energy calculations.
CONCLUSION
Overall, the in-silico evaluation of these phytochemicals with target proteins indicates their potential to inhibit both EBV and NPC which needs further in-vitro and in-vivo validations.
PubMed: 38805854
DOI: 10.1016/j.jaim.2024.100986 -
Frontiers in Cellular and Infection... 2024Acute respiratory infections (ARI) are the most common infections in the general population and are mainly caused by respiratory viruses. Detecting several viruses in a...
INTRODUCTION
Acute respiratory infections (ARI) are the most common infections in the general population and are mainly caused by respiratory viruses. Detecting several viruses in a respiratory sample is common. To better understand these viral codetections and potential interferences, we tested for the presence of viruses and developed quantitative PCR (Polymerase Chain Reaction) for the viruses most prevalent in coinfections: human rhinovirus (HRV) and respiratory syncytial virus (RSV), and quantified their viral loads according to coinfections and health status, age, cellular abundance and other variables.
MATERIALS AND METHODS
Samples from two different cohorts were analyzed: one included hospitalized infants under 12 months of age with acute bronchiolitis (n=719) and the other primary care patients of all ages with symptoms of ARI (n=685). We performed Multiplex PCR on nasopharyngeal swabs, and quantitative PCR on samples positive for HRV or/and RSV to determine viral loads (VL). Cellular abundance (CA) was also estimated by qPCR targeting the GAPDH gene. Genotyping was performed either directly from first-line molecular panel or by PCR and sequencing for HRV.
RESULTS
The risks of viral codetection were 4.1 (IC[1.8; 10.0]) and 93.9 1 (IC[48.7; 190.7]) higher in infants hospitalized for bronchiolitis than in infants in primary care for RSV and HRV respectively (p<0.001). CA was higher in samples positive for multiple viruses than in mono-infected or negative samples (p<0.001), and higher in samples positive for RSV (p<0.001) and HRV (p<0.001) than in negative samples. We found a positive correlation between CA and VL for both RSV and HRV. HRV VL was higher in children than in the elderly (p<0.05), but not RSV VL. HRV VL was higher when detected alone than in samples coinfected with RSV-A and with RSV-B. There was a significant increase of RSV-A VL when codetecting with HRV (p=0.001) and when co-detecting with RSV-B+HRV versus RSV-A+ RSV-B (p=0.02).
CONCLUSIONS
Many parameters influence the natural history of respiratory viral infections, and quantifying respiratory viral loads can help disentangle their contributions to viral outcome.
Topics: Humans; Viral Load; Coinfection; Infant; Respiratory Tract Infections; Female; Child, Preschool; Male; Rhinovirus; Child; Health Status; Adult; Respiratory Syncytial Virus Infections; Adolescent; Middle Aged; Respiratory Syncytial Virus, Human; Nasopharynx; Infant, Newborn; Young Adult; Aged; Real-Time Polymerase Chain Reaction; Acute Disease; Genotype; Multiplex Polymerase Chain Reaction; Aged, 80 and over
PubMed: 38803572
DOI: 10.3389/fcimb.2024.1380855 -
Computational and Structural... Dec 2024Since Epstein-Barr virus (EBV) was discovered in 1964, it has been reported to be associated with various malignancies as well as benign diseases, and the pathogenicity...
Since Epstein-Barr virus (EBV) was discovered in 1964, it has been reported to be associated with various malignancies as well as benign diseases, and the pathogenicity of EBV has been widely studied. Several databases have been established to provide comprehensive information on the virus and its relation to diseases and introduce convenient analysis tools. Although they have greatly facilitated the analysis of EBV at the genome, gene, protein, or epitope level, they did not provide enough insight into the genomic variants of EBV, which have been suggested as relevant to diseases by multiple studies. Here, we introduce dbEBV, a comprehensive database of EBV genomic variation landscape, which contains 942 EBV genomes with 109,893 variants from different tissues or cell lines in 24 countries. The database enables the visualization of information with varying global frequencies and their relationship with the human health of each variant. It also supports phylogenetic analysis at the genome or gene level in subgroups of different characteristics. Information of interest can easily be reached with functions such as searching, browsing, and filtering. In conclusion, dbEBV is a convenient resource for exploring EBV genomic variants, freely available at http://dbebv.omicsbio.info.
PubMed: 38803518
DOI: 10.1016/j.csbj.2024.04.043