Search Results (19)

With the concurrent circulations of SARS-CoV-2 omicron and influenza A viruses in the community, there is evidence showing co-infection with both viruses. However, disease severity may vary due to the complex immunity landscape of the patients and the neutralizing antibody waning status. The intrinsic dynamic relationship and pathological significance for such co-infections remain largely unknown. The replication kinetics and innate immune responses from the co-infections of SARS-CoV-2 (Omicron BA.1 and D614G variant) and influenza A viruses (pandemic H1N1, seasonal H3N2 and highly pathogenic avian H5N1) were characterized in human respiratory tissue explants, human airway, and alveolar epithelial cells. SARS-CoV-2 reduced the replication of influenza A viruses, but not vice versa, during co-infections in human bronchial tissues and airway epithelial cells. In lung tissues, the co-infections showed minimal effects on each other, but the viral replications of the two viruses were mutually reduced except for H1N1pdm in the alveolar epithelial cells irrespective of the enhancement of the ACE2 receptor. Notably, the co-infections showed a significant upregulation of the innate immune responses of SARS-CoV-2 in comparison to single infections in both respiratory epithelial cells, suggesting that co-infections of influenza A viruses potentially lead to more severe damage to the host than SARS-CoV-2 single infections. Full article

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings. Full article

Background: The COVID-19 pandemic from 2019 to 2022 devastated many aspects of life and the economy, with the commercial aviation industry being no exception. One of the major concerns during the pandemic was the degree to which the internal aircraft environment contributed to virus transmission between humans and, in particular, the stability of SARS-CoV-2 on contact surfaces in the aircraft cabin interior. Method: In this study, the stability of various major strains of SARS-CoV-2 on interior aircraft surfaces was evaluated using the TCID₅₀ assessment. Results: In contrast to terrestrial materials, SARS-CoV-2 was naturally less stable on common contact points in the aircraft interior, and, over a 4 h time period, there was a 90% reduction in culturable virus. Antiviral and surface coatings were extremely effective at mitigating the persistence of the virus on surfaces; however, their benefit was diminished by regular cleaning and were ineffective after 56 days of regular use and cleaning. Finally, successive strains of SARS-CoV-2 have not evolved to be more resilient to survival on aircraft surfaces. Conclusions: We conclude that the mitigation strategies for SARS-CoV-2 on interior aircraft surfaces are more than sufficient, and epidemiological evidence over the past three years has not found that surface spread is a major route of transmission. Full article

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients. Full article

Purpose: Bladder cancer (BCa) is one of the most common cancer types worldwide and is characterized by a high rate of recurrence. In previous studies, we and others have described the functional influence of plasminogen activator inhibitor-1 (PAI1) in bladder cancer development. While polymorphisms in PAI1 have been associated with increased risk and worsened prognosis in some cancers, the mutational status of PAI1 in human bladder tumors has not been well defined. Methods: In this study, we evaluated the mutational status of PAI1 in a series of independent cohorts, comprised of a total of 660 subjects. Results: Sequencing analyses identified two clinically relevant 3′ untranslated region (UTR) single nucleotide polymorphisms (SNPs) in PAI1 (rs7242; rs1050813). Somatic SNP rs7242 was present in human BCa cohorts (overall incidence of 72%; 62% in Caucasians and 72% in Asians). In contrast, the overall incidence of germline SNP rs1050813 was 18% (39% in Caucasians and 6% in Asians). Furthermore, Caucasian patients with at least one of the described SNPs had worse recurrence-free survival and overall survival (p = 0.03 and p = 0.03, respectively). In vitro functional studies demonstrated that SNP rs7242 increased the anti-apoptotic effect of PAI1, and SNP rs1050813 was related to a loss of contact inhibition associated with cellular proliferation when compared to wild type. Conclusion: Further investigation of the prevalence and potential downstream influence of these SNPs in bladder cancer is warranted. Full article

COVID-19, caused by SARS-CoV-2, created a devastating outbreak worldwide and consequently became a global health concern. However, no verifiable, specifically targeted treatment has been devised for COVID-19. Several emerging vaccines have been used, but protection has not been satisfactory. The complex genetic composition and high mutation frequency of SARS-CoV-2 have caused an uncertain vaccine response. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control various infectious diseases employing post-transcriptional gene silencing through the silencing of target complementary mRNA. Here, we designed two highly effective shRNAs targeting the conserved region of RNA-dependent RNA polymerase (RdRP) and spike proteins capable of significant SARS-CoV-2 replication suppression. The efficacy of this approach suggested that the rapid development of an shRNA-based therapeutic strategy might prove to be highly effective in treating COVID-19. However, it needs further clinical trials. Full article

Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease (ESRD) patients, and it can suppress erythropoiesis. We aimed to investigate the relationship between the consumption of erythropoiesis-stimulating agents (ESAs) and parathyroidectomy (PTX) in ESRD patients with SHPT and to determine the predictors for anemia improvement. The current standard of chronic kidney disease anemia therapy relies on the prescription of iron supplementation, and ESA. We retrospectively analyzed 81 ESRD patients with PTX at Ditmanson Medical Foundation Chiayi Christian Hospital from July 2004 to Dec 2018. The requirement of ESA therapy markedly declined from a dose of 41.6 (interquartile range [IQR], 0–91.2) to 10.3 (IQR, 0–59.5, p = 0.001) unit/kg/week. In addition, 63.7% of patients required iron replacement therapy preoperatively and the proportion reduced to 52.5% after PTX (p < 0.001). The hemoglobin (Hb) level showed an insignificant change from a median value of 10.7 g/dL (9.5–11.6 g/dL) before PTX to 10.5 g/dL (9.6–11.2 g/dL) at 6 months after PTX. A preoperative Hb level ≤ 10 mg/dL (odds ratio [OR], 20.1; 95% confidence interval [CI], 4.71–125, p < 0.001) and transferrin saturation (TSAT) < 25% (OR, 12.8; 95% CI, 2.51–129, p < 0.001) were predictors for anemia improvement. Our study demonstrated that PTX markedly decreased the requirement of ESA. Patients with a low preoperative Hb level or low TSAT showed an increase in the Hb level after PTX. PTX may be considered not only for SHPT with refractory anemia but also for high ESA-dependent patients. Full article

MicroRNAs (miRNAs) play an important role in gene regulation by degradation or translational inhibition of the targeted mRNAs. It has been experimentally shown that the way miRNAs interact with their targets can be used to explain the indirect interactions among their targets, i.e., competing endogenous RNA (ceRNA). However, whether the protein translated from the targeted mRNAs can play any role in this ceRNA network has not been explored. Here we propose a deterministic model to demonstrate that in a network of one miRNA interacting with multiple-targeted mRNAs, the competition between miRNA-targeted mRNAs is not sufficient for the significant change of those targeted mRNA levels, while dramatic changes of these miRNA-targeted mRNAs require transcriptional inhibition of miRNA by its target proteins. When applied to estrogen receptor signaling pathways, the miR-193a targets E2F6 (a target of estrogen receptor), c-KIT (a marker for cancer stemness), and PBX1 (a transcriptional activator for immunosuppressive cytokine, IL-10) in ovarian cancer, such that epigenetic silencing of miR-193a by E2F6 protein is required for the significant change of c-KIT and PBX1 mRNA level for cancer stemness and immunoevasion, respectively, in ovarian cancer carcinogenesis Full article

Recently developed non-invasive environmental DNA-based (eDNA) techniques have enlightened modern conservation biology, propelling the monitoring/management of natural populations to a more effective and efficient approach, compared to traditional surveys. However, due to rapid-expansion of eDNA, confusion in terminology and collection/analytical pipelines can potentially jeopardize research progression, methodological standardization, and practitioner adoption in several ways. Present investigation reflects the developmental progress of eDNA (sensu stricto) including highlighting the successful case studies in conservation management. The eDNA technique is successfully relevant in several areas of conservation research (invasive/conserve species detection) with a high accuracy and authentication, which gradually upgrading modern conservation approaches. The eDNA technique related bioinformatics (e.g., taxon-specific-primers MiFish, MiBird, etc.), sample-dependent methodology, and advancement of sequencing technology (e.g., oxford-nanopore-sequencing) are helping in research progress. The investigation shows that the eDNA technique is applicable largely in (i) early detection of invasive species, (ii) species detection for conservation, (iii) community level biodiversity monitoring, (iv) ecosystem health monitoring, (v) study on trophic interactions, etc. Thus, the eDNA technique with a high accuracy and authentication can be applicable alone or coupled with traditional surveys in conservation biology. However, a comprehensive eDNA-based monitoring program (ecosystem modeling and function) is essential on a global scale for future management decisions. Full article

Fermented fruits and vegetables play an important role in safeguarding food security world-wide. Recently, robust sequencing-based microbial community analysis platforms have improved microbial safety assessment. This study aimed to examine the composition of bacteria and evaluate the bacterial safety of fermented fruit products using high-throughput 16S-rRNA metagenomic analysis. The operational taxonomic unit-based taxonomic classification of DNA sequences revealed 53 bacterial genera. However, the amplicon sequencing variant (ASV)-based clustering revealed 43 classifiable bacterial genera. Taxonomic classifications revealed that the abundance of Sphingomonas, which was the predominant genus in the majority of tested samples, was more than 85–90% among the total identified bacterial community in most samples. Among these identified genera, 13 low abundance genera were potential opportunistic pathogens, including Acinetobacter, Bacillus, Staphylococcus, Clostridium, Klebsiella, Mycobacterium, Ochrobactrum, Chryseobacterium, Stenotrophomonas, and Streptococcus. Of these 13 genera, 13 major opportunistic pathogenic species were validated using polymerase chain reaction. The pathogens were not detected in the samples of different stages and the final products of fermentation, except in one sample from the first stage of fermentation in which S. aureus was detected. This finding was consistent with that of ASV-based taxonomic classification according to which S. aureus was detected only in the sample from the first stage of fermentation. However, S. aureus was not significantly correlated with the human disease pathways. These results indicated that fermentation is a reliable and safe process as pathogenic bacteria were not detected in the fermentation products. The hybrid method reported in this study can be used simultaneously to evaluate the bacterial diversity, their functional predictions and safety assessment of novel fermentation products. Additionally, this hybrid method does not involve the random detection of pathogens, which can markedly decrease the time of detection and food safety verification. Furthermore, this hybrid method can be used for the quality control of products and the identification of external contamination. Full article

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer. Full article

Breast cancer is one of the leading causes of death among cancer patients worldwide. To date, there are several drugs that have been developed for breast cancer therapy. In the 21st century, immunotherapy is considered a pioneering method for improving the management of malignancies; however, breast cancer is an exception. According to the immunoediting model, many immunosuppressive cells contribute to immunological quiescence. Therefore, there is an urgent need to enhance the therapeutic efficacy of breast cancer treatments. In the last few years, numerous combinatorial therapies involving immune checkpoint blockade have been demonstrated that effectively improve clinical outcomes in breast cancer and combining these with methods of targeting epigenetic regulators is also an innovative strategy. Nevertheless, few studies have discussed the benefits of epi-drugs in non-cancerous cells. In this review, we give a brief overview of ongoing clinical trials involving combinatorial immunotherapy with epi-drugs in breast cancer and discuss the role of epi-drugs in the tumor microenvironment, including the results of recent research. Full article

Gastric cancer (GC) is among the most treatment-refractory epithelial malignancies. Aberrant activation of Wnt/β-catenin-signaling has been implicated in a variety of human cancers, including gastric cancer. Here we report that the elevated expression of lymphoid enhancer binding factor 1 (Lef1) is associated with the TNM (tumor– node–metastasis) stage of gastric cancer. Subsequently, 2,4-diamino-quinazoline (2,4-DAQ), a selective inhibitor of Lef1, was identified to suppress the expression of Wnt/β-catenin target genes such as AXIN2, MYC and LGR5 and result in the suppression of gastric cancer cell growth through the apoptotic pathway. The 2,4-DAQ also exhibited an inhibitory effect on the migration/invasion of gastric cancer cells. Importantly, the treatment of human gastric tumor xenograft with 2,4-DAQ suppressed tumor growth in a nude mouse model. Furthermore, 2,4-DAQ appears effective on patient-derived organoids (PDOs). Transcriptome sequencing analysis also revealed that 2,4-DAQ are more effective on the gastric cancers that exhibit higher expression levels of Wnt-signaling pathway-related genes than their adjacent normal gastric tissues. Full article

MicroRNAs (miRNAs) have been shown to play a crucial role in the progression of human cancers, including urothelial carcinoma (UC), the sixth-most common cancer in the world. Among them, miR-34a has been implicated in the regulation of cancer stem cells (CSCs); however, its role in UC has yet to be fully elucidated. In this study, bioinformatics and experimental analysis confirmed that miR-34a targets CD44 (a CSC surface marker) and c-Myc (a well-known cell cycle regulator) in UC. We found that, surprisingly, most UC cell lines and patient samples did express miR-34a, although epigenetic silencing by promoter hypermethylation of miR-34a expression was observed only in UMUC3 cells, and a subset of patient samples. Importantly, overexpression of c-Myc, a frequently amplified oncogene in UC, was shown to upregulate CD44 expression through a competing endogenous RNA (ceRNA) mechanism, such that overexpression of the c-Myc 3′UTR upregulated CD44, and vice versa. Importantly, we observed a positive correlation between the expression of c-Myc and CD44 in clinical samples obtained from UC patients. Moreover, overexpression of a dominant-negative p53 mutant downregulated miR-34a, but upregulated c-Myc and CD44, in UC cell lines. Functionally, the ectopic expression of miR-34a was shown to significantly suppress CD44 expression, and subsequently, suppression of cell growth and invasion capability, while also reducing chemoresistance. In conclusion, it appears that aberrant promoter methylation, and c-Myc-mediated ceRNA mechanisms, may attenuate the function of miR-34a, in UC. The tumor suppressive role of miR-34a in controlling CSC phenotypes in UC deserves further investigation. Full article