Objectives: Human papillomavirus (HPV) is a major cause of cervical cancer, which is the second most common cancer in women. HPV E6 initiates degradation of cellular tumor suppressor protein p53, induces human telomerase reverse transcriptase (hTERT) activity, and then leads to progressive cervical carcinogenesis. Methods:Results: The positivity for the HPV E6/E7 messenger RNA (mRNA) assay was 94. 4%, 95.2%, 82.4%, 46.5%, 25.0%, and 1.1% in squamous cell carcinomas,, atypical squamous cellscannot exclude HSIL, low-grade squamous intraepithelial lesions, atypical squamous cells of undetermined significance, and normal cytology samples, respectively. Five cervical intraepithelial neoplasia grade 2+ samples were not detected by the HPV E6/E7 mRNA assay, but they exhibited positive signals in the hTERT mRNA assay. Notably, the hTERT mRNA expression level was increased in high-grade cervical lesions but was very low in all 288 normal samples. Conclusions:These data suggest that the combination of HPV E6/E7 and hTERT mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions and malignant tumors and might be useful as a predictive marker in monitoring low-grade cervical lesions.Cervical cancer, which develops from cervical intraepithelial neoplasia (CIN), is the second most common malignancy in women worldwide and is a major cause of morbidity and mortality. 1 While the overall incidence of cervical cancer is declining, 493,000 new cases and 274,000 deaths occur each year. 2 Human papillomavirus (HPV) is the most common sexually transmitted pathogen among women and men, and it has been estimated that 70% of sexually active women will acquire an HPV infection at some point during their lifetime. HPVs are small double-stranded DNA viruses that infect basal cells and replicate within the nucleus of squamous epithelial cells. 3 Cervical cancer is caused by persistent infection with oncogenic HPV genotypes that belong to a few phylogenetically related high-risk (HR) species. Some HPV genotypes are able to infect cutaneous tissues, resulting in the formation of warts on the hands or feet, while others infect the oral mucosa. HPV genotypes that infect the genital epithelia are well characterized and can be grouped as HR species because of their association with cervical cancer. As a result, testing for oncogenic HPV infection in cervical lesions could serve as an accurate means of identifying women who are at risk for developing cervical cancer. HR HPV genotypes, including 16, 18, 33, 45, 52, 58, 39, 51, 56, and 59, are detected in more than 90% of cervical cancer cases. 4 The HR HPV genotypes express two major transforming genes that code for the E6 and E7 proteins, which are required for the immortalization of human primary genital keratinocytes. 5 These two oncogenes are uniformly retained and highly expressed in cervical cancer cells, and their continuous expression is required for retention of

Mycobacteria cause a variety of illnesses that differ in severity and public health implications. The differentiation of Mycobacterium tuberculosis (MTB) from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. The diagnosis of diseases caused by NTM is difficult because NTM species are prevalent in the environment and because they have fastidious properties. In the present study, we evaluated 279 clinical isolates grown in liquid culture provided by The Catholic University of Korea, St. Vincent's Hospital using real-time PCR based on mycobacterial rpoB gene sequences. The positive rate of real-time PCR assay accurately discriminated 100% (195/195) and 100% (84/84) between MTB and NTM species. Comparison of isolates identified using the MolecuTech REBA Myco-ID(®) and Real Myco-ID® were completely concordant except for two samples. Two cases that were identified as mixed infection (M. intracellulare-M. massiliense and M. avium-M. massiliense co-infection) by PCRREBA assay were only detected using M. abscessus-specific probes by Real Myco-ID(®). Among a total of 84 cases, the most frequently identified NTM species were M. intracellulare (n=38, 45.2%), M. avium (n=18, 23.7%), M. massiliense (n=10, 13.2%), M. fortuitum (n=5, 6%), M. abscessus (n=3, 3.9%), M. gordonae (n=3, 3.9%), M. kansasii (n=2, 2.4%), M. mucogenicum (n=2, 2.4%), and M. chelonae (n= 1, 1.2%). Real Myco-ID(®) is an efficient tool for the rapid detection of NTM species as well as MTB and sensitive and specific and comparable to conventional methods.

Early diagnosis increases the treatment success rate for active tuberculosis (ATB) and decreases mortality. MicroRNAs (miRNAs) have been studied as blood-based markers of several infectious diseases. We performed miRNA profiling to identify differentially expressed (DE) miRNAs using whole blood samples from 10 healthy controls (HCs), 15 subjects with latent tuberculosis infection (LTBI), and 12 patients with ATB, and investigated the expression of the top six miRNAs at diagnosis and over the treatment period in addition to performing miRNA-target gene network and gene ontology analyses. miRNA profiling identified 84 DE miRNAs in patients with ATB, including 80 upregulated and four downregulated miRNAs. Receiver operating characteristic curves of the top six miRNAs exhibited excellent distinguishing efficiency with an area under curve (AUC) value > 0.85. Among them, miR-199a-3p and miR-6886-3p can differentiate between ATB and LTBI. Anti-TB treatment restored the levels of miR-199b-3p, miR-199a-3p, miR-16-5p, and miR-374c-5p to HC levels. Furthermore, 108 predicted target genes were related to the regulation of cellular amide metabolism, intrinsic apoptotic signaling, translation, transforming growth factor beta receptor signaling, and cysteine-type endopeptidase activity. The DE miRNAs identified herein are potential biomarkers for diagnosis and therapeutic monitoring in ATB.

The present study aimed to clinically evaluate the effect of T-cell dysfunction in hemodialysis (HD) patients with latent tuberculosis (TB) infection (LTBI) who were false-negatives in the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Whole blood samples from a total of 20 active TB patients, 83 HD patients, and 52 healthy individuals were collected, and the QFT-GIT test was used for measuring Mycobacterium tuberculosis (MTB)-specific interferon gamma (IFN-γ) level. The positive rate of the IFN-γ release assays (IGRAs) in HD patients was lower than the negative rate. The mean value of MTB-specific IFN-γ level, which determines the positive rate of the IGRA test, was highest in active TB, followed by HD patients and healthy individuals. Among HD patients, phytohemagglutinin A (PHA)-stimulated IFN-γ levels of approximately 40% were 10.00 IU/mL or less. However, there was no low level of PHA-stimulated IFN-γ in the healthy individuals. This reveals that T-cell function in HD patients was reduced compared to healthy individuals, which leads to the possibility that QFT-GIT results in HD patients are false-negative. The clinical manifestations of TB in patients on HD are quite non-specific, making timely diagnosis difficult and delaying the initiation of curative treatment, delay being a major determinant of outcome.

Tuberculosis (TB) management is important for prompt discrimination of latent TB infection (LTBI) from active TB and proper treatment. Whole blood Interferon-gamma (IFN-γ) release assay (IGRA) is used to diagnose LTBI based on the secretion of IFN-γ by T-cells in the whole blood by using a specific antigen of Mycobacterium tuberculosis. However, the ability of IGRA to distinguish active TB from LTBI is considerably limited. Distinguishing active TB from LTBI is necessary to identify indicators that can be used to effectively manage TB and develop diagnostic methods. In the present study, we used a Luminex multiplex bead array (a bead-based antibody–antigen sandwich method). The whole blood level of acute phase proteins (APPs), such as endoglin (ENG), procalcitonin (PCT), C-reactive protein (CRP), and α1-acid glycoprotein (AGP), in active TB, LTBI, and healthy individuals were analyzed and quantified. The APP test results for the serum and whole blood samples showed that the levels of PCT, CRP, and AGP were significantly increased (p < 0.0500; area under curve = 0.955) in active TB. The level of these markers in the whole blood of active TB, LTBI, and healthy individuals could provide data for effective diagnosis and treatment of TB.