Dual anticancer and antibacterial activity of fluorescent naphthoimidazolium salts.

Cancer has emerged as a significant global health challenge, ranking as the second leading cause of death worldwide. Moreover, cancer patients frequently experience compromised immune systems, rendering them susceptible to bacterial infections. Combining anticancer and antibacterial properties in a single drug could lead to improved overall treatment outcomes and patient well-being. In this context, the present study focused on a series of hydrophilic naphthoimidazolium salts with donor groups (NI-R), aiming to create dual-functional agents with antibacterial and anticancer activities. Among these compounds, NI-TPA demonstrated notable antibacterial activity, particularly against drug-resistant bacteria, with MIC value of 7.8 µg mL-1. Furthermore, NI-TPA exhibited the most potent cytotoxicity against four different cancer cell lines, with an IC50 range of 0.67-2.01 µg mL-1. The observed high cytotoxicity of NI-TPA agreed with molecular docking and dynamic simulation studies targeting c-Met kinase protein. Additionally, NI-TPA stood out as the most promising candidate for two-photo excitation, fluorescence bioimaging, and localization in lysosomes. The study findings open new avenues for the design and development of imidazolium salts that could be employed in phototheranostic applications for cancer treatment and bacterial infections.

Imidazolium-Based Heavy-Atom-Free Photosensitizer for Nucleus-Targeted Fluorescence Bioimaging and Photodynamic Therapy.

The development of heavy-atom-free photosensitizers (PSs) for photodynamic therapy (PDT) has encountered significant challenges in achieving simultaneous high fluorescence emission and reactive oxygen species (ROS) generation. Moreover, the limited water solubility of these PSs imposes further limitations on their biomedical applications. To overcome these obstacles, this study presents a molecular design strategy employing hydrophilic heavy-atom-free PSs based on imidazolium salts. The photophysical properties of these PSs were comprehensively investigated through a combination of experimental and theoretical analyses. Notably, among the synthesized PSs, the ethylcarbazole-naphthoimidazolium (NI-Cz) conjugate exhibited efficient fluorescence emission (ΦF = 0.22) and generation of singlet oxygen (ΦΔ = 0.49), even in highly aqueous environments. The performance of NI-Cz was validated through its application in fluorescence bioimaging and PDT treatment in HeLa cells. Furthermore, NI-Cz holds promise for two-photon excitation and type I ROS generation, nucleus localization, and selective activity against Gram-positive bacteria, thereby expanding its scope for the design of heavy-atom-free PSs and phototheranostic applications.

LMP1-EBV Gene Deletion Mutations and HLA Genotypes of Nasopharyngeal Cancer Patients in Vietnam.

Nasopharyngeal carcinoma (NPC) is the most common cancer among head and neck cancers in Vietnam. We aimed to identify the rate of a 30 bp deletion mutation of the LMP1-EBV gene in nasopharyngeal biopsy tissue samples, the HLA genotypes of NPC patients, and the relationship between these two targets. Patients with NPC at Can Tho Oncology Hospital from September 2014 to December 2018 were selected. A length of 30 bp of the del-LMP1-EBV gene was analyzed using a PCR technique, and the HLA genotypes in patients' blood samples were analyzed with PCR-SSO technology. HLA-B*15 gene carriers had the highest risk of 30 bp LMP1-EBV gene deletion mutation, which was found in 51 out of 70 patients (72.9%). Carriers of the HLA-B*15 allele had a 4.6-fold increased risk of a 30 bp del-LMP1-EBV gene compared with non-carriers of this allele. The initial identification of NPC was related to the 30 bp del-LMP1-EBV gene and high frequencies of the -A*02, -B*15, -DRB1*12, -DQB1*03, and -DQA1*01 HLA alleles. Our study results suggest an association of the 30 bp del-LMP1-EBV gene and the HLA-B*15 allele with NPC susceptibility.

Evaluation of the expression levels of BRAFV600E mRNA in primary tumors of thyroid cancer using an ultrasensitive mutation assay.

BACKGROUND: The BRAFV600E gene encodes for the mutant BRAFV600E protein, which triggers downstream oncogenic signaling in thyroid cancer. Since most currently available methods have focused on detecting BRAFV600E mutations in tumor DNA, there is limited information about the level of BRAFV600E mRNA in primary tumors of thyroid cancer, and the diagnostic relevance of these RNA mutations is not known. METHODS: Sixty-two patients with thyroid cancer and non-malignant thyroid disease were included in the study. Armed with an ultrasensitive technique for mRNA-based mutation analysis based on a two step RT-qPCR method, we analysed the expression levels of the mutated BRAFV600E mRNA in formalin-fixed paraffin-embedded samples of thyroid tissues. Sanger sequencing for detection of BRAFV600E DNA was performed in parallel for comparison and normalization of BRAFV600E mRNA expression levels. RESULTS: The mRNA-based mutation detection assay enables detection of the BRAFV600E mRNA transcripts in a 10,000-fold excess of wildtype BRAF counterparts. While BRAFV600E mutations could be detected by Sanger sequencing in 13 out of 32 malignant thyroid cancer FFPE tissue samples, the mRNA-based assay detected mutations in additionally 5 cases, improving the detection rate from 40.6 to 56.3%. Furthermore, we observed a surprisingly large, 3-log variability, in the expression level of the BRAFV600E mRNA in FFPE samples of thyroid cancer tissue. CONCLUSIONS: The expression levels of BRAFV600E mRNA was characterized in the primary tumors of thyroid cancer using an ultrasensitive mRNA-based mutation assay. Our data inspires further studies on the prognostic and diagnostic relevance of the BRAFV600E mRNA levels as a molecular biomarker for the diagnosis and monitoring of various genetic and malignant diseases.

DNA-HPV transition rate and related factors in HPV-infected women in Can Tho city, Vietnam.

OBJECTIVES: To determine DNA-HPV transition rates and related factors in HPV-infected women 18-69 years of age in Can Tho City from 2013 to 2018. METHODS: Both a retrospective and a prospective cohort study were done. Interviews, gynaecological examinations and HPV testing by PCR (cervical fluid) were used to collect data. The results were recorded and compared with those of HPV in 2013 to assess the development of HPV over time. Transition was defined as conversion to HPV-positive state in 2018 from a negative state in 2013. No transition was defined as clearance of HPV when the positive 2013 result was negative in 2018 or when the result remained negative or positive in 2013 and 2018. Factors related to the change were analysed. RESULTS: Among a sample size of 204 cases, the average age of participants was 48.9 ± 10.4 years. Women >45 comprised 63.2% of participants; 82.8% lived with their husbands, 6.4% were divorced, and 2.9% lived apart from their husbands due to work. After 5 years of observation, 16.2% of DNA-HPV cases had converted to HPV-positive state and 66.2% of DNA-HPV cases had cleared to HPV-negative state. Factors related to conversion to HPV-positive state were age ≤ 45 years (3.14 times higher risk of transition than in the >45 age group (95% CI: 1.12-8.8)); change of sexual partner (OR = 3.75 (95% CI: 1.15-12.2)); change of sexual partner by husband (OR = 3.69 (95% CI: 1.20-11.3); sexually transmitted diseases (OR = 5.19 (95% CI: 1.09-24.8)); and a history of vacuum aspiration or dilation and evacuation abortion (OR = 1.4 (95% CI: 0.29-6.4)). CONCLUSIONS: 16.2% of women with DNA-HPV transition converted to HPV-positive state. Changes in sexual habits increase the risk of developing HPV positivity.

TAUX DE TRANSITION ADN-VPH ET FACTEURS CONNEXES CHEZ LES FEMMES INFECTÉES PAR LE VPH À CAN THO CITY, VIETNAM: OBJECTIFS: Déterminer les taux de transition ADN-VPH et les facteurs connexes chez les femmes infectées par le VPH, âgées de 18 à 69 ans à Can Tho City de 2013 à 2018. MÉTHODES: Une étude de cohorte rétrospective et une prospective ont été effectuées. Des entretiens, des examens gynécologiques et des tests pour le VPH par PCR (liquide cervical) ont été utilisés pour collecter des données. Les résultats ont été enregistrés et comparés à ceux du VPH en 2013 afin d'évaluer l'évolution du VPH au fil du temps. La transition a été définie comme étant la conversion d'un état négatif au VPH en 2013 à un état positif en 2018. Aucune transition n'a été définie comme une élimination du VPH lorsque le résultat positif de 2013 était négatif en 2018 ou lorsque le résultat est resté négatif ou positif en 2013 et 2018. Les facteurs liés au changement ont été analysés. RÉSULTATS: Sur un échantillon de 204 cas, l'âge moyen des participantes était de 48,9 ± 10,4 ans. Les femmes > 45 ans représentaient 63,2% des participantes; 82,8% vivaient avec leur mari, 6,4% étaient divorcées et 2,9% vivaient séparées de leur mari à cause de leur travail. Après 5 ans d'observation, 16,2% des cas d'ADN-VPH étaient passés à l'état VPH positif et 66,2% des cas d'ADN-VPH avaient tout éliminé et étaient passés à l'état HPV négatif. Les facteurs liés à la conversion à l'état positif au VPH étaient les suivants: âge ≤ 45 ans (risque de transition de 3,14 fois supérieur à celui du groupe d'âge > 45 ans (IC95%: 1,12 à 8,8)), changement de partenaire sexuel (OR = 3,75 (IC95%: 1,15-12,2)), changement de partenaire sexuel par le mari (OR = 3,69 (IC95%: 1,20-11,3), maladies sexuellement transmissibles (OR = 5,19 (IC95%: 1,09-24,8)) et antécédents d'aspiration ou de dilatation et d'évacuation d'avortement (OR = 1,4 (IC95%: 0,29 à 6,4)). CONCLUSIONS: 16,2% des femmes présentant une transition ADN-VPH sont devenues positives au VPH. Les changements d'habitudes sexuelles augmentent le risque de développer une positivité au VPH.