Adult ; Diagnosis, Differential ; Genital Neoplasms, Male ; pathology ; surgery ; Hernia, Inguinal ; pathology ; Humans ; Male ; Myxoma ; pathology ; surgery ; Scrotum ; pathology

In order to study the susceptibility of murine vaginal mucosa to Candida albicans under different conditions, vaginal lavage fluid and vaginal tissue of mice were observed and compared between murine models with normal immune system (estrogen-treated mice) and immunosuppressed murine model, and between primary infection model of vaginal candidiasis and secondary infection one. The average level of colony forming unit (CFU) from the immuosuppressed group was higher than that from estrogen-treated group at each time point and the peak time was delayed. The differences between the two groups were statistically significant (P < 0.05) from the fourth day after inoculation. A significant difference existed in the average level of CFU between the control group and the estrogen-treated group (P < 0.05), and between the control group and the immuosuppressed group (P < 0.01). It was concluded that the vaginal mucosa from the immunosuppressed mice is more susceptible to Candida albicans and no difference is found in susceptibility between mice with primary infection and secondary infection.
Candida albicans/drug effects ; Candidiasis, Vulvovaginal/*etiology ; Candidiasis, Vulvovaginal/*immunology ; Disease Susceptibility ; Estrogens/*pharmacology ; Immunocompromised Host ; Mice, Inbred ICR ; Random Allocation ; Vagina/microbiology

More than 99% of cervical cancers have been associated with human papillomaviruses (HPVs), particularly HPV type 16. The clear association between HPV infection and cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic vaccines. Although the recently licensed preventive HPV vaccine, Gardasil, has been shown to be safe and capable of generating significant protection against specific HPV types, it does not have therapeutic effect against established HPV infections and HPV-associated lesions. Two HPV oncogenic proteins, E6 and E7, are consistently co-expressed in HPV-expressing cervical cancers and are important in the induction and maintenance of cellular transformation. Therefore, immunotherapy targeting E6 and/or E7 proteins may provide an opportunity to prevent and treat HPV-associated cervical malignancies. It has been established that T cell-mediated immunity is one of the most crucial components to defend against HPV infections and HPV-associated lesions. Therefore, effective therapeutic HPV vaccines should generate strong E6/E7-specific T cell-mediated immune responses. DNA vaccines have emerged as an attractive approach for antigen-specific T cell-mediated immunotherapy to combat cancers. Intradermal administration of DNA vaccines via a gene gun represents an efficient way to deliver DNA vaccines into professional antigen-presenting cells in vivo. Professional antigen-presenting cells, such as dendritic cells, are the most effective cells for priming antigen-specific T cells. Using the gene gun delivery system, we tested several DNA vaccines that employ intracellular targeting strategies for enhancing MHC class I and class II presentation of encoded model antigen HPV-16 E7. Furthermore, we have developed a strategy to prolong the life of DCs to enhance DNA vaccine potency. More recently, we have developed a strategy to generate antigen-specific CD4+ T cell immune responses to further enhance DNA vaccine potency. The impressive pre- clinical data generated from our studies have led to several HPV DNA vaccine clinical trials.
Female ; Humans ; Oncogene Proteins, Viral/genetics/immunology ; Papillomaviridae/*genetics/immunology ; Papillomavirus Infections/immunology/*prevention & control ; Papillomavirus Vaccines/*administration & dosage ; Repressor Proteins ; Uterine Cervical Neoplasms/*prevention & control ; Vaccines, DNA/*administration & dosage ; Viral Vaccines/administration & dosage

OBJECTIVETo investigate the effects of wild type p16 gene on the proliferation and metabolism of human keloid fibroblasts.

METHODSEukaryotic expression vector pcDNA3-p16 was constructed and imported into KFb by gene transfection mediated by liposome. And the positive clones were screened by G418. The transfected and untransfected KFbs were stained by Immunocytochemical method. The expression of p16 protein was observed. The changes of the proliferation and DNA synthesis of KFb before and after transfection were observed and compared by drafting cell growth curve and by (3)H-TdR incorporation method.

RESULTSThe recombinant vector pcDNA3-p16 was successfully constructed and identified by enzyme digestion. The positive clones were identified by G418 selection for 10 days from transfected KFb and with p16 protein expression. The growth rate of transfected KFb slowed down obviously and its DNA synthesis decreased significantly (P < 0.05) when compared with those of normal KFb.

CONCLUSIONp16 gene might inhibit the growth and DNA synthesis of KFb.

Cell Proliferation ; Cells, Cultured ; DNA ; biosynthesis ; Fibroblasts ; metabolism ; pathology ; Genes, p16 ; Genetic Therapy ; Humans ; Keloid ; genetics ; pathology ; Transfection

OBJECTIVETo examine the role of Epstein-Barr virus (EBV) infection in benign lymphoepithelial lesions with malignant transformation of salivary glands.

METHODS2 cases benign lymphoepithelial lesions with focal malignant transformation (BLEL-FMT), 14 cases of malignant lymphoepithelial lesion (MLEL) and 4 cases of benign lymphoepithelial lesion (BLEL) of salivary glands, 4 cases of nonspecific chronic sialadenitis were examined. Sections were cut from the paraffin blocks and performed in situ hybridization (ISH) for EBV encoded small RNA-1 (EBER-1) using 30-base synthesized oligonucleotide probe and polymerase chain reaction (PCR) for BamHI-W regein of EBV DNA (123 bp).

RESULTSIn ISH, strong signals for EBER-1 were obtained in most of epithelial cell nuclei in examined specimens of BLEL-FMT, no matter in benign or malignant areas and in all specimens of MLEL (14/14), PCR demonstrated a DNA fragment of 123 kbp in 2 cases of BLEL-FMT and 12 cases of MLEL (12/14). In contrast, there were no significant ISH/PCR signals in examined BLEL and nonspecific chronic sialadenitis.

CONCLUSIONSA few cases of MLEL may arise from BLEL and EBV may plays an important role in the pathogenesis of BLEL-FMT of salivary glands.

Epstein-Barr Virus Infections ; virology ; Herpesvirus 4, Human ; isolation & purification ; Humans ; In Situ Hybridization ; Polymerase Chain Reaction ; Salivary Gland Neoplasms ; pathology ; virology

Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.
Dendritic Cells/immunology ; Female ; Genetic Vectors ; Humans ; *Immunotherapy ; Papillomavirus Infections/*complications/therapy ; Papillomavirus Vaccines/therapeutic use ; *Translational Medical Research ; Uterine Cervical Neoplasms/*therapy ; Vaccines, DNA/therapeutic use ; Vaccines, Subunit/therapeutic use

Alzheimer's disease (AD) pathogenesis is characterized by senile plaques in the brain and evidence of oxidative damage. Oxidative stress may precede plaque formation in AD; however, the link between oxidative damage and plaque formation remains unknown. Presenilins are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer's disease. Presenilins physically interact with two antioxidant enzymes thiol-specific antioxidant (TSA) and proliferation-associated gene (PAG) of the peroxiredoxin family. The functional consequences of these interactions are unclear. In the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the fly. This caused phenotypes typical of Notch signaling loss-of-function mutations. We found that while expression of TSA or PAG alone produced no phenotype, co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-of-function phenotype. This phenotype was more severe and more penetrant than that caused by the expression of Psn alone. In order to determine whether these phenotypes were indeed affecting Notch signaling, this experiment was performed in a genetic background carrying an activated Notch (Abruptex) allele. The phenotypes were almost completely rescued by this activated Notch allele. These results link peroxiredoxins with the in vivo function of Presenilin, which ultimately connects two key pathogenetic mechanisms in AD, namely, antioxidant activity and plaque formation, and raises the possibility of a role for peroxiredoxin family members in Alzheimer's pathogenesis.
Amino Acid Sequence ; Animals ; Drosophila ; metabolism ; physiology ; Drosophila Proteins ; metabolism ; Molecular Sequence Data ; Peroxiredoxins ; chemistry ; genetics ; metabolism ; Presenilins ; chemistry ; metabolism ; Receptors, Notch ; metabolism ; Sequence Alignment ; Signal Transduction

*Abnormalities, Multiple/radiography ; Basilar Artery/*abnormalities ; Basilar Artery/radiography ; Carotid Artery, Internal/radiography ; Intracranial Aneurysm/*complications ; Intracranial Aneurysm/radiography ; Vertebral Artery/radiography

Objective: This study evaluated the validity of self-reported smartphone usage data against objectively-measured smartphone usage data by directly tracking the activities in the participants’ smartphone among Chinese adolescents and young adults in Hong Kong. Methods: A total of 187 participants were recruited (mean age 19.4, 71.7% female) between 2017 and 2018. A smartphone usage tracking app was installed on all participants’ smartphone for 7 consecutive days. After the 7-day monitoring period, they completed a selfadministered questionnaire on smartphone usage habits. Results: Although the correlation between self-reported and objectively-measured total smartphone usage time was insignificant (ρ=-0.10, p=0.18), in three out of the four usage domains were positively and significantly correlated, namely social network (ρ=0.21, p=0.005), instant messaging (ρ=0.27, p<0.001), and games (ρ=0.64, p<0.001). Participants’ self-report of the total time spent on smartphones exceeded the objective data by around 760 min per week (self-reported 1,930.3 min/wk vs. objectively-measured 1,170.7 min/wk, p<0.001). Most of the over-reporting was contributed by the web browsing domain (self-reported 447.8 min/wk vs. objectively-measured 33.3 min/wk, p<0.001). Conclusion Our results showed large discrepancies between self-reported smartphone and objectively-measured smartphone usage except for self-reported usage on game apps.