HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most common liver malignancy with a poor prognosis and increasing incidence, remains a serious health problem worldwide. Immunotherapy has been described as one of the ideal ways to treat HCC and is transforming patient management. However, the occurrence of immunotherapy resistance still prevents some patients from benefiting from current immunotherapies. Recent studies have shown that histone deacetylase inhibitors (HDACis) can enhance the efficacy of immunotherapy in a variety of tumors, including HCC. In this review, we present current knowledge and recent advances in immunotherapy-based and HDACi-based therapies for HCC. We highlight the fundamental dynamics of synergies between immunotherapies and HDACis, further detailing current efforts to translate this knowledge into clinical benefits. In addition, we explored the possibility of nano-based drug delivery system (NDDS) as a novel strategy to enhance HCC treatment.

Prevalence and Genotype of Trichomonas vaginalis among Men in Xinxiang City, Henan Province, China.

Trichomonas vaginalis (T. vaginalis) could cause trichomoniasis through sexual transmission, which was globally distributed. In this study, the prevalence and phylogenetic analyses of T. vaginalis among men in Xinxiang were conducted. From October 2018 to December 2019, a total of 634 male clinical samples were collected, including 254 samples of semen, 43 samples of prostate fluid, and 337 samples of urine. These samples were examined by nested PCR and a total of 32 (5.05%) T. vaginalis-positive samples were detected. Among these samples, the positive rates of T. vaginalis in semen, prostate fluid, and urine were 7.87% (20/254), 4.65% (2/43), and 2.97% (10/337), respectively. Three actin genes were successfully isolated and sequenced from the 32 positive DNA samples, and the analysis of the sequence and phylogenetic tree showed that the three actin gene sequences exhibited 99.7%-100% homology to the published actin gene sequence (EU076580) in NCBI, and the T. vaginalis strains in the three positive samples were identified as genotype E. Our results demonstrate a notable genotype of T. vaginalis in the male population and provide insight into the performance of these genetic markers in the molecular epidemiology of trichomoniasis. However, further studies are needed to research the association between the genotype and the pathogenicity of T. vaginalis.

Advanced diagnostic and therapeutic strategies in nanotechnology for lung cancer.

As a highly invasive thoracic malignancy with increasing prevalence, lung cancer is also the most lethal cancer worldwide due to the failure of effective early detection and the limitations of conventional therapeutic strategies for advanced-stage patients. Over the past few decades, nanotechnology has emerged as an important technique to obtain desired features by modifying and manipulating different objects on a molecular level and gained a lot of attention in many fields of medical applications. Studies have shown that in lung cancer, nanotechnology may be more effective and specific than traditional methods for detecting extracellular cancer biomarkers and cancer cells in vitro, as well as imaging cancer in vivo; Nanoscale drug delivery systems have developed rapidly to overcome various forms of multi-drug resistance and reduce detrimental side effects to normal tissues by targeting cancerous tissue precisely. There is no doubt that nanotechnology has the potential to enhance healthcare systems by simplifying and improving cancer diagnostics and treatment. Throughout this review, we summarize and highlight recent developments in nanotechnology applications for lung cancer in diagnosis and therapy. Moreover, the prospects and challenges in the translation of nanotechnology-based diagnostic and therapeutic methods into clinical applications are also discussed.

The molecular characterization and immune protection of adhesion protein 65 (AP65) of Trichomonas vaginalis.

BACKGROUND: Adherence to the surface of the host cell is the precondition for T. vaginalis parasitism and pathogenicity, causing urogenital infection. The AP65 of T. vaginalis (TvAP65) involves in the process of adhesion. So, the present study was aimed at investigating the molecular characterization and vaccine candidacy of TvAP65 for protecting the host from the onset of Trichomoniasis. METHODS: The open reading frame (ORF) of TvAP65 was amplified and then inserted into pET-32a (+) to clone recombinant TvAP65 (rTvAP65). The immunoblotting determined the immunogenicity and molecular size of TvAP65, while immunofluorescence staining visualized and the precise localization of TvAP65 in T. vaginalis trophozoites. Animal challenge and enzyme-linked immunosorbent assay (ELISA) test were used to evaluate the immunoprotection and the types of the immune response of TvAP65. RESULTS: By the sequence analysis, TvAP65 encoded a 63.13 kDa protein that consisted 567 amino acid residues with a high antigenic index. The western blotting revealed that rTvAP65 and native TvAP65 could interact with the antibodies in the rat serums post hoc rTvAP65 immunization and the serums from the mice that were experimentally infected with T. vaginalis, respectively. Immunofluorescence stained TvAP65 on the surface of T. vaginalis trophozoites. Moreover, following emulsification with Freund's adjuvant, rTvAP65 was subsequently administered to BALB/c mice three times at 0, 2, and 4 weeks and the results from this animal challenge experiments showed significant increases in immunoglobulins of IgG2a, IgG1, and IgG, and cytokine of IFN-γ, and IL-2, and 10. Lastly, rTvAP65 vaccinated animals had a prolonged survival time (26.80 ± 4.05) after challenged by T. vaginalis. CONCLUSIONS: TvAP65 mediated the adhesion of T. vaginalis to the host epithelia for the pathogenesis of the parasite and can be considered as a candidate protein for designing a functional vaccine that induces cell-mediated and humoral immunity against the T. vaginalis infection.

The Molecular Characterization and Immunity Identification of Trichomonas vaginalis Adhesion Protein 33 (AP33).

Trichomoniasis is caused by Trichomonas vaginalis (T. vaginalis), which is a widespread and serious sexually transmitted pathogen in humans. The procedure of T. vaginalis adherence to the host cell is the precondition for T. vaginalis parasitism and pathogenicity. The AP33 adhesin of T. vaginalis (TvAP33) plays a key role in the process of adhesion. In this study, the specific primers for polymerase chain reaction (PCR) were designed based on the sequence of TvAP33 (GenBank Accession No. U87098.1) to amplify the open reading frame (ORF), and the ORF was inserted into pET-32a (+) to produce recombinant TvAP33 (rTvAP33). The sequence analysis indicated that the TvAP33 gene encoded a protein of 309 amino acids with 32.53 kDa, and the protein was predicted to have a high antigen index. Western blotting assay showed rTvAP33 was successfully recognized by the sera of mice experimentally infected with T. vaginalis, while native TvAP33 in the somatic extract of T. vaginalis trophozoite was as well detected by sera from rats immunized with the rTvAP33. Immunofluorescence analysis using an antibody against rTvAP33 demonstrated that the protein was expressed and located on the surface of T. vaginalis trophozoites. The recombinant protein was emulsified in Freund's adjuvant and used to immunize BALB/C mice three times at days 0, 14, and 28. The result of animal challenge experiments revealed the levels of IgG, IgG1, and IgG2a, and IL-4, IL-10, and IL17 among rTvAP33 vaccinated animals were integrally increased. Moreover, the rTvAP33 vaccinated animals were apparently prolonged survival time (26.45 ± 4.10) after challenge infection with this parasite. All these results indicated that TvAP33 could be used as vaccine candidate antigen to induce cell-mediated and humoral immunity.

Development of a convenient detection method for Trichomonas vaginalis based on loop-mediated isothermal amplification targeting adhesion protein 65.

BACKGROUND: Trichomoniasis resulting from Trichomonas vaginalis (T. vaginalis) has been considered as a commonly seen disease with the transmission way of sex. At present, the detection methods of T. vaginalis mainly include wet mount microscopy, culture, PCR, immunofluorescence and ELISA. However, all of these detection methods exist shortcomings. METHODS: In this study, a loop-mediated isothermal amplification (LAMP) assay that targeted the species-specific sequence of adhesion protein 65 (AP65) gene had been conducted to detect T. vaginalis. The optimum reaction system and conditions were optimized in this rapid detection method. RESULTS: The results of sensitivity analysis showed that the LAMP assay targeting the AP65 gene was 1000 times more sensitive than the nested PCR targeting the actin gene commonly used for detection of T. vaginalis, and the detecting limitation of the former was 10 trichomonad. Moreover, the amplification of the target gene AP65 by LAMP assay exhibited high specificity and the product was exclusively from T. vaginalis. The detection technique of LAMP did not exhibit cross-reactivity with the common pathogens of Trichinella spiralis, Toxoplasma gondii, Escherichia coli, Candida albicans, Staphylococcus aureus, Haemophilus. CONCLUSIONS: According to the present study, the LAMP assay with the target of AP65 gene, was suitable for the early diagnosis of T. vaginalis infections. Consequently, the LAMP assay was proposed by the current study as a point-of-care examination and an alternative molecular tool which exhibited the potential value in the treatment, control and prevention of trichomoniasis transmission and relevant complication.