Artepillin C as a targeting survivin molecule in oral squamous cell carcinoma cells in vitro: A preliminary study.

BACKGROUND: Survivin, a member of the inhibitor of apoptosis family, is overexpressed in most human tumors, but undetectable in normal adult tissues. It is a promising target molecule in cancer treatment, as interference in its function promotes apoptosis. Artepillin C, a major, biologically active ingredient of Brazilian propolis, possesses anticancer activity against several cancer cells with different tissue origins. However, little is known about its bioactivity on oral squamous cell carcinoma cells or its effect on survivin expression. The aim of this study was to investigate the cytotoxic and antisurvivin activities of artepillin C in oral squamous cell carcinoma cells. METHODS: HSC-3 human oral squamous cell carcinoma cells were treated with varying doses of artepillin C for up to 72 hours. Cell viability was measured by WST-1, and the cytotoxic effects of artepillin C on HSC-3 cells were quantified with flow cytometry. The survivin levels were determined by ELISA. RESULTS: Artepillin C exhibited dose- and time-dependent cytotoxic effects on HSC-3 cells. Flow cytometric analysis showed that 22% of untreated HSC-3 cells underwent spontaneous cell death, whereas 77.32% of the cells were killed in response to the highest dose of artepillin C at 72 hours. Survivin expression was reduced in treated cells. CONCLUSIONS: HSC-3 cells are vulnerable to artepillin C in a dose- and time-dependent manner. HSC-3 cell death induced by artepillin C, at least in part, was a result of a decrease in survivin levels.

Mannose-specific lectins that inhibit HIV infection bind nonspecifically to HIV Env-expressing cells.

An approach to curing HIV/AIDS is to specifically kill all infected cells. Because the lectins, Hippeastrum hybrid agglutinin (HHA) and Galanthus nivalis agglutinin (GNA), are potent inhibitors of HIV infection and bind the oligomannans on the HIV Env protein, we hypothesized that they would bind specifically to cells expressing the HIV Env protein on their plasma membrane. Flow cytometry experiments indicated, however, that these lectins bind equivalently to both Env-expressing and control cells without Env.

Infection of the oral cavity with SARS-CoV-2 variants: Scope of salivary diagnostics.

Coronaviruses, including SARS-CoV-2, have caused pandemics in the past two decades. The most prevalent SARS-CoV-2 variants of concern can re-infect individuals who have been previously infected with other variants or had protection from vaccines targeting the original SARS-CoV-2 variant. Given the high risk of transmission of coronavirus via aerosols produced during dental procedures, it is important to understand the future risk of coronavirus infection for oral health professionals and to diagnose quickly early stages of outbreaks. Testing of saliva for coronavirus may be the least invasive and most convenient method for following the outbreak at the individual and community level. This review will describe strategies for diagnosis of coronavirus in saliva.

Differential and coordinated expression of defensins and cytokines by gingival epithelial cells and dendritic cells in response to oral bacteria.

BACKGROUND: Epithelial cells and dendritic cells (DCs) both initiate and contribute to innate immune responses to bacteria. However, much less is known about the coordinated regulation of innate immune responses between GECs and immune cells, particularly DCs in the oral cavity. The present study was conducted to investigate whether their responses are coordinated and are bacteria-specific in the oral cavity. RESULTS: The beta-defensin antimicrobial peptides hBD1, hBD2 and hBD3 were expressed by immature DCs as well as gingival epithelial cells (GECs). HBD1, hBD2 and hBD3 are upregulated in DCs while hBD2 and hBD3 are upregulated in GECs in response to bacterial stimulation. Responses of both cell types were bacteria-specific, as demonstrated by distinctive profiles of hBDs mRNA expression and secreted cytokines and chemokines in response to cell wall preparations of various bacteria of different pathogenicity: Fusobacterium nucleatum, Actinomyces naeslundii and Porphyromonas gingivalis. The regulation of expression of hBD2, IL-8, CXCL2/GRObeta and CCL-20/MIP3alpha by GECs was greatly enhanced by conditioned medium from bacterially activated DCs. This enhancement was primarily mediated via IL-1beta, since induction was largely attenuated by IL-1 receptor antagonist. In addition, the defensins influence DCs by eliciting differential cytokine and chemokine secretion. HBD2 significantly induced IL-6, while hBD3 induced MCP-1 to approximately the same extent as LPS, suggesting a unique role in immune responses. CONCLUSIONS: The results suggest that cytokines, chemokines and beta-defensins are involved in interaction of these two cell types, and the responses are bacteria-specific. Differential and coordinated regulation between GECs and DCs may be important in regulation of innate immune homeostasis and response to pathogens in the oral cavity.

Diagnostic dilemma of IgG4-related primary localized cervical lymphadenopathy associated with aberrant IL-6 expression level.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized inflammatory condition with single- or multi-organ involvement. The disease is characterized by tumefactive lesions with dense IgG4 plasmacytic infiltration (an elevated IgG4(+)/IgG(+) cell ratio of > 40 %), storiform fibrosis, and obliterative phlebitis, with or without elevated serum IgG4 levels. The diagnostic criteria for IgG4-RD, proposed in 2011, were quite comprehensive and practical; however, it is important to remember that other diseases, such as hyper-interleukin (IL)-6 syndromes, may have common histopathological findings. Therefore, the histopathology of suspected IgG4-RD is occasionally not diagnostic. Here, we report a case of IgG4-related primary localized cervical lymphadenopathy without any other organ involvement. To our knowledge, there have been no previous reports of this. Additionally, the disease was associated with a 20-fold increase in IL-6 levels compared to that of the normal range. CASE PRESENTATION: We report the case of a 52-year-old Japanese man who presented with a painless, somewhat diffuse swelling in the left submandibular region. Although the case fulfilled diagnostic criteria for IgG4-RD, the diagnosis was not straightforward due to abnormally high levels of serum IL-6. After systematic evaluation of the patient, a final diagnosis of IgG4-RD was established. Since then, a specialist in connective tissue disorders has evaluated the patient on a regular basis. Two years after his initial visit, no disease progress or systemic involvement has been noted. CONCLUSION: We present a case of an IgG4-related primary localized cervical lymphadenopathy mimicking hyper-IL-6 syndrome. This case can serve as an excellent reminder that the definitive diagnosis of IgG4-RD should be established using a systematic approach, in particular when it appears as an atypical manifestation.

A nonviral vector with transfection activity comparable with adenoviral transduction.

AIM: Viral vectors are used commonly in gene therapy trials, but their potential toxic effects are a serious concern. Identification of highly efficient nonviral vectors may alleviate these effects. Results & methodology: We compared the abilities of TransfeX, TransIT-LT1 and adenovirus to deliver the firefly luciferase and green fluorescent protein genes into HeLa cervical carcinoma, and HSC-3 and H357 oral squamous cell carcinoma cells. TransfeX mediated fourfold higher gene expression in HeLa cells than adenovirus, even at the highest multiplicity of infection. Flow cytometry indicated that a population of transfected cells expresses higher levels of green fluorescent protein than transduced cells. CONCLUSION: TransfeX may be useful for gene therapy applications, particularly where the use of adenovirus is contraindicated.

Phototoxicity of Liposomal Zn- and Al-phthalocyanine Against Cervical and Oral Squamous Cell Carcinoma Cells In Vitro.

Background Material and Methods Results Conclusions.

Regulation of dendritic cell survival and cytokine production by osteoprotegerin.

The TNF family ligand, RANKL, and its two TNFR family receptors, RANK and OPG, enable coordinated regulation between the skeletal and immune systems. Relatively little is known about how OPG influences RANKL-RANK interactions for the regulation of DCs. Here, we show that OPG KO bone marrow-derived DCs survive better and produce more TNF-alpha, IL-12p40, and IL-23 in response to Escherichia coli LPS than WT DCs. RANKL is induced on DCs within 24 h after LPS stimulation. OPG limits RANKL-RANK interactions between DCs, which can promote DC survival and elevated expression of proinflammatory cytokines. Survival of and cytokine production by OPG KO DCs are inhibited by soluble OPG; conversely, anti-OPG enhances survival and cytokine production by WT DCs. Bim KO DCs, like OPG KO, also survive longer and produce more TNF-alpha than WT DCs; however, unlike OPG KO, Bim KO DCs do not produce more IL-23. In addition, after inoculation with LPS, OPG KO mice produce more TNF-alpha and IL-12p40 than WT mice but not more IL-6. Thus, OPG regulates not only DC survival but also the nature of DC-dependent inflammatory responses.