B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells.

BACKGROUND: B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. METHODS: Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. RESULTS: BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. CONCLUSIONS: The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer.

Inhibition of pathogenic microbes in oral infectious diseases by natural products: Sources, mechanisms, and challenges.

The maintenance of oral health is of utmost importance for an individual's holistic well-being and standard of living. Within the oral cavity, symbiotic microorganisms actively safeguard themselves against potential foreign diseases by upholding a multifaceted equilibrium. Nevertheless, the occurrence of an imbalance can give rise to a range of oral infectious ailments, such as dental caries, periodontitis, and oral candidiasis. Presently, clinical interventions encompass the physical elimination of pathogens and the administration of antibiotics to regulate bacterial and fungal infections. Given the limitations of various antimicrobial drugs frequently employed in dental practice, the rising incidence of oral inflammation, and the escalating bacterial resistance to antibiotics, it is imperative to explore alternative remedies that are dependable, efficacious, and affordable for the prevention and management of oral infectious ailments. There is an increasing interest in the creation of novel antimicrobial agents derived from natural sources, which possess attributes such as safety, cost-effectiveness, and minimal adverse effects. This review provides a comprehensive overview of the impact of natural products on the development and progression of oral infectious diseases. Specifically, these products exert their influences by mitigating dental biofilm formation, impeding the proliferation of oral pathogens, and hindering bacterial adhesion to tooth surfaces. The review also encompasses an examination of the various classes of natural products, their antimicrobial mechanisms, and their potential therapeutic applications and limitations in the context of oral infections. The insights garnered from this review can support the promising application of natural products as viable therapeutic options for managing oral infectious diseases.

[Clinical efficacy and serum cobalt, chromium metal ion concentrations after total hip arthroplasty with three different hard-on-hard bearings].

OBJECTIVE: To compare the clinical efficacy and serum concentrations of cobalt, chromium metal ion in three different hard-on-hard bearings after total hip arthroplasty at 2-years postoperatively. METHODS: Ninety (90) THA patients were divided into ceramic-on-ceramic (COC), ceramic-on-metal (COM), metal-on-metal (MOM) group (n = 30 in each group). At preoperative and 3, 6, 12, 24 months postoperative 5 time points, serum concentrations of cobalt and chromium metal ion were measured, Harris hip score was evaluated, X-rays and color doppler ultrasound examination of the ipsilateral hip also were observed. RESULTS: The excellent rates of Harris hip score were 100% in three groups. Continuous X-rays showed no radiolucent line around the acetabular component, no osteolysis, and no inflammatory pseudotumor. After the THA operation, the metal ion levels in COM and MOM groups increased rapidly, and stabilized at 12 months, then showed a downward trend, but the chromium ion level of MOM continued to rise at 24 months, with a significant difference when compared with that at 12 months (an increase of 0.48 microg/L, P = 0.021). The serum concentrations of metal ion in COC group were relatively constant at all time points, and the cobalt, chromium ion levels of MOM group were significantly higher than those of COC and COM group. CONCLUSION: The postoperative functional recovery of the three hard-on-hard bearings all were good, and no inflammatory pseudotumor and osteolysis were found. The serum levels of cobalt, chromium ion of COM were lower than those of MOM, but higher than those of COC.

[Three-dimensional finite element analysis of acetabular prosthesis in an adult patient with total flip arthroplasty for high dislocation].

OBJECTIVE: To observe stress distributions around the acetabular prosthesis and the bones of a patient who underwent total hip arthroplasty (THA). METHODS: Finite element analysis (FEA) was performed with an osteoarthritis patient who underwent THA for her secondary hip high dislocations: Scenario A--deepened acetabulum at the true acetabulum with a small 44 mm cup; Scenario B--structural bone graft at lateral acetabular with a 48 mm cup; Scenario C--place tantalum metal acetabular reconstruction at the lateral acetabular with a 48 mm cup; Scenario D--the normal side of the hip. According to the Wasielewski methods, acetabular was divided into four zones, in the same way on the lining surface. Ten points were taken in each zone for measuring the Von Mises stress values. RESULTS: Scenario A generated significantly greater stress values in the bones in zone one than the other three scenarios. Significantly greater stress was also found in the inner surface of polyethylene over all of the four zones under scenario A compared with those of the scenario B and C, especially in zone one and two. The cup initial micro-mobility for scenario A was 49. 18 microm, 19 times of that of scenario B and 8 times of that of scenario C. CONCLUSION: (1) Deepened acetabulum with small cup can cause stress concentration in the acetabular bones and liner, leading to large cup initial micro-mobility. (2) Acetabular lateral structural bone grafting and placement of tantalum metal reconstruction have better biomechanical properties, which can enable the use of bigger cups.

XIAP 3'-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p.

The non-coding 3'-untranslated region (UTR) of genes play an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Herein, we report that ectopic expression of XIAP 3'UTR increased human breast cancer cells proliferation, colony formation, migration, invasion and xenograft tumor growth and suppressed tumor cell death. To investigate this process, we further correlated the genome-wide transcriptional profiling with the gene expression alterations after transfecting XIAP 3'UTR in MCF-7 cells. We identified a robust, genome-wide mechanism of cell migration, motility and epithelial to mesenchymal transition by which mediated by a previously described cellular component movement factor FSCN1. Expression of XIAP and FSCN1 were up-regulated synergistically after transfecting XIAP 3'UTR in vitro and in vivo. Interactions between XIAP and FSCN1 appear to be a key determinant of these processes. Co-transfection with Dicer siRNA reversed the XIAP 3'UTR-mediated oncogenicity, suggesting the miRNAs might be involved in that process. Furthermore, we demonstrated that one miRNA, miR-29a-5p, can bind to both the XIAP and FSCN1 3'UTRs and play an important role in that interactions. We showed that the 3'UTR of XIAP was able to antagonize miR-29a-5p, and resulted in the increased translation of XIAP and FSCN1. Thus, our findings reveal important new insights into how XIAP 3'UTR works, suggesting that the non-coding XIAP 3'UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by which XIAP 3'UTR frees the target mRNAs from being repressed.

Prognostic significance of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3 expression in human cutaneous melanoma.

Cutaneous malignant melanoma is one of the most common and aggressive forms of human cancers and has a poor prognosis. Activation of signal transducer and activator of transcription 3 (STAT3) has been found in several human cancers and is thought to correlate aggressive disease and poor response. In this study, we investigated the clinical role of STAT3 and its natural inhibitor, suppressor of cytokine signaling 3 (SOCS3), in human cutaneous melanoma development and progression. Immunohistochemical analysis of pSTAT3, SOCS3, matrix metalloproteinase (MMP)-2, and MMP-9 expression was performed on 90 primary melanomas and 43 common melanocytic nevi specimens. The expression of STAT3 mRNA was further detected by in-situ hybridization in the same cohort of patients. The association of STAT3 mRNA, pSTAT3, and SOCS3 protein expression with clinicopathological parameters and patient survival was analyzed. Altered expression of STAT3 mRNA, pSTAT3, and SOCS3 protein was observed in melanoma specimens, compared with benign melanocytic nevi. High expression of pSTAT3 was correlated to large tumor diameter, depth of tumor invasion, tumor lymph node metastasis, MMP-2 and MMP-9 expression, and poor patient survival. Decreased expression of SOCS3 was correlated to depth of tumor invasion, tumor lymph node metastasis, the expression of MMP-2, MMP-9, and pSTAT3, and poor patient survival. Moreover, the expression of pSTAT3 was conversely correlated to SOCS3 expression in melanoma. Our results indicate that deregulated expression of pSTAT3 and SOCS3 might possess potential roles in the development and progression of human cutaneous melanoma.