FDI-6 inhibits VEGF-B expression in metastatic breast cancer: a combined in vitro and in silico study.

Angiogenesis is the process by which new blood vessels are formed to meet the oxygen and nutrient needs of tissues. This process is vitally important in many physiological and pathological conditions such as tumor growth, metastasis, and chronic inflammation. Although the relationship of FDI-6 compound with FOXM1 protein is well known in the literature, its relationship with angiogenesis is not adequately elucidated. This study investigates the relationship of FDI-6 with angiogenesis and vascular endothelial growth factor B (VEGF-B) protein expression alterations. Furthermore, the study aims to elucidate the in silico interaction of FDI-6 with the VEGFR1 protein, a key player in initiating the angiogenic process, which is activated through its binding with VEGF-B. Our results demonstrate a significant effect of FDI-6 on cell viability. Specifically, we determined that the IC50 value of FDI-6 in HUVEC cells after 24 h of treatment is 24.2 µM, and in MDA-MB-231 cells after 24 h of application, it is 10.8 µM. These findings suggest that the cytotoxic effect of FDI-6 varies depending on the cell type. In wound healing experiments, FDI-6 significantly suppressed wound closure in MDA-MB-231 cells but did not show a similar effect in HUVEC cells. This finding suggests FDI-6 may have potential cell-type-specific effects. Molecular docking studies reveal that FDI-6 exhibits a stronger interaction with the VEGFR1 protein compared to its inhibitor, a novel interaction not previously reported in the literature. Molecular dynamic simulation results demonstrate a stable interaction between FDI-6 and VEGFR1. This interaction suggests that FDI-6 might modulate mechanisms associated with angiogenesis. Our Western blot analysis results show regulatory effects of FDI-6 on the expression of the VEGF-B protein. We encourage exploration of FDI-6 as a potential therapeutic agent in pathological processes related to angiogenesis. In conclusion, this study provides a detailed examination of the relationship between FDI-6 and both the molecular interactions and protein expressions of VEGF-B. Our findings support FDI-6 as a potential therapeutic agent in pathological processes associated with angiogenesis.

Does memantine show chemopreventive effect against mice 4T1 breast tumor model?

BACKGROUND: Cancer cells express higher levels of N-methyl-d-aspartate (NMDA) receptor. In this study, we aimed to use memantine as a potential blocker to inhibit the action of the NMDA receptor in cancer cells in vivo in order to investigate the potential chemopreventive effect of memantine in 4T1 tumor-bearing mice. METHODS: To determine the potential chemopreventive effect of the compound, mice weights, tumor volumes, spleen IL-6, and tumor DNA methylation levels were investigated. A total of 26 Balb/c female mice were allocated into three groups. G1 (n = 6): tumor control group, G2 (n = 10): low dose (5mg/kg) memantine group, G3: high dose (10 mg/kg) memantine group (n = 10). G1 was inoculated with 4T1 cells without any memantine treatment. G2 and G3 were pretreated with 5 and 10 mg/kg memantine daily intraperitoneal (ip) injection (weekend off) for 10 days, respectively. Both G2 and G3 were subdivided into two groups as G2a (n = 4) and G3a (n = 4): tumor free groups and G2b (n = 6) and G3b (n = 6) tumor bearing groups. RESULTS: Our results revealed that G3: high dose (10 mg/kg) memantine group, significantly (p = 0.0248) reduced the tumor volumes. We found that spleen IL-6 levels were significantly higher in memantine pretreated tumor free group p = 0.0204 ) We also found that high dose memantine treated tumor free group (G3a) has significantly lower genome-wide DNA methylation levels when compared to tumor control group (G1) p = 0.0012. DISCUSSION: To the best of our knowledge, it is the first study that highlights a potential chemopreventive effect of memantine in vivo in the mouse 4T1 breast tumor model. But further investigations should be carried out to explore the chemopreventive mechanism of action for memantine in cancer.

The outcomes of an impaired powerhouse in KRAS mutant lung adenocarcinoma cells by Elesclomol.

OBJECTIVES: Lung cancer stands out as the most common cancer type worldwide. The most common genetic alteration detected in adenocarcinoma patients is KRAS. KRAS mutated patients still cannot get benefit from precision medicine approaches and lack a targeted therapy. Elesclomol is an investigational agent for melanoma and other malignancies. In this study, we evaluated its effect on cellular apoptosis, survival, and metastasis mechanisms on KRAS mutant A549 and Calu-1 cell lines. METHODS: The cytotoxic effects of Elesclomol on A549 and Calu-1 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability test. Cells were treated with IC50 concentration and then apoptosis-related (Casp-3, Casp-9, Bcl-2, and Bcl-xL), survival-related (Akt, p-Akt, Erk, and p-Erk), and metastasis-related (E-cadherin, Vimentin, MMP-2, and MMP-9) protein expressions were determined by Western blot analysis. Elesclomol's effect on cell migration was evaluated by wound healing. Total oxidant, malondialdehyde (MDA), and glutathione (GSH) levels after Elesclomol treatment were assessed. RESULTS: Elesclomol not only induced apoptotic proteins but also inhibited metastatic protein expressions and migration in both cells. Also, p-Erk activity was diminished by Elesclomol treatment as a reflection of decreased proliferation. However, p-Akt was enhanced as a cellular survival mechanism. Although Elesclomol's effects on oxidative stress parameters were puzzling, it induced total oxidant status (TOS), and MDA in Calu-1 cells. CONCLUSION: Elesclomol might provide an alternative treatment approach for patients with KRAS mutant lung adenocarcinoma and other solid tumor malignancies that harbor KRAS mutations. This would enable the development of biomarker-driven targeted therapy for KRAS mutant adenocarcinoma patients.

Pneumonia in patients with novel influenza A (H1N1) virus in Southeastern Turkey.

The objective of this study was to describe the clinical characteristics and the radiological and laboratory findings of the hospitalised patients who had novel, laboratory-confirmed, swine-origin influenza A virus (S-OIV) infection with pneumonia. Between October and December 2009, 56 patients hospitalised for pneumonia who were tested for S-OIV infection were retrospectively evaluated. Thirty-three patients had positive S-OIV infections. In addition, 23 of the 56 patients who had negative test results for S-OIV infection were compared with the positive group. The mortality rate amongst the patients with S-OIV infection was 24.2%. Of the 33 patients, 42.4% had at least one underlying medical condition and 4 (12%) patients were pregnant or postpartum. Fourteen patients (42.4%) with S-OIV infection were followed up in an intensive care unit. The most common symptom was dyspnea. The mean peak body temperature during hospital stay (39.42 ± 0.70) was higher in this group than in the negative group (38.51 ± 1.05) (p = 0.001). Thrombocytopenia, increased creatine kinase and elevated lactate dehydrogenase levels were statistically significant. Bilateral infiltration was more common in the patients with S-OIV infection. Although some laboratory, radiological and clinical data show a significant difference between the patients with S-OIV pneumonia and the negative group, each patient presenting with signs of pneumonia during pandemia should be tested for Influenza A.

Nosocomial Oral Myiasis by Sarcophaga sp. in Turkey

We present a case of oral myiasis in a 15-year-old boy with tuberculosis meningitis. The diagnosis was based on the visual presence of wriggling larvae about 1 cm in size and on the microscopic features of the maggots, especially those relating to stigmatic structures. The larvae were identified as third stage larvae of Sarcophaga sp.

Anti-Toxoplasma gondii Antibodies in Haemodialysis Patients with Chronic Renal Failure

This study aimed to determine the prevalence of anti- Toxoplasma gondii antibodies in haemodialysis patients with chronic renal failure (CRF). Methods: One hundred and seventy three haemodialysis patients, and 40 healthy controls, were studied for the prevalence of anti-Toxoplasma gondii antibodies by a micro enzyme-linked immunosorbent assay (ELISA). Anti-T. gondii IgG antibodies were detected in 97 (56.06%) haemodialysis patients and 8 (20%) controls with a statistical significance. In addition, anti-T. gondii IgM antibodies were detected in 1.73% of patients, but none of the controls. In conclusion, a high percentage of positivity for Toxoplasma antibodies in patients with CRF undergoing haemodialysis was noticed, thus parasitological surveys of CRF patients should be periodically performed to prevent the possible dissemination of toxoplasmosis through the dialysis procedure.