Diminazene aceturate-induced cytotoxicity is associated with the deregulation of cell cycle signaling and downregulation of oncogenes Furin, c-MYC, and FOXM1 in human cervical carcinoma Hela cells.

Diminazene aceturate (DIZE) is an FDA-listed small molecule known for the treatment of African sleeping sickness. In vivo studies showed that DIZE may be beneficial for a range of human ailments. However, there is very limited information on the effects of DIZE on human cancer cells. The current study aimed to investigate the cytotoxic responses of DIZE, using the human carcinoma Hela cell line. WST-1 cell proliferation assay showed that DIZE inhibited the viability of Hela cells in a dose-dependent manner and the observed response was associated with the downregulation of Ki67 and PCNA cell proliferation markers. DIZE-treated cells stained with acridine orange-ethidium and JC-10 dye revealed cell death and loss of mitochondrial membrane potential (Ψm), compared with DMSO (vehicle) control, respectively. Cellular immunofluorescence staining of DIZE-treated cells showed upregulation of caspase 3 activities. DIZE-treated cells showed downregulation of mRNA for G1/S genes CCNA2 and CDC25A, S-phase genes MCM3 and PLK4, and G2/S phase transition/mitosis genes Aurka and PLK1. These effects were associated with decreased mRNA expression of Furin, c-Myc, and FOXM1 oncogenes. These results suggested that DIZE may be considered for its effects on other cancer types. To the best of our knowledge, this is the first study to evaluate the effect of DIZE on human cervical cancer cells.

Immunohistochemical localization of prolactin receptor (PRLR) to Hodgkin's and Reed-Sternberg cells of Hodgkin's lymphoma.

Prolactin receptor (PRLR), a type-1 cytokine receptor, is overexpressed in a number of cancer types. It has attracted much attention for putative pro-oncogenic roles, which however, remains controversial in some malignancies. In this study, we reported the localization of PRLR to the Hodgkin's and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL), a neoplasm of predominantly B cell origin. Immunohistochemistry performed on 5-µm thick FFPE sections revealed expression of PRLR in HRS cells. Cellular immunofluorescence experiments showed that the HL-derived cell lines, Hs445, KMH2 and L428 overexpressed PRLR. The PRLR immunofluorescent signal was depleted after treating the cell lines with 10 µM of siRNA for 48 h. We also tested whether PRLR is involved in the growth of HL, in vitro. One-way analysis of variance (ANOVA) on cell growth data obtain from WST-1 cell proliferation assay and trypan blue exclusion assay and hemocytometry showed that siRNA-depletion of PRLR expression resulted in decreased growth in all three cell lines. These results offered only a short insight into the involvement of PRLR in HL. As a result, further investigation is required to decipher the precise role(s) of PRLR in the pathogenesis of HL.

Putative Cellular and Molecular Roles of Zika Virus in Fetal and Pediatric Neuropathologies.

Although the World Health Organization declared an end to the recent Zika virus (ZIKV) outbreak and its association with adverse fetal and pediatric outcome, on November 18, 2016, the virus still remains a severe public health threat. Laboratory experiments thus far supported the suspicions that ZIKV is a teratogenic agent. Evidence indicated that ZIKV infection cripples the host cells' innate immune responses, allowing productive replication and potential dissemination of the virus. In addition, studies suggest potential transplacental passage of the virus and subsequent selective targeting of neural progenitor cells (NPCs). Depletion of NPCs by ZIKV is associated with restricted brain growth. And while microcephaly can result from infection at any gestational stages, the risk is greater during the first trimester. Although a number of recent studies revealed some of specific molecular and cellular roles of ZIKV proteins of this mosquito-borne flavivirus, the mechanisms by which it produces it suspected pathophysiological effects are not completely understood. Thus, this review highlights the cellular and molecular evidence that implicate ZIKV in fetal and pediatric neuropathologies.

Insights into the molecular roles of Zika virus in human reproductive complications and congenital neuropathologies.

The recent upsurge in the association of congenital neurological disorders and infection by the Zika virus (ZIKV) has resulted in increased research focus on the biology of this flavivirus. Studies in animal models indicate that ZIKV can breach the placental barrier and selectively infect and deplete neuroprogenitor cells (NPCs) of the developing fetus, resulting in changes of brain structures, reminiscent of human microcephaly. In vitro and ex vivo studies using human cells and tissues showed that human NPCs and placental cells are targeted by ZIKV. Also of concern is the impact of ZIKV on human reproductive structures, with the potential to cause infertility, as the virus appears to remain in the genital tract for extended periods of time. This review discusses the putative roles of ZIKV on human reproductive complications and congenital neuropathologies.

A comparative study of MAP2 immunostaining in areas 9 and 17 in schizophrenia and Huntington chorea.

Increasing evidence suggests that there may be significant morphological changes in the neuropil of the dorsolateral prefrontal cortex in schizophrenia. A controversial issue surrounding these deficits in the cortical neuropil is the confounding effects of antipsychotic (neuroleptic) medication as well as the question of generality to psychiatric disorders. To begin to address these issues we examined brains from Huntington's patients matched to a cohort of schizophrenics and controls. Many Huntington's patients take neuroleptics similar to schizophrenics; therefore, by comparing the two groups to controls we can begin to determine if neuroleptics play a role in the deficits reported in schizophrenia. Using MAP2 immunohistochemistry and thionin staining eight matched triplets of Huntington, schizophrenia and control, in areas 9 and 17 layers III and V were analyzed. Our results confirmed previous published data showing a schizophrenia-associated decrease in MAP2 in area 9 with no change in area 17. Similarly the Huntington's patients showed no change in area 9 layer III and no change in area 17. There was however, a modest decrease observed in layer V area 9 of the Huntington's patients. Neuron density measurements showed no change in either layer or brain region in any of the diagnostic categories. These observations suggest that antipsychotic medication may not be responsible for some of the morphological changes observed in the neuropil of the PFC in schizophrenia.