BackgroundTopotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata, was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro.Materials and methodsU937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment. Cell proliferation was assessed using cell proliferation assay upon treatment with both compounds separately and in combination. Cell-cycle study and apoptosis detection were performed by staining the cells with propidium iodide (PI) stain and Annexin V/PI stain, respectively, followed by flow cytometry analysis. Western blotting was used to assess the expression of various proteins involved in apoptotic pathways.ResultsBoth TP and andrographolide showed an antiproliferative effect in a dose-dependent manner when applied on U937 cells separately; however, pretreating the cells with andrographolide before applying TP exhibited a synergistic effect with lower inhibitory concentrations (half-maximal inhibitory concentration). Treating the cells with TP alone led to specific cell-cycle arrest at S phase that was more prominent upon pretreatment combination with andrographolide. Using Annexin V/PI staining to assess the proapoptotic effect following the pretreatment combination showed an increase in the number of apoptotic cells, which was supported by the Western blot results that manifested an upregulation of several proapoptotic proteins expression.ConclusionThe pretreatment of U937 with andrographolide followed by low doses of TP showed an enhancement in inducing apoptosis when compared to the application of each compound separately.

Background Viral infections in children and adolescents with malignancy are commonly encountered and have a significant impact on morbidity and mortality. Studies and epidemiological data regarding viral infections in children with cancer in developing countries are lacking. This retrospective cohort study aims to assess the burden of viral infections in children and adolescents with cancer, by assessing prevalence, risk factors, as well as morbidity and mortality of common viruses over a period of 8 years. Methods and findings Medical records of cancer patients treated at the Children Cancer Center of Lebanon were reviewed and 155 participants under the age of 21 were identified with at least one documented viral infection during the period from July 2009 to November 2017. This subset included 136 participants with active malignancy and 19 participants with a history of cancer who underwent hematopoietic stem cell transplantation [HSCT] and were in remission; the latter group was analyzed separately. Information regarding participant characteristics, hospital course, and complications were obtained. Associations between viral infections and certain factors were assessed. In the cohort, 64% were male, 81% were Lebanese. In participants with active malignancy, 90% received chemotherapy in the 6 months preceding the viral infection episode, 11% received radiotherapy. 51% of participants were neutropenic at the time of viral detection, and 77% were lymphopenic. 17% experienced a bacterial coinfection, and 3 experienced a viral co-infection. Among 162 viral infection episodes,

Intellectual disability (ID) is a prevalent neurodevelopmental disorder characterized by limitations in intellectual functioning and adaptive behavior. While the causes of ID are still largely unknown, it is believed to result from a combination of environmental exposures and genetic abnormalities. Recent advancements in genomic studies and clinical genetic testing have identified numerous genes associated with neurodevelopmental disorders (NDDs), including ID. One such gene is CHAMP1, which plays a role in chromosome alignment and has been linked to a specific type of NDD called CHAMP1 disease. This report presents the case of a 21-year-old Lebanese female patient with a de novo mutation in CHAMP1. In addition to ID and NDD, the patient exhibited various clinical features such as impaired language, dysmorphic features, macrocephaly, thoracic hyperkyphosis, decreased pain sensation, and metabolic syndrome. These findings expand the understanding of the clinical spectrum associated with CHAMP1 mutations and highlight the importance of comprehensive follow-up for improved prognosis. Overall, this case contributes to the knowledge of CHAMP1-related NDDs by describing additional clinical features associated with a CHAMP1 mutation. The findings underscore the need for accurate diagnosis, thorough follow-up, and personalized care for individuals with CHAMP1 mutations to optimize their prognosis.

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