MALAT-1 Is a Key Regulator of Epithelial-Mesenchymal Transition in Cancer: A Potential Therapeutic Target for Metastasis.

Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long intergenic non-coding RNA (lncRNA) located on chr11q13. It is overexpressed in several cancers and controls gene expression through chromatin modification, transcriptional regulation, and post-transcriptional regulation. Importantly, MALAT-1 stimulates cell proliferation, migration, and metastasis and serves a vital role in driving the epithelial-to-mesenchymal transition (EMT), subsequently acquiring cancer stem cell-like properties and developing drug resistance. MALAT-1 modulates EMT by interacting with various intracellular signaling pathways, notably the phosphoinositide 3-kinase (PI3K)/Akt and Wnt/ß-catenin pathways. It also behaves like a sponge for microRNAs, preventing their interaction with target genes and promoting EMT. In addition, we have used bioinformatics online tools to highlight the disparities in the expression of MALAT-1 between normal and cancer samples using data from The Cancer Genome Atlas (TCGA). Furthermore, the intricate interplay of MALAT-1 with several essential targets of cancer progression and metastasis renders it a good candidate for therapeutic interventions. Several innovative approaches have been exploited to target MALAT-1, such as short hairpin RNAs (shRNAs), antisense oligonucleotides (ASOs), and natural products. This review emphasizes the interplay between MALAT-1 and EMT in modulating cancer metastasis, stemness, and chemoresistance in different cancers.

Gene Expression and DNA Methylation as Prognostic Markers in Metastatic Castration-Resistant Prostate Cancer: Analysis of Circulating Tumor Cells and Paired Plasma-Derived Exosomes.

Prostate cancer (PCa) is the most prevalent cancer among men and is the second leading cause of cancer-related death in the United States [...].

Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes.

Prostate cancer (PCa) constitutes a significant cause of mortality, with over 37,000 new deaths each year [...].

MicroRNAs in Prostate Cancer: Implications for Treatment Response and Therapeutic Targets.

Cancer resistance to treatment is very common, represents one of the most significant challenges in the last few decades, and continues to impede all efforts to cure cancer [...].

Eprinomectin: a derivative of ivermectin suppresses growth and metastatic phenotypes of prostate cancer cells by targeting the ß-catenin signaling pathway.

PURPOSE: Prostate cancer (PCa) is the second leading cause of cancer death among men in the USA. The emergence of resistance to androgen deprivation therapy gives rise to metastatic castration-resistant prostate cancer. Eprinomectin (EP) is a member of a family of drugs called avermectins with parasiticide and anticancer properties. The pupose of this study was to evaluate the anticancer effects of EP against metastatic PCa using cellular models.  METHODS: In this study, we have investigated the effect of EP's anticancer properties and delineated the underlying mechanisms in the DU145 cellular model using several assays such as cell viability assay, colony formation assay, wound-healing assay, immunofluorescence, apoptosis assay, cell cycle analysis, and immunoblotting. RESULTS: Our results indicate that EP significantly inhibits the cell viability, colony formation, and migration capacities of DU145 cells. EP induces cell cycle arrest at the G0/G1 phase, apoptosis via the activation of different caspases, and autophagy through the increase in the generation of reactive oxygen species and endoplasmic reticulum stress. In addition, EP downregulates the expression of cancer stem cell markers and mediates the translocation of ß-catenin from the nucleus to the cytoplasm, indicating its role in inhibiting downstream target genes such as c-Myc and cyclin D1. CONCLUSION: Our study shows that EP has tremendous potential to target metastatic PCa cells and provides new avenues for therapeutic approaches for advanced PCa.

Polygodial, a Sesquiterpene Dialdehyde, Activates Apoptotic Signaling in Castration-Resistant Prostate Cancer Cell Lines by Inducing Oxidative Stress.

Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. Surgery, radiation therapy, chemotherapy, and androgen deprivation therapy are currently the standard treatment options for PCa. These have poor outcomes and result in the development of castration-resistant prostate cancer (CRPC), which is the foremost underlying cause of mortality associated with PCa. Taxanes, diterpene compounds approved to treat hormonal refractory PCa, show poor outcomes in CRPC. Polygodial (PG) is a natural sesquiterpene isolated from water pepper (Persicaria hydropiper), Dorrigo pepper (Tasmannia stipitata), and mountain pepper (Tasmannia lanceolata). Previous reports show that PG has an anticancer effect. Our results show that PG robustly inhibits the cell viability, colony formation, and migration of taxane-resistant CRPC cell lines and induces cell cycle arrest at the G0 phase. A toxicity investigation shows that PG is not toxic to primary human hepatocytes, 3T3-J2 fibroblast co-cultures, and non-cancerous BPH-1 cells, implicating that PG is innocuous to healthy cells. In addition, PG induces oxidative stress and activates apoptosis in drug-resistant PCa cell lines. Our mechanistic evaluation by a proteome profiler-human apoptotic array in PC3-TXR cells shows that PG induces upregulation of cytochrome c and caspase-3 and downregulation of antiapoptotic markers. Western blot analysis reveals that PG activates apoptotic and DNA damage markers in PCa cells. Our results suggest that PG exhibits its anticancer effect by promoting reactive oxygen species generation and induction of apoptosis in CRPC cells.

Oncopreventive and oncotherapeutic potential of licorice triterpenoid compound glycyrrhizin and its derivatives: Molecular insights.

Licorice (Glycyrrhiza glabra) is a well-known natural herb used to treat different ailments since ancient times. Glycyrrhizin (GL), which is the primary triterpenoid compound of licorice extract, has been known to have broad-spectrum pharmacological effects. GL is cleaved into glucuronide and the aglycone, glycyrrhetinic acid (GA), which exists in two stereoisomeric forms: 18α- and 18ß-GA. It is well documented that GL and GA have great potential as anti-inflammatory, anticancer, antiviral, anti-diabetic, antioxidant, and hepatoprotective agents. Studies undertaken during the coronavirus disease 2019 pandemic suggest that GL is effective at inhibiting the viral replication of severe acute respiratory syndrome coronavirus 2. The anticancer effects of GL and GA involve modulating various signaling pathways, such as the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B pathway, the mitogen-activated protein kinase, and the mammalian target of rapamycin/signal transducer and activator of transcription 3, which are mainly involved in regulating cancer cell death, oxidative stress, and inflammation. The potential of GL and GA in preventing cancer development and suppressing the growth and invasion of different cancer types has been reviewed in this paper. This review also provides molecular insights on the mechanism of action for the oncopreventive and oncotherapeutic effects of GL and its derivative, GA, which could help develop more specific forms of these agents for clinical use.

Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future.

BACKGROUND: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. OBJECTIVE: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. OUR APPROACH: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. ONGOING ACTIVITIES: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. CONCLUSION: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

Assessing the levels of HIV-related knowledge and attitudes toward HIV-infected patients among undergraduate dental students: a cross-sectional study.

PURPOSE: Worldwide, in the last decade, the numbers of new HIV infections and AIDS-related deaths have drastically decreased. Despite that, around 18 million infected individuals receive antiretroviral therapy and thus tend to live longer. This cross-sectional study was conducted to assess the level of HIV-related knowledge among undergraduate dental students at Ain Shams University (ASU) in Cairo, Egypt and to determine their attitudes toward treating HIV-positive patients. METHODS: The study sample included 247 undergraduate dental students of third, fourth, and fifth academic years at the Faculty of Dentistry, ASU who were randomly selected to participate in this survey. Data were collected using a self-administrated anonymous questionnaire. Chi square and ANOVA tests were used to measure differences in the level of knowledge and attitudes among students of the 3 years. Multiple linear regression analysis was performed with 95% confidence interval. RESULTS: Within the students' population, around 94% incorrectly considered dentists to be at high risk of acquiring HIV infection and 47% believed that saliva is a vehicle for its transmission. Moreover, the majority of students were unaware of the association between HIV and common oral manifestations such as oral candida, Kaposi sarcoma, and leukoplakia. Although 69% of the students were willing to deliver oral care to people living with HIV (PLHIV), only 33% perceived themselves knowledgeable enough to do so. CONCLUSION: Dental students were not adequately prepared to recognize and manage HIV-positive individuals. Thus, better education and training are required to raise their levels of HIV-related knowledge and enhance their capabilities to treat PLHIV.

Testing for the endogenous nature between women's empowerment and antenatal health care utilization: evidence from a cross-sectional study in Egypt.

Women's relative lack of decision-making power and their unequal access to employment, finances, education, basic health care, and other resources are considered to be the root causes of their ill-health and that of their children. The main purpose of this paper is to examine the interactive relation between women's empowerment and the use of maternal health care. Two model specifications are tested. One assumes no correlation between empowerment and antenatal care while the second specification allows for correlation. Both the univariate and the recursive bivariate probit models are tested. The data used in this study is EDHS 2008. Factor Analysis Technique is also used to construct some of the explanatory variables such as the availability and quality of health services indicators. The findings show that women's empowerment and receiving regular antenatal care are simultaneously determined and the recursive bivariate probit is a better approximation to the relationship between them. Women's empowerment has significant and positive impact on receiving regular antenatal care. The availability and quality of health services do significantly increase the likelihood of receiving regular antenatal care.