Cryptolepine Suppresses Colorectal Cancer Cell Proliferation, Stemness, and Metastatic Processes by Inhibiting WNT/ß-Catenin Signaling.

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths globally. Evidence shows that over 90% of CRC cases are initiated by a deregulated Wingless Integrated Type-1 (WNT)/ß-catenin signaling pathway. The WNT/ß-catenin pathway also promotes CRC cell proliferation, stemness, and metastasis. Therefore, modulators of the WNT/ß-catenin pathway may serve as promising regimens for CRC. This study investigated the effect of cryptolepine-a plant-derived compound-on the WNT/ß-catenin pathway in CRC. Two CRC cell lines, COLO205 and DLD1, were treated with cryptolepine or XAV 939 (a WNT inhibitor) in the presence or absence of WNT3a (a WNT activator). Using a tetrazolium-based assay, cryptolepine was found to reduce cell viability in a dose- and time-dependent manner and was a more potent inhibitor of viability than XAV 939. RT-qPCR analyses showed that cryptolepine reverses WNT3a-induced expression of ß-catenin, c-MYC, and WISP1, suggesting that cryptolepine inhibits WNT3a-mediated activation of WNT/ß-catenin signaling. Cryptolepine also repressed WNT3a-induced OCT4 and CD133 expression and suppressed colony formation of the cells, indicating that cryptolepine inhibits the stemness of CRC cells. Additionally, cryptolepine inhibited WNT3a-induced epithelial-to-mesenchymal transition by reducing the expression of SNAI1 and TWIST1 genes. In a wound healing assay, cryptolepine was found to suppress cell migration under unstimulated and WNT3a-stimulated conditions. Moreover, cryptolepine downregulated WNT3a-induced expression of MMP2 and MMP9 genes, which are involved in cancer cell invasion. Altogether, cryptolepine suppresses CRC cell proliferation, stemness, and metastatic properties by inhibiting WNT3a-mediated activation of the WNT/ß-catenin signaling pathway. These findings provide a rationale for considering cryptolepine as a potential WNT inhibitor in CRC.

Risk of Heavy Metal Poisoning From Consuming Grasscutter Digesta in Ghana.

Grasscutter (cane rat/Thryonomys swinderianus) digesta is used as a spice in Ghana. Research shows that heavy metals from the environment may accumulate in the internal organs of grasscutters, which raises concerns about the possible contamination of grasscutter digesta, too, with heavy metals. Although grasscutter meat in Ghana has been described as safe for consumption, information is lacking on the health risks associated with ingesting the digesta. This study, therefore, aimed to assess the knowledge and perceptions of a merchant and a consumer about the safety of ingesting grasscutter digesta and to evaluate potential health risks from exposure to heavy metals from the spice. A total of 12 digesta samples were analyzed to evaluate potential health risks from exposure to Cd, Fe, Hg, and Mn using a Varian AA240FS Atomic Absorption Spectrometer. The levels of Cd, Hg, and Mn were below the detection limit of 0.01 mg/kg digesta. Also, the estimated daily intake of Fe (0.02 mg/kg) was less than the maximum allowable dose recommended by the US EPA (0.7 mg/kg). The hazard indices of Fe for daily and weekly consumption were <1, suggesting that the consumers may be safe from iron poisoning. Because grasscutter digesta is a relatively expensive spice, it is unlikely to be consumed daily by the average Ghanaian. Moreover, if 10 g of digesta is consumed daily, it can be safely ingested about 971 times in a month. Domestication of grasscutters may be a useful approach to monitor their diet and consequently the quality of their digesta.

Inverse Comorbidity between Down Syndrome and Solid Tumors: Insights from In Silico Analyses of Down Syndrome Critical Region Genes.

An inverse comorbidity has been observed between Down syndrome (DS) and solid tumors such as breast and lung cancers, and it is posited that the overexpression of genes within the Down Syndrome Critical Region (DSCR) of human chromosome 21 may account for this phenomenon. By analyzing publicly available DS mouse model transcriptomics data, we aimed to identify DSCR genes that may protect against human breast and lung cancers. Gene expression analyses with GEPIA2 and UALCAN showed that DSCR genes ETS2 and RCAN1 are significantly downregulated in breast and lung cancers, and their expression levels are higher in triple-negative compared to luminal and HER2-positive breast cancers. KM Plotter showed that low levels of ETS2 and RCAN1 are associated with poor survival outcomes in breast and lung cancers. Correlation analyses using OncoDB revealed that both genes are positively correlated in breast and lung cancers, suggesting that they are co-expressed and perhaps have complementary functions. Functional enrichment analyses using LinkedOmics also demonstrated that ETS2 and RCAN1 expression correlates with T-cell receptor signaling, regulation of immunological synapses, TGF-ß signaling, EGFR signaling, IFN-γ signaling, TNF signaling, angiogenesis, and the p53 pathway. Altogether, ETS2 and RCAN1 may be essential for the development of breast and lung cancers. Experimental validation of their biological functions may further unravel their roles in DS and breast and lung cancers.

A multicenter study of the prevalence and risk factors of malaria and anemia among pregnant women at first antenatal care visit in Ghana.

BACKGROUND: Malaria in pregnancy remains a major public health problem in Africa and Ghana and has been associated with a variety of pregnancy-related adverse complications. The development of effective and timely health policies for the prevention and control of malaria and anemia in pregnancy; requires current and consistent data on the prevalence and risk factors. We report the prevalence and risk factors of malaria and anemia from three major hospitals across three regions in Ghana. METHODS: This multicenter cross-sectional study comprising a total of 628 pregnant women was conducted at the antenatal care units of the Achimota Hospital in the Greater Accra Region (n = 199), St. Michael's Hospital in the Ashanti Region (n = 221), and Effia Nkwanta Regional Hospital in the Western Region (n = 211). Questionnaires were administered to obtain socio-demographic, obstetrics and clinical data. Venous blood, stool and urine samples were collected for hematological profile and parasite identification using microscopy. Risk factors were evaluated using logistic regression models. RESULTS: The overall prevalence of P. falciparum malaria was 8.9%. Factors independently associated with malaria were self-reported mosquito exposure (moderate exposure: aOR = 3.11, 95% CI (1.12-8.61) and severe exposure: aOR = 10.46, 95% CI (3.86-28.34)) and non-use mosquito repellents (aOR = 3.29, 95% CI (1.70-6.39)). Multiparty (parity of 2: aOR = 0.19, 95% CI (0.05-0.70) and parity ≥3: aOR = 0.11, 95% CI (0.03-0.45)) and age (20-30 years old: aOR = 0.22, 95% CI (0.09-0.56)) reduced the odds of infection. The overall prevalence of anemia was 42.4%. The prevalence of mild, moderate and severe anemia were 35.7%, 6.1% and 0.6%, respectively. The use of water other than purified water (tap water: aOR = 3.05, 95% CI (2.06-4.51) and well water: aOR = 2.45, 95% CI (1.35-4.44)), increasing gestational age (second trimester: aOR = 2.05, 95% CI (1.41-2.97) and third trimester: aOR = 7.20, 95% CI (3.06-16.92)) and malaria (aOR = 2.40, 95% CI (1.27-4.53)) were independent risk factors for anemia. CONCLUSIONS: Although the prevalence of malaria is relatively low, that of anemia remains high. We recommend increasing efforts to make ITNs more available to strengthen malaria prevention. Public health education programs could help improve uptake and proper use of ITNs. To help reduce anemia in pregnancy, women should be empowered economically and interventions that reduce malnutrition should be encouraged. Women should be educated on early initiation of antenatal care to enhance surveillance, identification and treatment of anemia.