Maltese Mushroom (Cynomorium coccineum L.) as Source of Oil with Potential Anticancer Activity

The present study aimed to examine the potential anticancer properties of fixed oil obtained from Maltese mushroom (Cynomorium coccineum L.), an edible, non-photosynthetic plant, used in traditional medicine of Mediterranean countries to treat various ailments and as an emergency food during the famine. We investigated the effect of the oil, obtained from dried stems by supercritical fractioned extraction with CO₂, on B16F10 melanoma and colon cancer Caco-2 cell viability and lipid profile. The oil, rich in essential fatty acids (18:3n-3 and 18:2n-6), showed a significant growth inhibitory effect on melanoma and colon cancer cells. The incubation (24 h) with non-toxic oil concentrations (25 and 50 μg/mL) induced in both cancer cell lines a significant accumulation of the fatty acids 18:3n-3 and 18:2n-6 and an increase of the cellular levels of eicosapentaenoic acid (20:5n-3) with anticancer activity. Moreover, the oil exhibited the ability to potentiate the growth inhibitory effect of the antitumor drug 5-fluorouracil in Caco-2 cells and to influence the melanin content in B16F10 cells. The results qualify C. coccineum as a resource of oil, with potential benefits in cancer prevention, for nutraceutical and pharmaceutical applications.     

NCOA4-mediated ferritinophagy in macrophages is crucial to sustain erythropoiesis in mice

Nuclear receptor coactivator 4 (NCOA4) promotes ferritin degradation and Ncoa4-ko mice in a C57BL/6 background show microcytosis and mild anemia, aggravated by iron deficiency. To understand tissue-specific contributions of NCOA4-mediated ferritinophagy we explored the effect of Ncoa4 genetic ablation in the iron-rich Sv129/J strain. Increased body iron content protects these mice from anemia and, in basal conditions, Sv129/J Ncoa4-ko mice show only microcytosis; nevertheless, when fed a low-iron diet they develop a more severe anemia compared to that of wild-type animals. Reciprocal bone marrow (BM) transplantation from wild-type donors into Ncoa4-ko and from Ncoa4-ko into wild-type mice revealed that microcytosis and susceptibility to iron deficiency anemia depend on BM-derived cells. Reconstitution of erythropoiesis with normalization of red blood count and hemoglobin concentration occurred at the same rate in transplanted animals independently of the genotype. Importantly, NCOA4 loss did not affect terminal erythropoiesis in iron deficiency, both in total and specific BM Ncoa4-ko animals compared to controls. On the contrary, upon a low iron diet, spleen from wild-type animals with Ncoa4-ko BM displayed marked iron retention compared to (wild-type BM) controls, indicating defective macrophage iron release in the former. Thus, erythropoietin administration failed to mobilize iron from stores in Ncoa4-ko animals. Furthermore, Ncoa4 inactivation in thalassemic mice did not worsen the hematologic phenotype. Overall our data reveal a major role for NCOA4-mediated ferritinophagy in macrophages to favor iron release for erythropoiesis, especially in iron deficiency.     

Negative effect of lockdown on juvenile idiopathic arthritis patients

Clinical Rheumatology - The aim of this study is to evaluate a possible negative action of lockdown, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, in the...     

Recombinant human thyrotropin reduces serum vascular endothelial growth factor levels in patients monitored for thyroid carcinoma even in the absence of thyroid tissue

In this study, we have investigated in vivo the time-dependent effects of TSH on vascular endothelial growth factor (VEGF) production in patients monitored for thyroid carcinoma. Serum VEGF, thyroglobulin (Tg), and TSH levels were assayed at baseline and 6, 24, 30, 48, 72, and 96 h and 1 wk after administration of recombinant human TSH (rhTSH) in 45 thyroidectomized patients affected by differentiated thyroid carcinoma. At baseline, the patients with metastasis (18 cases) showed serum Tg and VEGF values significantly higher than those seen in the cured patients (27 cases). During rhTSH stimulation, the mean VEGF levels decreased significantly in both patient groups. In 60% of patients with metastasis, VEGF nadir occurred at the same time as serum TSH reached the highest values, whereas in 85.7% of the cured patients VEGF decreased after the TSH peak (P = 0.003). In conclusion, we demonstrate for the first time that short-term administration of rhTSH in patients monitored for differentiated thyroid carcinoma induces a significant reduction in serum VEGF values even in the absence of thyroid tissue. This result would suggest that TSH may be able in vivo to regulate VEGF production from tissues other than the thyroid gland.     

Topical methyl nicotinate-induced skin vasodilation in diabetic neuropathy

OBJECTIVE: To evaluate the vasodilation induced by topical application of methyl nicotinate (MN) and to compare it with the vasodilatory response to acetylcholine (ACh) and sodium nitroprusside (SNP) in healthy subjects and diabetic neuropathic patients. RESEARCH DESIGN AND METHODS: Ten diabetic patients with peripheral neuropathy (DN) and 10 age- and sex-matched healthy control subjects (C) were enrolled. The vasodilatory response to topical application of 1% MN and a placebo emulsion at the forearm and dorsum of the foot skin at 5, 15, 30, 60 and 120 min was measured using Laser Doppler Perfusion Imaging. The vasodilatory response to iontophoresis of 1% ACh and 1% SNP solutions was also evaluated. RESULTS: The maximal vasodilatory response to ACh, SNP and MN was similar at the forearm and foot level in the diabetic patients. In the control group, the responses to MN, ACh and SNP were similar on the forearm but in the foot, the MN vasodilatory response was higher when compared to the ACh and SNP responses. MN-related vasodilation was present 5 min after the application, reached its peak at 15-30 min and declined to pre-application levels 120 min afterward. CONCLUSIONS: Topical application of MN at the forearm and foot levels of diabetic neuropathic patients results in skin vasodilation that is comparable to the maximal vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for less than 2 h. Further studies will be required to explore the potential of MN to increase blood flow and to prevent diabetic foot problems in clinical practice.     

P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia

P-glycoprotein (P-gp), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression, and blast cell intracellular daunorubicin accumulation (IDA) were evaluated in 95 previously untreated cases of adult acute lymphoblastic leukaemia (ALL) using flow cytometry. Forty-five out of 95 (47%) patients were P-gp positive (+), 12/66 (18%) were LRP+ and 11/66 (17%) were MRP+. Eighteen out of 66 (28%) patients showed a simultaneous multidrug resistance (MDR)-related protein expression higher than controls for more than one protein, while 24/66 (36%) cases did not overexpress any protein. Twenty-one out of 24 (87%) cases overexpressing at least one MDR-related protein had a defect in accumulating daunorubicin into their blast cells, while only 4/24 (16%) cases who did not overexpress any protein had similar features. The complete remission rates were similar in MDR-positive and -negative (-) patients but relapses within 6 months were more frequent in P-gp+ cases, and therefore the disease-free survival duration was shorter in P-gp+ than in P-gp- patients (P = 0.01). The number of MRP+ and/or LRP+ cases was too small to be able to draw any conclusion on their role in affecting or predicting therapy outcome. In conclusion, P-gp overexpression associated with a defect in daunorubicin accumulation is a frequent feature in adult ALL at onset and seems to be related to poorer therapy outcome and, consequently, a shorter disease-free survival. LRP and MRP overexpression seems to be a rare event and no conclusion can be drawn on its prognostic role.     

Genetic haemochromatosis: genes and mutations associated with iron loading

Haemochromatosis is an autosomal recessive disorder common among Caucasians that leads to iron overload. Molecular studies have shown that the disease is prevalently due to a mutation in the HFE gene. Although C282Y in the homozygous state remains the most common patient's genotype, other genes and genetic mutations are associated with haemochromatosis. Haemochromatosis type 2, a severe form with juvenile onset, is due to mutations in an unidentified gene on chromosome 1q. Haemochromatosis type 3 is linked to a locus on 7q22 and is due to mutations in the transferrin receptor 2. Haemochromatosis type 4, the only autosomal dominant form, is caused by mutations in ferroportin 1 on 2q32. The genes responsible for African and neonatal forms of iron overload are still unknown. The identification of all of the genes associated with haemochromatosis is critical for molecular-based diagnosis and central to our understanding of the regulation of iron homeostasis.