Alpha-melanocyte stimulating hormone (α-MSH) and its receptor, melanocortin 1 receptor (MC1R), have been proposed as potential target for anti-cancer strategies in melanoma research, due to their ...tissue specific expression and involvement in melanocyte homeostasis. However, their role in prevention and treatment of melanoma is still debated and controversial. Although a large body of evidence supports α-MSH in preventing melanoma development, some preclinical findings suggest that the α-MSH downstream signalling may promote immune escape and cancer resistance to therapy. Additionally, in metastatic melanoma both MC1R and α-MSH have been reported to be overexpressed at levels much higher than normal cells. Furthermore, targeted therapy (e.g. BRAF inhibition in BRAFV600E mutant tumours) has been shown to enhance this phenomenon. Collectively, these data suggest that targeting MC1R could serve as an approach in the treatment of metastatic melanoma. In this review, we explore the molecular biology of α-MSH with particular emphasis into its tumor-related properties, whilst elaborating the experimental evidence currently available regarding the interplay between α-MSH/MC1R axis, melanoma and antitumor strategies.
is a zoonotic pathogen and the ingestion of tissue cysts by consumption of lamb or mutton has been identified as a possible cause of infection in humans. Many serological surveys in sheep have been ...performed, showing relevant serological rates; however, while the detection of antibodies indicates an exposure to
, this does not necessarily imply the presence of tissue cysts in edible tissue. The current study aims to provide further understanding on the occurrence of
in sheep muscles and the strength of correlation between serological positivity and presence of the parasite in sheep. From 349 sheep, samples (i.e., blood, heart and diaphragm) were collected and subjected to ELISA tests, real-time PCR and histological tests. Despite the high seroprevalence,
DNA was detected in the heart and/or the diaphragm from 13 out of the 349 tested sheep (3.7%); all were adults (13/191). Furthermore, the histological tests did not reveal the presence of
tissue cysts in any of the examined portions of interventricular septum. It should be considered that the likelihood of detecting genetic material of the parasite is probably influenced by the uneven distribution of the tissue cysts in the carcass as well as the methodology applied. The findings of this study support the importance of describing the uncertainty associated with the data used for risk assessment to reduce inaccurate estimation or risk overestimation.
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Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 ...responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.
GFI1B is a transcription factor essential for the regulation of erythropoiesis and megakaryopoiesis, and pathogenic variants have been associated with thrombocytopenia and bleeding. Analysing ...thrombocytopenic families by whole exome sequencing, we identified a novel GFI1B variant (c.648+5G>A), which causes exon 9 skipping and overexpression of a shorter p32 isoform. We report the clinical data of our patients and critically review the phenotype observed in individuals with different GFI1B variants leading to the same effect on the p32 expression. Since p32 is increased in acute and chronic leukemia cells, we tested the expression level of genes playing a role in various type of cancers, including hematological tumors and found that they are significantly dysregulated, suggesting a potential role for GFI1B in carcinogenesis regulation. Increasing the detection of individuals with GFI1B variants will allow us to better characterize this rare disease and determine whether it is associated with an increased risk of developing malignancies.
Recent studies have shown a direct correlation between C-reactive protein (CRP) level and obesity. There has also been increasing evidence that elevated CRP level is a significant risk factor for ...cardiac events and stroke. We wanted to evaluate whether CRP is altered by gastric bypass surgery. In addition, we wanted to investigate whether there was any correlation between reduced body mass index (BMI) and decreased CRP level.
CRP levels were obtained at 1 week preoperatively and then at 3 and 6 months postoperatively. Measurements of weight (kg), height (cm), and waist and hip circumferences (cm) were also measured at these time points. The BMI and CRP mean levels at the 3 time points were compared using a nonparametric Kruskal-Wallis 1-way analysis of variance test, with post hoc Z tests used for comparisons between the individual time periods. In addition, a linear regression analysis was performed at each time period to determine whether a significant correlation existed between the CRP level and the change in BMI.
Twenty subjects (19 females and 1 male) have been studied to date. There were significant decreases in BMI between the preoperative and 3-month periods, with a further significant decrease at 6 months (44.5 +/- 4.7, 35.7 +/- 5.1, and 31.5 +/- 4.3, respectively; P < .05). CRP level decreased significantly between the preoperative and 3-month periods (1.02 +/- 0.7 to 0.49 +/- 0.09, respectively; P < .05). (Normal CRP level is < 0.5 mg/dL.) There was a tendency toward a further decrease in CRP level from 3 to 6 months, although this did not reach statistical significance (6-month mean, 0.39 +/- 0.10; P > .05). There was no statistically significant correlation between the change in BMI and CRP levels at any of the time periods.
There were significant reductions in BMI and CRP levels after gastric bypass surgery. However, there was no statistically significant correlation between the decrease in BMI and the decrease in CRP levels.
Ingesting meat from lamb or mutton containing cysts of Toxoplasma gondii can lead to human infection, defined as toxoplasmosis. Many studies worldwide reported high antibody levels to T. gondii in ...sheep, but this does not always indicate that tissues destined for consumption contain infectious cysts. This study aimed to understand T. gondii occurrence in sheep muscles and the correlation between seropositivity and parasite presence. Samples from 349 sheep (blood, heart and diaphragm) underwent ELISA, real-time PCR and histological testing. Despite high seroprevalence rates, T. gondii DNA was found in only 3.7% of tested sheep (13/349), all adults. Histological tests did not detect T. gondii tissue cysts in any samples tested. The results agree with previously published research and might be influenced by the uneven distribution of tissue cysts in carcasses or muscle and by the analytical methods used. Toxoplasma gondii is a zoonotic pathogen and the ingestion of tissue cysts by consumption of lamb or mutton has been identified as a possible cause of infection in humans. Many serological surveys in sheep have been performed, showing relevant serological rates; however, while the detection of antibodies indicates an exposure to T. gondii, this does not necessarily imply the presence of tissue cysts in edible tissue. The current study aims to provide further understanding on the occurrence of T. gondii in sheep muscles and the strength of correlation between serological positivity and presence of the parasite in sheep. From 349 sheep, samples (i.e., blood, heart and diaphragm) were collected and subjected to ELISA tests, real-time PCR and histological tests. Despite the high seroprevalence, T. gondii DNA was detected in the heart and/or the diaphragm from 13 out of the 349 tested sheep (3.7%); all were adults (13/191). Furthermore, the histological tests did not reveal the presence of T. gondii tissue cysts in any of the examined portions of interventricular septum. It should be considered that the likelihood of detecting genetic material of the parasite is probably influenced by the uneven distribution of the tissue cysts in the carcass as well as the methodology applied. The findings of this study support the importance of describing the uncertainty associated with the data used for risk assessment to reduce inaccurate estimation or risk overestimation.
Abstract Background Despite implications for theory and treatment, commonality in responding to non-bereavement and bereavement losses are not well explicated. Method This study identified the factor ...structure of the three most common responses to bereavement, prolonged grief, posttraumatic stress, and major depression in a bereaved community sample ( n =151, 59% female, 68% white) from the U.S. recruited from Amazon’s MTurk using a cross-sectional survey design, then cross-validated the structure in samples where people had lost other potentially self-defining roles; one’s employment ( n =157, 47% female, 69% white) and one’s marriage ( n =116, 62% female, 80% white). Results Results indicated that symptoms of prolonged grief, posttraumatic stress, and major depression were distinct factors in the bereaved sample, the three-factor solution was a good fit for the job-loss and divorce samples, and levels of grief in each sample appeared to be best predicted by time since loss and centrality of the loss to one’s identity. Limitations Limitations include potential sample bias due to convenience sampling, and the cross-sectional design did not allow examination of the stability of factors over time. Conclusions These results suggest that grief is not a unique response to loss of loved one but instead may be a common phenomenology across types of loss. This implies that facilitating meaningful engagement in self-defining activities that compensate for the disrupting loss might be efficacious in promoting grief resolution without the need for working through individuals’ emotional attachment to a specific individual or processing one’s emotional responses to the loss.
The findings on the relationship between breastfeeding and children’s motor development are very poor, particularly in low and middle income countries, because of the use of inadequate measures of ...breastfeeding practices.
To assess the relationship between exclusive breastfeeding, measured by the deuterium-oxide turnover method (DTM), and the acquisition of motor development in a cohort of Senegalese children.
One hundred forty mother-infant (4–5 mo) pairs were recruited and monitored up to 18 mo. Breast milk intake and breastfeeding practices were measured by DTM. Six stages of motor development were assessed: “sitting without support,” “hands-and-knees crawling,” “standing with assistance,” “walking with assistance,” “standing alone,” and “walking alone.” Acquisition age of motor milestones between exclusively breastfed (EBF) and not exclusively breastfed (non-EBF) infants was compared using Student’s and Wilcoxon’s tests. Mixed linear regression, adjusted with confounding factors, was used to determine the association between EBF and motor development.
Overall, 32.9% of infants were EBF at the enrollment at 4–5 mo of age. Breast milk intake of EBF infants was significantly higher than that of non-EBF infants (1039 ± 193 g/d compared with 915 ± 211 g/d; P < 0.01). At 4–5 mo of age, only “sitting without support” (67.4% compared with 47.9%, P = 0.02) and “hands-and-knees crawling” (17.4% compared with 4.3%, P = 0.01) were completed significantly in the EBF group. At 18 mo, all children had completed all 6 motor developmental milestones. However, their acquisition age was significantly earlier in the EBF group after adjustment. Non-EBF infants had a delay of 0.4 to 0.5 mo on the acquisition of the first 5 stages compared to EBF infants. For “walking alone,” no difference was found after adjustment.
Motor skill acquisition is earlier in EBF infants compared to non-EBF infants. This finding highlights the need to strengthen the advocacy for EBF up to 6 mo.
This cross‐sectional study was conducted to determine the association between selected characteristics and body composition of mothers and children in early life. This study included 213 mother–child ...pairs 6 to 8 months involving in the cohort study of the Research and Development Project conducted in Kaffrine district. The main outcomes were fat‐free mass (FFM) and body fat (BF), measured using deuterium dilution method and anthropometry. Independent variables were sociodemographic, dietary diversity and health characteristics. Descriptive, correlation, bivariate and multiple regression analyses were conducted. According to body mass index (BMI), 23% of mothers were underweight, 12% were overweight/obese and 11% had excess BF. Four per cent of children were below −2 weight‐for‐length z‐score (WLZ), 10% were below −2 length‐for‐age z‐score (LAZ) and 40% had excess BF. Maternal FFM was positively correlated with child FFM (r = 0.25, P = 0.002). Similarly, mothers' BMI, FFM and BF were significantly and positively correlated with children's LAZ. Stepwise regression showed an increased association between minimum dietary diversity (MDD) and WLZ score, FFM and BF of children. Among mothers, being employee and doing reproductive health care were determinants of higher BMI, FFM and BF. This study found a strong association between maternal and child body composition in early life. Adequate diet is the main determinant of children nutritional status. Among the mothers, having a job and doing primary health care seem to be beneficial for the nutritional status. Improvement of women's empowerment, quality of health care and dietary diversity could have a positive impact on maternal and child nutrition.
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