Immunization with the hybrid protein vaccine, consisting of Leishmania major cysteine proteinases Type I (CPB) and Type II (CPA), partially protects against leishmaniasis

Cysteine proteinases (CPs) are enzymes that belong to the papain superfamily, which are found in a number of organisms from prokaryotes to mammals. On the parasitic protozoan Leishmania, extensive studies have shown that CPs are involved in parasite survival, replication and the onset of disease, and have, therefore, been considered as attractive drugs and/or vaccine targets for the control of leishmaniasis. We have previously shown that cysteine proteinases, Type I (CPB) and Type II (CPA), in Leishmania major (L. major), delivered as recombinant proteins or in plasmid DNA, induce partial protection against infection with the parasite in BALB/c mice. We had shown that the level of protection was greater if a cocktail of cpa and cpb containing DNA constructs was used. Therefore, to reduce the costs associated with the production of these vaccine candidates, a construct was developed, whereby the cpa and cpb genes were fused together to give rise to a single hybrid protein. The genes were fused in tandem where the C-terminal extension (CTE), encoding region of CPB, was located at the 3' of the fused genes, and ultimately expressed in the bacterial expression construct pET-23a. The expression of the CPA/B hybrid protein (60 kDa) was verified using rabbit anti-CPA and anti-CPB antibodies by SDS-PAGE and immunoblotting. The protective potential of the CPA/B hybrid protein against the infection with Leishmania was then assessed in BALB/c mice. The animals were vaccinated with CPA/B, challenged with live L. major promastigotes, and the degree of protection was examined by measuring footpad lesion sizes. It was found that there was a delay in the expansion of lesions size compared to control groups. Furthermore, an immunological analysis of antibody isotypes, before and after infection, showed high levels of IgG2a compared to IgG1 (more than five-fold) in the CPA/B hybrid protein vaccinated group. In addition, a predominant Th1 immune response characterized by in vitro IFN-gamma production was observed, along with little, if any, IL-5 production. This finding indicates that the hybrid CPA/B is able to elicit a protective immune response against L. major in the mice model. In addition, 54% of individuals tested, who had recovered from cutaneous leishmaniasis, produced more than 50 pg/ml IFN-gamma, in response to the CPA/B hybrid protein in an in vitro assay, demonstrating the importance of cysteine proteinases as targets of immune response in humans.     

Vitamin D Status and Risk of Breast Cancer in Iranian Women: A Case–Control Study

Objective: Considering the rising incidence of breast cancer and high prevalence of vitamin D deficiency in Iran, this case–control study aimed to investigate the relationship between serum concentration and intake of vitamin D and risk of breast cancer.

Methods: A total of 135 incident breast cancer cases at the Cancer Research Center of Shahid Beheshti University of Medical Sciences were matched with 135 controls by age and menopausal status. A validated and reliable 168-item food frequency questionnaire was completed by participant interviews. To determine the vitamin D content of foods we used the U.S. Department of Agriculture (USDA) nutrient database. To analyze the food frequency questionnaires we used the data collected in the Iranian Household Food Pattern Study, conducted by the National Nutrition and Food Technology Research Institute and the Iranian Ministry of Agriculture. Five-milliliter blood samples were collected to measure serum 25-hydroxyvitamin D (25(OH)D) using an enzyme-linked immunosorbent assay method.

Results: Women in the fourth quartile of serum 25(OH)D level had 3 times lower risk of developing breast cancer compared to those in the first quartile. In the adjusted model the inverse relationship remained significant (odds ratio [OR] = 0.269; 95% confidence interval [CI], 0.122–0.593). In the stratified model by menopausal status the inverse association was only seen in premenopausal women (OR = 0.25; 95% CI, 0.094–0.687).

Dietary intake of vitamin D was inversely associated with risk of breast cancer (OR fourth quartile [Q4] vs first quartile [Q1] = 0.39; 95% CI, 0.196–0.784; p = 0.008). After adjusting for the confounding factors, this inverse association remained significant.

Conclusion: Results from this case–control study support the protective effect of higher serum concentration of 25(OH)D against breast cancer. Moreover, dietary but not total intake of vitamin D was associated with decreased risk of breast cancer.     

Orbital metastasis as the initial finding of breast carcinoma: a ten-year survival

A 50-year-old woman with a clinically negative breast examination was diagnosed with metastatic breast cancer only after pathologic evidence of an orbital metastasis. She presented with pressure and pain above the right eye associated with enophthalmos and pseudo-Brown syndrome. The diagnosis of breast cancer based on initial ophthalmic findings requires a strong level of suspicion. Multiple reports show that survival in these cases is limited, usually only 1 year after diagnosis. We present a case of 10-year survival after the diagnosis of breast cancer presenting as an orbital mass. These new findings provoke us to continue aggressive systemic and ophthalmic treatment for such patients.     

Challenges in the Management of Giant Intraductal Breast Papilloma

The differential diagnosis of a large breast mass in a post‐menopausal woman can include both benign and malignant etiologies. Although rare, diagnosis of giant intraductal papilloma must be considered in the differential. Furthermore, although benign, papillomas presenting as a large breast mass affecting the skin require extensive breast surgical treatment.     

Effect of Q10 supplementation on body weight and body mass index: A systematic review and meta-analysis of randomized controlled clinical trials

AimsThis meta-analysis study was carried out to assess the effects of coenzyme Q10 supplementation on body weight and body mass index of patients in randomized controlled clinical trial studies.Materials and methodsA comprehensive systematic search of literature was performed through ISI web of sciences, PubMed, Scopus and Cochrane library databases up to February 2018 which was supplemented by manual search of the references list of included studies. From a total of 1579 identified articles, only 17 trials with 14 and 14 effect-sizes were included for pooling the effects of co-enzyme Q10 supplementation on body weight and body mass index, respectively.ResultsResults of random-effect size meta-analysis showed that supplementation with coenzyme Q10 had no significant decreasing effects on body weight (WMD: 0.28 kg; 95% CI = ?0.91, 1.47; P = 0.64) and BMI (WMD: ?0.03; 95% CI = ?0.4, 0.34; P = 0.86) of study participants. Subgroup analysis revealed that dosage of Q10 and trial duration could not differ the results of Q10 supplementation.ConclusionResults of this meta-analysis study failed to show any beneficial effect of coenzyme Q10 supplementation on body weight and BMI of patients in clinical trial studies.