Preclinical relevance of probiotics in type 2 diabetes: A systematic review

Type 2 diabetes (T2DM) is among the most prevalent metabolic diseases in the world and may result in several long‐term complications. The crosstalk between gut microbiota and host metabolism is closely related to T2DM. Currently, fragmented data hamper defining the relationship between probiotics and T2DM. This systematic review aimed at investigating the effects of probiotics on T2DM in animal models. We systematically reviewed preclinical evidences using PubMed/MEDLINE and Scopus databases, recovering 24 original articles published until September 27th, 2019. This systematic review was performed according to PRISMA guidelines. We included experimental studies with animal models reporting the effects of probiotics on T2DM. Studies were sorted by characteristics of publications, animal models, performed analyses, probiotic used and interventions. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool. Probiotics improved T2DM in 96% of the studies. Most studies (96%) used Lactobacillus strains, and all of them led to improved glycaemia. All studies used rodents as models, and male animals were preferred over females. Results suggest that probiotics have a beneficial effect in T2DM animals and could be used as a supporting alternative in the disease treatment. Considering a detailed evaluation of the reporting and methodological quality, the current preclinical evidence is at high risk of bias. We hope that our critical analysis will be useful in mitigating the sources of bias in further studies.     

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.     

Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection

OBJECTIVE: Helicobacter pylori (H. pylori) eradication rates in northern Sardinia using standard 1-wk triple therapies (i.e., a proton pump inhibitor and two antibiotics) are typically <60%, primarily because of antibiotic resistance. The aim of this study was to test b.i.d. quadruple therapy as primary and as salvage therapy in this population. METHODS: This was a prospective, single center study of consecutive dyspeptic H. pylori-infected patients. Therapy consisted of omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg, all b.i.d. with the midday and evening meals for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology before and 4-6 wk after therapy. Eradication was defined as no positive test. RESULTS: We enrolled 118 consecutive dyspeptic patients (mean age 46 yr; 73 men, including 15 with peptic ulcer disease). Of the patients, 42 (38%) had failed prior therapy: twice in 21 cases, three times in 12, and four or more times in nine. The intention-to-treat cure rate was 95% (110 of 116) (95% CI = 90-98%) overall, and 98% per protocol, irrespective of diagnosis, age, prior treatment failure, or smoking status. Moderate or severe side effects were experienced by only 5% of patients. CONCLUSIONS: Bismuth subcitrate-based b.i.d. quadruple therapy was an excellent primary and salvage therapy and should be considered as first line therapy.     

Development and characterization of a 99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

The aim of this work was to develop and evaluate a ^99mTc‐labeled neuropeptide Y derivative with affinity toward Y1‐receptor. The selected amino acid sequence included nine amino acids derived from the C‐terminal portion of the NPY complemented with the addition of one cysteine‐mercaptoacetic acid moiety to bind the radiometal. Labeling was achieved through the preparation of a 3 + 1 nitrido complex. Physicochemical evaluation, cell uptake, internalization and externalization studies, and competitive assays were performed. Biodistribution experiments were carried out in normal and tumor‐bearing mice. A single product with radiochemical purity >90% and high stability was obtained. In vitro analysis showed specific cellular uptake, IC₅₀ of 73.2 nM, and a high internalization rate (80%). Biodistribution studies showed low blood and renal uptake and combined hepatobiliary and urinary elimination. Preliminary studies in mice bearing induced breast tumors rendered promising uptake values.     

Human NK cells,their receptors and function

NK cells are cytotoxic components of innate lymphoid cells (ILC) that provide a first line of defense against viral infections and contribute to control tumor growth and metastasis. Their function is finely regulated by an array of HLA-specific and non-HLA-specific inhibitory and activating receptors which allow to discriminate between healthy and altered cells. Human NK cells gained a major attention in recent years because of the important progresses in understanding their biology and of some promising data in tumor therapy. In this review, we will outline well-established issues of human NK cells and discuss some of the open questions, debates, and recent advances regarding their origin, differentiation, and tissue distribution. Newly defined NK cell specializations, including the impact of inhibitory checkpoints on their function, their crosstalk with other cell types, and the remarkable adaptive features acquired in response to certain virus infections will also be discussed.     

Mammalian Erv46 localizes to the endoplasmic reticulum-Golgi intermediate compartment and to cis-Golgi cisternae

Yeast endoplasmic reticulum (ER) vesicle protein Erv46p is a novel membrane protein involved in transport through the early secretory pathway. Investigation of mammalian Erv46 (mErv46) reveals that it is broadly expressed in tissues and protein-secreting cells. By immunofluorescence microscopy, mErv46 displays a crescent-shaped perinuclear staining pattern that is characteristic of the Golgi complex. Quantitative immunoelectron microscopy indicates that mErv46 is restricted to the cis face of the Golgi apparatus and to vesicular tubular structures between the transitional ER and cis-Golgi. Minor amounts of mErv46 reside in ER membranes and later Golgi cisternae. On Brefeldin A treatment, mErv46 redistributes to punctate structures that costain for ERGIC53. Depletion of mErv46 protein by RNA interference caused no apparent structural changes in the intermediate compartment or Golgi complex. These findings place mErv46 in a group of itinerant proteins that cycle between the ER and Golgi compartments such as ERGIC53 and the p24 proteins.