Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicle (EV) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, Western blot (WB), nanoparticle tracking analysis, and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs, followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. The proteomics of lymphocytes sorted from EV-treated or untreated PBMCs was performed, and the IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by the proteomic analysis were connected in a single functional network (p = 1 × 10-16) and were involved in the "Immune System" (FDR: 1.10 × 10-24 and 3.69 × 10-19, respectively). Interestingly, the treatment of healthy donor-derived PBMCs with Capan-2 EVs but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. The proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among the major upstream regulators, as confirmed by ELISA. The proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune responses, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

Effects of GHRH Deficiency and GHRH Antagonism on Emotional Disorders in Mice.

Growth hormone (GH)-releasing hormone (GHRH) has been suggested to play a crucial role in brain function. We aimed to further investigate the effects of a novel GHRH antagonist of the Miami (MIA) series, MIA-602, on emotional disorders and explore the relationships between the endocrine system and mood disorders. In this context, the effects induced by MIA-602 were also analyzed in comparison to vehicle-treated mice with GH deficiency due to generalized ablation of the GHRH gene (GHRH knock out (GHRHKO)). We show that the chronic subcutaneous administration of MIA-602 to wild type (+/+) mice, as well as generalized ablation of the GHRH gene, is associated with anxiolytic and antidepressant behavior. Moreover, immunohistochemical and Western blot analyses suggested an evident activation of Nrf2, HO1, and NQO1 in the prefrontal cortex of both +/+ mice treated with MIA-602 (+/+ MIA-602) and homozygous GHRHKO (-/- control) animals. Finally, we also found significantly decreased COX-2, iNOS, NFkB, and TNF-α gene expressions, as well as increased P-AKT and AKT levels in +/+ MIA-602 and -/- control animals compared to +/+ mice treated with vehicle (+/+ control). We hypothesize that the generalized ablation of the GHRH gene leads to a dysregulation of neural pathways, which is mimicked by GHRH antagonist treatment.

Anti-Inflammatory and Vasorelaxant Effects Induced by an Aqueous Aged Black Garlic Extract Supplemented with Vitamins D, C, and B12 on Cardiovascular System.

Multiple studies demonstrated biological activities of aged black garlic, including anti-inflammatory, antioxidant, and cardioprotective effects. We aimed to investigate the protective effects of an aged black garlic water extract (ABGE) alone or in association with multivitamins consisting of combined Vitamins D, C, and B12, on mouse heart specimens exposed to E. coli lipopolysaccharide (LPS). Moreover, we studied the hydrogen sulphide (H2S) releasing properties and the membrane hyperpolarization effect of the Formulation composed by ABGE and multivitamins, using Human Aortic Smooth Muscle Cells (HASMCs). ABGE, vitamins D and C, and the Formulation suppressed LPS-induced gene expression of cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, nuclear factor-kB (NF-kB), and inducible nitric oxide synthase (iNOS) on mouse heart specimens. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin. The Formulation also increased fluorescence values compared to the vehicle, and it caused a significant membrane hyperpolarization of HASMCs compared to ABGE. To conclude, our present findings showed that ABGE, alone and in association with multivitamins, exhibited protective effects on mouse heart. Moreover, the Formulation increased intracellular H2S formation, further suggesting its potential use on cardiovascular disease.

Color vision study to assess the impaired retina-brain cortex pathway in type 2 diabetes: a pilot study in Calabria (Southern Italy).

The present pilot study was undertaken to investigate the impaired acquired color vision on Calabrian male sample showing this parameter as a biological marker in type 2 diabetes. All patients and controls underwent three pseudo-isochromatic clinical test batteries: Ishihara test, Farnsworth test, and City University test. The results show a specific loss of short-wavelength (blue sensitivity) and typical tritan responses in diabetic patients. Generally, in later stages of the disease, the red-green mechanisms are involved. By the impaired color vision study in diabetic patients, we can confirm the impaired retina-brain cortex pathway. We believe that the above not invasive test analysis can support the other instrumental and imaging analysis to study the impaired retina-brain cortex pathway. Moreover, we think that the present clinical method can be useful in terms of preventive medicine.

The discovery of beri-beri and scurvy vitamins - two hundred and two years from its discovery.

The history of the discovery of vitamins was the history of their deficiency disorders. Casimir Funk, the father of vitaminic therapy, studied the interrelationships in the human body of those elements that Christiaan Eijkman demonstrated in animals, particularly birds. In 1911, he designated these factors vitamins (vita = life and amine, a nitrogenous substance essential for life); this name was accepted by the scientific community in 1912. Here, we intend to give an illustrative view on the early days of vitamin research as carried out by Casimir Funk.

Impairment of acquired color vision in multiple sclerosis: an early diagnostic sign linked to the greatness of disease.

OBJECTIVE: To assess the type and degree of both red-green and blue-yellow color vision deficiencies of Calabrian males affected by multiple sclerosis. MATERIAL: Eighty Calabrian male patients were enrolled (age range 18-70 years; mean age 40.6 ± 12.4 years) showing a disease duration mean of 10.6 ± 8.2 years (range = 0.5-46 years) coming from the Institute of Neurology, Magna Graecia University, Catanzaro. Optic neuritis present in the medical histories of the 21 patients does not influence color vision. Excluding seven colorblind subjects and one affected by a bilateral maculopathy, the analyzed sample group was 72. Seventy controls were matched for age and sex. METHOD: An ophthalmologist examined all patients and controls in order to rule out diabetic retinopathy, cataracts, senile maculopathy, or ocular fundus' anomalies. The Ishihara test identified the colorblind patients. The City University Test screened for people with abnormal color vision by grading the severity of color vision deficiency. The second part of the City University Test as well as the Farnsworth Test confirmed both the color vision deficiency type and degree. RESULTS: Fifty-one percentage (37/72) of the patients showing a color vision deficiency were subdivided into two subgroups: subgroup one showed red-green deficiency (57%, 21/37); subgroup two showed a coupled red-green and blue-yellow deficiency (43%, 16/37). Furthermore, we found two distinct curves showing a groove within the first 10 years of the disease. Both monocular and binocular analyses allowed us to identify the patients showing the monocular color vision deficiency, but they were well compensated by binocular vision. CONCLUSION: We think that the majority of the patients with the red-green deficiency will develop the coupled red-green and blue-yellow deficiency in the latter years of multiple sclerosis.

Epilepsy in popular Medicine from the Classic Age to the Modern Age: a study on elk hoof as an original treatment.

European people believed that epilepsy was both a sacred and demoniac disease in the pre- and post-Hippocratic Age, and this belief continued into the Christian era. Epilepsy was wrapped in mystery. The present work shows an epileptic treatment using elk (Alces alces) hoof, which was better known among Northern European people, and explains its historical and popular origins that lead to its importance and success within the Official Medicine in the sixteenth and seventeenth centuries until its gradual decline as a specific treatment in the subsequent centuries. We study authors from both Antiquity and the Modern Age. The present work concludes by highlighting the relationship between epilepsy and its magic-religious inheritance. It could be considered a valid example showing how a popular treatment can earn honors in the Official Pharmacopoeia, but later be excluded.

On the illness of Politian (Agnolo Ambrogini, 1454-1494): syphilis at its identification in Europe.

The authors investigated the life, the works and the illness of the humanist and poet Agnolo Ambrogini, better known as Politian, and the cause of his death, shedding evidence on the ambiguous meaning of the term scabies that is included in the titles of two works ascribed to Politian, namely 'Sylva in scabiem' and 'De scabie'. These two works tell us the illness that will kill Politian who describes them in detail as a new illness that does appear in other important works dated between the end of the 15th century and the beginning of the 16th. This new illness will be called 'syphilis'. Syphilis was virulent in Europe soon after it appeared and it killed Politian within one year. He seems to have been the first famous European who was not a physician who described his own syphilis. Others include the poet Niccolò Campani (1478-1523), the writer and humanist Ulrich Von Hutten (1488-1523), the sculptor and writer Benvenuto Cellini (1500-1571) and Joseph Grunpeck (1473-1532), and secretary to Emperor Maximilian I (1459-1519). The origins of this serious condition have been ascribed to the crew who accompanied Christopher Columbus (1451-1506).

Treating epilepsy in Italy between XIX and XX century.

Epilepsy is a neurological disorder which has been recognized since antiquity. This paper evaluates the prophylactic and therapeutic remedies used by folk medicine to cure epilepsy in Italy. The data has been collected by reviewing written sources of physicians, ethnographers, folklorists between the late nineteenth and mid twentieth century. This approach leads to unearthing of 78 heterogeneous healing methods that have been divided into 16 (20%) magical, 20 (26%) religious and 42 (54%) natural remedies. The latter has been subdivided into 18 (43%) animal remedies, 17 (40%) plant remedies and 7 (17%) other remedies. Religious and magical remedies were used with the conviction that they would be able to provide recovery from epilepsy and to ward off evil spirits which had taken possession of the sick. Interestingly, the herbal remedies highlighted 12 (70%) plants that play or might play an important role with respect to the mechanisms that generate the epileptic seizures. This leads us to reconsider the historical significance of folk medicine, too often it is underestimated owing to its use of ineffective remedies, born of incompetence and superstition.