Promising activities of marine natural products against hematopoietic malignancies

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially available marine-derived compounds for the treatment of various hematopoietic cancers (e.g., leukemia and lymphoma), two molecules in clinical trials, and series of compounds and/or extracts from marine micro-and macroorganisms which have shown promising properties. In addition, the mechanisms of action of several active compounds and extracts are still unknown and require further study. The continuous upgrading of omics technologies has also allowed identifying enzymes with possible bioactivity (e.g., L-asparaginase is currently used for the treatment of leukemia) or the enzymes involved in the synthesis of bioactive secondary metabolites which can be the target of heterologous expression and genetic engineering

Immune effects of four Fusarium-Toxins ( FB1, ZEA, NIV, DON) on the proliferation of Jurkat cells and porcine lymphocytes: in vitro study.

Fusarium toxins are secondary metabolites produced by fungi belonging to Fusarium spp., commonly found as contaminants in products of vegetable origin, particularly in cereal grains, in regions with temperate climate in Europe, America and Asia. Numerous toxic effects are attributed to mycotoxins both in humans and animals, such as mutagenic, cencerogenic and teratogenic properties. Moreover, some of them can alter normal immune responses when they are present in food at levels lower than those necessary to cause the symptoms of mycotoxicosis. In the present work, we evaluated the immunomodulatory effects of four Fusarium toxins (FB1, ZEA, NIV, DON) using two different experimental models: Jurkat cells and porcine lymphocytes. In addition to the activity of single mycotoxins, we evaluated possible interactions between Fusarium toxins to reproduce experimental conditions in vitro as near as possible to field conditions. Our results revealed the immunomodulatory properties of the mycotoxin objects of the current study. They also underline the interest in studying possible interactions among different mycotoxins, particularly among those mainly present in food such as Fusarium mycotoxins, not only regarding their toxicodinamic aspect but also to define tolerable maximum levels of Fusarium toxins in food

Seroprevalence of ehrlichia spp., anaplasma spp., borrelia burgdorferi sensu lato, and dirofilaria immitis in stray dogs, from 2016 to 2019, in southern Italy

Canine vector-borne diseases (CVBD) are an important and emerging health concern for humans and animals worldwide. The purpose of the presented study was to assess, from 2016 to 2019, the seroprevalence of CVBD agents and clarify the epidemiology of tick-borne disease in stray dogs living in the Campania Region, Southern Italy. For this purpose, blood samples were collected from January 2016 to December 2019 from 1023 dogs in authorized kennels located in the five municipalities of the Campania Region. SNAP® 4DX® from IDEXX® Laboratories was used for detection of Ehrlichia spp., Anaplasma spp., Borrelia burgdorferi sensu lato (s.l.), and Dirofilaria immitis antibodies. The overall seroprevalence of CVBD in stray dogs was 19.6% (95% Confidence Intervals (CI): 17.2–22.8%; 201/1023). The most common pathogen was Ehrlichia spp., with a percentage of positivity of 16.03%, followed by Anaplasma spp. with 7.8%. B. burgdorferi s.l. and D. immitis were detected in only 0.2% of dogs; co-infection was detected in 4.5% of stray dogs tested. No link was detected between the gender, age, location, and CVBD seropositivity, except for Ehrlichia spp. for which location (Avellino Province; p = 0.007) and gender (male, p = 0.002) were risk factors for seropositivity. Our results demonstrated that animals are exposed to at least one of the four etiological agents (Ehrlichia spp., Anaplasma spp. Borrelia burgdorferi s.l., and Dirofilaria immitis) transmitted by vectors. Finally, this study highlighted the utility of serological monitoring in stray dogs, housed in kennels, given the threat posed by CVBD to animals and the zoonotic implications of these etiological agents and their vectors on human health

Curcumin Modulates Nitrosative Stress, Inflammation, and DNA Damage and Protects against Ochratoxin A-Induced Hepatotoxicity and Nephrotoxicity in Rats.

Ochratoxin A (OTA) is a fungal toxin of critical concern for food safety both for human health and several animal species, also representing a cancer threat to humans. Curcumin (CURC) is a natural polyphenol that has anti-apoptotic, anti-inflammatory, and antioxidant effects. The aim of this study was to investigate the cytoprotective effect of CURC against OTA-induced nephrotoxicity and hepatotoxicity through the study of the nitrosative stress, pro-inflammatory cytokines, and deoxyribonucleic acid (DNA) damage. Sprague Dawley rats were daily treated with CURC (100 mg/kg b.w.), OTA (0.5 mg/kg b.w), or CURC with OTA by oral gavage for 14 days. Our results demonstrated that OTA exposure was associated with significant increase of pro-inflammatory and DNA oxidative-damage biomarkers. Moreover, OTA induced the inducible nitric oxide synthase, (iNOS) resulting in increased nitric oxide (NO) levels both in kidney and liver. The co-treatment OTA + CURC counteracted the harmful effects of chronic OTA treatment by regulating inflammation, reducing NO levels and oxidative DNA damage in kidney and liver tissues. Histology revealed that OTA + CURC treatment determinates mainly an Iba1+ macrophagic infiltration with fewer CD3+ T-lymphocytes in the tissues. In conclusion, we evidenced that CURC exerted cytoprotective and antioxidant activities against OTA-induced toxicity in rats

Effects of the antioxidant crocin on frozen-thawed buffalo (Bubalus bubalis) sperm

This work aimed to evaluate the effect of crocin on frozen-thawed sperm quality in buffalo. Spermatozoa were incubated in Tyrode’s Albumin Lactate Pyruvate medium supplemented with 0, 0.5, 1, and 2 mM crocin for 2 h. Sperm motility was evaluated by phase-contrast microscopy, viability and acrosome integrity by Trypan blue Giemsa staining, and membrane functional integrity by the hypoosmotic swelling test. The DNA fragmentation was evaluated by Tunel and ROS levels by spectrofluorometric analysis. The treatment with 2 mM of crocin increased (P <.05) sperm membrane functional integrity compared to the control group (59.1 ± 1.6 vs 53.3 ± 1.5) and reduced sperm DNA fragmentation, compared to the other groups (11.3 ± 1.1, 13.3 ± 1.2, 13.6 ± 1.2 and 6.0 ± 0.7, respectively in 0, 0.5, 1 and 2 mM crocin; P <.01). Finally, a dose-dependent decrease (P <.01) in superoxide anion production in the presence of crocin was observed, as indicated by Dihydroethidium values (922.6 ± 13.0, 596.8 ± 7.4, 498.9 ± 5.3 and 421.4 ± 5.0 a.u., respectively in 0, 0.5, 1 and 2 mM crocin; P <.01). The results of this study demonstrated a positive effect of 2 mM crocin on frozen-thawed buffalo sperm, as indicated by the improvement of sperm membrane integrity and the reduction of DNA fragmentation and ROS levels.Highlights Crocin improves buffalo sperm quality. Crocin improves sperm membrane integrity and reduces DNA fragmentation. Crocin decreases oxidative stress in buffalo sperm

Vascular calcification progression modulates the risk associated with vascular calcification burden in incident to dialysis patients

Background: It is estimated that chronic kidney disease (CKD) accounts globally for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Traditional as well as non-traditional CV risk factors such as vascular calcification are believed to drive this disproportionate risk burden. We aimed to investigate the association of coronary artery calcification (CAC) progression with all-cause mortality in patients new to hemodialysis (HD). Methods: Post hoc analysis of the Independent study (NCT00710788). At study inception and after 12 months of follow-up, 414 patients underwent computed tomography imaging for quantification of CAC via the Agatston methods. The square root method was used to assess CAC progression (CACP), and survival analyses were used to test its association with mortality. Results: Over a median follow-up of 36 months, 106 patients died from all causes. Expired patients were older, more likely to be diabetic or to have experienced an atherosclerotic CV event, and exhibited a significantly greater CAC burden (p = 0.002). Survival analyses confirmed an independent association of CAC burden (hazard ratio: 1.29; 95% confidence interval: 1.17–1.44) and CACP (HR: 5.16; 2.61–10.21) with all-cause mortality. CACP mitigated the risk associated with CAC burden (p = 0.002), and adjustment for calcium-free phosphate binder attenuated the strength of the link between CACP and mortality. Conclusions: CAC burden and CACP predict mortality in incident to dialysis patients. However, CACP reduced the risk associated with baseline CAC, and calcium-free phosphate binders attenuated the association of CACP and outcomes, suggesting that CACP modulation may improve survival in this population. Future endeavors are needed to confirm whether drugs or kidney transplantation may attenuate CACP and improve survival in HD patients

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidants, oncolytic virus, engineered exosomes, and natural products obtained from marine organisms that could pave the way for new therapeutic approaches for CML patients