Algal Biotechnology: Properties of Bioactive Derivatives and Pharmaceutical Applications

Continuous development of new pathologies and mutations together with the increment of drug resistance make the research of new treatments and therapies more urgent and essential. Among the renewable resources, algae and related bioactive compounds are strongly considered. Algae are eukaryotic organisms characterised by high therapeutic potential. Indeed, because of biotic and abiotic factors, algae produce a wide variety of metabolites, which are useful for treating dysfunctions and diseases. The most produced metabolites are proteins, carbohydrates, lipids, vitamins, polyphenols, and pigments, which find several applications in daily life, as indicated in Fig. 1. The different classes of metabolites are relevant to the species they belong to; they are also divided into groups according to their medical properties. Over the years, advantages and performances of algae derivatives have been demonstrated by a growing number of analyses and researches, especially in recent years. Among the various properties of algae metabolites, anti-inflammatory, antiviral, antibacterial, antioxidant and antidiabetic are the most promising. Pigments (e.g. fucoxanthin) and polyphenols are the main compounds with anti-inflammatory activity; the latter also show antiviral, antidiabetic and antibacterial effects. Other compounds with antidiabetic activity are some xanthophylls and some polysaccharides (e.g. fucoidan and alginate). Among the antioxidant metabolites of algae, the most useful are flavonoids (i.e. polyphenols), carotenoids, pigments, vitamins, minerals and enzymes. Fatty acids show antibacterial ability, while carrageenans and other polysaccharides show both antibacterial and antiviral effects. Supporting algal research is a valid strategy to improve ongoing trials, expand or confirm obtained results, discover and include new molecules in biotechnology applications with the aim to introduce novel medical and pharmacological uses in modern medicine. A typical example is related to diabetes mellitus, which is a disease in constant growth. Nowadays, numerous trials are ongoing to develop innovative and more efficient treatments and several algae are analysed with respect to this pathology. Indeed, some algal bioactive compounds, in particular polyphenol derivatives, polysaccharides and pigments, have antidiabetic properties; these metabolites inhibit the enzymes α-glucosidase, α-amylase and aldose reductase, reduce reactive oxygen species, decrease lipid peroxidation and interfere on metabolic pathways. The results are decrement of blood glucose levels and increment of insulin values, which are critical in diabetic patients.

Herpes simplex virus-type1 (HSV-1) impairs DNA repair in cortical neurons

Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions

Drug conjugation to hyaluronan widens therapeutic indications for ovarian cancer

Management of ovarian cancer still requires improvements in therapeutic options. A drug delivery strategy was tested that allows specific targeting of tumor cells in combination with a controlled release of a cytotoxic molecule. To this aim, the efficacy of a loco-regional intraperitoneal treatment with a bioconjugate (ONCOFID-S) derived by chemical linking of SN-38, the active metabolite of irinotecan (CPT-11), to hyaluronan was assessed in a mouse model of ovarian carcinomatosis. In vitro, the bioconjugate selectively interacted with ovarian cancer cells through the CD44 receptor, disclosed a dose-dependent tumor growth inhibition efficacy comparable to that of free SN-38 drug, and inhibited Topoisomerase I function leading to apoptosis by a mechanism involving caspase-3 and -7 activation and PARP cleavage. In vivo, the intraperitoneal administration of ONCOFID-S in tumor-bearing mice did not induce inflammation, and evidenced an improved therapeutic efficacy compared with CPT-11. In conclusion, SN-38 conjugation to hyaluronan significantly improved the profile of in vivo tolerability and widened the field of application of irinotecan. Therefore, this approach can be envisaged as a promising therapeutic strategy for loco-regional treatment of ovarian cancer

O6-alkylguanine-DNA Alkyltransferases in Microbes Living on the Edge: From Stability to Applicability

The genome of living cells is continuously exposed to endogenous and exogenous attacks, and this is particularly amplified at high temperatures. Alkylating agents cause DNA damage, leading to mutations and cell death; for this reason, they also play a central role in chemotherapy treatments. A class of enzymes known as AGTs (alkylguanine-DNA-alkyltransferases) protects the DNA from mutations caused by alkylating agents, in particular in the recognition and repair of alkylated guanines in O6-position. The peculiar irreversible self-alkylation reaction of these enzymes triggered numerous studies, especially on the human homologue, in order to identify effective inhibitors in the fight against cancer. In modern biotechnology, engineered variants of AGTs are developed to be used as protein tags for the attachment of chemical ligands. In the last decade, research on AGTs from (hyper)thermophilic sources proved useful as a model system to clarify numerous phenomena, also common for mesophilic enzymes. This review traces recent progress in this class of thermozymes, emphasizing their usefulness in basic research and their consequent advantages for in vivo and in vitro biotechnological applications

The risk of bleeding and encephalopathy in surgical patients with liver cirrhosis

Liver cirrhosis is a disease with an increasing incidence. Surgical procedures in patients with cirrhosis are also increasing, due to a longer life expectancy in these patients and also to the improvement of therapeutic and diagnostic resources. Digestive hemorrhage in the cirrhotic patient requires emergency medical intervention (intensive therapy, endoscopic or even surgical approaches), being at the same time a factor that precipitates episodes of encephalopathy, i.e. the conventional complication of cirrhosis. Hepatic encephalopathy represents one of the most severe clinical events of cirrhosis, being associated with high morbidity and mortality. The causes of hepatic encephalopathy are briefly presented in this paper. Therapeutic approaches currently available consist in the administration of non-absorbable disaccharides such as lactulose and non-absorbable antibiotics such as rifaximin. New therapeutic perspectives are under evaluation, e.g. ammonia scavengers and the modulation of gut microbiota. Clotting disorders in patients with liver cirrhosis are more severe as the disease progresses and involves complex mechanisms, as presented in this review. The correction of possible disorders of hemostasis should be promptly made as a sine qua non condition prior to surgery

Reverse immunoediting: When immunity is edited by antigen

Immune selective pressure occurring during cancer immunoediting shapes tumor features revealed at clinical presentation. However, in the "Escape" phase, the tumor itself has the chance to influence the immunological response. Therefore, the capacity of the immune response to sculpt the tumor characteristics is only one side of the coin and even the opposite is likely true, i.e. that an antigen can shape the immune response in a sort of "reverse immunoediting". This reciprocal modeling probably occurs continuously, whenever the immune system encounters a tumor/foreign antigen, and can be operative in the pathogen/immune system interplay, thus possibly permeating the protective immunity as a whole. In line with this view, the characterization of a T cell response as well as the design of both active and passive immunotherapy strategies should also take into account all Ag features (type, load and presentation). Overall, we suggest that the "reverse immunoediting" hypothesis could help to dissect the complex interplay between antigens and the immune repertoire, and to improve the outcome of immunotherapeutic approaches, where T cell responses are manipulated and reprogrammed

Impact of γ-chain cytokines on EBV-specific T cell cultures

<p>Abstract</p> <p>Background</p> <p>Recent preclinical adoptive immunotherapy studies in murine models prompt to employ "proper" rather than "as many as possible" antigen-specific T cells to gain better therapeutic results. Ideally, "proper" T cells are poorly differentiated <it>in vitro</it>, but retain the capacity to fully differentiate into effector cells <it>in vivo</it>, where they can undergo long-term survival and strong proliferation. Such requirements can be achieved by modifying culture conditions, namely using less "differentiating" cytokines than IL-2.</p> <p>Methods</p> <p>To evaluate this issue in human T cell cultures, we exploited a well characterized and clinical-grade protocol finalized at generating EBV-specific CTL for adoptive immunotherapy. In particular, we studied the impact of IL-7, IL-15 and IL-21 compared to IL-2 on different aspects of T cell functionality, namely growth kinetics, differentiation/activation marker expression, cytokine production, and short-term and long-term cytotoxicity.</p> <p>Results</p> <p>Results disclosed that the culture modifications we introduced in the standard protocol did not improve activity nor induce substantial changes in differentiation marker expression of EBV-specific CTL.</p> <p>Conclusions</p> <p>Our data indicated that the addition of γ-chain cytokines other than IL-2 for the generation of EBV-specific T cell cultures did not produce the improvements expected on the basis of recent published literature. This fact was likely due to the intrinsic differences between murine and human models and highlights the need to design <it>ad hoc </it>protocols rather than simply modify the cytokines added in culture.</p

Characteristics and Treatment Outcome of Cerebrospinal Fluid Shunt-Associated Infections in Adults: A Retrospective Analysis over an 11-Year Period

Background. Data on infections associated with cerebrospinal fluid (CSF) shunts among adults are limited. Therefore, we performed a retrospective study of shunt-associated infections in adults. Methods. Patients aged ⩾12 years with infections associated with CSF shunts and admitted to our institution (University Hospital Basel, Basel, Switzerland) from January 1996 through December 2006 were included retrospectively. Hospital charts were reviewed, and follow-up was performed by assessment of later hospitalizations and telephone contact with patients, their families, and general practitioners. Results. Seventy-eight episodes of infection associated with ventriculoperitoneal shunt (65 episodes), ventriculoatrial shunt (7), lumboperitoneal shunt (5), and central nervous system reservoir (1) were included. Median patient age was 50 years (range, 12-80 years); 49 (63%) of the patients were men. Most infections (48 [62%]) manifested within 1 month after shunt surgery. Fever was present in 61 episodes (78%), neck stiffness was present in 35 (45%), and local signs of infection were present in 38 (49%). In CSF, leukocyte count was >5×106 cells/L in 80% of episodes, and lactate level was >1.9 mmol/L in 81% of episodes. Leukocyte counts were significantly higher in CSF obtained by use of lumbar puncture (median leukocyte count, 573×106 cells/L; P=.001) and valve puncture (median leukocyte count, 484×106 cells/L; P=.016) than in ventricular CSF (median leukocyte count, 8.5×106 cells/L). Overall, results of CSF cultures were positive in 66% of episodes (48 of 73 episodes for which CSF was collected), and microorganisms were isolated more often from valve puncture CSF specimens (91% of specimens) and ventricular CSF specimens (70%) than from lumbar CSF specimens (45%). The most prevalent organisms were coagulase-negative staphylococci (found in 37% of specimens), Staphylococcus aureus (18%), and Propionibacterium acnes (9%). A surgical procedure was performed to treat infection in 63 (81% of the episodes) (shunt removal in 37 episodes and shunt replacement in 26). The shunt was retained without surgery for 15 episodes (19% of episodes). Median duration of patient follow-up was 4.6 years (range, 0.1-11.1 years), with favorable treatment outcome in 75 (96%) of 78 cases. One of the 63 patients who underwent surgical treatment of shunt-associated infection experienced infection relapse; of the 15 patients who received treatment with antibiotics alone, 1 experienced infection relapse and 1 died. The 2 relapses involved rifampin-resistant coagulase-negative staphylococci. Conclusions. Shunt-associated infections among adults often present with nonspecific clinical signs, and affected patients can have normal CSF leukocyte counts and lactate levels; therefore, a high index of suspicion and improved methods are required for diagnosing shunt-associated infectio

Object and object’s image

This  essay  discusses  the  object  and  the  object’s  image  under  the light  of  concepts   drawn  from  discussions  and  texts  about  the  New Museology,  1989,  and  Key  Concepts   of  Museology,  2013,  using  the case  of  the  Museum  of  Clothing  and  Fashion  /MIMo,  its   constitution, interfaces  and  actions,  evaluating  the  results  obtained,  during  the brief  existence  of  five  years  ,  dissemination  and  promotion  of  doing and knowing  in  a  digital   museum.Este ensaio discute o objeto e a imagem do objeto sob a luz de conceitos extraídos de debates e publicação de textos sobre a Nova Museologia, 1989, e Conceitos‐chave de Museologia, 2013, utilizando o estudo de caso o Museu da Indumentária e da Moda/MIMo, sua constituição, interfaces e ações, avaliando os resultados obtidos, durante a breve existência de cinco anos, na divulgação e promoção de fazeres e saberes em um museu digital

Intersectional inequalities and the U.S. opioid crisis:Challenging dominant narratives and revealing heterogeneities

Dominant narratives of prescription opioid misuse (POM) in the U.S. have portrayed it as an issue primarily affecting White communities. In this study we explore POM as reported in data from the 2015 National Survey on Drug Use and Health, using an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). We map the risk of POM through a series of multilevel models with individuals (N = 43,409) nested within strata formed by the intersections of gender, race/ethnicity, income, and age. We find meaningful heterogeneity between and within strata. The ten strata with the greatest risk for POM were comprised of individuals identifying as White, African American, and non-White Hispanic, and included individuals of low, medium, and high income. We uncover intersections of social position with high risk for POM that are often excluded from dominant narratives, including young high-income African American women. Intersectional approaches are essential for advancing our understanding of health inequalities and unfolding epidemics such as that of POM in the U.S