Oxidative stress and inflammation: determinants of anthracycline cardiotoxicity and possible therapeutic targets

Chemotherapy with anthracycline-based regimens remains a cornerstone of treatment of many solid and blood tumors but is associated with a significant risk of cardiotoxicity, which can manifest as asymptomatic left ventricular dysfunction or overt heart failure. These effects are typically dose-dependent and cumulative and may require appropriate screening strategies and cardioprotective therapies in order to minimize changes to anticancer regimens or even their discontinuation. Our current understanding of cardiac damage by anthracyclines includes a central role of oxidative stress and inflammation. The identification of these processes through circulating biomarkers or imaging techniques might then be helpful for early diagnosis and risk stratification. Furthermore, therapeutic strategies relieving oxidative stress and inflammation hold promise to prevent heart failure development or at least to mitigate cardiac damage, although further evidence is needed on their efficacy, either alone or as part of combination therapies with neurohormonal antagonists, which are the current adopted standard

Genome-Wide Analysis of the “Cut-and-Paste” Transposons of Grapevine

Background: The grapevine is a widely cultivated crop and a high number of different varieties have been selected since its domestication in the Neolithic period. Although sexual crossing has been a major driver of grapevine evolution, its vegetative propagation enhanced the impact of somatic mutations and has been important for grapevine diversity. Transposable elements are known to be major contributors to genome variability and, in particular, to somatic mutations. Thus, transposable elements have probably played a major role in grapevine domestication and evolution. The recent publication of the complete grapevine genome opens the possibility for an in deep analysis of its transposon content. Principal Findings: We present here a detailed analysis of the ‘‘cut-and-paste’ ’ class II transposons present in the genome of grapevine. We characterized 1160 potentially complete grapevine transposons as well as 2086 defective copies. We report on the structure of each element, their potentiality to encode a functional transposase, and the existence of matching ESTs that could suggest their transcription. Conclusions: Our results show that these elements have transduplicated and amplified cellular sequences and some of them have been domesticated and probably fulfill cellular functions. In addition, we provide evidences that the mobility o

Remote Ischemic Conditioning in Ischemic Stroke and Myocardial Infarction: Similarities and Differences

Acute myocardial infarction and ischemic stroke are leading causes of morbidity and mortality worldwide. Although reperfusion therapies have greatly improved the outcomes of patients with these conditions, many patients die or are severely disabled despite complete reperfusion. It is therefore important to identify interventions that can prevent progression to ischemic necrosis and limit ischemia-reperfusion injury. A possible strategy is ischemic conditioning, which consists of inducing ischemia – either in the ischemic organ or in another body site [i.e., remote ischemic conditioning (RIC), e.g., by inflating a cuff around the patient's arm or leg]. The effects of ischemic conditioning have been studied, alone or in combination with revascularization techniques. Based on the timing (before, during, or after ischemia), RIC is classified as pre-, per-/peri-, or post-conditioning, respectively. In this review, we first highlight some pathophysiological and clinical similarities and differences between cardiac and cerebral ischemia. We report evidence that RIC reduces circulating biomarkers of myocardial necrosis, infarct size, and edema, although this effect appears not to translate into a better prognosis. We then review cutting-edge applications of RIC for the treatment of ischemic stroke. We also highlight that, although RIC is a safe procedure that can easily be implemented in hospital and pre-hospital settings, its efficacy in patients with ischemic stroke remains to be proven. We then discuss possible methodological issues of previous studies. We finish by highlighting some perspectives for future research, aimed at increasing the efficacy of ischemic conditioning for improving tissue protection and clinical outcomes, and stratifying myocardial infarction and brain ischemia patients to enhance treatment feasibility

The role of Locus Coeruleus in neuroinflammation occurring in Alzheimer's disease

Alzheimer's Disease (AD) represents the main degenerative dementia. Its neuropathological hallmarks are β-amyloid plaques (APs) and neurofibrillary tangles (NFT), which lead to neuronal loss and brain atrophy. Recent data show that, early in the course of AD, hyperphosphorylated Tau proteins accumulate in Locus Coeruleus (LC) neuronal bodies. The fact that similar alterations have been found also in the entorhinal cortex suggests a causal relationship, although no final causal evidence exists. Later on, in the course of the disease, frank LC neuronal loss occurs, which is associated with marked cerebral NE reduction. In AD, neuroinflammation plays a pivotal role early in the process of APs deposition. LC degeneration is likely to play a key role in AD pathogenesis. In fact, NE modulates growth factors expression as well as integrity and functioning of the blood-brain barrier, and it also directly affects neuroinflammation. For instance, LC modulates microglia and astrocyte function, and this is evident following damage to LC, which induces astro- and micro-gliosis around APs, as well as interleukins secretion. These phenomena are dependent on the activation of beta-adrenergic receptors. The present review provides evidence about immune-mediated mechanisms through which LC may impact the course of AD. Some findings are consolidated in animal models. Should these data be confirmed in humans, adrenergic agents might represent potential therapeutic approaches acting on neuroinflammation to slow down the progression of AD

Portable technologies for digital phenotyping of bipolar disorder: A systematic review

Background: Bias-prone psychiatric interviews remain the mainstay of bipolar disorder (BD) assessment. The development of digital phenotyping promises to improve BD management. We present a systematic review of the evidence about the use of portable digital devices for the identification of BD, BD types and BD mood states and for symptom assessment. Methods: We searched Web of KnowledgeSM, Scopus ®, IEEE Xplore, and ACM Digital Library databases (until 5/1/2021) for articles evaluating the use of portable/wearable digital devices, such as smartphone apps, wearable sensors, audio and/or visual recordings, and multimodal tools. The protocol is registered in PROSPERO (CRD42020200086). Results: We included 62 studies (2325 BD; 724 healthy controls, HC): 27 using smartphone apps, either for recording self-assessments (n = 10) or for passively gathering metadata (n = 7) or both (n = 10); 15 using wearable sensors for physiological parameters; 17 analysing audio and/or video recordings; 3 using multiple technologies. Two thirds of the included studies applied artificial intelligence (AI)-based approaches. They achieved fair to excellent classification performances. Limitations: The included studies had small sample sizes and marked heterogeneity. Evidence of overfitting emerged, limiting generalizability. The absence of clear guidelines about reporting classification performances, with no shared standard metrics, makes results hardly interpretable and comparable. Conclusions: New technologies offer a noteworthy opportunity to BD digital phenotyping with objectivity and high granularity. AI-based models could deliver important support in clinical decision-making. Further research and cooperation between different stakeholders are needed for addressing methodological, ethical and socio-economic considerations

A 4.0 Automated Warehouse Storage and Picking System for Order Fulfillment

Despite the number of scientific contributions on the topic, there are still several challenges to be faced before the principles of Industry 4.0 become widely applicable. This study aims precisely to overcome some of the limitations of existing technologies and applications for material handling and picking. The current market solutions often require high investment costs being unsustainable by small and medium-sized enterprises and suitable exclusively for managing large volumes and a mix of highly diversified products. In this study, the authors aimed to conceptualize and design an automatic order fulfillment system applicable to small and medium-sized companies performing frequent shipments characterized by low volumes, variable product mix, reduced overall dimensions for products and products typically sold in bulk, such as those operating in the beauty and cosmetics sector. The proposed solution consists of a series of smart drawers, controlled by a communication architecture designed in 4.0 Logic, equipped with hardware and software interfaces that can be easily integrated with any existing management or departmental system. By the Cloud and WEB Portal, the warehouse thus conceived can be monitored and controlled in real-time from any part of the Globe. The solution is completely modular and easily adaptable to future changes in quantities and mixes in stock. The proposed system, as demonstrated by the cost vs. benefit analysis conducted on a real case, allows getting a significant saving in terms of manpower and space, as well as a strong increase in terms of precision, efficiency in order fulfillment and safety

Oxidative stress and inflammation in the evolution of heart failure: From pathophysiology to therapeutic strategies

Both oxidative stress and inflammation are enhanced in chronic heart failure. Dysfunction of cardiac mitochondria is a hallmark of heart failure and a leading cause of oxidative stress, which in turn exerts detrimental effects on cellular components, including mitochondria themselves, thus generating a vicious circle. Oxidative stress also causes myocardial tissue damage and inflammation, contributing to heart failure progression. Furthermore, a subclinical inflammatory state may be caused by heart failure comorbidities such as obesity, diabetes mellitus or sleep apnoeas. Some markers of both oxidative stress and inflammation are enhanced in chronic heart failure and hold prognostic significance. For all these reasons, antioxidants or anti-inflammatory drugs may represent interesting additional therapies for subjects either at high risk or with established heart failure. Nonetheless, only a few clinical trials on antioxidants have been carried out so far, with several disappointing results except for vitamin C, elamipretide and coenzyme Q10. With regard to anti-inflammatory drugs, only preliminary data on the interleukin-1 antagonist anakinra are currently available. Therefore, a comprehensive, deep understanding of our current knowledge on oxidative stress and inflammation in chronic heart failure is key to providing some suggestions for future research on this topic

The ergoreflex: how the skeletal muscle modulates ventilation and cardiovascular function in health and disease

The control of ventilation and cardiovascular function during physical activity is partially regulated by the ergoreflex, a cardiorespiratory reflex activated by physical activity. Two components of the ergoreflex have been identified: the mechanoreflex, which is activated early by muscle contraction and tendon stretch, and the metaboreflex, which responds to the accumulation of metabolites in the exercising muscles. Patients with heart failure (HF) often develop a skeletal myopathy with varying degrees of severity, from a subclinical disease to cardiac cachexia. HF-related myopathy has been associated with increased ergoreflex sensitivity, which is believed to contribute to dyspnoea on effort, fatigue and sympatho-vagal imbalance, which are hallmarks of HF. Ergoreflex sensitivity increases significantly also in patients with neuromuscular disorders. Exercise training is a valuable therapeutic option for both HF and neuromuscular disorders to blunt ergoreflex sensitivity, restore the sympatho-vagal balance, and increase tolerance to physical exercise. A deeper knowledge of the mechanisms mediating ergoreflex sensitivity might enable a drug or device modulation of this reflex when patients cannot exercise because of advanced skeletal myopathy

Colchicine for the treatment of coronary artery disease

Inflammation plays an important role in atherosclerosis. Acute coronary syndromes (ACS), and particularly myocardial infarction (MI), are associated with a systemic inflammatory response that may accelerate coronary atherosclerotic processes, leading to plaque destabilization and increased risk of further cardiovascular events. These considerations provide a conceptual framework for the use of anti-inflammatory therapies in patients with chronic coronary syndrome or ACS. Following the diverging results of trials on canakinumab and methotrexate, the Colchicine Cardiovascular Outcomes Trial (COLCOT) and the Low-Dose Colchicine trial-2 (LoDoCo2) have sparked new interest in the perspective of an anti-inflammatory therapy for CAD by showing that colchicine confers a prognostic benefit in patients with a recent MI or CCS, respectively. Colchicine blocks multiple steps of the inflammatory cascade and modulates also platelet function and endothelial activation. It has a better safety profile than canakinumab and is a very inexpensive drug throughout the world. We deemed it useful to reappraise the available literature on colchicine and coronary artery disease to assess the likelihood that it might become part of the therapeutic armamentarium of this condition