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1.
Update on vitamin D role in severe infections and sepsis.
Cutuli, SL, Ferrando, ES, Cammarota, F, Franchini, E, Caroli, A, Lombardi, G, Tanzarella, ES, Grieco, DL, Antonelli, M, De Pascale, G
Journal of anesthesia, analgesia and critical care. 2024;(1):4
Abstract
Severe infections frequently require admission to the intensive care unit and cause life-threatening complications in critically ill patients. In this setting, severe infections are acknowledged as prerequisites for the development of sepsis, whose pathophysiology implies a dysregulated host response to pathogens, leading to disability and mortality worldwide.Vitamin D is a secosteroid hormone that plays a pivotal role to maintain immune system homeostasis, which is of paramount importance to resolve infection and modulate the burden of sepsis. Specifically, vitamin D deficiency has been widely reported in critically ill patients and represents a risk factor for the development of severe infections, sepsis and worse clinical outcomes. Several studies have demonstrated the feasibility, safety and effectiveness of vitamin D supplementation strategies to improve vitamin D body content, but conflictual results support its benefit in general populations of critically ill patients. In contrast, small randomised clinical trials reported that vitamin D supplementation may improve host-defence to pathogen invasion via the production of cathelicidin and specific cytokines. Nonetheless, no large scale investigations have been designed to specifically assess the impact of vitamin D supplementation on the outcome of critically ill septic patients admitted to the intensive care unit.
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2.
Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.
de Fátima Dos Santos Sampaio, M, de Paiva, YB, Sampaio, TB, Pereira, MG, Coimbra, NC
Basic & clinical pharmacology & toxicology. 2024
Abstract
Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.
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3.
Driving factors of neuronal ferroptosis.
Jacquemyn, J, Ralhan, I, Ioannou, MS
Trends in cell biology. 2024
Abstract
Ferroptosis is an oxidative form of iron-dependent cell death characterized by the accumulation of lipid peroxides on membranes. Iron and lipids containing polyunsaturated fatty acids are essential for this process. Ferroptosis is central to several neurological diseases and underlies the importance of balanced iron and polyunsaturated fatty acid metabolism in the brain, particularly in neurons. Here, we reflect on the potential links between neuronal physiology and the accumulation of iron and peroxidated lipids, the mechanisms neurons use to protect themselves from ferroptosis, and the relationship between pathogenic protein deposition and ferroptosis in neurodegenerative disease. We propose that the unique physiology of neurons makes them especially vulnerable to ferroptosis.
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4.
The influence of modern living conditions on the human microbiome and potential therapeutic opportunities for allergy prevention.
Zhang, G, Le Souëf, P
The World Allergy Organization journal. 2024;(1):100857
Abstract
Modern living conditions and the recent surge in global urbanization have transformed the human microbiome. This transformation is believed to be a significant factor in the recent spike of common chronic inflammatory diseases like asthma and allergies worldwide, evident in both developed and developing nations. Immigrants from less developed regions who settle in highly urbanized and affluent areas present an ideal demographic for research. Investigating immigrant populations can yield valuable insights, particularly when studying microbiome changes that occur as individuals transition from areas with low asthma prevalence to regions with a high prevalence of the condition. The application of prebiotics and probiotics as potential treatments for asthma and allergies faces challenges. This is due to the complex interplay of numerous factors that contribute to their aetiology. Exploring the interaction between the human microbiome and potential epigenetic changes in specific populations, such as immigrants adapting to new, urbanized environments, may offer crucial insights. Such research could underscore the role of prebiotics and probiotics in preventing allergic conditions. Recognizing the changes in the human microbiome in the context of a Western/modern environment might be essential in addressing the increasing prevalence of allergic diseases. Persistent research in this domain is pivotal for devising effective interventions such as dietary supplementation with prebiotics and probiotics.
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5.
Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation.
Shi, B, Li, H, He, X
Gut microbes. 2024;(1):2323237
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Abstract
The gut microbiome is known as the tenth system of the human body that plays a vital role in the intersection between health and disease. The considerable inter-individual variability in gut microbiota poses both challenges and great prospects in promoting precision medicine in cardiovascular diseases (CVDs). In this review, based on the development, evolution, and influencing factors of gut microbiota in a full life circle, we summarized the recent advances on the characteristic alteration in gut microbiota in CVDs throughout different life stages, and depicted their pathological links in mechanism, as well as the highlight achievements of targeting gut microbiota in CVDs prevention, diagnosis and treatment. Personalized strategies could be tailored according to gut microbiota characteristics in different life stages, including gut microbiota-blood metabolites combined prediction and diagnosis, dietary interventions, lifestyle improvements, probiotic or prebiotic supplements. However, to fulfill the promise of a lifelong cardiovascular health, more mechanism studies should progress from correlation to causality and decipher novel mechanisms linking specific microbes and CVDs. It is also promising to use the burgeoning artificial intelligence and machine learning to target gut microbiota for developing diagnosis system and screening for new therapeutic interventions.
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6.
The aminosalicylate - folate connection.
London, RE
Drug metabolism reviews. 2024;(1):80-96
Abstract
Two aminosalicylate isomers have been found to possess useful pharmacological behavior: p-aminosalicylate (PAS, 4AS) is an anti-tubercular agent that targets M. tuberculosis, and 5-aminosalicylate (5AS, mesalamine, mesalazine) is used in the treatment of ulcerative colitis (UC) and other inflammatory bowel diseases (IBD). PAS, a structural analog of pABA, is biosynthetically incorporated by bacterial dihydropteroate synthase (DHPS), ultimately yielding a dihydrofolate (DHF) analog containing an additional hydroxyl group in the pABA ring: 2'-hydroxy-7,8-dihydrofolate. It has been reported to perturb folate metabolism in M. tuberculosis, and to selectively target M. tuberculosis dihydrofolate reductase (mtDHFR). Studies of PAS metabolism are reviewed, and possible mechanisms for its mtDHFR inhibition are considered. Although 5AS is a more distant structural relative of pABA, multiple lines of evidence suggest a related role as a pABA antagonist that inhibits bacterial folate biosynthesis. Structural data support the likelihood that 5AS is recognized by the DHPS pABA binding site, and its effects probably range from blocking pABA binding to formation of a dead-end dihydropterin-5AS adduct. These studies suggest that mesalamine acts as a gut bacteria-directed antifolate, that selectively targets faster growing, more folate-dependent species.
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7.
Role of SLC7A11/xCT in Ovarian Cancer.
Fantone, S, Piani, F, Olivieri, F, Rippo, MR, Sirico, A, Di Simone, N, Marzioni, D, Tossetta, G
International journal of molecular sciences. 2024;(1)
Abstract
Ovarian cancer is one of the most dangerous gynecologic cancers worldwide and has a high fatality rate due to diagnosis at an advanced stage of the disease as well as a high recurrence rate due to the occurrence of chemotherapy resistance. In fact, chemoresistance weakens the therapeutic effects, worsening the outcome of this pathology. Solute Carrier Family 7 Member 11 (SLC7A11, also known as xCT) is the functional subunit of the Xc- system, an anionic L-cystine/L-glutamate antiporter expressed on the cell surface. SLC7A11 expression is significantly upregulated in several types of cancers in which it can inhibit ferroptosis and favor cancer cell proliferation, invasion and chemoresistance. SLC7A11 expression is also increased in ovarian cancer tissues, suggesting a possible role of this protein as a therapeutic target. In this review, we provide an overview of the current literature regarding the role of SLC7A11 in ovarian cancer to provide new insights on SLC7A11 modulation and evaluate the potential role of SLC7A11 as a therapeutic target.
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8.
Standards for the care of people with cystic fibrosis; establishing and maintaining health.
Southern, KW, Addy, C, Bell, SC, Bevan, A, Borawska, U, Brown, C, Burgel, PR, Button, B, Castellani, C, Chansard, A, et al
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2024;(1):12-28
Abstract
This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.
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9.
Pathophysiology and management of enteric hyperoxaluria.
Desenclos, J, Forté, V, Clément, C, Daudon, M, Letavernier, E
Clinics and research in hepatology and gastroenterology. 2024;:102322
Abstract
Enteric hyperoxaluria is a metabolic disorder resulting from conditions associated with fatty acid malabsorption and characterized by an increased urinary output of oxalate. Oxalate is excessively absorbed in the gut and then excreted in urine where it forms calcium oxalate crystals, inducing kidney stones formation and crystalline nephropathies. Enteric hyperoxaluria is probably underdiagnosed and may silently damage kidney function of patients affected by bowel diseases. Moreover, the prevalence of enteric hyperoxaluria has increased because of the development of bariatric surgical procedures. Therapeutic options are based on the treatment of the underlying disease, limitation of oxalate intakes, increase in calcium salts intakes but also increase in urine volume and correction of hypocitraturia. There are few data regarding the natural evolution of kidney stone events and chronic kidney disease in these patients, and there is a need for new treatments limiting kidney injury by calcium oxalate crystallization.
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10.
Therapeutic potential of saffron in brain disorders: From bench to bedside.
Bej, E, Volpe, AR, Cesare, P, Cimini, A, d'Angelo, M, Castelli, V
Phytotherapy research : PTR. 2024
Abstract
Saffron is a spice derived from the flower of Crocus sativus L., which has been used for centuries as a coloring and flavoring agent, as well as a source of medicinal compounds. Saffron contains various bioactive constituents, such as crocin, crocetin, safranal, picrocrocin, and kaempferol, that have shown potential benefits for human health. Among them, crocin is the most abundant and characteristic constituent of saffron, responsible for its bright red color and antioxidant properties. One of the most promising applications of saffron and its constituents is in the prevention and treatment of neurological disorders, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, and other brain disorders. Saffron and its constituents have been reported to exert neuroprotective effects through various mechanisms, such as modulating neurotransmitters, enhancing neurogenesis, reducing neuroinflammation, regulating oxidative stress, activating the Nrf2 signaling pathway, and modulating epigenetic factors. Several clinical and preclinical studies have demonstrated the efficacy and safety of saffron and its constituents in improving cognitive function, mood, and other neurological outcomes. In this review, we summarize the current evidence on the therapeutic potential of saffron and its constituents in neurological disorders, from bench to bedside. We also discuss the challenges and future directions for the development of saffron-based therapies for brain health.