Journey of anthraquinones as anticancer agents – a systematic review of recent literature

Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of various anticancer agents. However, the emergence of drug-resistant cancers warrants the development of new anticancer agents. The research endeavours towards new anthraquinone-based compounds are increasing rapidly in recent years. They are used as a core chemical template to achieve structural modifications, resulting in the development of new anthraquinone-based compounds as promising anticancer agents. Mechanistically, most of the anthraquinone-based compounds inhibit cancer progression by targeting essential cellular proteins. Herein, we review new anthraquinone analogues that have been developed in recent years as anticancer agents. This includes a systematic review of the recent literature (2005–2021) on anthraquinone-based compounds in cell-based models and key target proteins such as kinases, topoisomerases, telomerases, matrix metalloproteinases and G-quadruplexes involved in the viability of cancer cells. In addition to this, the developments in PEG-based delivery of anthraquinones and the toxicity aspects of anthraquinone derivatives are also discussed. The review dispenses a compact background knowledge to understanding anthraquinones for future research on the expansion of anticancer therapeutics.

Anthraquinones are privileged chemical motifs with diverse therapeutic applications, especially in the treatment of cancer. The extensive literature highlights the significance of anthraquinones as potent anticancer agents.     

Bleomycin for orbital and peri-orbital veno-lymphatic malformations – A systematic review

BackgroundOrbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such malformations.ObjectiveThe purpose of this systematic review is to synthesize evidence on the safety and efficacy of bleomycin/pingyangmycin sclerotherapy for the treatment of orbital and peri-orbital VLM.MethodsWe searched Medline, Embase, Scopus and Cochrane database for studies reporting outcomes of bleomycin/pingyangmycin sclerotherapy for orbital and peri-orbital VLM between 1974 to April 5th, 2019. Nine retrospective cohort studies enrolling 132 patients were included. Two reviewers independently screened and extracted data and assessed the risk of bias. Predefined outcome measures were subjective and objective reduction of the lesion and associated complications.ResultsSubjective reduction of the lesions was seen in 96.2% of the studies. Objective reduction of the lesion and symptomatic improvement were reported in 91.6 and 95% of the studies respectively. Non responders were 9.0%. Minor adverse events were reported in 18.1% of the studies. Major complications like pulmonary toxicity or pulmonary fibrosis was not encountered in any of the included studies. Quality of evidence was generally low.ConclusionBleomycin/pingyangmycin sclerotherapy is very effective and relatively safe for the treatment of orbital and periorbital VLM and is not associated with any major side effects including pulmonary fibrosis.Limitations: The systematic review is limited mainly due to low quality of the included studies with retrospective design.     

Beliefs about food allergies in adolescents aged 11–19 years: A systematic review

AimsResearch suggests of people with food allergy (FA), adolescents have the highest risk of fatal allergic reactions to food, yet understanding of this population and how they manage their condition is limited. Understanding beliefs and how they affect behaviour could inform ways to reduce risk taking behaviour and fatal reactions in adolescents. This systematic review aimed to explore beliefs adolescents hold about their FA, and how these may be associated with FA management.DemographicsAdolescents aged 11–19 years with FA.MethodologyA systematic search of seven databases was conducted. Papers of any design were included that reported on the beliefs about FA in adolescents aged 11–19 years. Data was systemised by narrative thematic analysis.Findings20 studies were included. Themes included navigating FA in different environments, carriage and use of adrenaline auto‐injectors, management of the risk of anaphylaxis, behaviour and understanding of others, and food‐allergic identity.ImplicationsAdolescents with FA hold a variety of condition beliefs; some beliefs were related to behaviour that could lead to an allergic reaction, while other beliefs were related to protective behaviours. Further research into understanding adolescent beliefs in order to inform clinical management and reduce the risk of potential fatal reactions is essential.     

Contact allergens in moisturizers in preventative emollient therapy – A systematic review

BackgroundResults of preventative emollient therapy on atopic dermatitis and food allergy trials are inconsistent. In addition to the ingredients considered beneficial, the moisturizers may contain potentially harmful haptens. This study aimed to assess the prevalence of haptens in moisturizers used in studies to prevent atopic dermatitis or food allergy and assess their correlations to the trial results.MethodsA systematic search of studies investigating the role of emollient usage in preventing atopic dermatitis or food allergy in infants was performed from inception to December 2020. Haptens were identified based on the nine common patch test series (European, American, and Australian).Results12 clinical trial studies were included in the review. In total, 16 different emollients were applied as an intervention. The vast majority (75%) of preparations contained at least one hapten from which several substances pose high allergic or irritant potential. Quantitative data synthesis of the findings regarding food allergy and atopic dermatitis prevention was not possible due to the significant heterogeneity of preparations used.ConclusionsCareful selection of emollient should consider the absence of potentially harmful ingredients, particularly when used in youngest children. Chronic skin exposure to haptens promotes the development of allergic contact dermatitis and moreover, via deterioration of the skin barrier and subclinical inflammation, may facilitate epicutaneous sensitization and promote atopic dermatitis; however further research is needed to validate our suppositions.     

The phytochemistry,pharmacology and traditional medicinal use of Glechomae Herba – a systematic review

Glechomae Herba is a Chinese herb, which has been used in China for thousands of years, mainly for the treatment of nephrolithiasis. This paper summarizes the modern research progress on Glechomae Herba from the aspects of botany, traditional medicinal use, phytochemistry, pharmacology, pharmacokinetics, analytical methods and quality control. In addition, it also points out the deficiencies of current research on this herb and provides possible directions for its development. So far, more than 190 chemical components have been isolated and identified from Glechomae Herba, including organic acids and their esters, volatile oils, flavonoids and their glycosides, terpenes and other chemical components. Its extracts and compounds have a wide range of pharmacological effects, including anti-stone, anti-inflammatory, bacteriostatic, cholagogic and diuretic, effect on ileum smooth muscle, anti-tumor effect on tumor and hypoglycemic effects. However, future studies should focus on drug metabolism, clarify its pharmacodynamic mechanism, and establish a reasonable quality control standards for Glechomae Herba.

Glechomae Herba is a Chinese herb, which has been used in China for thousands of years, mainly for the treatment of nephrolithiasis.     

Interventions regarding physicians’ sickness certification practice – a systematic literature review with meta-analyses

ObjectiveA variety of interventions aiming to influence physicians’ sickness certification practice have been conducted, most are, however, not evaluated scientifically. The aim of this systematic literature review was to obtain updated knowledge about interventions regarding physicians’ sickness certification practice and to summarize their possible effects, in terms of sickness absence (SA) or return to work (RTW) among patients.MethodsWe searched PubMed and Web of Science up through 15 June 2020 and selected peer-reviewed studies that reported effects of controlled interventions that aimed to improve physicians’ sickness certification practice and used SA or RTW among patients as outcome measures. Meta-analyses were conducted using random-effect models.ResultsOf the 1399 identified publications, 12 studies covering 9 interventions were assessed as relevant and included in the review. Most (70%) were from the Netherlands, two had a controlled, and seven a randomized controlled study design. All interventions included some type of training of physicians, and two interventions also included IT-support. Regarding the outcomes of SA/RTW, 30 different effect measures were used. In the meta-analyses, no statistically significant effect in favor of the interventions was observed for having any RTW (i.e. first, partial, or full) nor full RTW.ConclusionsThe individual studies showed that physicians’ sickness certification practice might be influenced by interventions in both the intended and non-intended direction, however, no statistically significant effect was indicated by the meta-analysis. The included studies varied considerably concerning intervention content and effect measures.

KEY POINTS

• The knowledge is very limited regarding the content of interventions directed to physician’s sickness certification practice
• The identified interventions included some type of training of physicians, and some of them also included IT-support for physicians
• There was a great heterogeneity among the interventions concerning effect measures used regarding return to work among patients
• The individual studies showed that physicians’ sickness certification practice might be influenced by interventions in both intended and non-intended directions, however, the overall meta-analysis did not indicate an effect.

     

Bench-to-bedside review: Pulmonary–renal syndromes – an update for the intensivist

The term Pulmonary–renal syndrome refers to the combination of diffuse alveolar haemorrhage and rapidly progressive glomerulonephritis. A variety of mechanisms such as those involving antiglomerular basement membrane antibodies, antineutrophil cytoplasm antibodies or immunocomplexes and thrombotic microangiopathy are implicated in the pathogenesis of this syndrome. The underlying pulmonary pathology is small-vessel vasculitis involving arterioles, venules and, frequently, alveolar capillaries. The underlying renal pathology is a form of focal proliferative glomerulonephritis. Immunofluorescence helps to distinguish between antiglomerular basement membrane disease (linear deposition of IgG), lupus and postinfectious glomerulonephritis (granular deposition of immunoglobulin and complement) and necrotizing vasculitis (pauci-immune glomerulonephritis). Patients may present with severe respiratory and/or renal failure and require admission to the intensive care unit. Since the syndrome is characterized by a fulminant course if left untreated, early diagnosis, exclusion of infection, close monitoring of the patient and timely initiation of treatment are crucial for the patient's outcome. Treatment consists of corticosteroids in high doses, and cytotoxic agents coupled with plasma exchange in certain cases. Renal transplantation is the only alternative in end-stage renal disease. Newer immunomodulatory agents such as those causing TNF blockade, B-cell depletion and mycophenolate mofetil could be used in patients with refractory disease.     

Alginate gels crosslinked with chitosan oligomers – a systematic investigation into alginate block structure and chitosan oligomer interaction

Three alginates with fundamentally different block structures, poly-M, poly-G, and poly-MG, have been investigated upon ionic crosslinking with chitosan oligosaccharides (CHOS), using circular dichroism (CD), rheology, and computer simulations, supporting the previously proposed gelling principle of poly-M forming zipper-like junction zones with chitosan (match in charge distance along the two polyelectrolytes) and revealing a unique high gel strength poly-MG chitosan gelling system. CD spectroscopy revealed an increased chiroptical activity exclusively for the poly-M chitosan gelling system, indicative of induced conformational changes and higher ordered structures. Rheological measurement revealed gel strengths (G′ < 900 Pa) for poly-MG (1%) CHOS (0.3%) hydrogels, magnitudes of order greater than displayed by its poly-M analogue. Furthermore, the ionically crosslinked poly-MG chitosan hydrogel increased in gel strength upon the addition of salt (G′ < 1600 at 50 mM NaCl), suggesting a stabilization of the junction zones through hydrophobic interactions and/or a phase separation. Molecular dynamics simulations have been used to further investigate these findings, comparing interaction energies, charge distances and chain alignments. These alginates are displaying high gel strengths, are known to be fully biocompatible and have revealed a broad range of tolerance to salt concentrations present in biological systems, proving high relevance for biomedical applications.

Three alginates with different block structures, poly-M, poly-G, and poly-MG, were investigated upon ionic crosslinking with chitosan oligomers, using circular dichroism, rheology, and simulations, revealing a unique high gel strength poly-MG chitosan gelling system.     

Year in review 2005: Critical Care – cardiology

This review summarizes key research papers published in the fields of cardiology and intensive care during 2005 in Critical Care. The papers have been grouped into categories: haemodynamic monitoring; goal-directed therapy; cardiac enzymes and critical care; metabolic considerations in cardiovascular performance; thrombosis prevention; physiology; and procedures and techniques.     

Year in review 2005: Critical Care – nephrology

We summarize original research in the field of critical care nephrology accepted or published in 2005 in Critical Care and, when considered relevant or directly linked to this research, in other journals. The articles have been grouped into four categories to facilitate a rapid overview. First, physiopathology, epidemiology and prognosis of acute renal failure (ARF): an extensive review and some observational studies have been performed with the aim of describing aspects of ARF physiopathology, precise epidemiology and long-term outcomes. Second, several authors have performed clinical trials utilizing a potential nephro-protective drug, fenoldopam, with different results. Third, the issue of continuous renal replacement therapies dose has been addressed in a small prospective study and a large observational trial. And fourth, alternative indications to extracorporeal treatment of ARF and systemic inflammatory response syndrome have been explored by three original clinical studies.     

Interaction between functionalized graphene and sulfur compounds in a lithium–sulfur battery – a density functional theory investigation

Lithium–sulfur (Li–S) batteries are emerging as one of the promising candidates for next generation rechargeable batteries. However, dissolution of lithium polysulfides in the liquid electrolyte, low electrical conductivity of sulfur and large volume change during electrochemical cycling are the main technical challenges for practical applications. In this study, a systematic first-principles density functional theory calculation is adopted to understand the interactions between graphene and graphene with oxygen containing functional groups (hydroxyl, epoxy and carboxyl groups) and sulphur (S₈) and long chain lithium polysulfides (Li₂S₈ and Li₂S₄). We find the adsorption is dominated by different mechanisms in sulphur and lithium polysulfides, i.e. van der Waals attraction and formation of coordinate covalent Li–O bonds. The adsorption strength is dependent on the inter-layer distance and electron rich functional groups. Through these mechanisms, sulphur and lithium polysulfides can be successfully retained in porous graphene, leading to improved conductivity and charge transfer in the cathode of Li–S batteries.

Functionalized graphene can successfully anchor sulfur compounds via moderate interactions, leading to improved conductivity and charge transfer in the cathode of Li–S batteries.     

Bench-to-bedside review: Brain-lung interaction in the critically ill – a pending issue revisited

Brain and/or lung injury is the most frequent cause of admission to critical care units and patients in this setting frequently develop multiple organ dysfunction with high rates of morbidity and mortality. Mechanical ventilation is commonly used in the management of these critically ill patients and the consequent inflammatory response, together with other physiological factors, is also thought to be involved in distal organ dysfunction. This peripheral imbalance is based on a multiple-pathway cross-talk between the lungs and other organs, including the brain. Interestingly, acute respiratory distress syndrome survivors frequently present some cognitive deterioration at discharge. Such neurological dysfunction might be a secondary marker of injury and the neuroanatomical substrate for downstream impairment of other organs. Brain-lung interactions have received little attention in the literature, but recent evidence suggests that both the lungs and brain are promoters of inflammation through common mediators. This review addresses the current status of evidence regarding brain-lung interactions, their pathways and current interventions in critically ill patients receiving mechanical ventilation.     

The pioneering role of metal–organic framework-5 in ever-growing contemporary applications – a review

MOF-5 with a Zn(ii) cluster and terephthalic acid is a distinctive porous material among the metal–organic frameworks (MOFs), with unique physical, chemical and mechanical properties. MOF-5 based composites possess ample applications in modern chemistry. Huge surface area, suitable pore dimensions and scope of tunability make MOF-5 noteworthy in advanced materials. The extensive features of MOF-5 provided an opportunity for researchers to explore atomic/molecular scale materials. Various MOF-5 based composites have been designed with revamped properties appropriate to the application by altering and fabricating MOF-5 in situ or using a post-synthetic approach. Surface modification via the dispersion and impregnation of active substances into the pores of MOF-5 enhances its applicability. The boundless topologies and morphologies of MOF-5 combined with other chemical entities has provided opportunities in various fields, including catalysis, gas storage and sensors. The present review illuminates the leading role of MOF-5 and its composites in contemporary applications based on the current literature in heterogeneous catalysis, H₂ and CO₂ storage and sensors.

MOF-5 with a Zn(ii) cluster and terephthalic acid is a distinctive porous material among the metal–organic frameworks (MOFs), with unique physical, chemical and mechanical properties.     

Year in review 2005: Critical Care – resource management

During 2005 Critical Care published several original papers dealing with resource management. Emphasis was placed on sepsis, especially the coagulation cascade, prognosis and resuscitation. The papers highlighted important aspects of the pathophysiology of coagulation and inflammation in sepsis, as well as dealing with the proper use of newly developed compounds. Several aspects of prognosis in critically ill patients were investigated, focusing on biological markers and clinical indexes. Resuscitation received great attention, dealing with the effects of fluid infusion in hemodynamics and the lung. The information obtained can be used to address unknown effects of established therapies, to enlighten current clinical discussion on controversial topics, and to introduce novel medical resources and strategies. Future clinical work will rely heavily on these preclinical and laboratory data.     

Clinical review: Agitation and delirium in the critically ill – significance and management

Agitation is a psychomotor disturbance characterized by a marked increase in motor and psychological activity in a patient. It occurs very frequently in the intensive care setting. It may be isolated, or accompanied by other mental disorders, such as severe anxiety and delirium. Frequently, agitation is a sign of brain dysfunction and, as such, may have adverse consequences, for at least two reasons. First, agitation can interfere with the patient's care and second, there is evidence demonstrating that the prognosis of agitated (and delirious) patients is worse than that of non-agitated (non-delirious) patients. These conditions are often under-diagnosed in the intensive care unit (ICU). Consequently, a systematic evaluation of this problem in ICU patients should be conducted. Excellent tools are presently available for this purpose. Treatment, including prevention, must be undertaken without delay, and the ICU physician should follow logical, strict and systematic rules when applying therapy.     

Ethics review: Dark angels – the problem of death in intensive care

Critical care medicine has expanded the envelope of debilitating disease through the application of an aggressive and invasive care plan, part of which is designed to identify and reverse organ dysfunction before it proceeds to organ failure. For a select patient population, this care plan has been remarkably successful. But because patient selection is very broad, critical care sometimes yields amalgams of life in death: the state of being unable to participate in human life, unable to die, at least in the traditional sense. This work examines the emerging paradox of somatic versus brain death and why it matters to medical science.