ResearchPad - minireviews https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Protein Assays on Organic Electronics: Rational Device and Material Designs for Organic Transistor‐Based Sensors]]> https://www.researchpad.co/article/elastic_article_8330 OFETs go next: Organic field‐effect transistors (OFETs) functionalized with artificial receptors offer simple methods for the sensitive and selective detection of proteins and their chemical information, such as post‐translational modifications. Thus, the OFETs will be new caididates for the next‐generation electronic devices for healthcare applications.

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<![CDATA[Late‐Stage Diversification of Tryptophan‐Derived Biomolecules]]> https://www.researchpad.co/article/elastic_article_8325 Pd‐mediated reactions have emerged as a powerful tool for the site‐selective and bioorthogonal late‐stage diversification of amino acids, peptides and related compounds. Halotryptophans are accessible by biocatalytic approaches opening the application of a variety of cross‐coupling reactions for late‐stage modification of halotryptophan containing biomolecules.

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<![CDATA[Development of Glucose Transporter (GLUT) Inhibitors]]> https://www.researchpad.co/article/elastic_article_8235 Potent glucose transporter (GLUT) inhibitors have been developed over the last years. This Minireview serves as an overview of the origin (natural products, natural product‐inspired, non‐natural compounds, and virtual screening) of these molecules.John Wiley & Sons, Ltd.

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<![CDATA[Regulation of macrophage activation in the liver after acute injury: Role of the fibrinolytic system]]> https://www.researchpad.co/article/Ne12a3063-6e08-4a79-880e-7d732e8344ba The liver functions, in part, to prevent exposure of the body to potentially harmful substances ingested in the diet. While it is highly efficient at accomplishing this, it is frequently prone to liver injury due to the biotransformation of xenobiotics into toxic metabolites. To counter this injury, the liver has evolved a unique capacity to rapidly and efficiently repair itself. Successful resolution of acute liver injury relies on hepatic macrophage populations that orchestrate the reparative response. After injury, Kupffer cells, the resident macrophages of the liver, become activated and secrete proinflammatory cytokines. These cytokines recruit other immune cells, including monocyte-derived macrophages, to the liver where they contribute to the repair process. Monocyte-derived macrophages traffic into the necrotic foci where they rapidly phagocytose dead cell debris. Simultaneous with this process, these cells change phenotype from a proinflammatory macrophage to a pro-restorative macrophage that produce pro-mitogenic growth factors and anti-inflammatory cytokines. Ultimately this process triggers resolution of inflammation, and along with proliferation of other hepatic cells, restores the liver architecture and function. While the mechanisms regulating specific macrophage functions during repair remain to be elucidated, recent studies indicate a key role for the fibrinolytic system in coordinating macrophage function during repair. In this review, we will highlight the function and role of hepatic macrophages in repair after acute liver injury, and will discuss the role of the fibrinolytic enzyme, plasmin, in regulation of these various processes.

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<![CDATA[Therapeutic advances in non-alcoholic fatty liver disease: A microbiota-centered view]]> https://www.researchpad.co/article/N0f0713cc-ef99-4101-ad3e-a7abba1a5f6e Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide, especially in the West. There are no drugs available at present to treat NAFLD, and the primary therapeutic options include weight loss and the combination of healthy diet and exercise. Therefore, novel interventions are required that can target the underlying risk factors. Gut microbiota is an “invisible organ” of the human body and vital for normal metabolism and immuno-modulation. The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus, and is most abundant in the intestine. Since dysregulated gut microbiota is an underlying pathological factor of NAFLD, it is a viable therapeutic target that can be modulated by antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbial metabolites. In this review, we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies, and critically evaluate novel targets and strategies for treating NAFLD.

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<![CDATA[Sequencing of systemic treatment for hepatocellular carcinoma: Second line competitors]]> https://www.researchpad.co/article/Nf38ea49a-ff23-4122-94ca-097b66dac081 During the last decades, further knowledge of hepatocellular carcinoma (HCC) molecular mechanisms has led to development of effective systemic treatments including tyrosine kinase inhibitors (TKIs) and immunotherapy. In this review, we describe first and second line systemic treatment options for advanced HCC. Several trials have evaluated new drugs for the treatment of HCC patients: In first line, lenvatinib resulted non-inferior to sorafenib and it can be used as alternative, even in the lack of evidence for sequential treatment options in second line after lenvatinib. Recently, atezolizumab plus bevacizumab have shown superiority over sorafenib in first-line. Sorafenib-regorafenib sequential administration in selected patients has opened a new paradigm of treatment in advanced HCC with a life expectancy exceeding two years. Other TKIs for second line treatment include cabozantinib and ramucirumab (specifically for patients with Alpha-fetoprotein values ≥ 400 ng/mL). The combination of TKIs with immunotherapy may represent a big step forward for these patients in the near future.

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<![CDATA[Evolution and current status of the subclassification of intermediate hepatocellular carcinoma]]> https://www.researchpad.co/article/N4c889940-440b-4991-af4c-3eebe3b2f90f

The staging and treatment of intermediate hepatocellular carcinoma (HCC) remains controversial. According to the recommendations of Barcelona Clinic Liver Cancer staging system, patients with intermediate HCC are candidates for transcatheter arterial chemoembolization. However, not all patients with intermediate HCC benefit from transcatheter arterial chemoembolization. Therefore, it is meaningful to propose a novel staging system of intermediate HCC in order to allocate different treatments for different subgroups. Bolondi et al proposed the first subclassification system of intermediate HCC. Subsequently, investigators performed studies to validate the feasibility of Bolondi s criteria and proposed several novel staging systems. The present study reviewed the literatures and provided a general overview of the evolution and current status of the subclassification of intermediate HCC. We propose to expand the indication of liver resection and add radical treatments as the first option of the treatment for patients with intermediate HCC.

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<![CDATA[Importance of genetic polymorphisms in liver transplantation outcomes]]> https://www.researchpad.co/article/N958ba129-93db-4414-95b4-f7664d82275c

Although, liver transplantation serves as the only curative treatment for patients with end-stage liver diseases, it is burdened with complications, which affect survival rates. In addition to clinical risk factors, contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes. Determination of single nucleotide polymorphisms (SNPs) is one of the most important tools in development of personalized transplant approach. To provide a better insight in recent developments, we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation: Acute cellular rejection, development of new-onset diabetes mellitus and non-alcoholic fatty liver disease, hepatocellular carcinoma recurrence, and tacrolimus concentration variability. Reviewed studies confirmed previously established SNP prognostic factors, such as PNPLA3 rs738409 for non-alcoholic fatty liver disease development, or the role of CYP3A5 rs776746 in tacrolimus concentration variability. They also identified several novel SNPs, with a reasonably strong association, which have the potential to become useful predictors of post-transplant complications. However, as the studies were typically conducted in one center on relatively low-to-moderate number of patients, verification of the results in other centers is warranted to resolve these limitations. Furthermore, of 29 reviewed studies, 28 used gene candidate approach and only one implemented a genome wide association approach. Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.

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<![CDATA[Oesophageal atresia: The growth gap]]> https://www.researchpad.co/article/Naaea8246-3ef4-4280-afda-022582f7ab28

Poor growth is an under-recognised yet significant long-term sequelae of oesophageal atresia (OA) repair. Few studies have specifically explored the reasons for growth impairment in this complex cohort. The association between poor growth with younger age and fundoplication appears to have the strongest supportive evidence, highlighting the need for early involvement of a dietitian and speech pathologist, and consideration of optimal medical reflux management prior to referring for anti-reflux surgery. However, it remains difficult to reach conclusions regarding other factors which may negatively influence growth, due to conflicting findings, inconsistent definitions and lack of validated tool utilisation. While swallowing and feeding difficulties are particularly frequent in younger children, their relationship with growth remains unclear. It is possible that these morbidities impact on the diet of children with OA, but detailed analysis of dietary composition and quality, and its relationship with these complications and growth, has not yet been conducted. Another potential area of research in OA is the role of the microbiota in growth and nutrition. While the microbiota has been linked to growth impairment in other paediatric conditions, it is yet to be investigated in OA. Further research is needed to identify the most important contributory factors to poor growth, the role of the intestinal microbiota, and effective interventions to maximise growth and nutritional outcomes in this cohort.

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<![CDATA[The gut microbiota and its interactions with cardiovascular disease]]> https://www.researchpad.co/article/N12abbdda-fc24-4fb4-a7fc-1f5ca76b6266

Summary

The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

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<![CDATA[Ultrasound‐mediated therapies for the treatment of biofilms in chronic wounds: a review of present knowledge]]> https://www.researchpad.co/article/N44c0d2f4-067a-411c-b16e-08a8345ec14d

Summary

Bacterial biofilms are an ever‐growing concern for public health, featuring both inherited genetic resistance and a conferred innate tolerance to traditional antibiotic therapies. Consequently, there is a growing interest in novel methods of drug delivery, in order to increase the efficacy of antimicrobial agents. One such method is the use of acoustically activated microbubbles, which undergo volumetric oscillations and collapse upon exposure to an ultrasound field. This facilitates physical perturbation of the biofilm and provides the means to control drug delivery both temporally and spatially. In line with current literature in this area, this review offers a rounded argument for why ultrasound‐responsive agents could be an integral part of advancing wound care. To achieve this, we will outline the development and clinical significance of biofilms in the context of chronic infections. We will then discuss current practices used in combating biofilms in chronic wounds and then critically evaluate the use of acoustically activated gas microbubbles as an emerging treatment modality. Moreover, we will introduce the novel concept of microbubbles carrying biologically active gases that may facilitate biofilm dispersal.

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<![CDATA[Bioengineered Escherichia coli Nissle 1917 for tumour‐targeting therapy]]> https://www.researchpad.co/article/N2a92b180-411e-4877-913f-e3d30721d4d1

Summary

Bacterial vectors, as microscopic living ‘robotic factories’, can be reprogrammed into microscopic living ‘robotic factories’, using a top‐down bioengineering approach to produce and deliver anticancer agents. Most of the current research has focused on bacterial species such as Salmonella typhimurium or Clostridium novyi. However, Escherichia coli Nissle 1917 (EcN) is another promising candidate with probiotic properties. EcN offers increased applicability for cancer treatment with the development of new molecular biology and complete genome sequencing techniques. In this review, we discuss the genetics and physical properties of EcN. We also summarize and analyse recent studies regarding tumour therapy mediated by EcN. Many challenges remain in the development of more promising strategies for combatting cancer with EcN.

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<![CDATA[Distal esophageal spasm: Update on diagnosis and management in the era of high-resolution manometry]]> https://www.researchpad.co/article/N69a49440-2347-4523-8324-b5237c19527b

Distal esophageal spasm (DES) is a rare major motility disorder in the Chicago classification of esophageal motility disorders (CC). DES is diagnosed by finding of ≥ 20% premature contractions, with normal lower esophageal sphincter (LES) relaxation on high-resolution manometry (HRM) in the latest version of CCv3.0. This feature differentiates it from achalasia type 3, which has an elevated LES relaxation pressure. Like other spastic esophageal disorders, DES has been linked to conditions such as gastroesophageal reflux disease, psychiatric conditions, and narcotic use. In addition to HRM, ancillary tests such as endoscopy and barium esophagram can provide supplemental information to differentiate DES from other conditions. Functional lumen imaging probe (FLIP), a new cutting-edge diagnostic tool, is able to recognize abnormal LES dysfunction that can be missed by HRM and can further guide LES targeted treatment when esophagogastric junction outflow obstruction is diagnosed on FLIP. Medical treatment in DES mostly targets symptomatic relief and often fails. Botulinum toxin injection during endoscopy may provide a temporary therapy that wears off over time. Myotomy through peroral endoscopic myotomy or via surgical Heller myotomy can provide long term relief in cases with persistent symptoms.

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<![CDATA[Nitric oxide in dengue and dengue haemorrhagic fever: necessity or nuisance?]]> https://www.researchpad.co/article/N0c930179-e77b-4862-bdda-33052c470caf

Abstract

Advances in free radical research show that reactive oxygen and nitrogen oxide species, for example superoxide, nitric oxide (NO) and peroxynitrite, play an important role in the pathogenesis of different viral infections, including dengue virus. The pathogenic mechanism of dengue haemorrhagic fever (DHF) is complicated and is not clearly understood. The hallmarks of the dengue disease, the antibody‐dependent enhancement, the shift from T‐helper type 1 (Th1) to Th2 cytokine response and the cytokine tsunami resulting in vascular leakage can now be explained much better with the knowledge gained about NO and peroxynitrite. This paper makes an effort to present a synthesis of the current opinions to explain the pathogenesis of DHF/shock syndrome with NO on centre stage.

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<![CDATA[Antimicrobial peptides and proteins, exercise and innate mucosal immunity]]> https://www.researchpad.co/article/Nb77df613-a02e-4394-8f6a-85bbcbe1ad7d

Abstract

This review examines the question of whether exercise can be used as an experimental model to further our understanding of innate antimicrobial peptides and proteins (AMPs) and their role in susceptibility to infection at mucosal surfaces. There is strong evidence to suggest that AMPs, in combination with cellular and physical factors, play an important role in preventing infection. Although AMPs act directly on microorganisms, there is increasing recognition that they also exert their protective effect via immunomodulatory mechanisms, especially in noninflammatory conditions. Further studies that manipulate physiologically relevant concentrations of AMPs are required to shed light on the role they play in reducing susceptibility to infection. Evidence shows that in various form prolonged and/or exhaustive exercise is a potent modulator of the immune system, which can either sharpen or blunt the immune response to pathogens. The intensity and duration of exercise can be readily controlled in experimental settings to manipulate the degree of physical stress. This would allow for an investigation into a potential dose–response effect between exercise and AMPs. In addition, the use of controlled exercise could provide an experimental model by which to examine whether changes in the concentration of AMPs alters susceptibility to illness.

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<![CDATA[Vascular endothelium: the battlefield of dengue viruses]]> https://www.researchpad.co/article/Nfb740227-ef78-406e-b39f-6ce3d3195c9f

Abstract

Increased vascular permeability without morphological damage to the capillary endothelium is the cardinal feature of dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). Extensive plasma leakage in various tissue spaces and serous cavities of the body, including the pleural, pericardial and peritoneal cavities in patients with DHF, may result in profound shock. Among various mechanisms that have been considered include immune complex disease, T‐cell‐mediated, antibodies cross‐reacting with vascular endothelium, enhancing antibodies, complement and its products, various soluble mediators including cytokines, selection of virulent strains and virus virulence, but the most favoured are enhancing antibodies and memory T cells in a secondary infection resulting in cytokine tsunami. Whatever the mechanism, it ultimately targets vascular endothelium (making it a battlefield) leading to severe dengue disease. Extensive recent work has been done in vitro on endothelial cell monolayer models to understand the pathophysiology of vascular endothelium during dengue virus (DV) infection that may be translated to help understand the pathogenesis of DHF/DSS. The present review provides a broad overview of the effects of DV infection and the associated host responses contributing towards alterations in vascular endothelial cell physiology and damage that may be responsible for the DHF/DSS.

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<![CDATA[Proteomic strategies for the discovery of novel diagnostic and therapeutic targets for infectious diseases]]> https://www.researchpad.co/article/N0e8d66ca-a00c-4e45-ab67-45918e276d8f

Abstract

Viruses have developed numerous and elegant strategies to manipulate the host cell machinery to establish a productive infectious cycle. The interaction of viral proteins with host proteins plays an important role in infection and pathogenesis, often bypassing traditional host defenses such as the interferon response and apoptosis. Host–viral protein interactions can be studied using a variety of proteomic approaches ranging from genetic and biochemical to large‐scale high‐throughput technologies. Protein interactions between host and viral proteins are greatly influenced by host signal transduction pathways. In this review, we will focus on comparing proteomic information obtained through differing technologies and how their integration can be used to determine the functional aspect of the host response to infection. We will briefly review and evaluate techniques employed to elucidate viral–host interactions with a primary focus on Protein Microarrays (PMA) and Mass Spectrometry (MS) as potential tools in the discovery of novel therapeutic targets. As many potential molecular markers and targets are proteins, proteomic profiling is expected to yield both clearer and more direct answers to functional and pharmacologic questions.

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<![CDATA[Dengue in infants: an overview]]> https://www.researchpad.co/article/Nd04c3c93-6eb3-470e-97e2-cc77c4b2d10f

Abstract

Dengue virus (DV) infection causes either a benign syndrome, dengue fever, or a severe syndrome, dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS), that is characterized by systemic capillary leakage, thrombocytopaenia and hypovolaemic shock. DHF/DSS occur mainly due to secondary infection by a heterotype DV infection in children and adults but in infants even primary infection by DV causes DHF/DSS. Clinical manifestations of DHF/DSS are more significantly associated with death in infants compared with older children. Vertical transmission of DV and anti-DV IgG has been well reported and is responsible for the pathogenesis of DV disease and its manifestations in infants. The complex pathogenesis of DHF/DSS during primary dengue in infants, with multiple age-related confounding factors, offers unique challenges to investigators. Dengue in infants is not often studied in detail due to practical limitations, but looking at the magnitude of DHF/DSS in infants and the unique opportunities this model provides, there is a need to focus on this problem. This paper reviews existing knowledge on this aspect of DV infection and the challenges it provides.

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<![CDATA[Activation of influenza viruses by proteases from host cells and bacteria in the human airway epithelium]]> https://www.researchpad.co/article/Nd648dcab-06b7-4a97-878a-9c9fb11262e1

Abstract

Influenza is an acute infection of the respiratory tract, which affects each year millions of people. Influenza virus infection is initiated by the surface glycoprotein hemagglutinin (HA) through receptor binding and fusion of viral and endosomal membranes. HA is synthesized as a precursor protein and requires cleavage by host cell proteases to gain its fusion capacity. Although cleavage of HA is crucial for virus infectivity, little was known about relevant proteases in the human airways for a long time. Recent progress in the identification and characterization of HA‐activating host cell proteases has been considerable however and supports the idea of targeting HA cleavage as a novel approach for influenza treatment. Interestingly, certain bacteria have been demonstrated to support HA activation either by secreting proteases that cleave HA or due to activation of cellular proteases and thereby may contribute to virus spread and enhanced pathogenicity. In this review, we give an overview on activation of influenza viruses by proteases from host cells and bacteria with the main focus on recent progress on HA cleavage by proteases HAT and TMPRSS2 in the human airway epithelium. In addition, we outline investigations of HA‐activating proteases as potential drug targets for influenza treatment.

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<![CDATA[The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics]]> https://www.researchpad.co/article/N0b54253f-48d3-4c26-a99b-24cea86d7aa6

Abstract

Detection of early infectious disease may be challenging due to the low copy number of organisms present. To overcome this limitation and rapidly measure low concentrations of the pathogen, we developed a novel technology: Nanotrap particles, which are designed to capture, concentrate, and protect biomarkers from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that are capable of antigen capture through the coupling of affinity baits to the particles. Here, we describe recent findings demonstrating that Nanotrap particles are able to capture live infectious virus, viral RNA, and viral proteins. Capture is possible even in complex mixtures such as serum and allows the concentration and protection of these analytes, providing increased performance of downstream assays. The Nanotrap particles are a versatile sample preparation technology that has far reaching implications for biomarker discovery and diagnostic assays.

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