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Topic Review
Filamentous Bacteriophage for Immunotherapeutic Strategies
The pharmaceutical use of bacteriophages as safe and inexpensive therapeutic tools is collecting renewed interest. The use of lytic phages to fight antibiotic-resistant bacterial strains is pursued in academic and industrial projects and is the object of several clinical trials. On the other hand, filamentous bacteriophages used for the phage display technology can also have diagnostic and therapeutic applications. Filamentous bacteriophages are nature-made nanoparticles useful for their size, the capability to enter blood vessels, and the capacity of high-density antigen expression. In the last decades, filamentous bacteriophage ‘fd’ was employed as antigen delivery system, able to trigger all arms of the immune response, with particular emphasis on the ability of the MHC class I restricted antigenic determinants displayed on phages to induce strong and protective cytotoxic responses.Moreover, fd bacteriophages, engineered to target mouse dendritic cells (DCs), activate innate and adaptive responses without the need of exogenous adjuvants, and more recently was employed for the display of immunologically active lipids.
  • 1.2K
  • 20 Feb 2021
Topic Review
Suprachoroidal Delivery of Therapeutic Agents
Suprachoroidal drug delivery technology has advanced rapidly and emerged as a promising administration route for a variety of therapeutic candidates, targeting multiple ocular diseases, ranging from neovascular age-related macular degeneration to choroidal melanoma. This entry summarizes the latest preclinical and clinical progress in suprachoroidal delivery of therapeutic agents, focusing on small molecule suspensions.
  • 1.2K
  • 22 Sep 2021
Topic Review
Acute Kidney Injury
Acute kidney injury is a common complication in critically ill patients with sepsis and/or septic shock. Further, some essential antimicrobial treatment drugs are themselves nephrotoxic. For this reason, timely diagnosis and adequate therapeutic management are paramount. Of potential acute kidney injury (AKI) biomarkers, non-protein-coding RNAs are a subject of ongoing research.
  • 1.2K
  • 09 Oct 2020
Topic Review
Takotsubo Syndrome
Takotsubo syndrome (TTS) represents a form of acute heart failure featured by reversible left ventricular systolic dysfunction. The management during the acute phase is mainly performed with supportive pharmacological (diuretics, ACE-inhibitors/angiotensin-receptor blockers (ARBs), anticoagulants, antiarrhythmics, non-catecholamine inotropics (levosimendan), and non-pharmacological (mechanical circulatory and respiratory support) therapy, due to the wide clinical presentation and course of the disease. However, there is a gap in evidence and there are no randomized and adequately powered studies on clinical effectiveness of therapeutic approaches. Some evidence supports the use ACE-inhibitors/ARBs at long-term. A tailored approach based on cardiovascular and non-cardiovascular risk factors is strongly suggested for long-term management. The urgent need for evidence-based treatment approaches is also reflected by the prognosis following TTS. The acute phase of the disease can be accompanied by various cardiovascular complications. In addition, long term outcome of TTS patients is also related to non-cardiovascular comorbidities. Physical triggers such as hypoxia and acute neurological disorders in TTS are associated with a poor outcome.
  • 1.2K
  • 14 Feb 2021
Topic Review
Glucocorticoid Resistance
Glucocorticoids (GCs) are steroid hormones that regulate the physiology of all mammalian tissues throughout life due to their diverse roles in development, growth, metabolism, and inflammation. In response to physiological cues and stressors, the hypothalamic-pituitary-adrenal (HPA) axis coordinates the systemic production and secretion of GCs from the adrenal glands in a circadian and stress-related manner to maintain tissue homeostasis. In turn, GCs mediate negative feed-back inhibiting secretion of the hypothalamic corticotropin-releasing hormone (CRH) and the adrenocorticotropic hormone (ACTH), limiting GC production.
  • 1.2K
  • 27 Oct 2021
Topic Review
FtsZ
FtsZ is an essential and central protein for cell division in most bacteria. Because of its ability to organize into dynamic polymers at the cell membrane and recruit other protein partners to form a “divisome”, FtsZ is a leading target in the quest for new antibacterial compounds. 
  • 1.2K
  • 24 Mar 2021
Topic Review
Pulmonary Arterial Hypertension
Recognition of and response to pathogens and tissue injury is driven by the innate immune system via activation of pattern recognition receptors. One of the many patterns recognized is RNA and, while several receptors bind RNA, Toll-like receptor 3 (TLR3) is well placed for initial recognition of RNA molecules due to its localization within the endosome. There is a growing body of work describing a role for TLR3 in maintenance of vascular homeostasis. For example, TLR3 deficiency has been shown to play repair and remodeling roles in the systemic vasculature and in lung parenchyma. A hallmark of pulmonary arterial hypertension (PAH) is pulmonary vascular remodeling, yet drivers and triggers of this remodeling remain incompletely understood. Based on its role in the systemic vasculature, our group discovered reduced endothelial TLR3 expression in PAH and revealed a protective role for a TLR3 agonist in rodent models of pulmonary hypertension.
  • 1.2K
  • 29 Oct 2020
Topic Review
Nanoparticles in Male Infertility
Advancement in the field of nanotechnology has prompted the need to elucidate the deleterious effects of nanoparticles (NPs) on reproductive health. Many studies have reported on the health safety issues related to NPs by investigating their exposure routes, deposition and toxic effects on different primary and secondary organs but few studies have focused on NPs’ deposition in reproductive organs. Noteworthy, even fewer studies have dealt with the toxic effects of NPs on reproductive indices and sperm parameters (i.e. sperm number, motility and morphology) by evaluating, for instance, the histopathology of seminiferous tubules and testosterone levels. To date, the research suggests that NPs can easily cross the blood testes barrier and, after accumulation in the testis, induce adverse effects on spermatogenesis.
  • 1.2K
  • 12 Mar 2021
Topic Review
Ozanimod
Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.
  • 1.2K
  • 18 Dec 2020
Topic Review
Nano-Based Transdermal Delivery Systems
Microneedling significantly enhanced transdermal delivery of both ALA and TMP in vitro. The MN hydrogel-forming system was comparable with the MN dissolving system for ALA delivery (~3000 nmol/cm2over 6h), however superior for delivery of the much larger TMP molecule (~14 nmol/cm2over 24h, compared to 0.15 nmol/cm2). Thus, these results have opened the potential for investigating microneedling with many other PSs.
  • 1.2K
  • 11 Aug 2021
Topic Review
Autoimmune Polyendocrine Syndrome Type 1
Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare but severe monogenetic autoimmune endocrine disease caused by failure of the Autoimmune Regulator (AIRE). AIRE regulates the negative selection of T cells in the thymus, and the main pathogenic mechanisms are believed to be T cell-mediated, but little is known about the role of B cells.
  • 1.2K
  • 03 Jan 2022
Topic Review
Flavonoids and Their Anti-Diabetic Effects
Diabetes mellitus (DM) is a prevailing global health metabolic disorder, with an alarming incidence rate and a huge burden on health care providers. DM is characterized by the elevation of blood glucose due either to a defect in insulin synthesis, secretion, binding to receptor, or an increase of insulin resistance. The internal and external factors such as obesity, urbanizations, and genetic mutations could increase the risk of developing DM. Flavonoids are phenolic compounds existing as secondary metabolites in fruits and vegetables as well as fungi. Their structure consists of 15 carbon skeletons and two aromatic rings (A and B) connected by three carbon chains. Flavonoids are furtherly classified into 6 subclasses: flavonols, flavones, flavanones, isoflavones, flavanols, and anthocyanidins. Naturally occurring flavonoids possess anti-diabetic effects. As in vitro and animal model’s studies demonstrate, they have the ability to prevent diabetes and its complications.The aim of this review is to summarize the current knowledge addressing the anti-diabetic effects of dietary flavonoids and their underlying molecular mechanisms on selected pathways: Glucose transporter, hepatic enzymes,tyrosine kinase inhibitor, AMPK, PPAR, and NF-B. Flavonoids improve the pathogenesis of diabetes and its complications through the regulation of glucose metabolism, hepatic enzymes activities, and lipid profile. Most studies illustrate a positive role of specific dietary flavonoids on diabetes, but the mechanisms of action and the side effects need more clarification. Overall, more research is needed to provide a better understanding of the mechanisms of diabetes treatment using flavonoids.
  • 1.2K
  • 26 Jul 2021
Topic Review
Atypical Antipsychotics and Metabolic Syndrome
Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life expectancy and poor adherence. Importantly, there is clear evidence that early metabolic disturbances can precede weight gain, even if the latter still remains the hallmark of AAPs use. In fact, AAPs interfere profoundly with glucose and lipid homeostasis acting mostly on hypothalamus, liver, pancreatic β-cells, adipose tissue, and skeletal muscle. Their actions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5′AMP-activated protein kinase (AMPK) activity, thus producing a supraphysiological sympathetic outflow augmenting levels of glucagon and hepatic glucose production. In addition, altered insulin secretion, dyslipidemia, fat deposition in the liver and adipose tissues, and insulin resistance become aggravating factors for MetS. In clinical practice, among AAPs, olanzapine and clozapine are associated with the highest risk of MetS, whereas quetiapine, risperidone, asenapine and amisulpride cause moderate alterations. The new AAPs such as ziprasidone, lurasidone and the partial agonist aripiprazole seem more tolerable on the metabolic profile. However, these aspects must be considered together with the differences among AAPs in terms of their efficacy, where clozapine still remains the most effective. Intriguingly, there seems to be a correlation between AAP’s higher clinical efficacy and increase risk of metabolic alterations. Finally, a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS. In addition, pharmacological treatments are discussed as well.
  • 1.2K
  • 23 Mar 2021
Topic Review
Veterinary Diagnostics of Honeybee Diseases
This entry is a review dealing with the veterinary diagnostic approach in honeybee colonies especially in case of common virus diseases. It presents the step-by-step methods a veterinarian should perform when facing an ill honeybee colony and focusses on virus diseases in adult honeybees. 
  • 1.2K
  • 02 Dec 2020
Topic Review
Bluetongue Virus Vector Vaccines
In this work, we show a deep revision of the viral vector vaccines that have been developed to counteract bluetongue virus (BTV), an arthropod-borne disease that whips domestic and wild ruminants. We analyzed the main advantages and disadvantages of every of them, as well as the immunological features and efficacy that these candidates provided in both murine models and natural hosts.
  • 1.2K
  • 08 Jan 2021
Topic Review
Alcoholic Korsakoff Syndrome
Alcoholic Korsakoff syndrome (AKS), Korsakoff syndrome is an amnestic disorder caused by thiamine (vitamin B1) deficiency associated with prolonged ingestion of alcohol. There is a similar condition seen in non-alcoholic Korsakoff syndrome. This neurological disorder is caused by a lack of thiamine in the brain, and is also exacerbated by the neurotoxic effects of alcohol. When Wernicke encephalopathy accompanies alcoholic Korsakoff syndrome the combination is called Wernicke–Korsakoff syndrome; however, a recognized episode of Wernicke encephalopathy is not always obvious. The syndrome and psychosis are named after Sergei Korsakoff, a Russian neuropsychiatrist who discovered the syndrome during the late 19th century.
  • 1.2K
  • 14 Nov 2022
Topic Review
Race-Based Traumatic Stress
Race-based traumatic stress is the traumatic response to stress following a racial encounter. Robert T. Carter's (2007) theory of race-based traumatic stress implies that there are individuals of color who experience racially charged discrimination as traumatic, and often generate responses similar to post-traumatic stress. Race-based traumatic stress combines theories of stress, trauma and race-based discrimination to describe a particular response to negative racial encounters. Despite the limited research that examines race-based traumatic stress specifically, trauma research suggests that an individual's response to a stressor is highly dependent on that person's perception of the stressor; what one person may experience as traumatic, another person may not experience as such. These differing responses have been found to be strongly associated with each individual's ability to cope with the said stressor. According to Carter, a professor at Columbia University, race-based traumatic stress is an individual's response to racial discrimination as traumatic or outside of their ability to cope. Race-based traumatic stress can be experienced both directly and indirectly and can occur on an interpersonal level, institutional level, or cultural level. As such, research indicates that race-based traumatic stress can be demonstrated as a number of negative outcomes, including psychopathological symptoms, social inequities, and internalized racial oppression. Research has indicated that children, as well as adults, can experience and be impacted by the reaches of race-based traumatic stress. Through direct experience from peers and/or authority figures, as well as indirectly through media exposure and/or bearing witness to the racial discrimination of their parents, research suggests children of color are particularly vulnerable to race-based traumatic stress.
  • 1.2K
  • 14 Oct 2022
Topic Review
Glycemic Status Assessment
The advanced and performing technologies of glucose monitoring systems provide a large amount of glucose data that needs to be properly read and interpreted by the diabetology team in order to make therapeutic decisions as close as possible to the patient’s metabolic needs. For this purpose, new parameters have been developed, to allow a more integrated reading and interpretation of data by clinical professionals. The new challenge for the diabetes community consists of promoting an integrated and homogeneous reading, as well as interpretation of glucose monitoring data also by the patient himself. The purpose of this review is to offer an overview of the glycemic status assessment, opened by the current data management provided by latest glucose monitoring technologies. Furthermore, the applicability and personalization of the different glycemic monitoring devices used in specific insulin-treated diabetes mellitus patient populations will be evaluated.
  • 1.2K
  • 19 Nov 2020
Topic Review
Multifaceted Mechanisms of Metformin
While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.
  • 1.2K
  • 09 Mar 2021
Topic Review
Serum Bilirubin in Obese Individuals
Bilirubin, the end product of heme metabolism, is a potent endogenous antioxidant with anti-inflammatory, immunomodulatory, antithrombotic, and endocrine properties. Serum bilirubin concentrations depend on the complex interactions between bilirubin production, consumption (depending on oxidative stress and inflammation), metabolism, and elimination. Importantly, numerous studies have shown that serum bilirubin levels are inversely associated with obesity, metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and other oxidative-stress-mediated diseases, including atherosclerosis. Moreover, serum bilirubin levels were recently proposed as a potential pre-disease biomarker for developing metabolic syndrome in asymptomatic middle-aged individuals. 
  • 1.2K
  • 07 Sep 2021
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