Acute aortic syndromes, including aortic dissection (AD), are rare. The AD detection risk score (ADDRS) and associated investigation pathway were developed to reduce missed diagnosis of AD. The methodology for its development was sub-optimal and it has not been robustly validated in the emergency department chest pain population. Recent research suggests that it will drive over-investigation and that the risks of missed diagnosis may not be in balance with the risks of the testing strategy. There are serious doubts about whether the score and investigation pathway are fit for purpose.

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 spread globally and creates an alarming situation. Following the SARS-CoV-2 paradigm, therapeutic efficacy is achieved via repurposing several antiviral, antibacterial, and antimalarial drugs. Innate and adaptive immune cells work close to combat infection through the intricate production of antibodies (Abs) and inflammatory cytokines. As an essential component of the immune system, Abs play an important role in eliminating viruses and maintaining homeostasis. B lymphocytes (B cells) are effector cells, stringent to produce neutralizing Abs to combat infection. After recognizing SARS-CoV-2 antigens by a surface receptor called B cell receptors (BCRs) on the plasma membrane, the BCRs transmembrane signal transduction and immune activation results in Ab production and development of immune memory. Thus, it ensures that plasma B cells can quickly start an intricate immune response to generate efficient protective Abs to clear the pathogen. Nevertheless, considering therapeutic challenges in the context of the new coronavirus pandemic, this review addresses the molecular mechanism of the immune activation and function of novel SARS-CoV-2 specific B cells in the production of SARS-CoV-2 specific Abs. Additionally, these studies highlighted the Ab-mediated pathogenesis, the intriguing role of nano-scale signaling subunits, non-structural proteins during COVID-19 infection, and structural insights of SARS-CoV-2 specific Abs.

Understanding the interactions of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with humans is deeply grounded in immunology, from the diagnosis to pathogenesis, from the clinical presentations to the epidemiology, prevention, and treatment. However, the difficulty of capturing the complex and changeable array of immunological concepts and incorporating them into the strategies of control of the SARS-CoV-2 pandemic poses significant hindrances to establish optimal public health policies. The contribution of immunology to the control of the pandemic is to shed light on the features and mechanisms of the protective immunity elicited by SARS-CoV-2 infection and vaccines. Do they induce effective protective immunity? How? For how long? What is the effect of vaccination on individuals who were previously infected? To appropriately answer these questions, it is necessary to get rid of the outdated notion of a naïve, static, and closed immune system, which leads to misconceptions about susceptibility, specificity, immunological memory, and protective immunity. The present essay discusses these issues based on current immunological concepts.

There are various types of skin immune responses including inflammatory skin diseases and skin malignancy. Macrophages and fibroblasts are skin resident cells that had been overlooked in terms of immunological research targets. In this review, cross talk among macrophages, fibroblasts, and migratory immune cells in skin diseases such as atopic dermatitis (AD), contact hypersensitivity, psoriasis, systemic sclerosis, melanoma, and cutaneous T-cell lymphoma is described. Macrophages are important in AD by antigen-presenting phagocytosis, production of inflammatory cytokines, removal of apoptotic cells, and mediating clusters between dendritic cells (DCs) and T cells. They are also increased in lesional skin of psoriasis, especially in stable plaques, and an increased ratio of M1/M2 macrophages and tumor necrosis factor-α production by macrophages are essential for development of psoriasis. The progression of skin malignancy is mediated by macrophages through promotion of tumor survival pathways via expression of cytokines and growth factors, interaction with regulatory T cells (Tregs) and myeloid-derived suppressor cells, and suppression of function of tumor-infiltrating T cells by immunosuppressive cytokines and programmed death-ligand (PD-L)1. Fibroblasts play important roles in development and maintenance of AD lesions through expression of CC chemokine ligand (CCL)17, CCL11, CCL26, C-X-C motif chemokine ligand (CXCL)12, CCL19, and periostin, interacting with T helper (Th)2 cells, natural killer T (NKT) cells, DCs, and keratinocytes. They also play important roles in psoriasis, expressing interleukin (IL)-8 and vascular endothelial growth factor, production of fibronectin, and changes in the proteomic profiles. Fibroblasts have a critical role in the progression skin malignancy via expression of cytokines, suppression natural killer (NK) functions, and establishment of Th2-dominant microenvironment. Thus, cross talk among macrophages, fibroblasts, and migratory immune cells including T cells, DCs, and NK cells in skin diseases is important and those skin-resident cells are attracting therapeutic targets in the near future.

Cancer is an aging-associated disease and caused by genomic instability that is driven by the accumulation of mutations and epimutations in the aging process. Although Ca²⁺ signaling, reactive oxygen species (ROS) accumulation, DNA damage response (DDR) and senescence inflammation response (SIR) are processed during genomic instability, the underlying mechanism for the cause of genomic instability and cancer development is still poorly understood and needs to be investigated. Nociceptive transient receptor potential (TRP) channels, which firstly respond to environmental stimuli, such as microbes, chemicals or physical injuries, potentiate regulation of the aging process by Ca²⁺ signaling. In this review, the authors provide an explanation of the dual role of nociceptive TRP channels in regulating cancer progression, initiating cancer progression by aging-induced genomic instability, and promoting malignancy by epigenetic regulation. Thus, therapeutically targeting nociceptive TRP channels seems to be a novel strategy for treating cancers.

With the advent of various vaccines and antimicrobial agents during the 20th century, the control and containment of infectious diseases appeared to be a matter of time. However, studies unveiled the diverse natures of microbes, their lifestyle, and pathogenetic potentials. Since the ground-breaking discovery of the hepatitis B virus (HBV) by Baruch Blumberg and the subsequent development of a vaccine in the early 1980s, the main task of the scientific community has been to develop a proper management strategy for HBV-induced chronic liver diseases. In the early 1980’s, standard interferon (IFN) induced a reduction of HBV DNA levels, followed by the normalization of serum transaminases (alanine aminotransferase, ALT), in some chronic hepatitis B (CHB) patients. However, in the course of time, the limitations of standard IFN became evident, and the search for an alternative began. In the late 1980’s, nucleoside analogs entered the arena of CHB treatment as oral drugs with potent antiviral capacities. At the beginning of the 21st century, insights were developed into the scope and limitations of standard IFN, pegylated-IFN as well as nucleoside analogs for treating CHB. Considering the non-cytopathic nature of the HBV, the presence of covalently closed circular DNA (cccDNA) in the nucleus of the infected hepatocytes and HBV-induced immune-mediated liver damages, a new field of CHB management was initiated by modulating the hosts’ immune system through immune therapy. This review will discuss the nature and design of innovative immune therapy for CHB.

There have been significant developments in the design of nanostructured scaffolds for eliciting robust immune responses named vaccine. The technique is to produce strong immune responses is to manipulate the appearance of a pathogen. Subsequently pathogens such as viruses and bacteria often demonstrate of multiple copies of ligands on their surfaces, the immune system is predominantly sensitive towards multivalent presentations of antigens. Consequently, when designing a vaccine, it is beneficial to garnish a nanostructured surface with multiple copies of an antigen so it can effectively act as an immune booster. Different methods are there for the development of the vaccine, from them most of the techniques are well developed and reported and some of in the developing state. This review focuses primarily on cellular and non-cellular vaccines, the whole cells or cellular proteins either as the source of antigens or the platform in which to deliver the antigens. Purpose of this review, understand and discussion on the various vaccine platforms which will contribute noteworthy information to vaccine research and development (R and D).

Current evidence indicates that neurodegeneration of dopaminergic neurons of the substantia nigra associated to Parkinson’s disease is a consequence of a neuroinflammatory process in which microglial cells play a central role. The initial activation of microglial cells is triggered by pathogenic protein inclusions, which are mainly composed by α-synuclein. Importantly, these pathogenic forms of α-synuclein subsequently induce a T-cell-mediated autoimmune response to dopaminergic neurons. Depending on their functional phenotype, these autoreactive T-cells might shape the functional features of activated microglia. T-cells bearing pro-inflammatory phenotypes such as T-helper (Th)1 or Th17 promote a chronic inflammatory behaviour on microglia, whilst anti-inflammatory T-cells, such as regulatory T-cells (Treg) favour the acquisition of neuroprotective features by microglia. Thus, T-cells play a fundamental role in the development of neuroinflammation and neurodegeneration involved in Parkinson’s disease. This review summarizes the evidence indicating that not only CD4⁺ T-cells, but also CD8⁺ T-cells play an important role in the physiopathology of Parkinson’s disease. Next, this review analyses the different T-cell epitopes derived from the pathogenic forms of α-synuclein involved in the autoimmune response associated to Parkinson’s disease in animal models and humans. It also summarizes the requirement of specific alleles of major histocompatibility complexes (MHC) class I and class II necessaries for the presentation of CD8⁺ and CD4⁺ T-cell epitopes from the pathogenic forms of α-synuclein in both humans and animal models. Finally, this work summarizes and discusses a number of experimental immunotherapies that aim to strengthen the Treg response or to dampen the inflammatory T-cell response as a therapeutic approach in animal models of Parkinson’s disease.

Phosphoinositides are membrane phospholipids involved in a variety of cellular processes like growth, development, metabolism, and transport. This review focuses on the maintenance of cellular homeostasis of phosphatidylinositol 4,5-bisphosphate (PIP₂), and phosphatidylinositol 3,4,5-trisphosphate (PIP₃). The critical balance of these PIPs is crucial for regulation of neuronal form and function. The activity of PIP₂ and PIP₃ can be regulated through kinases, phosphatases, phospholipases and cholesterol microdomains. PIP₂ and PIP₃ carry out their functions either indirectly through their effectors activating integral signaling pathways, or through direct regulation of membrane channels, transporters, and cytoskeletal proteins. Any perturbations to the balance between PIP₂ and PIP₃ signaling result in neurodevelopmental and neurodegenerative disorders. This review will discuss the upstream modulators and downstream effectors of the PIP₂ and PIP₃ signaling, in the context of neuronal health and disease.

Biliary tract cancers (BTCs) are aggressive tumors arising from different portions of the biliary tree and classified according to the anatomical location in intrahepatic (i) cholangiocarcinoma (CCA, iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). Due to their silent behavior, BTCs are frequently diagnosed at advanced stages when the prognosis is poor. The available chemotherapeutic options are palliative and unfortunately, most patients will die from their disease between 6 and 18 months from diagnosis. However, over the last decade, amounting interest has been posed on the genomic landscape of BTCs and deep-sequencing studies have identified different potentially actionable driver mutations. Hence, the promising results of the early phase clinical studies with targeted agents against isocitrate dehydrogenase (IDH) 1 mutation or fibroblast growth factor (FGF) receptor (FGFR) 2 aberrations inintrahepatic tumors, and other agents against humanepidermal growth factor receptor (HER) 2 overexpression/mutations, neurotrophic tyrosine receptor kinase (NTRK) fusions or B-type Raf kinase (BRAF) mutations across different subtypes of BTCs, have paved the way for a “precision medicine” strategy for BTCs. Moreover, despite the modest results when used as monotherapy, beyond microsatellite instability-high (MSI-H) tumors, immune checkpoint inhibitors are being evaluated in combination with platinum-based chemotherapy, possibly further expanding the therapeutic landscape of advanced BTCs. This review aims to provide an overview of the approved systemic therapies, the promising results, and the ongoing studies to explore the current and future directions of advanced BTC systemic treatment.

Cholangiocarcinoma (CCA) is a disease with a very poor prognosis and limited treatment options. Although targeted therapies directed towards specific mutations found in CCA are becoming available and are showing great potential, many tumors do not carry actionable mutations and, in those that do, the emergence of drug resistance is a likely consequence of treatment. Therapeutic targeting of enzymes and other proteins that show elevated activity in CCA cells but which are not altered by mutation is a potential strategy for the treatment of target negative and drug-resistant disease. Protein kinase CK2 (CK2) is a ubiquitously expressed kinase that has increased expression and increased activity in a variety of cancer types including CCA. Several potent CK2 inhibitors are in pre-clinical development or under assessment in a variety of clinical trials often in combination with drugs that induce DNA damage. This review outlines the importance of CK2 in CCA and assesses the progress that has been made in the evaluation of CK2 inhibition as a treatment strategy in this disease. Targeting CK2 based on the expression levels or activity of this protein and/or in combination with drugs that induce DNA damage or inhibit cell cycle progression, could be a viable option for tumors that lack actionable mutations, or for tumors that develop resistance to targeted treatments.

Spinal cord injury (SCI) induces several destructive events that develop immediately after the primary insult. These phenomena increase tissue damage; that is why, numerous therapeutic approaches are studied in order to neutralize these destructive mechanisms. In line with this, several studies indicate that after injury, neural tissue could be protected by an adaptive immune response directed against self-antigens. Immunization with neural-derived peptides (INDP) reduces secondary degeneration of neurons after spinal cord insult and promotes a significant motor recovery. The combination of antioxidants or other immunomodulatory peptides after SCI can improve the protective effect induced by INDP. INDP in acute SCI is a promising strategy, so further studies should be addressed to be able to formulate the best strategy.

Both innate and adaptive immune cells exist in the skin, predominantly in the dermis layer. Recent studies have focused on how and which circadian rhythms contribute to maintain good health. Over recent years, we have gained a better understanding of the molecular mechanisms that control biological clocks and circadian rhythms. Circadian rhythms maintain homeostasis by providing day and night information to various physiological functions of our body. However, excessively high immune system activity can lead to a risk of developing autoimmune or allergic diseases. Recently, increasing numbers of studies with human and mouse models have been conducted to investigate the mechanisms underlying circadian regulation of the skin homeostasis. In this review, circadian regulation in the skin will be discussed from different points of view. Skin is referred as the largest organ of the body and is directly exposed to the external environment, including large changes in diurnal temperature, light, and pathogens. Immune cells as well as skin cells are the ones protecting us from these stimulants. Associations of the circadian system and these cells have been revealed in many ways, however, the specific roles of the peripheral clocks in these cells remain unknown. Circadian regulation in the skin diseases is discussed specifically in atopic dermatitis and other skin allergic symptoms as well as psoriasis.

Familial early-onset Alzheimer’s disease (AD) is more probable in individuals coming from mothers diagnosed with AD than from fathers diagnosed with AD. Studies in animal models have shown maternal imprinting due to the transmission to the embryo of altered material in the ovum. In the case of transgenic animals harboring a mutated form of the human amyloid precursor protein (APP), offspring from crosses with wild-type (WT) fathers and transgenic mothers display more abnormalities than offspring from crosses with transgenic fathers and WT mothers. Expression of the mutated APP in the ovum may lead to alterations that may be genetic and/or epigenetic in the nuclear and/or the mitochondrial DNA. These modifications that are transmitted to the new living beings affect more mitochondrial proteins and, therefore, the mitochondrial function may be affected in adulthood by trends present in the ovum.