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Topic Review
Updated Understanding of Cancer
       Cancer is a tumorigenesis process that forms a mass of cells that we call a tumor. During tumorigenesis, the cells that compose the tumor can be benign or malignant. When the cells in the tumor are normal but old, the tumor is termed benign. When the cells in the tumor are abnormal and can grow uncontrollably, the tumor is malignant. Sometimes a benign tumor can transform into a malign one if the normal old cells begin to develop abnormalities, such as DNA mutations, and grow rapidly. - by Cristian Muresanu
  • 2.0K
  • 30 Oct 2020
Topic Review
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease. Chronic lung inflammation is linked to the pathogenesis of IPF. DROSHA, a class 2 ribonuclease III enzyme, has an important role in the biogenesis of microRNA (miRNA). The function of miRNAs has been identified in the regulation of the target gene or protein related to inflammatory responses via degradation of mRNA or inhibition of translation. The absent-in-melanoma-2 (AIM2) inflammasome is critical for inflammatory responses against cytosolic double stranded DNA (dsDNA) from pathogen-associated molecular patterns (PAMPs) and self-DNA from danger-associated molecular patterns (DAMPs). The AIM2 inflammasome senses double strand DNA (dsDNA) and interacts with the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which recruits pro-caspase-1 and regulates the maturation and secretion of interleukin (IL)-1β and IL-18. A recent study showed that inflammasome activation contributes to lung inflammation and fibrogenesis during IPF. In the current review, we discuss recent advances in our understanding of the DROSHA–miRNA–AIM2 inflammasome axis in the pathogenesis of IPF.
  • 2.0K
  • 26 Oct 2020
Topic Review
Milk Exosomes
Milk contains various extracellular vesicles and non-vesicular structures: exosomes (with diameter 40-100 nm), vesicles of other size, fat globules (with diameter 4-6 mkm, containing milk fat globule membranes), and their aggregates. Due to the biocompatibility of milk exosomes, these vesicles have a wide potential as vehicles for oral delivery of therapeutically relevant molecules (drugs and therapeutic nucleic acids).
  • 1.9K
  • 21 Sep 2020
Topic Review
BH3-Only Proteins Noxa and Puma in Apoptosis Regulation
Apoptosis is an evolutionarily conserved and tightly regulated cell death pathway. Physiological cell death is important for maintaining homeostasis and optimal biological conditions by continuous elimination of undesired or superfluous cells. The BH3-only pro-apoptotic members are strong inducers of apoptosis. The pro-apoptotic BH3-only protein Noxa activates multiple death pathways by inhibiting the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family protein, Mcl-1, and other protein members leading to Bax and Bak activation and mitochondrial outer membrane permeabilization (MOMP). On the other hand, Puma is induced by p53-dependent and p53-independent apoptotic stimuli in several cancer cell lines. Moreover, this protein is involved in several physiological and pathological processes, such as immunity, cancer, and neurodegenerative diseases. Future heat shock research could disclose the effect of hyperthermia on both Noxa and BH3-only proteins. This suggests post-transcriptional mechanisms controlling the translation of both Puma and Noxa mRNA in heat-shocked cells. 
  • 1.9K
  • 10 Mar 2022
Topic Review
TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage
Subarachnoid hemorrhage (SAH) is a complex condition with high morbidity and mortality. Numerous different factors contributing to brain injury after SAH have been identified. Despite treatment of complications of early brain injury, such as rise of intracranial pressure, disturbance of the blood–brain barrier, cerebral edema, and decrease in cerebral perfusion, the outcome of many patients remains devastating. Neuroinflammation within the brain parenchyma with associated neuronal cell death has been described as a leading mechanism for additional secondary brain injury. It involves complex signaling cascades in which the upregulation of inflammatory genes is induced. Consequently, the release of different inflammatory cytokines and chemokines leads to self-reinforcement of the immune system with concomitant neuronal cell death, destroying the brain. The immune system within the central nervous system (CNS) fulfills a special role. It is privileged and differs in its standards from the peripheral immune response. 
  • 1.9K
  • 10 Nov 2022
Topic Review
Tolerogenic Vaccines to Induce Antigen-Specific Tolerance
Conventional therapies for immune-mediated diseases, including autoimmune disorders, transplant reactions, and allergies, have undergone a radical evolution in the last few decades; however, they are still not specific enough to avoid widespread immunosuppression. The idea that vaccine usage could be extended beyond its traditional immunogenic function by encompassing the ability of vaccines to induce antigen-specific tolerance may revolutionize preventive and therapeutic strategies in several clinical fields that deal with immune-mediated disorders. 
  • 1.9K
  • 22 Sep 2022
Topic Review
Atherosclerosis
Macrophages are key target immune cells in atherosclerosis. A hallmark of atherosclerosis is the accumulation of pro-inflammatory macrophages in coronary arteries that respond to pro-atherogenic stimuli and failure of digesting lipids that contribute to foam cell formation in atherosclerotic plaques.
  • 1.9K
  • 29 Jan 2022
Topic Review
Induction of heme oxygenase-1 Expression
Heme oxygenase-1 (HO-1) catalyzes the degradation of heme molecules releasing equimolar amounts of biliverdin, iron and carbon monoxide. Its expression is induced in response to stress signals such as reactive oxygen species and inflammatory mediators with antioxidant, anti-inflammatory and immunosuppressive consequences for the host. Interestingly, several intracellular pathogens responsible for major human diseases have been shown to be powerful inducers of HO-1 expression in both host cells and in vivo. Studies have shown that this HO-1 response can be either host detrimental by impairing pathogen control or host beneficial by limiting infection induced inflammation and tissue pathology. These properties make HO-1 an attractive target for host-directed therapy (HDT) of the diseases in question, many of which have been difficult to control using conventional antibiotic approaches.
  • 1.9K
  • 10 Dec 2020
Topic Review
Microglia Activation and Noradrenergic System
The nervous system requires immune cells to fight foreign body invasion including the pathogenic infection. This function is accomplished by microglia, which also play many other roles in the central nervous system including elimination of apoptotic cells, synaptic pruning, supporting neuronal survival, clearing debris, etc. Under healthy conditions, cyto-morphologically, microglia possess long thin processes and a small cell body, useful for debris clearance. However, upon exposure to inflammation, it becomes “activated” to function as immune cells of the central nervous system and develop short, thick processes and a larger cell body. They phagocytose the pathogens, release inflammatory mediators, and regulate T-cell activity. A variety of neurotransmitter receptors are expressed on the microglia which facilitate bidirectional communication between neurons and microglia. It has been shown that withdrawal of noradrenaline (NA) is a necessity for generation of rapid eye movement sleep (REMS). It has been proposed that REMS has evolved to maintain NA level in the brain. Further, NA exerts neuromodulatory action on microglia and facilitates immune function of the brain. Thus, REMS modulates immune functions of the brain.
  • 1.9K
  • 29 Dec 2022
Topic Review
CD38: T Cell Immuno-Metabolic Modulator
CD38 is a major mammalian NAD+ glycohydrolase (NADase), expresses on T cells following activation and appears to be an essential modulator of intracellular NAD+ levels. The enzymatic activity of CD38 in the process of generating the second messenger cADPR utilizes intracellular NAD+, and thus limits its availability to differentNAD+ consuming enzymes (PARP, ART, and sirtuins) inside the cells.
  • 1.9K
  • 27 Oct 2020
Topic Review
B-Cell-Based Immunotherapy
The field of immunotherapy has undergone radical conceptual changes over the last decade. There are various examples of immunotherapy, including the use of monoclonal antibodies, cancer vaccines, tumor-infecting viruses, cytokines, adjuvants, and autologous T cells carrying chimeric antigen receptors (CARs) that can bind cancer-specific antigens known as adoptive immunotherapy.
  • 1.9K
  • 15 Jun 2022
Topic Review
Macrophage, Meta-Inflammation, and Inflammaging
Macrophages are central players in systemic inflammation associated with obesity and aging, termed meta-inflammation and inflammaging. Activities of macrophages elicited by the two chronic conditions display shared and distinct patterns mechanistically, resulting in multifaceted actions for their pathogenic roles. Drastically expanded tissue macrophage populations under obesity and aging stress attribute to both enhanced recruitment and local expansion.
  • 1.8K
  • 25 Nov 2022
Topic Review
TILs in rabbit mammary carcinomas
Tumor infiltrating lymphocytes (TILs) are key components of the tumor microenvironment that mediate the anti-tumor immune response. In breast cancer of humans, TILs represent prognostic and predictive biomarkers. For their standardized evaluation in routinely (hematoxylin and eosin) stained tissue sections, international guidelines exist. Recently, TILs have also been analyzed in pet rabbit mammary carcinomas according to these international guidelines. Results of the study on rabbit mammary carcinomas showed a statistically significant association between higher TIL numbers in stromal TIL hotspot areas and microscopic parameters indicative of a better tumor differentiation, i.e. decreased mitotic count, lower histological tumor grade and higher percentage of calponin positive tumor cells. These findings suggest that in rabbit mammary carcinomas TIL hotspot areas may exert an influence on the biological behavior of these tumors. The present study contributes to comparative pathology. In addition, it provides the basis for further investigations into the impact of TILs on clinical parameters of pet rabbit mammary carcinomas.
  • 1.8K
  • 27 Oct 2020
Topic Review
The Complement System in Human Viral Diseases
The complement system (CS) is part of the human immune system, consisting of more than 30 proteins that play a vital role in the protection against various pathogens and diseases, including viral diseases. Activated via three pathways, the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP), the complement system leads to the formation of a membrane attack complex (MAC) that disrupts the membrane of target cells, leading to cell lysis and death. Due to the increasing number of reports on its role in viral diseases, which may have implications for research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • 1.8K
  • 28 Feb 2022
Topic Review
Inflammatory Bowel Disease Treatments
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time.
  • 1.8K
  • 05 Jul 2022
Topic Review
Role of Langerhans Cells in Skin Inflammation
Langerhans cells (LCs) constitute a cellular immune network across the epidermis. Because they are located at the skin barrier, they are considered immune sentinels of the skin. These antigen-presenting cells are capable of migrating to skin draining lymph nodes to prime adaptive immune cells, namely T- and B-lymphocytes, which will ultimately lead to a broad range of immune responses.  LCs have been shown to possess important roles in the anti-cancer immune responses.
  • 1.8K
  • 26 Dec 2022
Topic Review
Keratin 6, 16 and 17
Located at the skin surface, keratinocytes (KCs) are constantly exposed to external stimuli and are the first responders to invading pathogens and injury. Upon skin injury, activated KCs secrete an array of alarmin molecules, providing a rapid and specific innate immune response against danger signals. However, dysregulation of the innate immune response of KCs may lead to uncontrolled inflammation and psoriasis pathogenesis. Keratins (KRT) are the major structural intermediate filament proteins in KCs and are expressed in a highly specific pattern at different differentiation stages of KCs. While KRT14-KRT5 is restricted to basal proliferative KCs, and KRT10-KRT1 is restricted to suprabasal differentiated KCs in normal skin epidermis, the wound proximal KCs downregulate KRT10-K1 and upregulate KRT16/KRT17-KRT6 upon skin injury. Recent studies have recognized KRT6/16/17 as key early barrier alarmins and upregulation of these keratins alters proliferation, cell adhesion, migration and inflammatory features of KCs, contributing to hyperproliferation and innate immune activation of KCs in response to an epidermal barrier breach, followed by the autoimmune activation of T cells that drives psoriasis. 
  • 1.8K
  • 21 Mar 2022
Topic Review
Inflammatory Tumor Microenvironment
The development of tumors requires an initiator event, usually exposure to DNA damaging agents that cause genetic alterations such as gene mutations or chromosomal abnormalities, leading to deregulated cell proliferation. Although the mere stochastic accumulation of further mutations may cause tumor progression, it is now clear that an inflammatory microenvironment has a major tumor-promoting influence on initiated cells, in particular when a chronic inflammatory reaction already existed before the initiated tumor cell was formed. Moreover, inflammatory cells become mobilized in response to signals emanating from tumor cells. In both cases, the microenvironment provides signals that initiated tumor cells perceive by membrane receptors and transduce via downstream kinase cascades to modulate multiple cellular processes and respond with changes in cell gene expression, metabolism, and morphology. Cytokines, chemokines, and growth factors are examples of major signals secreted by immune cells, fibroblast, and endothelial cells and mediate an intricate cell-cell crosstalk in an inflammatory microenvironment, which contributes to increased cancer cell survival, phenotypic plasticity and adaptation to surrounding tissue conditions. Eventually, consequent changes in extracellular matrix stiffness and architecture, coupled with additional genetic alterations, further fortify the malignant progression of tumor cells, priming them for invasion and metastasis.
  • 1.8K
  • 29 Mar 2022
Topic Review
Immunity (Medical)
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens irrespective of their antigenic make-up. Other components of the immune system adapt themselves to each new disease encountered and can generate pathogen-specific immunity. Immunity is a complex biological system that can recognize and tolerate whatever belongs to the self, and to recognize and reject what is foreign (non-self).
  • 1.8K
  • 23 Nov 2022
Topic Review
Lamin-A/C expression in immune cells
Nuclear envelope lamin A/C type-V intermediate filaments are a major constituent of the mammalian nuclear lamina, a dense fibrous protein meshwork located in the nuclear interior. Lamin A/C proteins control nuclear mechanics and structure and modify cellular signaling, gene transcription, epigenetic regulation, cell cycle progression, cell differentiation, and cell migration. The immune system is constituted by the innate and adaptive immunity. Innate immune response is mediated by myeloid cells such as neutrophils, macrophages, and dendritic cells. These cells produce a rapid and nonspecific response through phagocytosis, cytokine production, and complement activation, as well as activating adaptive immunity. Specific adaptive immune response is provoked by antigen presentation by antigen presenting cells (APCs) and the cytokine milieu, and is mainly mediated by the cellular functions of T cells and the production of antibodies by B cells. Unlike most cell types, immune cells regulate their lamin A/C protein expression relatively rapidly to exert their functions, with expression increasing in macrophages, reducing in neutrophils, and increasing transiently in T cells. In this article, it is discussed and summarized studies that have addressed the regulation of the expression of lamin A/C in cells of the innate and adaptive immune system.
  • 1.7K
  • 27 Oct 2020
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