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Topic Review
Vascular Calcification
A variety of actively regulated processes on cellular and systemic level with various contributing and inhibiting factors can result in vascular calcification (VC). Currently, treatment is limited to management of risk factors including regulation of the calcium-phosphate metabolism. Due to the complex pathophysiology, the mechanisms underlying ectopic calcification are studied in various, distinctly different research models. Beside in vitro models using cells of different origin, ex vivo settings using aortic tissue are available. In addition, various in vivo disease-induced animal models are currently used in research. All of these experimental settings depict (patho)physiologic mechanisms within the vascular calcification process.
  • 986
  • 29 Oct 2020
Topic Review
Immunosuppressive Cells
Tumor-associated macrophages (TAMs) produce various chemokines and angiogenic factors that promote tumor development, along with other immunosuppressive cells. TAMs generated from monocytes develop into functional, fully activated macrophages, and TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment. The main population of TAMs comprises CD163+ M2 macrophages, and CD163+ TAMs release soluble (s)CD163 and several proinflammatory chemokines as a result of TAM activation to induce an immunosuppressive tumor microenvironment. Since direct blockade of PD1/PD-L1 signaling between tumor cells and tumor-infiltrating T cells is mandatory to induce an anti-immune response by anti-PD1 Abs. Understanding the crosstalk between TAMs and immunosuppressive cells is important for optimizing PD1 Ab-based immunotherapy.
  • 982
  • 03 Aug 2020
Topic Review
Macrophages in Cancer
Macrophages in cancer represent a major part of the immune cells within the TME and they are more frequently associated with a bad prognosis.
  • 982
  • 21 Feb 2021
Topic Review
Sarcoidosis: Clinical Manifestations
Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans, Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age.
  • 982
  • 20 Apr 2021
Topic Review
Antibodies in HIV-infection and HIV-vaccine development
The structure of HIV-envelope changes as the infection progresses and is one of the biggest obstacles in developing of HIV-vaccine. HIV-infection can cause the production of various natural autoantibodies, including catalytic antibodies hydrolyzing DNA, myelin basic protein, histones, HIV-integrase, HIV-reverse transcriptase, β-casein, serum albumin, and some other natural substrates. Currently, there are various directions for the development of HIV vaccines: stimulation of the immune response on the mucous membranes; induction of cytotoxic T cells, which lyse infected cells and hold back HIV-infection; immunization with recombinant Env proteins or vectors encoding Env; mRNA-based vaccines and some others. 
  • 982
  • 22 Mar 2022
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.
  • 978
  • 15 Jun 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.
  • 975
  • 29 Mar 2022
Topic Review
Human Coronavirus (HCoV)
Coronaviruses (CoVs) were identified in the 1930s as zoonotic spherical pathogens causing mostly respiratory or enteric diseases. Coronaviruses vary in size and are enveloped with club-shaped spikes on their surface. A helically symmetrical nucleocapsid comprising positive-sense single-stranded RNA is one of the largest virus genomes, ranging from 26 to 32 kilobases in length. Although CoVs are distributed mainly among mammals and birds, since 1960 seven species of human coronaviruses (HCoVs) have been described and some HCoVs infections (SARS-CoV, MERS-CoV and SARS-CoV-2) have resulted in lethal epidemics. The global range and high fatality rate of the newest HCoV pandemic has made SARS-CoV-2 the focus of the scientific world.
  • 971
  • 17 Dec 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. 
  • 971
  • 10 Mar 2022
Topic Review
A Telemedicine Approach to Covid-19
        COVID-19 is an RNA virus that has caused a pandemic leading to death and disability on a global scale. The virus gains entry into the cell using host protein angiotensin-converting enzyme-2 (ACE-2) receptor. The viral envelope fuses with the cell membrane through the endosomal pathway, allowing the viral particle to enter the host cell, where it can release its RNA and replicate. After an initial asymptomatic period, common presenting signs and symptoms of COVID-19 infection are non-specific and may include those of a common cold or influenza such as fever, dry cough, myalgia, headache and fatigue. Sore throat and nasal congestion may also be noted. Gastrointestinal and other symptoms may occur and loss of sense of taste and smell is a frequent early symptom that may distinguish COVID-19 from other respiratory infections. The virus is highly contagious and there is no cure. In order to avoid transmission, social distancing, mask wearing and reduced person-to-person interaction are key.  Definitive diagnosis is based on reverse-transcription PCR of nasopharyngeal and oropharyngeal swab samples. The clinical spectrum of the disease ranges from mild to moderate or severe. In order to minimize spread of COVID-19 to both patients and healthcare workers, virtual evaluation of suspected cases is being widely implemented and has necessitated an adjustment to the new medium by all participants. The use of virtual technology for real-time telemedicine assessment for COVID-19 provisional diagnosis and categorization of severity allows patients to receive an appropriate level of care without endangering others. We created a protocol for implementing a remote visit using a computer or mobile device. This enables patient assessement without direct contact to determine the need to visit a healthcare facility or alternatively, to be managed at home. If stable, the patient can isolate and be monitored so that should their condition worsen, they can be directed to in-person care at a hospital. Vigilance in checking on the patient's condition is crucial because those who develop severe COVID-19 may not experience dyspnea and other signs of rapid deterioration until about 5-8 days after symptom onset.  
  • 970
  • 04 Feb 2021
Topic Review
Current Regulation of Anti-COVID-19 mRNAs
COVID-19 vaccines were developed and approved rapidly in response to the urgency created by the pandemic. No specific regulations existed at the time they were marketed. The regulatory agencies therefore adapted them as a matter of urgency. Now that the pandemic emergency has passed, it is time to consider the safety issues associated with this rapid approval. The mode of action of COVID-19 mRNA vaccines should classify them as gene therapy products (GTPs), but they have been excluded by regulatory agencies.
  • 970
  • 27 Jun 2023
Topic Review
Serum lipidomics in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. Changes in the lipid profile at a molecular level in RA are still poorly understood. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid profile, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.
  • 957
  • 15 Jan 2021
Topic Review
Thrombospondin-1 in the Tumor Microenvironment
The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. 
  • 953
  • 23 Jun 2021
Topic Review
Herd Immunity against Viral Diseases
Microbiome is the preeminent factor to maintain the efficacy of vaccine platform. The inception of herd immunity in society is depending upon food habits, microbiome symbiosis, environmental factors, and network among people with each other.  Rigorous pan-India polio vaccination program for the last 30 years develops heterologous immunity providing cardinal protection against the COVID-19.
  • 950
  • 09 Nov 2020
Topic Review
Molecular Characterization of LAG-3
Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule comparable to PD-1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. LAG-3 is the third inhibitory receptor to be exploited in human anti-cancer immunotherapies, and it is considered a potential next-generation cancer immunotherapy target in human therapy, right next to PD-1 and CTLA-4. Unlike PD-1 and CTLA-4, the exact mechanisms of action of LAG-3 and its relationship with other immune checkpoint molecules remain poorly understood. This is partly caused by the presence of non-conventional signaling motifs in its intracellular domain that are different from other conventional immunoregulatory signaling motifs but with similar inhibitory activities.
  • 948
  • 25 Jun 2021
Topic Review
Bacterial Lipopolysaccharides
Bacterial lipopolysaccharides (LPS), also referred to as endotoxins, are major outer surface membrane components present on almost all Gram-negative bacteria and are major determinants of sepsis-related clinical complications including septic shock. LPS acts as a strong stimulator of innate or natural immunity in a wide variety of eukaryotic species ranging from insects to humans including specific effects on the adaptive immune system.
  • 947
  • 25 Aug 2022
Topic Review
ZIKA Virus and Male Infertility
Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.
  • 945
  • 01 Nov 2020
Topic Review
Urogenital Schistosomiasis
Schistosomiasis is the most important helminthiasis worldwide in terms of morbidity and mortality. Most of the infections occurs in Africa, which about two thirds are caused by Schistosoma haematobium. The infection with S. haematobium is considered carcinogenic leading to squamous cell carcinoma (SCC) and urothelial carcinoma of the urinary bladder.
  • 945
  • 30 Sep 2021
Topic Review
NF-κB Signaling and Virus Infection
The nuclear factor κB (NF-κB) family are the master transcription factors that control cell proliferation, apoptosis, the expression of interferons and proinflammatory factors, and viral infection. During viral infection, host innate immune system senses viral products, such as viral nucleic acids, to activate innate defense pathways, including the NF-κB signaling axis, thereby inhibiting viral infection. In these NF-κB signaling pathways, diverse types of ubiquitination have been shown to participate in different steps of the signal cascades. Recent advances find that viruses also modulate the ubiquitination in NF-κB signaling pathways to activate viral gene expression or inhibit host NF-κB activation and inflammation, thereby facilitating viral infection. Understanding the role of ubiquitination in NF-κB signaling during viral infection will advance our knowledge of regulatory mechanisms of NF-κB signaling and pave the avenue for potential antiviral therapeutics. 
  • 945
  • 07 Apr 2021
Topic Review
Cyclolinopeptide A
A cyclic nonapeptide Cyclolinopeptide A (CLA) was isolated from linen seeds oil. The consequences of manipulations in structure and amino acid composition of native cyclolinopeptide A (CLA) from linen seeds, and its linear precursor on their biological activities and mechanisms of action, are reviewed.
  • 945
  • 16 Jun 2021
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