Balanced immune regulation is crucial for recognizing an invading pathogen, its killing, and elimination. Toll‐like receptors (TLRs) are the key regulators of the innate immune system. It helps in ...identifying between self and nonself‐molecule and eventually eliminates the nonself. Endosomal TLR, mainly TLR3, TLR7, TLR8, and membrane‐bound TLR4, has a role in the induction of cytokine storms. TLR7/8 recognizes the ssRNA SARS‐COV‐2 and when it replicates to dsRNA, it is recognized by TLR3 and drives the TRIF‐mediated inflammatory signaling like NF‐κB, MAPK. Such signaling leads to significant transcription and translation of pro‐inflammatory genes, releasing inflammatory molecules into the systemic circulation, causing an imbalance in the system. So, whenever an imbalance occurs, a surge in the pro‐inflammatory mediators is observed in the blood, including cytokines like interleukin (IL)‐2, IL‐4, IL‐6, IL‐1β, IL‐8, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α. IL‐6 and IL‐1β are one of the driving factors for bringing the cytokine storm into the systemic circulation, which migrates into the other organs, causing multiple organ failures leading to the death of the individual with severe illness.
Highlights
The imbalanced and hyper responsive immune system leads to a surge leading to death of the infected patients in COVID‐19.
It has been observed that cytokine surge is TLR induced, mainly through activation of TLR3, TLR4, TLR7, TLR8 receptors.
The cytokine storm migrates into the other organ through systemic circulation. The inflammation and the organ damage occur due to the TLR mediated NF‐κB, MAPK pathway. Hence blocking these specific TLRs may alleviate the chance of SARS‐COV‐2 infection.
Endogenous RNAs that control posttranscriptional gene expression are microRNAs (miRNAs). These small regulatory molecules play a crucial role in certain biological processes and their expression is ...often strictly regulated. They are small 21–24 nucleotide molecules that act as major regulators of gene expression at the posttranscriptional level. One of the mechanisms by which miRNAs control the gene expression is to interact the interaction of the seeds with the 3ʹ‐end and and more seldom the 5ʹ‐end of mRNA transcribed by the target genes. miRNAs have been identified as important cytoplasmic regulators of gene expression. miRNAs function as posttranscriptional regulators of their messenger RNA (mRNA) targets by mRNA degradation and/or translational repression. It is becoming evident, however, that miRNAs have nuclear functions as well. About the cell type, the physiological state of the body, and various external factors, the following explanation will summarize the complex multilevel regulation of miRNA expression. A better understanding of the molecular mechanisms controlling miRNA expression will provide clarification of the variations in the expression of protein‐coding genes.
MicroRNAs (miRNAs) are a type of small RNA molecule that controls gene expression after it has been transcribed.
The discovery of miRNAs has given us a new perspective on how complex gene regulatory networks work.
The majority of miRNAs are transcribed from DNA sequences as primary miRNAs, which are then processed into precursor miRNAs and mature miRNAs.
miRNA‐target gene interactions are dynamic and are influenced by a number of factors such as miRNA subcellular location, miRNA and target messenger RNA (mRNA) abundance, and miRNA–mRNA interaction affinity.
The increasing demands from consumers for fresh-like 'minimally' processed foods have led to unprecedented research into novel non-thermal food processing technologies. This trend has drawn interest ...in the use of cold plasma systems in the past decade. The nonthermal technologies have been defined as preservation treatments effective at ambient or sublethal temperatures, that minimize undesirable thermal effects on nutritional and quality parameters of foods.
Examination of the unconventional food processing technologies generally tends to be from the standpoint of microbiology, often subordinating their impact on the chemistry of foods. However, cold plasma has been shown to affect chemical components of foods, thereby affecting quality. This review selectively focuses on dairy proteins and their interaction with cold plasma. It briefly describes the nature of cold plasma and their effects on structural configurations of proteins. Furthermore, the review combines this information with the chemistry of dairy proteins to expound upon how functional properties of milk proteins can be modified using cold plasma processing. Finally, the review draws inference from, the analysis of effective enhancement of some functional properties of wheat flour, zein films, pea protein isolate and whey protein isolate mentioned in literature.
Further studies focused on optimization of treatment parameters are required to completely elucidate the effects of cold plasma species on structures and properties of dairy proteins. An understanding of the reactive species of plasma and protein interactions will be a guide for manipulation of functional properties of the dairy proteins.
Protective variables for Coronavirus Disease 2019 (COVID-19) are unknown. "Trained immunity" of the populace as a result of Bacille Calmette-Guérin (BCG) vaccination policy implementation and ...coverage had been suggested to be one of the factors responsible for the differential impact of COVID-19 on different countries. Several trials are underway to evaluate the potential protective role of BCG vaccination in COVID-19. However, the lack of clarity on the use of appropriate controls concerning the measures of "trained immunity" or the heterologous cell-mediated immunity conferred by BCG vaccination has been a cause of concern leading to more confusion as exemplified by a recently concluded trial in Israel that failed to find any protective correlation with regard to BCG vaccination. Whereas, when we analyze the COVID-19 epidemiological data of European countries without any regard for BCG vaccination policy but with similar age distribution, comparable confounding variables, and the stage of the pandemic, the prevalence of tuberculin immunoreactivity-a measure of cell-mediated immunity persistence as a result of Mycobacterium spp. (including BCG vaccine) exposure of the populations-is found consistently negatively correlated with COVID-19 infections and mortality. We seek to draw attention toward the inclusion of controls for underlying "trained immunity" and heterologous cell-mediated immunity prevalence that may be preexisting or resulting from the intervention (e.g., BCG vaccine) in such trials to arrive at more dependable conclusions concerning potential benefit from them.
Increased body weight and metabolic disorder including insulin resistance, type 2 diabetes and cardiovascular complications together constitute metabolic syndrome. The pathogenesis of metabolic ...syndrome involves multitude of factors. A number of studies however indicate, with some conformity, that oxidative stress along with chronic inflammatory condition pave the way for the development of metabolic diseases. Oxidative stress, a state of lost balance between the oxidative and anti-oxidative systems of the cells and tissues, results in the over production of oxidative free radicals and reactive oxygen species (ROS). Excessive ROS generated could attack the cellular proteins, lipids and nucleic acids leading to cellular dysfunction including loss of energy metabolism, altered cell signalling and cell cycle control, genetic mutations, altered cellular transport mechanisms and overall decreased biological activity, immune activation and inflammation. In addition, nutritional stress such as that caused by high fat high carbohydrate diet also promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation, and decreased antioxidant system and reduced glutathione (GSH) levels. These changes lead to initiation of pathogenic milieu and development of several chronic diseases. Studies suggest that in obese person oxidative stress and chronic inflammation are the important underlying factors that lead to development of pathologies such as carcinogenesis, obesity, diabetes, and cardiovascular diseases through altered cellular and nuclear mechanisms, including impaired DNA damage repair and cell cycle regulation. Here we discuss the aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy.
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The progression of cancer is not only about the tumor cell itself, but also about other involved players including cancer cell recruited immune cells, their released pro-inflammatory factors, and the ...extracellular matrix. These players constitute the tumor microenvironment and play vital roles in the cancer progression. Neutrophils-the most abundant white blood cells in the circulation system-constitute a significant part of the tumor microenvironment. Neutrophils play major roles linking inflammation and cancer and are actively involved in progression and metastasis. Additionally, recent data suggest that neutrophils could be considered one of the emerging targets for multiple cancer types. This review summarizes the most recent updates regarding neutrophil recruitments and functions in the tumor microenvironment as well as potential development of neutrophils-targeted putative therapeutic strategies.
The growing incidence of parasitic resistance against generic pentavalent antimonials, specifically for visceral disease in Indian subcontinent, is a serious issue in Leishmania control. ...Notwithstanding the two treatment alternatives, that is amphotericin B and miltefosine are being effectively used but their high cost and therapeutic complications limit their use in endemic areas. In the absence of a vaccine candidate, identification, and characterization of novel drugs and targets is a major requirement of leishmanial research. This review describes current drug regimens, putative drug targets, numerous natural products that have shown promising antileishmanial activity alongwith some key issues and strategies for future research to control leishmaniasis worldwide.
Chemokines, a subfamily of the cell cytokines, are low molecular weight proteins known to induce chemotaxis in leukocytes in response to inflammatory and pathogenic signals. A plethora of literature ...demonstrates that chemokines and their receptors regulate tumor progression and metastasis. With these diverse functionalities, chemokines act as a fundamental link between the tumor cells and their microenvironment. Recent studies demonstrate that the biology of chemokines and their receptor in metastasis is complex as numerous chemokines are involved in regulating site-specific tumor growth and metastasis. Successful treatment of disseminated cancer is a significant challenge. The most crucial problem for treating metastatic cancer is developing therapy regimes capable of overcoming heterogeneity problems within primary tumors and among metastases and within metastases (intralesional). This heterogeneity of malignant tumor cells can be related to metastatic potential, response to chemotherapy or specific immunotherapy, and many other factors
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In this review, we have emphasized the role of chemokines in the process of metastasis and metastatic heterogeneity. Individual chemokines may not express the full potential to address metastatic heterogeneity, but chemokine networks need exploration. Understanding the interplay between chemokine-chemokine receptor networks between the tumor cells and their microenvironment is a novel approach to overcome the problem of metastatic heterogeneity. Recent advances in the understanding of chemokine networks pave the way for developing a potential targeted therapeutic strategy to treat metastatic cancer.
Neutrophils in the Tumor Microenvironment Wu, Lingyun; Saxena, Sugandha; Singh, Rakesh K
Advances in Experimental Medicine and Biology,
01/2020, Letnik:
1224
Journal Article, Book Chapter
Recenzirano
Odprti dostop
Neutrophils are the first responders to inflammation, infection, and injury. As one of the most abundant leukocytes in the immune system, neutrophils play an essential role in cancer progression, ...through multiple mechanisms, including promoting angiogenesis, immunosuppression, and cancer metastasis. Recent studies demonstrating elevated neutrophil to lymphocyte ratios suggest neutrophil as a potential therapeutic target and biomarker for disease status in cancer. This chapter will discuss the phenotypic and functional changes in the neutrophil in the tumor microenvironment, the underlying mechanism(s) of neutrophil facilitated cancer metastasis, and clinical potential of neutrophils as a prognostic/diagnostic marker and therapeutic target.
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