Epithelial Barrier: Protector and Trigger of Allergic Disorders

The epithelial barrier has been classically considered as only the first line of defense against irritants, pathogens, and allergens, but it is now known that it also plays an essential role in the immunological response against exogenous agents. In fact, recent reports postulate the epithelial barrier hypothesis as a possible explanation for the increasing incidence and severity of allergic diseases. The epithelial barrier preserves the isolation of the inner tissues from potential external threats. Moreover, a coordinated interaction between epithelial and immune cells ensures the unique immune response taking place in mucosal tissues and that is has been reported to be dysregulated in allergic diseases. Herein, we and others have demonstrated that in severe allergic phenotypes, the epithelial barrier experiments several histological modifications and increased in immune cells infiltration, leading to its dysfunction. This is common in atopic dermatitis, asthma, and/or food allergy. However, the precise role of the epithelial barrier in the mucosal biology during allergic diseases progression is not well understood yet. In this review, we aim to compile recent knowledge regarding the histological structure and immunological function of the epithelial barrier and to shed light on the role of this compartment in the onset, and progression of allergic diseases.

GDF15 in Appetite and Exercise: Essential Player or Coincidental Bystander?

Growth differentiation factor 15 (GDF15) has recently moved to the forefront of metabolism research. When administered pharmacologically, GDF15 reduces food intake and lowers body weight via the hindbrain-situated receptor GFRAL (glial cell-derived neurotrophic factor family receptor alpha like). Endogenous GDF15 is a ubiquitous cellular stress signal that can be produced and secreted by a variety of cell types. Circulating levels are elevated in a series of disease states, but also in response to exogenous agents such as metformin, colchicine, AICAR and cisplatin. Recently, exercise has emerged as a relevant intervention to interrogate GDF15 physiology. Prolonged endurance exercise increases circulating GDF15 to levels otherwise associated with certain pathological states and in response to metformin treatment. Yet, the jury is still out as to whether GDF15 is a functional ‘exerkine’ mediating organ-to-brain cross-talk or whether it is a coincidental bystander. In this review, we discuss the putative physiological implication of exercise-induced GDF15, focusing on the potential impact on appetite and metabolism.

Transcriptomic Analyses Reveal 2 and 4 Family Members of Cytochromes P450 (CYP) Involved in LPS InflammatoryResponse in Pharynx of Ciona robusta

Cytochromes P450 (CYP) are enzymes responsible for the biotransformation of most endogenous and exogenous agents. The expression of each CYP is influenced by a unique combination of mechanisms and factors including genetic polymorphisms, induction by xenobiotics, and regulation by cytokines and hormones. In recent years, Ciona robusta, one of the closest living relatives of vertebrates, has become a model in various fields of biology, in particular for studying inflammatory response. Using an in vivo LPS exposure strategy, next-generation sequencing (NGS) and qRT-PCR combined with bioinformatics and in silico analyses, compared whole pharynx transcripts from naïve and LPS-exposed C. robusta, and we provide the first view of cytochrome genes expression and miRNA regulation in the inflammatory response induced by LPS in a hematopoietic organ. In C. robusta, cytochromes belonging to 2B,2C, 2J, 2U, 4B and 4F subfamilies were deregulated and miRNA network interactions suggest that different conserved and species-specific miRNAs are involved in post-transcriptional regulation of cytochrome genes and that there could be an interplay between specific miRNAs regulating both inflammation and cytochrome molecules in the inflammatory response in C. robusta.

A Review on Potential Antimutagenic Plants of Saudi Arabia

Mutagenic complications can cause disease in both present as well as future generations. The disorders are caused by exogenous and endogenous agents that damage DNA beyond the normal repair mechanism. Rapid industrialization and the population explosion have contributed immensely to changes in the environment, leading to unavoidable exposure to mutagens in our daily life. As it is impossible to prevent exposure, one of the better approaches is to increase the intake of anti-mutagenic substances derived from natural resources. This review summarizes some of the important plants in Saudi Arabia that might have the potential to exhibit anti-mutagenic activity. The data for the review were retrieved from Google scholar, NCBI, PUBMED, EMBASE and the Web of Science. The information in the study has importance since one of the major reasons for mutation is viral infection. Considering the pandemic situation due to novel coronavirus and its aftermath, the native plants of Saudi Arabia could become an important source for reducing mutagenic complications associated with exogenous agents, including viruses.

Effect of environmental stressors on the mRNA expression of ecdysone cascade genes in Chironomus riparius

Chemical compounds produced by humans are continuously reaching the environment. In this work, we characterised the expression patterns of important endocrine-related genes involved in the ecdysone pathway in the fourth larval instar of the model species Chironomus riparius after exposure to three chemicals: ethinyl oestradiol (EE), nonylphenol (NP) and bis(tributyltin) oxide (TBTO). We used real-time PCR to analyse the gene expression levels of ecdysone receptor (EcR) and ultraspiracle (usp), two genes that encode the dimerising partners of the functional ecdysone receptor; the orphan receptor ERR (oestrogen-related receptor), with an unknown function in invertebrates; and E74, an early response gene induced by ecdysteroids. We estimated the bioaccumulation potential, bioavailability and physicochemical properties of these chemicals, together with a number of other exogenous agents known to interfere with the hormonal system. We also provide a review of previous transcriptional studies showing the effect of all these chemicals on ecdysone cascade genes. This analysis provides useful data for future ecotoxicological studies involving invertebrate species. Capsule Changes in transcriptional activities of EcR, E74, usp and ERR genes after exposure to endocrine-disrupting chemicals would be useful as molecular bioindicators of endocrine disruption in Chironomus riparius.

125I –Amoxicillin preparation as a guide tracer for inflammation detection

The objective of this study is to label Amoxicillin with radioactive iodine (125I-AC) via direct electrophilic substitution to act as a promising tracer for inflammation imaging. The highest labeling yield of 80% was achieved after studying all the parameters affecting the labeling reaction using Iodogen (IG) as an oxidizing agent. Molecular Modeling Structure was done using MOE program to predict the suitable 125I position. The product structure was established by a cold iodination reaction using Iodine-127. Biological evaluation of (125I-AC) was carried out using groups of inflamed mice with different exogenous agents such as E.Coli and Turpentine oil. The (125I-AC) shows an in vitro stability of about 97% after 24 h.While doing in vivo studies over 4 h, the tracer stability of 99% was observed.

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.

Effect of Environmental Stressors on the mRNA Expression of Ecdysone Cascade Genes in Chironomus Riparius.

Chemical compounds produced by humans are continuously reaching the environment. In this work, we characterised the expression patterns of important endocrine-related genes involved in the ecdysone pathway in the fourth larval instar of the model species Chironomus riparius after exposure to three chemicals: ethinyl oestradiol (EE), nonylphenol (NP) and bis(tributyltin) oxide (TBTO). We used real-time PCR to analyse the gene expression levels of: ecdysone receptor (EcR) and ultraspiracle (usp), two genes that encode the dimerising partners of the functional ecdysone receptor; the orphan receptor ERR (oestrogen-related receptor), with an unknown function in invertebrates; and E74, an early response gene induced by ecdysteroids. We estimated the bioaccumulation potential, bioavailability and physicochemical properties of these chemicals, together with a number of other exogenous agents known to interfere with the hormonal system. We also provide a review of previous transcriptional studies showing the effect of all these chemicals on ecdysone cascade genes. This analysis provides useful data for future ecotoxicological studies involving invertebrate species.

A Peek Inside the Machines of Bacterial Nucleotide Excision Repair

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). Below, we discuss the architecture of key proteins in bacterial NER and recent biochemical, structural and single-molecule studies that shed light on the lesion recognition steps of both the GGR and the TCR sub-pathways. Although a great deal has been learned about both of these sub-pathways, several important questions, including damage discrimination, roles of ATP and the orchestration of protein binding and conformation switching, remain to be addressed.

A Metal-polyphenolic Nanosystem with NIR-II Fluorescence-guided Combined Photothermal Therapy and Radiotherapy

Photothermal therapy (PTT) achieves substantive therapeutic progress in certain tumor types without exogenous agents but is hampered by the over-activated inflammatory response or tumor recurrence in some cases. Herein, we...