The ability of epithelial cells to organize through cell–cell adhesion into a functioning epithelium serves the purpose of a tight epithelial protective barrier. Contacts between adjacent cells are made up of tight junctions (TJ), adherens junctions (AJ), and desmosomes with unique cellular functions and a complex molecular composition. These proteins mediate firm mechanical stability, serves as a gatekeeper for the paracellular pathway, and helps in preserving tissue homeostasis. TJ proteins are involved in maintaining cell polarity, in establishing organ-specific apical domains and also in recruiting signaling proteins involved in the regulation of various important cellular functions including proliferation, differentiation, and migration. As a vital component of the epithelial barrier, TJs are under a constant threat from proinflammatory mediators, pathogenic viruses and bacteria, aiding inflammation and the development of disease. Inflammatory bowel disease (IBD) patients reveal loss of TJ barrier function, increased levels of proinflammatory cytokines, and immune dysregulation; yet, the relationship between these events is partly understood. Although TJ barrier defects are inadequate to cause experimental IBD, mucosal immune activation is changed in response to augmented epithelial permeability. Thus, the current studies suggest that altered barrier function may predispose or increase disease progression and therapies targeted to specifically restore the barrier function may provide a substitute or supplement to immunologic-based therapies. This review provides a brief introduction about the TJs, AJs, structure and function of TJ proteins. The link between TJ proteins and key signaling pathways in cell proliferation, transformation, and metastasis is discussed thoroughly. We also discuss the compromised intestinal TJ integrity under inflammatory conditions, and the signaling mechanisms involved that bridge inflammation and cancer.

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Claudins, a group of membrane proteins involved in the formation of tight junctions, are mainly found in endothelial or epithelial cells. These proteins have attracted much attention in recent years and have been implicated and studied in a multitude of diseases. Claudins not only regulate paracellular transepithelial/transendothelial transport but are also critical for cell growth and differentiation. Not only tissue-specific but the differential expression in malignant tumors is also the focus of claudin-related research. In addition to up- or down-regulation, claudin proteins also undergo delocalization, which plays a vital role in tumor invasion and aggressiveness. Claudin (CLDN)-1 is the most-studied claudin in cancers and to date, its role as either a tumor promoter or suppressor (or both) is not established. In some cancers, lower expression of CLDN-1 is shown to be associated with cancer progression and invasion, while in others, loss of CLDN-1 improves the patient survival. Another topic of discussion regarding the significance of CLDN-1 is its localization (nuclear or cytoplasmic vs perijunctional) in diseased states. This article reviews the evidence regarding CLDN-1 in cancers either as a tumor promoter or suppressor from the literature and we also review the literature regarding the pattern of CLDN-1 distribution in different cancers, focusing on whether this localization is associated with tumor aggressiveness. Furthermore, we utilized expression data from The Cancer Genome Atlas (TCGA) to investigate the association between CLDN-1 expression and overall survival (OS) in different cancer types. We also used TCGA data to compare CLDN-1 expression in normal and tumor tissues. Additionally, a pathway interaction analysis was performed to investigate the interaction of CLDN-1 with other proteins and as a future therapeutic target.

Cadmium is a known environmental pollutant targeting various organs. Often implicated in cadmium toxicology is the formation of reactive oxygen species, overwhelming the free radical scavenging mechanisms and inducing oxidative stress. Acute cadmium intoxication has been shown to reduce antioxidant enzyme activity and induce oxidative stress. However, chronic intoxication has obscure outcomes in oxidative stress while the cell makes adjustments to overcome the toxicant load. Also linked with the occurrence of oxidative stress is inflammation. Stimulation of acute or chronic inflammation is mediated by different cascades. However, key events include activation of transcription factor, NF-κB and release of pro-inflammatory cytokines. Both oxidative stress and inflammation are implicated simultaneously in pathogenesis and induction of multi-organ tissue damage under cadmium exposure. This article reviews the impact of acute and chronic cadmium intoxication on inducing oxidative stress, inflammation and thereby inflicting tissue damage.

Diet plays a major role in the body physiology and metabolism. The quantity, nature and stability of the macronutrients present in the diet have a major impact on the composition of gut microbiota. Gut microbiota plays a major role in the body metabolism and leads to obese or lean phenotype. Bacteriodetes, Firmicutes, Proteobacteria and Actinobacteria are the major microbes that inhabit in the region of the gut. We made an attempt to study the effects of Cafeteria (CAF) diets and normal chow diets on diet consumption, weight gain, metabolism and composition of gut microbiota in fecal and cecum samples from three weeks old Sprague Dawley (SD) rats (n = 18/group) using 16S rDNA high throughput sequencing. Results revealed that distinctive diet based phenotypical changes were observed in some of the Cafeteria diet fed rats. Interestingly, some weight gain resistant (WGR) animals in Cafeteria diet fed groups show similar trend like that of control normal chow fed rats. Fecal microbiome analysis indicates that the ratio of Bacteriodetes is higher than the Firmicutes in cecum samples of Cafeteria diet fed rats whereas no significant difference is found in fecal samples of Cafeteria diet fed rats and as well as in control rats. Further analysis of other taxa at the level of family and genus of microbial abundance are also discussed. Our study suggests that contribution of gut microbiota towards obesity is not at the phylum level, and microbiome composition even at the level of species or strain may exert impact on the metabolism of the Cafeteria diet.