Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

/pdf/short-chain-fatty-acids-scfas-mediated-gut-epithelial-and-9f96a2ebvf.pdf

Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases.

There is now an abundance of evidence to show that short-chain fatty acids (SCFAs) play an important role in the maintenance of health and the development of disease. SCFAs are a subset of fatty acids that are produced by the gut microbiota during the fermentation of partially and nondigestible polysaccharides. The highest levels of SCFAs are found in the proximal colon, where they are used locally by enterocytes or transported across the gut epithelium into the bloodstream. Two major SCFA signaling mechanisms have been identified, inhibition of histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs). Since HDACs regulate gene expression, inhibition of HDACs has a vast array of downstream consequences. Our understanding of SCFA-mediated inhibition of HDACs is still in its infancy. GPCRs, particularly GPR43, GPR41, and GPR109A, have been identified as receptors for SCFAs. Studies have implicated a major role for these GPCRs in the regulation of metabolism, inflammation, and disease. SCFAs have been shown to alter chemotaxis and phagocytosis; induce reactive oxygen species (ROS); change cell proliferation and function; have anti-inflammatory, antitumorigenic, and antimicrobial effects; and alter gut integrity. These findings highlight the role of SCFAs as a major player in maintenance of gut and immune homeostasis. Given the vast effects of SCFAs, and that their levels are regulated by diet, they provide a new basis to explain the increased prevalence of inflammatory disease in Westernized countries, as highlighted in this chapter.

The role of short-chain fatty acids in health and disease.

Structure–function relationships of immunostimulatory polysaccharides: A review

Butyrate: A Double-Edged Sword for Health?

Introduction Japanese encephalitis (JE) is among the most important viral encephalitides in Asia, especially in rural and suburban areas where rice culture and pig farming coexist. (1-3) It has also occurred rarely and sporadically in northern Australia and parts of the Western Pacific. (4-6) JE is due to infection with the JE virus (JEV), a mosquito-borne flavivirus. The main JEV transmission cycle involves Culex tritaeniorhynchus mosquitoes and similar species that lay eggs in rice paddies and other open water sources, with pigs and aquatic birds as principal vertebrate amplifying hosts. (1,2,7) Humans are generally thought to be dead-end JEV hosts, i.e. they seldom develop enough viremia to infect feeding mosquitoes. Fewer than 1% of human JEV infections result in JE. Approximately 20-30% of JE cases are fatal and 30-50% of survivors have significant neurologic sequelae. (8) JE is primarily a disease of children and most adults in endemic countries have natural immunity after childhood infection, but all age groups are affected. In most temperate areas of Asia, JEV is transmitted mainly during the warm season, when large epidemics can occur. In the tropics and subtropics, transmission can occur year-round but often intensifes during the rainy season. (1-3) The global incidence of JE is unknown because the intensity and quality of JE surveillance and the availability of diagnostic laboratory testing vary throughout the world. Countries that have implemented high-quality childhood JE vaccination programmes have seen a dramatic decline in JE incidence. Although JE is reportable to the World Health Organization (WHO) by its Member States, reporting is highly variable and incomplete. In the late 1980s, Burke and Leake estimated that 50 000 new cases of JE occurred annually among the 2.4 billion people living in the 16 Asian countries considered endemic at the time (approximate overall annual incidence: 2 per 100 000). (2) In the intervening two decades, despite major population growth, urbanization, changes in agricultural practices and increased use of the JE vaccine in many countries, this figure has been widely quoted, including very recently. (9-13) In 2000, assuming an annual, age-group-specific incidence of 25 cases per 100 000, Tsai estimated that in the absence of vaccination 175 000 cases of JE would occur annually among Asian children aged 0-14 years living in rural areas. (14) The current study used more recent, published, local or national incidence estimates and current population data to produce an updated estimate of the annual global incidence of JE. Methods We approximated the JE-affected territory of each of the 24 countries endemic for JE using a recent update (15) of an earlier approximation by Tsai (16) with some modifications (Table 1, available at: http://www.who.int/bulletin/ volumes/89/10/10-085233). Based on these same approximations, (15,16) we then stratified the JE-affected territory of some countries (e.g. China excluding Taiwan, India and Nepal) into two or more incidence strata. Because suitable studies of JE incidence were not available for every endemic country or incidence stratum, we sorted JE-endemic countries and incidence strata into 10 incidence groups (A, B, C1, C2 and D through I) based primarily on geographic proximity, ecologic similarity, vaccine programme similarity. Table 1 briefly describes the status of each endemic country's JE vaccination programme as of 2009, according to recent publications and unpublished sources. (8,17-20) Incidence data We identified studies that contained potentially useful data on the incidence of JE in Asia in a manner similar to the one used in a recent study of global typhoid fever incidence. (21) Whenever possible, this review followed the relevant guidelines for Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). (22) The review process is described as follows and no protocol is available. …

Estimated Global Incidence of Japanese Encephalitis: A Systematic review/Estimation De L'incidence Mondiale De L'encephalite Japonaise: Une Evaluation Systematique/ Incidencia Global Estimada De la Encefalitis Japonesa: Una Revision Sistematica

The term industry has always been a very controversial point in the area of industrial jurisprudence. However, there have been some judgments in a string of cases, which have tried to resolve the dispute and lay down an adequate definition whenever question arose. Later it has been realized that these definitions have created huge confusion. To pacify the situation the definition of industry under section 2(j) of the IDA was considered by the Supreme Court in the land mark judgment of Bangalore Water Supply and Sewerage Board Vs A.Rajjapa and Ors 1 , wherein the court laid down the broad interpretation of the term industry. This judgment holds importance because it was for the first time that a comparatively clear definition of the term was given. The phrases labour laws' and 'industrial laws' are used synonymously and refer to those laws and legal rules which regulate the employer-employee relations. Some of these laws impose certain obligations or confer certain rights upon the employers or the employees so that in the ultimate analysis they can be deemed to impinge upon employer-employee relations.

Growth and development of industrial jurisprudence in india

Background: Serotonin transporter (SLC6A4; SERT) plays a key role in regulating the availability of 5-HT (5-hydroxytryptamine, a neurotransmitter and hormone) in the brain and the gut mucosa. A decrease in intestinal SERT expression, associated with increased availability of 5-HT, is implicated in the pathogenesis of infectious and inflammatory disorders of the gut. Therefore, it is critical to understand the regulation of SERT, as a novel target for the treatment of gastrointestinal disorders. In this regard, long noncoding RNAs (LncRNAs, small transcripts >200 nucleotides) are known to modulate gene expression via chromatin remodeling, transcriptional and posttranscriptional mechanisms. Notably, elevated levels of LncRNA H19 are observed in IBD patients and mouse models of inflammation and are known to promote mucosal regeneration and wound healing and restore the intestinal homeostasis. Whether LncRNA H19 regulates SERT expression remains unknown and was the focus of the current study. Methods: Caco-2 cells were transiently transfected with either H19 mammalian expression vector or H19 siRNA using Lipofectamine 2000. Protein and mRNA expression was measured by immunoblotting and real-time PCR, respectively. Age-matched H19 lncRNA- deficient mice and wild-type (WT) littermates were used to determine the role of genetic deletion of H19 on SERT expression in ileum. Results: H19 overexpression in Caco-2 cells increased SERT mRNA levels (~13-fold; p<0.05) at 48h post-transfection compared to an empty vector. Consistent with the mRNA levels, H19 also increased SERT protein expression (~2-fold, p<0.05). Furthermore, siRNA-mediated knockdown of H19 in Caco-2 cells resulted in a significant decrease in SERT mRNA levels (~80%, p<0.05). Parallel to the in vitro results, H19 deficient mice also showed a significant decrease in SERT mRNA expression (~69 %, p<0.05) in the ileum compared to the WT mice. Interestingly, in comparison to WT, the expression of other key transporters involved in intestinal NaCl absorption (SLC9A3, SLC26A3, and SLC26A6) remained unaltered in H19 deficient mice. Conclusion: These data demonstrate a novel role of LncRNA H19 in regulating the expression of SERT in the intestine under physiological conditions. We speculate that H19 mediated increase in SERT expression may provide valuable insights into the mechanisms restoring decreased SERT expression in inflammatory or infectious diseases of the gut. (Supported by VA/NIH). VA and NIH This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

LncRNA H19 Regulates Intestinal Serotonin Transporter (SERT) Expression

Inflammatory Bowel Diseases (IBD), including Crohn’s Disease (CD) and ulcerative colitis (UC), are associated with chronic inflammation of the gastrointestinal tract. While it is a multifactorial disease, recently the aryl hydrocarbon receptor (AhR) has been identified as a susceptibility gene for IBD. AhR is a ubiquitously expressed transcription factor and its activation results in xenobiotic detoxification by CYP1A1 and CYP1B1, as well as induction of anti‐inflammatory pathways such as IL‐10 and IL‐22. In the gut, AhR is vital in maintaining immune cell populations, proliferation, and motility. Previous studies utilizing constitutive knock out of AhR in IECs showed exacerbated inflammation in acute DSS model. How intestinal epithelial cell (IEC) AhR deficiency impacts chronic colitis resembling human IBD is not yet known. Here, we investigated the effect of removing of IEC AhR in an inducible manner utilizing DSS induced chronic colitis (resembling Th1/Th17 and Th2 infiltration as seen in CD patients) and elucidated underlying mechanisms.

Intestinal epithelial specific AhR deficient mice exhibit increased severity of experimentally induced chronic colitis

Background: The colon targeted drug delivery system is mainly useful for the topical treatment of colon diseases such as ulcerative colitis, Crohn’s disease OR colorectal cancers where we attain high local concentration and minimum side effects. In the present study we have synthesized some colon targeted Ethylene diamine tetra acetic acid (EDTA)-antimicrobial drug conjugates. Objectives: The goal of synthesizing EDTA-antimicrobial drug conjugates are that they reach intact in the colon and not be absorbed in the upper GIT, this is because of high molecular weight (&gt;500) of the conjugates (Lipinski’s rule of 5). Materials and Methods: A series of EDTA-antimicrobial drug conjugates (E1-E5) were synthesized by stirring tetra sodium EDTA with antimicrobial drugs viz. Metronidazole (MTZ), Ornidazole (OZ), Ciprofloxacin (CF), Norfloxacin (NF) and Sulfamethoxazole (SM) in presence of EDAC ((1-ethyl-3(3-dimethylaminopropyl) carbodiimide). All the synthesized conjugates were characterized by FTIR, NMR (1H and 13C), Mass spectrometry and elemental analysis to identify structural components. The synthesized conjugates were screened for antimicrobial (antibacterial) and colon release studies. Results and Discussion: On the basis of chemical and spectral analysis EDTA-antimicrobial drug conjugates were synthesized and synthesized conjugates showed good antimicrobial (antibacterial) activity against tested stains. In-vitro release studies of the synthesized conjugates of the series have shown good release results which indicates that synthesized conjugates release the parent drug (antimicrobial drugs) to the colon. Conclusion: Synthesized conjugates improve drug delivery to the intestinal region. Release studies result suggest that the drugs begin to release from the conjugates in the distal intestinal region and appreciable release in the colon has been observed. 

Synthesis, Characterization and Release Studies of Ethylene Diamine Tetraacetic Acid (EDTA)-Antimicrobial Drug Conjugates for Colon Release

Physical characterization of Clove Oil based Self Nano-Emulsifying Formulations of Cefpodoxime Proxetil: Assessment of Dissolution rate, Antioxidant & Antibacterial activity

Anoop Kumar

Papers

Growth and development of industrial jurisprudence in india

LncRNA H19 Regulates Intestinal Serotonin Transporter (SERT) Expression

Intestinal epithelial specific AhR deficient mice exhibit increased severity of experimentally induced chronic colitis

Synthesis, Characterization and Release Studies of Ethylene Diamine Tetraacetic Acid (EDTA)-Antimicrobial Drug Conjugates for Colon Release

Physical characterization of Clove Oil based Self Nano-Emulsifying Formulations of Cefpodoxime Proxetil: Assessment of Dissolution rate, Antioxidant & Antibacterial activity