Utilization of dietary mixed-linkage ß-glucans by the Firmicute Blautia producta.

The ß-glucans are structurally varied, naturally occurring components of the cell walls, and storage materials of a variety of plant and microbial species. In the human diet, mixed-linkage glucans [MLG - ß-(1,3/4)-glucans] influence the gut microbiome and the host immune system. Although consumed daily, the molecular mechanism by which human gut Gram-positive bacteria utilize MLG largely remains unknown. In this study, we used Blautia producta ATCC 27340 as a model organism to develop an understanding of MLG utilization. B. producta encodes a gene locus comprising a multi-modular cell-anchored endo-glucanase (BpGH16MLG), an ABC transporter, and a glycoside phosphorylase (BpGH94MLG) for utilizing MLG, as evidenced by the upregulation of expression of the enzyme- and solute binding protein (SBP)-encoding genes in this cluster when the organism is grown on MLG. We determined that recombinant BpGH16MLG cleaved various types of ß-glucan, generating oligosaccharides suitable for cellular uptake by B. producta. Cytoplasmic digestion of these oligosaccharides is then performed by recombinant BpGH94MLG and ß-glucosidases (BpGH3-AR8MLG and BpGH3-X62MLG). Using targeted deletion, we demonstrated BpSBPMLG is essential for B. producta growth on barley ß-glucan. Furthermore, we revealed that beneficial bacteria, such as Roseburia faecis JCM 17581T, Bifidobacterium pseudocatenulatum JCM 1200T, Bifidobacterium adolescentis JCM 1275T, and Bifidobacterium bifidum JCM 1254, can also utilize oligosaccharides resulting from the action of BpGH16MLG. Disentangling the ß-glucan utilizing the capability of B. producta provides a rational basis on which to consider the probiotic potential of this class of organism.

An in silico approach for identification of lead compound as FtsZ inhibitor.

The remarkable conservation of the FtsZ among Gram-positive and Gram-negative bacteria, a crucial GTPase in bacterial cell division, has emerged as a promising antibacterial drug target to combat antibacterial resistance. There have been several coordinated efforts to develop inhibitors against FtsZ which can also serve as potential candidates for future antibiotics. In the present study, a natural product-like library (≈50,000 compounds) was employed to conduct HTVS against Staphylococcus aureus FtsZ protein (PDB Id: 6KVP). Additionally, molecular docking was carried out in two modes, SP and XP docking, using the Schrödinger suite. The glide scores of ligands obtained by XP docking were further summarized and compared with the control ligands (ZI1- co-crystal and PC190723-a compound undergoing clinical trial). Using the Prime-MM-GBSA approach, BFE calculations were performed on the top XP-scored ligands (≈598 compounds). These hits were also evaluated for ADMET parameters using the Qikprop algorithm, SwissADME, and in silico carcinogenicity testing using Carcinopred-El. Based on the results, ligand 4-FtsZ complex was considered for the 300 ns MDS analysis to get insights into its binding modes within the catalytic pocket of FtsZ protein. The analysis revealed that the amide linkage sandwiched between the triazole and 1-oxa-8-azaspirodecan-8-ium moiety (Val203) as well as the aminoethyl group present at 1st position on the triazole moiety (Leu209, Leu200, Asp210, and Ala202) were responsible for the FtsZ inhibitory activity, owing to their crucial interactions with key amino acid residues. Further, the complex also displayed good protein-ligand stability, ultimately predicting ligand 4 as a potent lead compound for the inhibition of FtsZ. Thus, our in silico findings will serve as a framework for in-depth in-vitro and in-vivo investigations encouraging the development of FtsZ inhibitors as a new generation of antibacterial agents.

Macroalgal dietary glycans: potential source for human gut bacteria and enhancing immune system for better health.

Macroalgae are the diverse group of photosynthetic algae found at the intertidal regions of oceans. Recent advances suggest that macroalgal derived glycans have tremendous potential to maintain gut microbiome and immune system. The human gut bacteria harbor unique arsenals for utilizing a variety of macroalgal glycans, and produce a variety of oligosaccharides in vivo. Those oligosaccharides interact with immune cell receptors, and also are available for microbial fermentation, thus play magnificent roles in balancing the gut homeostasis. However, this area of research is still in infancy condition in term to understand their molecular interactions. For wooing this area, we urge to emphasize more studies on mechanistic level sympathetic of depolymerizing marine dietary glycans by gut bacteria and elucidating molecular aspect of glycans to cell receptors interactions. This will invent new nutraceutical strategies to purposefully manipulate the microbial composition to improve health. Therefore, review focuses on the recent development of mechanistic understanding of human gut bacterial communities for utilizing macroalgal derived glycans. Recent trends of application of glycans in modulating immune system at mechanistic level and their available evidences are discussed.

Intrarectal Capsazepine Administration Modulates Colonic Mucosal Health in Mice.

Antagonism of transient receptor potential vanniloid-1 (TRPV1) and desensitization of transient receptor potential ankyrin-1 (TRPA1) nociceptors alleviate inflammatory bowel diseases (IBD)-associated chronic pain. However, there is limited literature available about their role in regulating the mucosal layer, its interaction with host physiology, and luminal microbial community. The present study focuses on the effects' intra rectal administration of capsazepine (modulator of TRPA1/TRPV1 expressing peptidergic sensory neurons) on colonic mucus production and gut health. We performed histological analysis, gut permeability alteration, gene expression changes, metabolite profiling, and gut microbial abundance in the ileum, colon, and cecum content of these animals. Intra rectal administration of capsazepine modulates TRPA1/TRPV1-positive nociceptors (behavioral pain assays) and resulted in damaged mucosal lining, increased gut permeability, and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response, and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. These results suggest that caution must be exercised before employing TRPA1/TRPV1 modulation as a therapeutic option to alleviate pain caused due to IBD.

Biochemical Basis of Xylooligosaccharide Utilisation by Gut Bacteria.

Xylan is one of the major structural components of the plant cell wall. Xylan present in the human diet reaches the large intestine undigested and becomes a substrate to species of the gut microbiota. Here, we characterised the capacity of Limosilactobacillus reuteri and Blautia producta strains to utilise xylan derivatives. We showed that L. reuteri ATCC 53608 and B. producta ATCC 27340 produced ß-D-xylosidases, enabling growth on xylooligosaccharide (XOS). The recombinant enzymes were highly active on artificial (p-nitrophenyl ß-D-xylopyranoside) and natural (xylobiose, xylotriose, and xylotetraose) substrates, and showed transxylosylation activity and tolerance to xylose inhibition. The enzymes belong to glycoside hydrolase family 120 with Asp as nucleophile and Glu as proton donor, as shown by homology modelling and confirmed by site-directed mutagenesis. In silico analysis revealed that these enzymes were part of a gene cluster in L. reuteri but not in Blautia strains, and quantitative proteomics identified other enzymes and transporters involved in B. producta XOS utilisation. Based on these findings, we proposed a model for an XOS metabolism pathway in L. reuteri and B. producta strains. Together with phylogenetic analyses, the data also revealed the extended xylanolytic potential of the gut microbiota.

Preparative and Kinetic Analysis of ß-1,4- and ß-1,3-Glucan Phosphorylases Informs Access to Human Milk Oligosaccharide Fragments and Analogues Thereof.

The enzymatic synthesis of oligosaccharides depends on the availability of suitable enzymes, which remains a limitation. Without recourse to enzyme engineering or evolution approaches, herein we demonstrate the ability of wild-type cellodextrin phosphorylase (CDP: ß-1,4-glucan linkage-dependent) and laminaridextrin phosphorylase (Pro_7066: ß-1,3-glucan linkage-dependent) to tolerate a number of sugar-1- phosphate substrates, albeit with reduced kinetic efficiency. In spite of catalytic efficiencies of <1 % of the natural reactions, we demonstrate the utility of given phosphorylase-sugar phosphate pairs to access new-to-nature fragments of human milk oligosaccharides, or analogues thereof, in multi-milligram quantities.

Bromopyrrole Alkaloids of the Sponge Agelas oroides Collected Near the Israeli Mediterranean Coastline.

Chemical investigation of the Mediterranean Sea sponge, Agelas oroides, collected off the Tel Aviv coast, yielded eight new bromopyrrole metabolites, agesamine C (1), dioroidamide A (2), slagenin D (3), (-)-monobromoagelaspongin (4), (-)-11-deoxymonobromoagelaspongin (5), (-)-11-O-methylmonobromoagelaspongin (6), E-dispacamide (7), and pyrrolosine (8), along with 18 known bromopyrrole alkaloids and a known bromotyrosine derivative. The structures of the new metabolites were elucidated by analysis of the spectroscopic and spectrometric data, including 1D and 2D NMR, ECD, and high-resolution mass spectrometry. The sponge extract exhibited antimicrobial activity against pathogenic and environmental bacteria, and quorum sensing inhibitory activity (QSI) against Chromobacterium violaceum. QSI guided separation of the extract established oroidin, benzosceptrin C, and 4,5-dibromopyrrole-2-carboxamide as the active components. The latter compounds were tested for inhibition of growth and biofilm formation in Pseudomonas aeruginosa PAO1. The most active and available compound, oroidin, was assayed for inhibition of growth and biofilm formation in bacteria that were isolated from the sponge and its environment.

Glycan utilisation system in Bacteroides and Bifidobacteria and their roles in gut stability and health.

Gut residential hundred trillion microbial cells are indispensable for maintaining gut homeostasis and impact on host physiology, development and immune systems. Many of them have displayed excellence in utilising dietary- and host-derived complex glycans and are producing useful postbiotics including short-chain fatty acids to primarily fuel different organs of the host. Therefore, employing individual microbiota is nowadays becoming a propitious target in biomedical for improving gut dysbiosis conditions of the host. Among other gut microbial communities, Bacteroides and Bifidobacteria are coevolved to utilise diverse ranges of diet- and host-derived glycans through harmonising distinct glycan utilisation systems. These gut symbionts frequently share digested oligosaccharides, carbohydrate-active enzymes and fermentable intermediate molecules for sustaining gut microbial symbiosis and improving fitness of own or other communities. Genomics approaches have provided unprecedented insights into these functions, but their precise mechanisms of action have poorly known. Sympathetic glycan-utilising strategy of each gut commensal will provide overview of mechanistic dynamic nature of the gut environment and will then assist in applying aptly personalised nutritional therapy. Thus, the review critically summarises cutting edge understanding of major plant- and host-derived glycan-utilising systems of Bacteroides and Bifidobacteria. Their evolutionary adaptation to gut environment and roles of postbiotics in human health are also highlighted.

Quorum Quenching Strategy Targeting Gram-Positive Pathogenic Bacteria.

Quorum sensing (QS) is a cell density-dependent regulatory system that orchestrates the group behavior of unicellular organisms by synchronizing the expression of certain gene(s) within the clonal community of same species. Bacterial pathogens often employ QS system to establish efficiently an infection. A large part of low GC Gram-positive bacteria belonging to phylum Firmicutes use thiolactone/lactone peptides as communication signals so-called autoinducing peptides (AIPs) to coordinate QS circuit. In particular, QS of staphylococci, enterococci, and clostridia have been intensively studied in terms of alternative target of anti-pathogenic chemotherapy independent of bactericidal antibiotics. Thus far, a number of quorum quenching (QQ) agents that targeting the QS circuit of these Gram-positive pathogens have been developed by random screening of natural compounds or rationale design of AIP antagonists. This review summarizes those QQ agents and previews their potential as post-antibiotic drugs.

Antimicrobial compounds from seaweeds-associated bacteria and fungi.

In recent decade, seaweeds-associated microbial communities have been significantly evaluated for functional and chemical analyses. Such analyses let to conclude that seaweeds-associated microbial communities are highly diverse and rich sources of bioactive compounds of exceptional molecular structure. Extracting bioactive compounds from seaweed-associated microbial communities have been recently increased due to their broad-spectrum antimicrobial activities including antibacterial, antifungal, antiviral, anti-settlement, antiprotozoan, antiparasitic, and antitumor. These allelochemicals not only provide protection to host from other surrounding pelagic microorganisms, but also ensure their association with the host. Antimicrobial compounds from marine sources are promising and priority targets of biotechnological and pharmaceutical applications. This review describes the bioactive metabolites reported from seaweed-associated bacterial and fungal communities and illustrates their bioactivities. Biotechnological application of metagenomic approach for identifying novel bioactive metabolites is also dealt, in view of their future development as a strong tool to discover novel drug targets from seaweed-associated microbial communities.

Elucidating the role of chemokines in inflammaging associated atherosclerotic cardiovascular diseases.

Age-related inflammation or inflammaging is a critical deciding factor of physiological homeostasis during aging. Cardiovascular diseases (CVDs) are exquisitely associated with aging and inflammation and are one of the leading causes of high mortality in the elderly population. Inflammaging comprises dysregulation of crosstalk between the vascular and cardiac tissues that deteriorates the vasculature network leading to development of atherosclerosis and atherosclerotic-associated CVDs in elderly populations. Leukocyte differentiation, migration and recruitment holds a crucial position in both inflammaging and atherosclerotic CVDs through relaying the activity of an intricate network of inflammation-associated protein-protein interactions. Among these interactions, small immunoproteins such as chemokines play a major role in the progression of inflammaging and atherosclerosis. Chemokines are actively involved in lymphocyte migration and severe inflammatory response at the site of injury. They relay their functions via chemokine-G protein-coupled receptors-glycosaminoglycan signaling axis and is a principal part for the detection of age-related atherosclerosis and related CVDs. This review focuses on highlighting the detailed intricacies of the effects of chemokine-receptor interaction and chemokine oligomerization on lymphocyte recruitment and its evident role in clinical manifestations of atherosclerosis and related CVDs. Further, the role of chemokine mediated signaling for formulating next-generation therapeutics against atherosclerosis has also been discussed.

Emerging roles of SnoRNAs in the pathogenesis and treatment of autoimmune disorders.

SnoRNAs (small non-coding RNAs) have recently gained prominence in autoimmune diseases, revealing their crucial role in modulating the immune response and contributing to disease pathogenesis. Initially known for their involvement in ribosomal RNA processing and modification, molecular biology and genomics advancements have uncovered their broader impact on cellular function, especially in autoimmune disorders. Autoimmune diseases represent conditions characterized by the immune system's erroneous attacks on self-tissues, encompassing disorders like systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The complex etiology of these conditions involves a delicate interplay of genetic and environmental factors. Emerging evidence suggests that snoRNAs initially recognized for their housekeeping roles, extend their influence on immune regulation through diverse mechanisms. SnoRNAs have been implicated in epigenetic modification, directly affecting the gene expression profiles of immune cells. Their ability to guide site-specific changes on ribosomal RNAs and other non-coding RNAs can significantly influence the translation of proteins involved in immune response pathways. Moreover, snoRNAs interact with key immune-related proteins, modulating their functions and subsequently impacting immune cell development, activation, and tolerance. Dysregulation of snoRNA expression has been observed in various autoimmune diseases, underscoring their potential as biomarkers for disease diagnosis, prognosis, and therapeutic targets. Manipulating snoRNA expression or activity is a promising therapeutic intervention avenue, offering the potential for personalized treatment strategies in autoimmune diseases. However, there remains a need for comprehensive research efforts to elucidate the precise molecular mechanisms underlying snoRNA-mediated immune modulation. Further investigations in this domain are essential to unravel the potential of snoRNAs in autoimmune disorders.

Unravelling the role of long non-coding RNAs in modulating the Hedgehog pathway in cancer.

Cancer is a multifactorial pathological condition characterized by uncontrolled cellular proliferation, genomic instability, and evasion of regulatory mechanisms. It arises from the accumulation of genetic mutations confer selective growth advantages, leading to malignant transformation and tumor formation. The intricate interplay between LncRNAs and the Hedgehog pathway has emerged as a captivating frontier in cancer research. The Hedgehog pathway, known for its fundamental roles in embryonic development and tissue homeostasis, is frequently dysregulated in various cancers, contributing to aberrant cellular proliferation, survival, and differentiation. The Hh pathway is crucial in organizing growth and maturation processes in multicellular organisms. It plays a pivotal role in the initiation of tumors as well as in conferring resistance to conventional therapeutic approaches. The crosstalk among the Hh pathway and lncRNAs affects the expression of Hh signaling components through various transcriptional and post-transcriptional processes. Numerous pathogenic processes, including both non-malignant and malignant illnesses, have been identified to be induced by this interaction. The dysregulation of lncRNAs has been associated with the activation or inhibition of the Hh pathway, making it a potential therapeutic target against tumorigenesis. Insights into the functional significance of LncRNAs in Hedgehog pathway modulation provide promising avenues for diagnostic and therapeutic interventions. The dysregulation of LncRNAs in various cancer types underscores their potential as biomarkers for early detection and prognostication. Additionally, targeting LncRNAs associated with the Hedgehog pathway presents an innovative strategy for developing precision therapeutics to restore pathway homeostasis and impede cancer progression. This review aims to elucidate the complex regulatory network orchestrated by LncRNAs, unravelling their pivotal roles in modulating the Hedgehog pathway and influencing cancer progression.

MicroRNA-21's role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology.

MicroRNA-21 (miR-21) was recognized as a key figure in the intricate web of tumor biology, with a prominent role in regulating the PTEN tumor suppressor gene and the PI3K/AKT cascade. This review elucidates the multifaceted interactions between miR-21, PTEN, and the PI3K/AKT signaling, shedding light on their profound implications in cancer initiation, progression, and therapeutic strategies. The core of this review delves into the mechanical intricacies of miR-21-mediated PTEN suppression and its consequent impact on PI3K/AKT pathway activation. It explores how miR-21, as an oncogenic miRNA, targets PTEN directly or indirectly, resulting in uncontrolled activation of PI3K/AKT, fostering cancerous cell survival, proliferation, and evasion of apoptosis. Furthermore, the abstract emphasizes the clinical relevance of these molecular interactions, discussing their implications in various cancer types, prognostic significance, and potential as therapeutic targets. The review provides insights into ongoing research efforts to develop miR-21 inhibitors and strategies to restore PTEN function, offering new avenues for cancer treatment. This article illuminates the critical function of miR-21 in PTEN suppression and PI3K/AKT activation, offering profound insights into its implications for cancer biology and the potential for targeted interventions.

ß-glucans: a potential source for maintaining gut microbiota and the immune system.

The human gastrointestinal (GI) tract holds a complex and dynamic population of microbial communities, which exerts a marked influence on the host physiology during homeostasis and disease conditions. Diet is considered one of the main factors in structuring the gut microbiota across a lifespan. Intestinal microbial communities play a vital role in sustaining immune and metabolic homeostasis as well as protecting against pathogens. The negatively altered gut bacterial composition has related to many inflammatory diseases and infections. ß-glucans are a heterogeneous assemblage of glucose polymers with a typical structure comprising a leading chain of ß-(1,4) and/or ß-(1,3)-glucopyranosyl units with various branches and lengths as a side chain. ß-glucans bind to specific receptors on immune cells and initiate immune responses. However, ß-glucans from different sources differ in their structures, conformation, physical properties, and binding affinity to receptors. How these properties modulate biological functions in terms of molecular mechanisms is not known in many examples. This review provides a critical understanding of the structures of ß-glucans and their functions for modulating the gut microbiota and immune system.

Biochemical characterization of bifunctional enzymatic activity of a recombinant protein (Bp0469) from Blautia producta ATCC 27340 and its role in the utilization of arabinogalactan oligosaccharides.

Human consumption of larch arabinogalactan has a significant effect on enhancing probiotic microflora in the gut, and it also promotes the production of short-chain fatty acids. Bacterial members of Lachnospiraceae family are important and play significant roles in maintaining our gut health. However, it is less known about biochemistry of members of this family by which they utilize non-cellulosic fiber in the gut. For enhancing this understanding, we studied that B. producta ATCC 27340 grew on arabinogalactan oligosaccharides (AGOs) as compared to polysaccharide form of arabinogalactan. Recombinant protein (Bp0469) was heterologously expressed in Escherichia coli BL21 (DE3) and revealed the optimum pH and temperature at 7.4 in phosphate buffer and 45 °C, respectively. Catalytic efficiency of recombinant Bp0469 for p-nitrophenyl (pNP)-α-L-arabinofuranoside was about half of pNP-ß-D-galactopyranoside. It also cleaved natural substrates (lactose, arabinobiose and 3-O-(ß-d-galactopyranosyl)-d-galactopyranose) and characterized AGOs in this study. Based on genomic, structural models, and biochemical characteristics, identified Bp0469 is a peculiar enzyme with two distinct domains that cleave α1-5 linked arabinobiose and ß-D-Galp-1-3/4 linkages. Overall, the study enhances the knowledge on nutritional perspective of B. producta ATCC 27340 for thriving on non-cellulosic biomass, and identified enzyme can also be used for producing industrial important AGOs.

Immobilization of α-transglucosidase on silica-coated magnetic nanoparticles and its application for production of isomaltooligosaccharide from the potato peel.

In this study, the production of isomaltooligosaccharide from potato peel starch was carried out in three steps: liquefaction, saccharification, and transglucosylation. Further, cloning α-transglucosidase gene from Aspergillus niger (GH31 family), transforming into E. coli BL21 (DE3), overexpressing and purifying the resulting protein for the production of α-transglucosidase. The generated α-transglucosidase was then bound with magnetic nanoparticles, which improved reusability up to 5 cycles with more than 60% activity. All the modifications were characterized using the following methods: Fourier transform infra-red analysis, Transmission Electron Microscopy, Field Emission Scanning Electron Microscopy, Energy Dispersive X-ray spectroscopy, X-Ray Diffraction Spectroscopy, Thermogravimetric Analysis, and Dynamic Light Scattering (DLS) analysis. Further, the optimum conditions for transglucosylation were determined by RSM as follows: enzyme-to-substrate ratio 6.9 U g-1, reaction time 9 h, temperature 45 °C, and pH 5.5 with a yield of 70 g l-1 (± 2.1). MALDI-TOF-MS analysis showed DP of the IMOs in ranges of 2-10. The detailed structural characterization of isomaltooligosaccharide by GC-MS and NMR suggested the α-(1 → 4) and α-(1 → 6)-D-Glcp residues as major constituents along with minor α-(1 → 2) and α-(1 → 3) -D-Glcp residues.

Unlocking new approaches to Urolithiasis management via Nutraceutical.

Urolithiasis, commonly known as kidney stones, is characterized by the formation of hard deposits in the urinary tract. These stones can cause severe pain and discomfort, and their management typically involves a combination of medical interventions and lifestyle modifications. According to the literature, 30% and 50% of urolithiasis cases recur. Between 9 and 12% of persons in industrialised countries are predicted to have urolithiasis at some time. Due to the high frequency of stone formation, recurrent nature, and prevalence in adults, it has a significant impact on society, the person, and the health care system. Adopting the best prophylactic measures is crucial in light of these developments to decrease the impact of urolithiasis on individuals and society. In recent years, there has been growing interest in the potential role of nutraceuticals in the management of urolithiasis. Nutraceuticals, such as herbal extracts, vitamins, minerals, and probiotics, have gained recognition for their potential in promoting urinary health and reducing the risk of urolithiasis. These compounds can aid in various ways, including inhibiting crystal formation, enhancing urine pH balance, reducing urinary calcium excretion, and supporting kidney function. Additionally, nutraceuticals can help alleviate symptoms associated with urolithiasis, such as pain and inflammation. While medical interventions remain crucial, incorporating nutraceuticals into a comprehensive management plan can offer a holistic approach to urolithiasis, improving patient outcomes and quality of life. Therefore, nutraceuticals may be a desirable choice for treating and avoiding recurring urolithiasis for patients and medical professionals. Therefore, the present study has focused on nutraceuticals' role in preventing urolithiasis.

New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs.

Recent understanding of human milk oligosaccharides in establishing infant gut microbiome and roles in immune system.

Human milk oligosaccharides (HMOs) are complex sugars with distinctive structural diversity present in breast milk. HMOs have various functional roles to play in infant development starting from establishing the gut microbiome and immune system to take it up to the mature phase. It has been a major energy source for human gut microbes that confer positive benefits on infant health by directly interacting through intestinal cells and generating short-chain fatty acids. It has recently become evident that each species of Bifidobacterium and other genera which are resident of the infant gut employ distinct molecular mechanisms to capture and digest diverse structural HMOs to avoid competition among themselves and successfully maintain gut homeostasis. HMOs also directly modulate gut immune responses and can decoy receptors of pathogenic bacteria and viruses, inhibiting their binding on intestinal cells, thus preventing the emergence of a disease. This review provides a critical understanding of how different gut bacteria capture and utilize selective sugars from the HMO pool and how different structural HMOs protect infants from infectious diseases.