New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons and orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response in the CNS. The sources of activation of the inflammatory response in MDD are immense, however, in recent years, it is becoming increasingly evident that the gastrointestinal tract with gut-associated lymphoid tissue (GALT) and increased intestinal permeability to bacterial LPS and food-derived antigens contribute to activation of low-grade inflammatory response with subsequent psychiatric manifestations. Furthermore, an excessive permeability to gut-derived antigenic material may lead to subsequent autoimmunities which are also known to be comorbid with MDD. In this chapter, we discuss fascinating interactions between the gastrointestinal tract, increased intestinal permeability, intestinal microbiota, and glia-neuron crosstalk, and their roles in the pathogenesis of the inflammatory hypothesis of MDD. To emphasize those crucial intercommunications for the brain functions, we propose the term of microbiota-gut-immune-glia (MGIG) axis.

Gut microbiota plays a critical role in physiological regulation throughout life and is specifically modified to meet the demands of individual life stages and during pregnancy. Maternal gut microbiota is uniquely adapted to the pregnancy demands of the mother and the developing fetus. Both animal studies in pregnant germ-free rodents and human studies have supported a critical association between the composition of maternal microbiota during pregnancy and fetal development. Gut microbiota may also contribute to the development of the fetal gut-brain axis (GBA), which is increasingly recognized for its critical role in health and disease. Most studies consider birth as the time of GBA activation and focus on postnatal GBA development. This review focuses on GBA development during the prenatal period and the impact of maternal gut microbiota on fetal GBA development. It is hypothesized that adaptation of maternal gut microbiota to pregnancy is critical for the GBA prenatal development and maturation of GBA postnatally. Consequently, factors affecting maternal gut microbiota during pregnancy, such as maternal obesity, diet, stress and depression, infection, and medication, also affect fetal GBA development and are critical for GBA activity postnatally. Altered maternal gut microbiota during gestation has been shown to have long-term impact postnatally and multigenerational effects. Thus, understanding the impact of maternal gut microbiota during pregnancy on fetal GBA development is crucial for managing fetal, neonatal, and adult health, and should be included among public health priorities.

Diet plays a pivotal role in the overall health of an individual. Not only does it help carry out and regulate certain physiological functions, but it also can determine the composition of the gut microbiome. While the relative number of microorganisms that make up the gut microbiome vary between individuals and can be dependent on different environmental factors, there is evidence to suggest that composition of the microbiome can correlate with overall health or disease. When the GI microbiome is disturbed or suddenly changes it results in microbiome dysbiosis, a condition that correlates with the presence of certain diseases. Diseases linked to microbiome dysbiosis range from metabolic disorders, inflammatory bowel diseases to disorders of the brain. Many of these diseases are linked to the connection between the brain and the gut, known as the brain-gut axis. This bidirectional communication is important to maintain normal intestinal function, but is also responsible for the GI response to emotions as well as the emotional response to GI disturbances. By exploiting the interaction between microbiome health and nutrition, diet can be used to alleviate disease symptoms, protect against the development of certain conditions, and better maintain overall health. This review will examine the effects of nutrition on the microbiome, diseases linked to disruption of the normal microbiome, and the way that altering the diet can mitigate symptoms or prevent disease.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.

(1) Background: Heavy and chronic alcohol intake causes altered gut-permeability and dysfunction; and exhibits a unique pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by alcohol administration; however, the impact of altered gut-derived changes on thyroid function is unclear. This study investigated the role of gut-dysfunction and pro-inflammatory activity on thyroid function in patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n=44) were grouped as Gr.1 with normal thyroid stimulating hormone (TSH) levels (n=28, 0.8≤TSH≤3 mIU/L); and Gr.2 with clinically elevated TSH levels (n=16, TSH> 3 mIU/l). Demographics, drinking measures, comprehensive metabolic panel, and candidate thyroid markers (TSH, circulating triiodothyronine [T3] and free thyroxine [fT4]) were tested. Plasma-derived gut-dysfunction associated markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], and LPS-induced pathogen-associated protein [CD14]), and cytokine profile (IL1-β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were analyzed and compared with the thyroid, demographic, and drinking markers. (3) Results: Both groups presented with a borderline overweight category of BMI. Gr.2 presented with numerically higher level of chronic and heavy drinking patterns vs Gr.1. fT4 levels were elevated while T3 was within normal limits in both the groups. Gut-dysfunction markers LBP and CD14 were numerically elevated in Gr.2 vs Gr.1 suggesting subtle ongoing changes; however, the difference was not statistically significant. All pro-inflammatory cytokines were significantly elevated in Gr.2 among IL1-, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect of gut-immune-pituitary response (r=0.896, p=0.002) on TSH levels in a multivariate regression model with LBP, CD14, and PAI-1 levels as upstream variables; this assessment was not significant in Gr.1. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area=0.774, p<0.001) and TNF- (area=0.708, p=0.017) among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4 as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation employing the gut-brain axis. These results also strongly emphasize potential directions to strongly consider thyroid dysregulation in the overall medical management of AUD.

This review investigates the multifaceted role of the p66Shc adaptor protein and the gut microbiota in regulating mitochondrial function and oxidative stress, and their collective impact on the pathogenesis of chronic diseases. The study delves into molecular mechanisms by which p66Shc influences cellular stress responses through Rac1 activation, Forkhead-type transcription factors inactivation, and mitochondria-mediated apoptosis, alongside modulatory effects of gut microbiota-derived metabolites and endotoxins. Employing an integrative approach, the review synthesizes findings from a broad array of studies, including molecular biology techniques and analyses of microbial metabolites' impacts on host cellular pathways. The results underscore a complex interplay between microbial metabolites, p66Shc activation, and mitochondrial dysfunction, highlighting the significance of the gut microbiome in influencing disease outcomes through oxidative stress pathways. Conclusively, the review posits that targeting the gut microbiota-p66Shc-mitochondrial axis could offer novel therapeutic strategies for mitigating the development and progression of metabolic diseases. This underscores the potential of dietary interventions and microbiota modulation in managing oxidative stress and inflammation, pivotal factors in chronic disease etiology.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

The “Gut-Liver Axis” refers to physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of modifications of gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions expose cholangiocytes to an increasing amount of microorganisms and may exacerbate inflammatory responses thus leading to fibrotic remodeling of the organ. The present review focuses on the role of the gut liver axis in the pathogenesis of cholangiopathies.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Background: IBD is a spectrum of pathologies characterized by dysregulated immune activation leading to uncontrolled response against intestinal, thus resulting in chronic gut inflammation and tissue damage. Due to its complexity, the molecular mechanisms responsible for disease onset and progression are still elusive, thus requiring intense research effort. In this context, the development of models recapitulating the etiopathology of IBD is critical.Methods: Colon from C57BL/6 or BALB/c mice were cultivated in a gut-ex-vivo system (GEVS), exposed 5h to DNBS 1,5 or 2,5 mg/ml, and the main hallmarkers of IBD were evaluated.Results: Gene expression analysis revealed a DNBS-induced: i) compromised Tight junction organization, responsible for tissue permeability dysregulation; induction of ER stress, and iii) tissue inflammation in colon of C57BL/6 mice. Moreover, the concomitant DNBS-induced apoptosis and ferroptosis pathways was evident in colon from both BALB/c and C57BL/6 mice.Conclusions: Overall, we have provided results demonstrating that GEVS is a consistent, reliable, and cost-effective system for modeling DNBS-induced IBD, useful for studying the onset and progression of human disease at the molecular level, while also reducing animal suffering.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by poor social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome-gut-brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders, and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function, and microbiota metabolites in ASD. Although a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity, and the microbiome-gut-brain axis in the development of autistic symptoms severity and, a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via microbiome-gut-brain axis in a feedback circuit.

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mecha-nisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duo-denum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatographic mass-spectrometry, re-spectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were sig-nificantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration in-dicated that populations of three bacterial families –Autopobiaceae (Up), Desulfovibrionaceae (Up) and Akkermanasiaceae (Down) – were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.

The UNUSUAL FLORAL ORGANS (UFO) gene is an essential regulatory factor of class B genes and plays a vital role in the process of inflorescence primordial and flower primordial development. We investigated the role of UFO genes in soybean to better understand the development of floral organs through gene cloning, expression analysis, and gene knockout. In situ hybridization demonstrated predominant expression of the GmUFO1 gene in the flower primordium. Phenotypic observation of GmUFO1 knockout mutant lines (Gmufo1) showed obvious alteration in floral organ number and shape, and mosaic organ formation. In contrast, GmUFO2 knockout mutant lines (Gmufo2) showed no obvious difference in floral organs. However, the GmUFO1 and GmUFO2 double knockout lines (Gmufo1ufo2) showed a more severe mutant phenotype than the Gmufo1 lines. Gene expression analysis also showed differences in the expression of major ABC function genes in the knockout lines. Based on the phenotypic and expression analysis, our results suggest the major role of GmUFO1 in the regulation of flower organ formation in soybean and that GmUFO2 does not have any direct effect, but it might have an interaction role with GmUFO1 in the regulation of flower development. In conclusion, the present study identified UFO genes in soybean and improved our understanding of floral development that could be useful for flower design in hybrid soybean breeding.

The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, characterization of intestinal disease processes are increasingly gaining more attention as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models they offer more translational value, and many different GOC models have been presented over the past years. Here, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely 1) the biological research questions, 2) chip fabrication and materials, 3) tissue engineering, and 4) the environmental and biochemical cues to add or measure in the GOC. Examples are presented of GOC studies in the two major areas of preclinical intestinal research: 1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and 2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.

The relative paucity of donor livers suitable for transplantation has sparked innovations to preserve and recondition organs to expand the pool of transplantable organs. Currently, machine perfusion techniques have led to the improvement of the quality of marginal livers and to prolonged cold ischemia time and allowed for the prediction of graft function through analysis of the organ during perfusion, improving the rate of organ use. In the future, the implementation of organ modulation might expand the scope of machine perfusion beyond its current usage. The aim of this review was to provide an overview of the current clinical use of machine perfusion devices in liver transplantation and provide a perspective for future clinical use, including therapeutic interventions in perfused donor liver grafts.

Why do the eyes remain comparatively large whereas the cornea is reduced in most troglobiont mysids? Are there any important organ size-dependent functions served by non-visual eye rudiments? This issue was approached by measuring eye structures in five troglobiont species of Mysida and two Stygiomysida compared with 14 troglophile and 49 trogloxene Mysida species. The Organ of Bellonci (OB) was found in all Mysida and as first records also in Stygiomysida. The length of OBs increased with individual body length and eye length in four examined species: from postnauplioid larvae to adult stage in a troglophile and a trogloxene mysid species examined; and from juveniles to adults in a troglobiont mysid and a troglobiont stygiomysid. At the interspecific level, eye length was on average 26% shorter at a given body length while the OB was 40% longer at a given body length and 54% longer at a given eye length, respectively, in adult troglobionts compared with trogloxene mysids. The OB is clearly proliferating while the cornea is reduced in troglobionts. This points to sensory functions (possibly together with other functions). The sensory pore organ was found in all 15 Mysida species whose eyes were mounted on slides, and a first record of this organ was also found in Stygiomysida.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

Systemic sclerosis (SSc) is a progressive autoimmune disorder that mainly affects the skin. There are other clinical manifestations as renal, pulmonary, cardiovascular, and gastrointestinal tract involvements. Based on the skin involvement there are two subtypes of SSc, as limited cutaneous SSc (lSSc) which involves the acral part of the body and diffuse cutaneous SSc (dSSc) resulting in significant skin thickening of the body. The lSSc has usually moderate internal organ manifestations, except for the late-onset pulmonary arterial hypertension (PAH) mainly appearing in this form. In dSSc the severity of the organ manifestations or failure is more intensive such as scleroderma renal crisis (RSC), interstitial lung disease (ILD), myocardial fibrosis, and chronic gastrointestinal dysmotility with consequent malabsorption

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

Many centers worldwide raised the concern that immunocompromised patients for solid organ transplantation may be at high risk of developing a severe respiratory disease by COVID-19. Currently, there are no specific data on the COVID-19 in patients with generalized immunosuppression and transplantation.In this narrative review, we reported the main data of COVID-19 in patients with solid organ transplantation presented in the literature. The aim is to elaborate a strategy for tailored management, from diagnosis to therapy.The management of adult patients with solid organ transplantation and COVID-19 is a challenge for the clinicians. There is a lack of data in the literature, but three key-points are crucial: in the “pandemic era,” consider the symptomatic patient as positive for COVID-19 until proven otherwise; adjust/stop immunosuppressive agents; protect graft function with adequate route and dose administration of glucocorticoid and supportive measures. For pediatric patients, data are scarce. It is unclear if immunosuppression in patients with solid organ transplantation alters the predisposition to acquiring COVID-19 or if the disease implications are modified for better or for worse. Further studies are needed.

Background: Immunosuppressant blood levels should be measured at regular periods in order to keep them within the therapeutic index. Although LC-MS/MS is preferred as a reliable method, some molecules like radiopaque agents in blood matrix may lead to false results. The aim of this study is to investigate the effect of seven different radiopaque agents on immunosuppressant drugs. Methods: Seven different radiopaque agents were added into control materials containing tacrolimus, everolimus, sirolimus and cyclosporine A drugs. Measurements were performed by LC-MS/MS instrument. The amount of deviations from target values were calculated. Results: Immunosuppressant blood levels significantly changed after the administration of radiopaque agents. Seven different radiopaque products led to false negative results in tacrolimus and cyclosporine A levels at a rate of 19.77% to 44.45%. The smallest deviations were seen in everolimus levels with administration of RM6 (gadodiamide) and in sirolimus levels with RM1 (gadobutrol) at rates of 4.04% and 2.11%, respectively. The highest deviations were observed with RM3 (iohexol) administration in everolimus and sirolimus levels at rates of 153.72% and 171.41%, respectively. Conclusions: False immunosuppressant results associated with radiopaque agents may result in organ rejection. Preferring radiopaque agents that cause the least interference risk is important to reduce the organ rejection risk. However, the least risky method is to obtain samples for drug levels before contrast-enhanced imaging.

Nanoparticles (NPs) are widely used in diverse disciplines, including biology, medicine science. The central question that need to be answered is whether NPs have toxic effects on biological cells and molecules or are they safe. The safety of NPs including targeted drug delivery is critical and so is their toxicity in the environment. In recent years, in vitro and in vivo research on animals has generated abundant information about the toxicity of NPs. However, due to varying laboratory conditions, the comparison of the results from ensuing studies is somewhat unreliable. It should be noted that, depending on the type of production, NPs can enter the body through inhalation, skin and via digestive routes. Due to the diversity of NPs and their properties, there is paucity of accurate information on their toxicological effects; particle size, shape, surface area and the chemical levels are considered as key factors in creating health and toxicological effects. Consequently, there is a need for reliable information about their effects on various organs so as to deal with NPs effectively and their impact on health and the environment. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

The gastrointestinal tract is inhabited by the gut microbiota. The main phyla are Firmicutes and Bacteroidetes. In non-alcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), an increase in Firmicutes and Bacteroidetes abundance promotes its pathogenesis and evolution into non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma. For this reason, an early treatment is necessary to disfavor its progression. The aim of the present narrative review is to evaluate the different therapeutic approaches to MAFLD. The most important treatment for MAFLD is lifestyle changes. In this regard, the Mediterranean diet could be considered the gold standard in the prevention and treatment of MAFLD. In contrast, a Western diet should be discouraged. Probiotics and fecal microbiota transplantation seem to be valid, safe, and effective alternatives for MAFLD treatment. However, more studies with a longer follow up and with a larger cohort of patients are needed to underline the more effective ap-proaches to contrasting MAFLD.

The pleiotropic biochemical and antioxidant functions of Vitamin C (Vit C) have recently sparked interest in its application in intensive care. Vit C protects important organ systems such as the cardiovascular, neurologic and renal system during inflammation and oxidative stress. Vit C also influences the systems of coagulation and inflammation and its application might prevent the development of organ damage. The current evidence of Vit C’s effect on the pathophysiological reactions during various acute stress events, such as sepsis, shock, trauma, burn and ischemia-reperfusion injury imposes the question, if the application of Vit C might be especially beneficial for cardiac surgery patients, who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of Vit C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between Vit C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence regarding the administration of Vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage and most the appropriate application strategy.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

Fecal Microbial Transplant (FMT) has been emerging as a prominent therapeutics in the modern science to modulate and correct the dysbiotic state of gut microbiome that leads to various metabolic and gastro-enteric diseases. A similar concept called as “panchagavya prasahan” exists in Ayurveda. This technique unlike the FMT involves the use of Cive by- products of cow viz. Cow dung, urine, milk, curd, ghee mixed in a copper vessel. In this study we assess the microbial composition of this preparation before and after the mixing in the copper vessel. We used the 16S rRNA gene based amplicon sequencing approach to understand the bacterial composition in the panchagavya preparation. We observed signiCicant decrease in the abundance of genera Pseudomonas and Streptococcus (p

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

Background: Chronic kidney disease (CKD) is a common complication of non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD), increased serum creatinine ≥50%, renal replacement therapy (RRT), and death in pre-transplant, peri-transplant and post-transplant period. Results: 74 patients were studied (7 heart transplant, 34 liver transplants, and 33 lung transplant). Patients who were not followed-up by nephrology in the pre-transplant (p<0.027), peri-transplant (p<0.046), and the longest time until outpatient clinic follow-up (HR 1,032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred higher risk than liver or hear transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxic and the number of hospital admissions were significantly associated to present a creatinine increase ≥50% and develop ESKD. Conclusion: An early follow-up by the nephrology department was associated with a decrease in the worsening of renal function.

The orchid market is a dynamic horticultural business in which novelty and beauty command high prices. The development of miniature to large and showy flowers, in addition to fragrance, is mainly of interest. Overall organ size might be modified by doubling the chromosome number, which can be accomplished by careful study of meiotic chromosome disjunction in hybrids or species. Meiosis is the process in which diploid (2n) pollen mother cells recombine their DNA sequences and then undergo two rounds of division to give rise to four haploid (n) cells called sporads. Thus, by interfering in chromosome segregation, one can induce the development of diploid recombinant sporads called dyads. These dyads may be used for breeding polyploid progenies with enhanced fertility and large flower size. This review gives an overview of developments in orchid breeding placed in the large context of ploidy breeding in higher plants to facilitate innovation

Granulomatosis with polyangiitis (GPA) is an autoimmune disease which is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that frequently affects the lungs and kidneys. However, GPA limited to a single organ has also been reported. A 73-year-old man was admitted for back pain and fever. We detected elevated levels of inflammatory markers and myeloperoxidase-ANCA. Magnetic resonance imaging indicated diffuse inflammation of the back and psoas muscles. Histology showed degenerated muscle fibers and granulomatosis vasculitis with mixed lymphoplasma cell infiltration. High-dose methylprednisolone therapy improved his symptoms. A final diagnosis of GPA limited to the muscles was made.

Organ-on-Chip is a game-changing technology born from the convergence of tissue engineering and microfluidic technology. Organ-on-Chip devices (OoCs) are expected to offer effective solutions to persisting problems in drug development and personalized disease treatments. This opinion paper surveys the current landscape in research, development, application and market opportunities for OoCs to help establishing a global and multi-stakeholder OoC ecosystem. Based on a bibliometric study, a market analysis, expert interviews, and panel discussions held at the ORCHID Vision Workshop (Stuttgart, 23 May 2018), we outline presently unmet needs, key challenges, barriers and perspectives of the field, and finally propose recommendations towards the definition of a comprehensive roadmap that could render OoCs realistic models of human (patho)physiology in the near future.

The gut microbiome is a collection of microorganisms and parasites that reside in the gastrointestinal tract. There are many factors that can affect the composition of this community, such as age, sex, medications, and environmental triggers. The relationship between the human host and the gut microbiota is very important for both the survival and development of the organism. The disruption of this relationship can lead to the development of various inflammatory diseases. CBD and THC are used to treat muscle spasticity associated with multiple sclerosis. It is now clear these compounds also benefit patients with neuroinflammation. A study that investigated the role of gut microbiota in treating the inflammation and paralysis in a mouse model demonstrated that treatment with CBD and THC produced significant decrease in the inflammation levels. They also exhibited a significant increase in the number of anti-inflammatory cytokines. The presence of certain cannabinoids can suppress neuroinflammation and prevent microbial dysbiosis. Several studies have revealed the role of the gut microbiota in the development and maintenance of skeletal integrity and bone mineral density. The gut is a major source of nutrients, including vitamins B and K. It can also influence the development and maintenance of bone matrix. The presence of the gut microbiota can influence the actions of certain T regulatory cells, which can lead to the development of bone formation and proliferation. In addition, its metabolites can prevent bone loss. The gut microbiota can help maintain the bone's equilibrium and prevent the development of metabolic diseases, such as osteoporosis. In this review, the dual functions gut microbiota plays in the regulation of gut-bone axis and gut-brain axis and the impact of CBD on these roles are discussed in detail.

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, genetic conditions such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis, and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease from other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver cirrhosis.

Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulate over decades. Observations from recent studies have accounted for the involvement of the gut-liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis cause the intestinal microbiome to serve as the main source of portal-vein endotoxins such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on the clinical as well as animal studies involving the gut microbiota with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, as key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.

In the last years evidence has emerged that neurodegenerative diseases (NDs) are strongly associated with the microbiome composition in the gut. Parkinson’s disease (PD) is the most intensively studied neurodegenerative disease in this context. In this review, we performed a systematic evaluation of published literature comparing changes in colonic microbiome in PD to the ones observed in other NDs including Alzheimer’s Disease (AD), Multiple system atrophy (MSA), Multiple sclerosis (MS), Neuromyelitis optica (NMO) and Amyotrophic lateral sclerosis (ALS). To warrant comparability of different studies, only human case-control studies were included. Several studies showed an increase of Lactobacillus, Bifidobacterium, Verrucomicrobiaceae and Akkermansia in PD. A decrease in PD was observed of Faecalibacterium spp., Coprococcus spp., Blautia spp., Prevotella spp. and Prevotellaceae. On low taxonomic resolution, like phylum level, the changes are not disease specific and inconsistent. However, on higher taxonomic resolution like genus or species level, a minor overlap was observed between PD and MSA, both alpha synucleinopathies. We show that a methodical standardization of sample collection and analysis is necessary for ensuring the reproducibility and comparability of data. We also provide the evidence, that assessing the microbiota composition at high taxonomic resolution, reveals changes in relative abundance, that may be specific or characteristic for one disease, or a disease-group and might evolve discriminative power. The interactions between bacterial species and strains and moreover the co-abundances must be more deeply investigated before assumptions of the effects of specific bacteria on the host can be made with certainty.

Background: The liver has emerged as a frequent transplanted organ which can transmit T. gondii between seropositive donors and seronegative recipients. Associated with the immunosuppressive therapy of recipients, the presence of cysts in donor livers elevate the risk of severe toxoplasmosis in recipients. Objectives: The objective of the study was to verify the frequencies of positive serology in liver graft donors and their respective recipients, as well as to verify whether their clinical signs presented post-transplant are associated with the serological status of recipients. Patients and methods: All data on liver transplant recipients from 2008 to 2018 were obtained from the MVPeP electronic medical records of the Liver Transplant Service of FUNFARME/FAMERP. IgM and IgG anti-T. gondii antibody serology was investigated by chemiluminescence. According to the serological profile, four groups of recipients were assessed (G1: IgG-/IgM-; G2: IgG+/IgM-; G3: IgG+/IgM+, G4: IgG-/IgM+). Results: The numbers of recipients according to the serological profile groups were: G1: 20 (41.7%), G2: 26 (54.1%; G3: 2 (4.2%). No cases were found for G4. Post-transplant clinical manifestations such as fever without defined cause, lung nodules, headache, hepatosplenomegaly, encephalopathy and hepatitis (A, B and C) were reported in all groups. Conclusions: This study demonstrates that there is a high prevalence of T. gondii infection in liver recipients and, therefore, screening should be intensified. Furthermore, a high incidence of co-infection with hepatitis A was identified especially in patients who died in the post-transplant period.

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

Background and objectivesː Physical examination is the predominant method for evaluating pelvic floor defects. Magnetic Resonance Imaging (MRI) is a radiological technique useful to identify the underlying defects of pelvic floor structures that require surgery. The primary aim was to find correspondence between the clinical and radiological staging of pelvic organ prolapse (POP) before and after vaginal surgery. A secondary endpoint was to investigate, through clinical and MRI findings if surgery influences continence mechanisms. Finally, we reported changes in the quality of life in women who underwent surgery for prolapse. Materials and methodsː Twenty-five women with prolapse stage ≥ 2 POP-Q were recruited in this prospective study. They underwent preoperative clinical examination, MRI at rest and under the Valsalva maneuver, and quality of life questionnaires. Three months after vaginal surgery they repeated clinical and radiological evaluation. Resultsː Twenty women completed the study. Both clinical and MRI evaluations showed an improvement in prolapse and symptoms after surgery. There were some discrepancies between clinical and radiological staging. MRI parameters did not show differences between pre and postoperative at rest; under the Valsalva maneuver instead, the measurements changed after surgery. Continence was not worsening by the widening of the vesicourethral angle. Patients reported improvement in quality of life. Conclusionsː MRI is an accurate and objective method to define the stage of prolapse but the clinical evaluation alone is sufficient to stage prolapse before surgery and evaluate the result at follow-up. It is an accurate method to visualize some pelvic structures that can be compromised because of pelvic organ prolapse. MRI showed that vaginal surgery doesn’t affect continence mechanisms.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 hours after admission. Forty-five (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 hours after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01. Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels that coincided with severity of tissue damage and mortality. CX-01 inhibited systemic HMGB1 release, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

Injuries from exposure to blasts are of significant concern in military operational settings, including tactical training, and is associated with self-reported concussion-like symptomology and physiological changes as increased intestinal permeability (IP) investigated herein. Timeseries gene expression and IP biomarker data were generated from “breachers” exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre, post, follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and slowed thinking, dissipating ~16hrs following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p=0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n=23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mTBI and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive performance. These preliminary findings show for the first

End-stage heart failure (ESHF) leads to hypoperfusion and edema formation in the whole body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. Our aim was to explore the relationship between the clinical outcome of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at transplantation after opening the pericardial sac. The clinical data and the interleukin, adipokine and lipoprotein levels in the pericardial fluid of twenty recipients were investigated. Outcome variables included primer graft dysfunction (PGD), need for posttransplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥ 2R rejection and mortality. Recipient risk scores were also investigated. Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 [IQR: 5.55-6.62]; versus 7.54 [IQR=6.71-10.44]; p = 0.029). Higher ApoCII levels (median: 14.91 [IQR: 11.55-21.30] versus 10.31 [IQR=10.02-13.07]; p = 0.042) and ApoCIII levels (median: 60.32 [IQR: 43.00-81.66] versus 22.84 [IQR=15.84-33.39]; p=0.005) were found in patients (n=5) who died in the first 5 years after HTX. In patients who had rejection (n=4) in the first month after transplantation, the levels of adiponectin (median: 74.48 [IQR: 35.51-131.70] versus 29.96 [IQR: 19.86-42.28]; p=0.039), ApoCII (median: 20.11 [IQR: 13.06-23.54] versus 10.32 [IQR: 10.02-12.84]; p=0.007) and ApoCIII (median: 70.97 [IQR: 34.72-82.22] versus 26.33 [IQR: 17.18-40.17; p=0.029) were higher than those in the nonrejection group. Moreover, the pericardial thyroxine (T4) levels (median: 3.96 [IQR: 3.49-4.46] versus 4.69 [IQR: 4.23-5.77]; p=0.022) were lower in patients with rejection than in patients who did not develop rejection. Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecast of early and late complications.

Personality changes have been reported to occur following organ transplantation, and most commonly among heart transplant recipients. We set out to examine whether personality changes do occur following transplantation, and specifically, what types of changes occur among heart transplant recipients compared to other organ recipients. A cross-sectional study was conducted in 2022, in which 47 participants (23 heart recipients and 24 other organ recipients) completed an online survey. In this study, 89% of all transplant recipients reported experiencing personality changes after receiving their organ transplant, which was similar for heart and other organ recipients. With the exception of physical attributes, the types of personality changes reported were similar between the two groups. These finding indicate that heart transplant recipients are not unique in their reported experience of personality changes following organ transplantation. Further studies are needed to deepen our understanding of what causes these personality changes following organ transplantation.

Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

Heavy load carrying of water, firewood, and sand/stones is a ubiquitous activity for women living in developing countries. Although the intra-abdominal pressure associated with heavy load carrying is hypothesized to increase the risk of pelvic organ prolapse (POP) among women, relevant epidemiologic data are lacking. We conducted a comparative study involving two exploratory cross-sectional studies among convenience samples of women carrying heavy loads, with different characteristics: (1) as part of their activities for daily living, in Shinyanga region, Tanzania; and (2) working as sand miners in Pokhara, Nepal. Women were categorized has having “low” or “high” load-carrying exposures based on the measured weights of the loads being carried at the time of the survey, as well as on self-reported duration and frequency of load carrying. A summary score for lower abdominal discomfort suggestive of POP was generated using questions from the Pelvic Organ Prolapse Distress Inventory (POPDI-6). Women with higher load carrying exposures had on average higher discomfort scores in both Tanzania (adjusted prevalence difference (PDa)=3.7; 95% CI: -3.8-11.3; p=0.33) and Nepal (PDa=9.3; 95% CI: -4.9-23.6; p=0.18). We identified trends suggestive of an association between increasing heavy load carrying exposures and symptoms of lower abdominal discomfort. Our findings underscore the need for larger epidemiologic studies of the potential adverse reproductive health effects of heavy load carrying activities on women in developing countries.

Objectives: To demonstrate the efficacy of Gemtuzumab ozogamicin in refractory AML patients with organ dysfunctions and poor performance status. Three refractory AML patients with are described. One of them was pretreated by intensive chemotherapy, two other patients progressed during Azacitidine treatment. WHO performance status III . Two patients had respiratory failure grade 2, the other one suffered from acute kidney insufficiency. Two patients were highly febrile with elevated CRP level. Gemtuzumab ozogamicin administration was performed in three patients followed by further switch to Gemtuzumab ozogamicin + Azacitidine or “7+3” treatment. Results: Gemtuzumab ozogamicin administration resulted in abrupt fever cessation in two febrile patients simultaneously with CRP level decrease and fast gradual resolution of respiratory failure. Recovery of kidney function was noticed in patient with renal insufficiency. WHO performance status have elevated in all three patients. No adverse effects grade II-III were noticed. Further treatment made two patients eligible for intensive chemotherapy, one patient was transplanted, patient with kidney failure obtained complete remission. Conclusions: Gemtuzumab ozogamicin therapy appeared to be safe and highly efficacious in relapsed/refractory AML patients with organ dysfunctions and poor performance status.

Cisplatin induces early-onset ototoxicity, resulting in hearing loss. The exact mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase(RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in animal models. Sprague–Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were was measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H-E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. H-E stains outlined necroptotic changes in the organ of Cortis (OCs) and spiral ganglion neurons (SGNs). Additionally, immunohistochemistry and western blot analysis showed overexpression of RIP3 in the OCs and SGNs that were treated with cisplatin. These results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.

Recently scientific research began to shift their focus on looking at both the gut and the skin microbiota as having a reciprocal and integral relationship with one another, rather than assessing them as separate and unrelated fields. In the past five years, the field of microbial endocrinology emerged, which examines how our gut microbiota influences and modulates hormones. We’ve known for decades that hormones greatly affect the condition of the skin, and many skin conditions are often treated with oral hormonal therapy as means to internally treat skin conditions visible on the dermis. Now, a growing body research and discourse examining this triad of biological spheres – gut microbiota, skin microbiota, and the endocrine system – as interconnected rather than binary and unrelated. While there is ample research established and being conducted examining the gut-skin axis, the gut-brain axis, and the gut-hormone axis, through this paper I will review and synthesize some of the significant advancements in this emerging and inclusive field of science to suggest that the fields need to expand the axis and their modality for researching these fields as a connected whole in order to better understand the role of the microbiota in disease prevention as a whole.

The microbiome gut brain (MGB) axis involves bidirectional routes of communication and has emerged as a potential therapeutic target for multiple medical specialities including psychiatry. Significant numbers of preclinical trials have taken place with some transitioning to clinical studies in more recent years. Some positive results have been reported secondary to probiotic administration in both healthy populations and specific patient groups. This review aims to summarise the current understanding of the MGB axis and the preclinical and clinical findings relevant to psychiatry. The link between the gut microbiome and irritable bowel syndrome (IBS) is well established. Significant differences have been identified between the microbiome of patients with a diagnosis of depressive disorder and healthy controls. Similar findings have occurred in patients diagnosed with bipolar affective disorder. A probiotic containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum produced clinically measurable symptom improvement in patients with depressive disorder. To date some promising results have suggested that probiotics could play a role in the treatment of stress-related psychiatric disease. However, more well-controlled clinical trials are required to determine which clinical conditions are likely to benefit most significantly from this novel approach.

Purpose The objective of this study was to eliminate any ambiguity by examining the correlation between gut microbiota and both AMD and glaucoma. Methods Mendelian randomization studies were conducted utilizing the data sourced from the GWAS database for the gut microbiome, AMD, and glaucoma. SNP estimates were summarized through five MR methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables. Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Results IVW suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggests that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggests that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. Conclusions This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Besides, reverse MR found that glaucoma led to increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked with en-hanced immunity, regeneration, improved cognitive function, maintenance of gut mi-crobiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because the respiratory and gastrointestinal tracts are rich in microbial diversity and contain high ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity and the potential use of functional foods as a strategy to combat these effects.

The microbiota–gut–brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota–gut–brain axis, offering hope for improved management of this challenging condition.

Abstract: Early life gut microbiota have been increasingly recognized as major contributors to short and/or long-term human health and diseases. Numerous studies have demonstrated that human gut microbial colonization begins at birth but continues to develop a succession of taxonomic abundances for two to three years until the gut microbiota reaches adult-like diversity and proportions. Several factors, including gestational age (GA), delivery mode, birth weight, feeding types, antibiotic exposure, maternal microbiome and diet influence the diversity, abundance and function of the early life gut microbiota. Gut microbial life is essential for assisting with the digestion of food substances to release nutrients, exerting control over pathogens, stimulating or modulating the immune system and influencing many systems such as the liver, brain, and endocrine system. Microbial metabolites play multiple roles in these interactions. Furthermore, studies provide evidence supporting that imbalances of the gut microbiota in early life, referred to as dysbiosis, are associated with specific childhood or adult disease outcomes, such as asthma, atopic dermatitis, diabetes, allergic diseases, obesity, cardiovascular diseases (CVD) and neurological disorders. These findings support that the human gut microbiota may play a fundamental role in the risk of acquiring diseases that may be programmed during the early life stage. In fact, it is critical to explore the role of the human gut microbiota in early life. In this review, we summarize the general understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the relationship between the gut microbiota composition and their metabolites, and immune functions, which could significantly influence long-term health and disease. We then review known pathophysiological interactions of the early gut microbiome with a number of well characterized diseases and pose potential etiological mechanisms.

The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut-brain-reproductive axis, resulting in male reproductive infertility. This article will explore how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut-brain-reproductive axis, concluding with recommendations for prevention and treatment.

Because data on the fungal gut community structure of African children are scarce, we aimed to describe by reanalysing rRNA ITS1 and ITS2metabarcoding data from a study designed to assess the influence of microbiota in malaria susceptibility in Malian children from the Dogon country. More specifically, we aimed to establish the core gut mycobiome and compare the gut fungal community structure of breastfed children, aged 0-2 years, with other age groups. Briefly, DNA was extracted from 296 children’s stool samples. Both rRNA ITS1 and ITS2 genomic barcodes were amplified and subjected to Illumina MiSeq sequencing. The ITS2 barcode generated 1,975,320 reads and 532 operational taxonomic units (OTUs), while the ITS1 barcode generated 647,816 reads and 532 OTUs. The alpha diversity was significantly higher by using the ITS1 compared to the ITS2 barcode (p

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

The mammalian gut ecosystem plays critical roles in multiple functions related to health and homeostasis. In many cases, disturbances in the gut ecosystem are associated with a large number of metabolic and chronic diseases and disorders such as diabetes, cancer, and obesity. A diverse community of microorganisms ranging from viruses to bacteria comprise the gut microbiota, which is often considered as an organ in itself. Recent studies have profiled the influence of lifestyles and dietary behavior by comparing the gut microbiome of populations with different cultural underpinnings. In this review, we provide an overview of the studies which report the influence on the gut microbial composition of dietary and lifestyle patterns in different contexts such as western industrialized countries and indigenous cultures (corresponding to different lifestyle gradients such as hunter-gatherers and pastoralists) and how this association may influence health and disease.

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

We present the case of a 28-year-old male with a history of alcohol dependency and smoking, who presented with chest pain, shortness of breath, and altered sensorium. He exhibited severe metabolic acidosis, low platelet count, and acute kidney injury. Alcoholic ketoacidosis (AKA) was suspected due to ketonuria, metabolic acidosis, and ketonemia, compounded by electrolyte abnormalities and radiographic findings of pneumonia.Prompt intervention included electrolyte correction, thiamine supplementation, broad-spectrum antibiotics, and diuretics. Thiamine played a pivotal role in the patient's recovery, with significant improvement in consciousness observed within a day. After six days, the patient was discharged in stable condition, showing normal renal and hepatic function during follow-up.This case emphasizes the need for early recognition and comprehensive management in AKA, highlighting thiamine's crucial role in treatment success.

Alcohol abuse can result in detrimental multisystem effects. Chronic alcohol abuse is known to be associated with pathophysiological changes in multiple organs often resulting in life threatening clinical outcomes e.g. breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, alcohol-induced cardiomyopathy and heart failure as well as central nervous system disorders. In this review article, we will discuss the multisystemic effects of alcohol abuse and explore in greater detail alcohol’s impact on two main systems that result in pathophysiological changes i.e. the cardiovascular and central nervous systems.

The gut-liver axis plays a pivotal role in the development of liver diseases, necessitating exploration into substances capable of modulating the microbiota to prevent dysbiosis. Over the past decade, diverse therapeutic approaches have emerged to target pathogenic factors involved in the hepatic gut microbiota axis. This study investigated the impact of a supplement with hepatoprotective activity, containing extracts of Silybum marianum, prebiotics, probiotics, n-3 polyunsaturated fatty acids, minerals, and vitamins on hematological markers of liver functions and on the intestinal microbiota of 10 adult dogs with metabolic liver disease over a 35-day time span. Animals underwent clinical and laboratory evaluations every 7 days, before administration of the supplement (T0) and after 7, 14, 21, 28 and 35 days (T1, T2, T3, T4 and T5). In comparison to T0, a significant (P<0.05) decrease of AST activity was measured at T2, T3, T4 and T5. The activity of ALP, glucose and CRP significantly decreased (P<0.05) at T3, T4, and T5. The alpha diversity of the fecal microbiota significantly decreased (P<0.05) only at T1, a high variability was observed between dogs. The total short-chain fatty acid and lactic acid were also lower at T1 (P<0.05) in comparison to the other times of sampling. The beta diversity of fecal microbiota failed to find a clear pattern in relation to the sampling times. These results underscore the usefulness of the supplement on liver function and highlight high individual variability in its interaction with the fecal microbiome.

This mini-review examines the complex relationship between the gut microbiota and human health, with a special focus on its role in conditions such as inflammatory bowel disease (IBD) and cardiovascular disease (CVD). It explores how dietary patterns can affect the composition of the gut microbiota, thus contributing to the development of various diseases. The gut microbiota is crucial in the production of metabolites such as trimethylamine N-oxide (TMAO), which play a significant role in the development of both IBD and CVD. High levels of TMAO and other metabolites, such as phenylacetylglutamine, have been linked to an increased risk of CVD. The review highlights the potential of dietary interventions and therapies designed to modulate the gut microbiota in reducing these risks. Following a Mediterranean diet may offer cardiovascular protection, emphasizing the need for further research into the molecular mechanisms of diet-related changes in the microbiota.

The determination of a causal relationship between gut microbiota and a range of dyslipidemia remains uncertain. To clarify these associations, we employed a two-sample mendelian randomization (MR) analysis utilizing the inverse-variance weighted (IVW) method. This comprehensive analysis investigated the genetic variants that exhibited a significant association (p<1e-5) with 129 distinct gut microbiota genera, and their potential link to diverse forms of dyslipidemia. The results indicated a potential causal relationship between 22 gut microbiota genera and dyslipidemia in humans. Furthermore, these findings suggested that the impact of gut microbiota on dyslipidemia regulation is dependent on the specific phylum, family, and genus. Bacillota phylum demonstrated the greatest diversity, with 15 distinct genera distributed among 8 families. Notably, gut microbiota derived from the Lachnospiraceae and Lactobacillaceae families exhibit statistically significant associations with lipid levels that contribute to overall health (p<0.05). The sensitivity analysis indicated that our findings possess robustness (p>0.05). The findings of our investigation provide compelling evidence that supports a causal relationship between the gut microbiota and dyslipidemia in the human body. It is noteworthy to highlight the significant influence of the Bacillota phylum as a pivotal regulator of lipid levels, and the families Lachnospiraceae and Lactobacillaceae should be acknowledged as probiotics that make substantial contributions to this metabolic process.

Modulating the gut microbiota with probiotics has been identified as a promising therapeutic method for the management of gastrointestinal illnesses. The effectiveness of probiotics in the treatment of gastrointestinal disorders can only be determined by delving into their underlying mechanisms of action. Through an analysis of the underlying processes, this study hopes to provide light on the potential benefits of probiotics for treating a variety of gastrointestinal conditions. The study covers a wide variety of gastrointestinal conditions, such as IBS, IBD, and antibiotic-associated diarrhea. Modifying the gut microbiota composition, strengthening the gut barrier function, modulating the immune system, and producing beneficial metabolites are among mechanisms of action that have been investigated. The strain- and dose-specific variables essential to getting the best treatment results are also highlighted. This review, which synthesizes the current information, gives a thorough overview of the effectiveness of probiotics in treating a variety of gastrointestinal illnesses and illuminates potential avenues for further study and therapeutic use.

There is a bidirectional relationship between the heart and the gut. Gut microbiome is an excellent gut-homeostasis keeper since controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting that diet rich in fatty acid can be metabolized and converted by gut microbiome and hepatic enzymes to trimethyl-amine N-oxide (TMAO) a product that is associated with atherogenesis, platelet dysfunction, thrombotic events, coronary artery disease, stroke, heart failure and ultimately death. Heart failure, by inducing gut ischemia and congestion and consequently gut barrier dysfunction promote an intestinal leak of microbes or even of their products, facilitating their entrance into the circulation and thus stimulating the low-grade inflammation and hence the immune response. Drugs used for heart failure may alter the gut microbiome, and conversely gut microbiome may modify the pharmacokinetic properties of the drugs. Modification of lifestyle based mainly on exercise and Mediterranean diet along with the use of pre- or probiotics may be beneficial to some extent for the gut microbiome environment. The potential role of gut microbiome in heart failure development and outcomes is a fruitful area of future research.

The stability of the gut barrier is very important for keeping the gut healthy and stopping dangerous substances from getting into the bloodstream. Several diseases, including cancer, have been linked to the gut barrier being broken. Live bacteria called probiotics that are good for the host have been shown to have the ability to improve the gut barrier and lower the risk of cancer in the gastrointestinal system. This review looks at how probiotics affect the health of the gut barrier and what that might mean for preventing cancer. Researchers have found that probiotics strengthen the connections between intestine cells, encourage the production of protective mucins, and change the make-up and balance of the gut bacteria. These processes help keep the gut barrier strong and stop harmful chemicals from getting into the bloodstream. Probiotics may help lower the chance of cancer by reducing inflammation throughout the body and protecting the GI tract from harmful substances. But more study is needed to fully understand the benefits of different probiotic strains, the best amounts to take, and how they affect the health of the gut barrier. Understanding how probiotics, the health of the gut barrier, and the risk of cancer all work together can help us come up with new ways to avoid and treat cancer.

The mammalian or mechanistic target of rapamycin (mTOR) integrates multiple intracellular and extra-cellular upstream signals involved in the regulation of anabolic and catabolic processes in cells, and plays a key regulatory role in cell growth and metabolism. Activation of the mTOR signaling pathway has been reported to be associated with a wide range of human diseases. A growing number of in vivo and in vitro studies have demonstrated that the gut microbes and its complex metabolites can regulate host metabolic and immune responses through the mTOR pathway, and result in disorders of host phys-iological functions. In this review, we summarize the regulatory mechanisms of gut microbes and mTOR in different diseases, and discuss the crosstalk between gut microbes and their metabolites and mTOR in the disorders in gastrointestinal tract, liver, heart and other organs. We also discuss the promising appli-cation of multiple potential drugs that can adjust the gut microbiota and mTOR signal pathways. Despite the limited findings between gut microbes and mTOR, elucidating their relationship may provide new clues for the prevention and treatment of various diseases.

As a first step a unification of the gravitational with the electromagnetic interaction within a classical framework is proposed. It is based on a V₅-geometry, with x₅ = q/m. The sole source term is mechanical stress energy, positioned along x₅. The trajectories of test-bodies are placed in V₄ (x₅ = const)-slices. The resulting field equation couples a geometric G-tensor to mechanical stress energy, its momentum with respect to V₅ and the change of this momentum with proper time τ. The following step proceeds to the quantization of space-time to enable the formalization of elementary particles und strong interaction. This is complimented by the inclusion of spin and the weak force, leading finally to a grand total equation, the stationary version of which corresponds to Schroedinger´s equation, the instationary version to the Einstein equation of General Relativity.

Bifidobacterium are a beneficial and dominant member of the breast-fed infant gut microbiome. However, the health benefits of Bifidobacterium are partially species dependent. Here we characterize the species and subspecies of Bifidobacterium present in breastfed infants around the world. Across populations, three distinct patterns of Bifidobacterium colonization emerged: 1) Dominance of Bifidobacterium longum subspecies infantis, 2) Prevalent Bifidobacterium of multiple species, and 3) Frequent absence of Bifidobacterium. These patterns appear related to country history of breastfeeding, with infants in countries with historically high rates of long duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter duration breastfeeding. These findings highlight the need to consider historical and cultural influences on gut commensal survival influence present day colonization patterns in order to understand epidemiological transmission patterns of Bifidobacterium and other major gut commensals.

Rotavirus (RV) and norovirus (NoV) are the leading cause of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections, since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive and Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections there are too many discrepancies that prevent drawing conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances, enteric viral infection. The ways microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restricts infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responders and non-responders individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and the intestinal viruses, new avenues will be open for the development of novel anti-NoV and anti-RV therapies.

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3^-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ^9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome-cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.

This review examines the evidence supporting the role of dysbiosis in the development of obses-sive-compulsive disorders (OCD). We review the molecular mechanisms and role of the microbiota in the microbiota-gut-brain axis, focusing on the endocrine, nervous, and immune pathways. We then propose a model that positions dysbiosis as the central unifying element in the neurochemi-cal, immunological, genetic, and environmental factors leading to OCD. Based on this, we review the animal and human clinical evidence for the use of microbial reprogramming strategies such as probiotic or fecal microbiota transplants to treat OCD. Finally, we discuss the unique challenges that must be addressed in future clinical interventions.

Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, namely trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated to common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota and its metabolites, and the host immune system could reveal promising insight into ACVD development, prognostic factors, and treatments.

(1) Background: The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and disease activity and organ mani-festations in SLE patients. (2) Methods: We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4, and interleukin-6 (IL-6) levels, and antinu-clear and antiphospholipid antibody profiles. (3) Results: The median serum levels of sTfR (p>0.000001) and IL-4 (p<0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p<0.0001), a lower iron concentration (p=0.008), a lower value of total iron-binding capacity (TIBC) (p=0.03), and lower counts of RBC (p=0.004), HCT (p=0.0004), PLT (p=0.04), neutrophil (p=0.04), and lymphocyte (p<0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p=0.0005), HGB (p=0.0001) and HCT (p=0.008), and positively correlated with IL-4 (p=0.01). Elevated serum sTfR >2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71–464.78; p=0.001), ischemic heart disease (OR: 3.25 95 CI 1.02–10.40; p=0.04), lung manifestations (OR: 4.48 95 CI 1.44–13.94; p=0.01), and hematological manifestations (OR: 2.07 95 CI 1.13–3.79; p=0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22–0.80; p=0.008). Serum IL-4 was negatively correlated with CRP (p=0.003), and elevated serum IL-4 levels > 0.17 mg/l were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26–0.90; p=0.02). (4) Conclusions: In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, like diabetic foot ulcers, have increased significantly in the last years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: Methicillin-Resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had not proteolytic effects. MRSA infections increased cytokines expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to determine the therapeutic potential of these compounds by testing them in A375 cell-line derived xenograft in nu/nu mice. Animals were randomized into four groups (n=12/group) to receive subcutaneous administration of vehicle, 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 three times per week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results suggest a therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

Alzheimer’s disease (AD) is a significant health concern worldwide with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells like microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms.

(1) Background: In the United Kingdom, Ireland, Iceland, France, Spain, Portugal, and Italy a subject participating in a (bio) medical experiment is termed a guinea pig. In Germany (Versuchskaninchen), The Netherlands, all of Scandinavia, and most of Eastern Europe, the term rabbit is used for such a subject. We have searched for potential differences in attitudes towards biomedical research by inhabitants of the respective European countries by making an analysis of frequency and motivation to participate in biomedical experiments on both sides of the European rabbit borderline. (2) Methods: We have performed an analysis of the use of experimental animals for research in European countries as well as country specific scientific output in PubMed indexed literature. Attitudes towards biomedical research in European countries was derived from EU questionnaires. (3) Results: In biomedical experiments with animals, more guinea pigs are used in laboratories in “rabbit countries” than in “guinea pig countries”. Inhabitants of “rabbit countries” have a higher participation rate in biomedical experiments and donation of blood than people from “guinea pig” countries. The reasons to participate in a medical experiment are not purely altruistic, especially in “rabbit countries”. (4) Conclusions: inhabitants of European countries in which a person who participates in a biomedical experiment is labeled as an (experimental) rabbit participate more in biomedical experiments as well as tissue and organ donation. Motives to do so are not just altruistic, because financial reasons also play a role.

Organ transplantation centers set criteria for candidate qualification, which has led to disparate healthcare resource allocation practices affecting those with a substance use history. These individuals are denied organ transplants by committees and healthcare providers who assign them lower priority status. The lower priority argument claims that healthcare resources should not be provided equally to individuals failing to share responsibility for not doing enough in addressing the diseases associated with substance use. The purpose of this work is to explore the interrelatedness between the ethics of a merit-based system of moral responsibility and lower priority setting involved in healthcare resource allocation pertaining to those with substance use histories. An integral approach to the argument against the lower prioritists with a focus on the relationship between different organ allocation practices affecting substance users and the justification for resource allocation practices in healthcare and transplant committees. Lower priority setting is challenged, and an argument offered in which substance users are assigned higher priority when relying on “doing enough” in a merit-based system of moral responsibility. It is determined that one cannot substantiate assigning a lower priority status since a lack of success in rehab does not imply a lack of effort. Additionally, neither to confirmatory behavior, nor to non-conforming behavior may freedom be justifiably ascribed in a merit-based system of responsibility because freedom to choose can neither be established a priori, nor a posteriori with respect to meritorious behavior.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

Intestinal commensal microbes, called the gut microbiota, play a critical role in host immune homeostasis through active microbial metabolites and innate and adaptive immune responses. Dysbiosis or imbalance of the gut microbiota composition is associated with inflammatory bowel disease (IBD) which includes Crohn’s disease and ulcerative colitis. The incidence and prevalence rates of IBD have been increasing worldwide. It is well recognized that butyrate, a microbial metabolite of diet fibers, is a major energy source for colonocytes and plays a crucial role in regulating immune function and maintaining epithelial barrier function and intestinal homeostasis. Emerging evidence suggests that butyrate might be a potential therapeutic agent to treat IBD. In this review, we discuss about gut microbial metabolites, particularly butyrate, the synthesis and metabolism of butyrate, mechanisms of butyrate in immune and epithelial barrier function. Furthermore, we review the current research on various therapeutic implications of butyrate in IBD.

Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiome in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiome axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiome. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiome on PD and whether this may be a new paradigm for treating this devastating disease.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to significant global health implications. Although the respiratory manifestations of COVID-19 are widely recognized, emerging evidence suggests that the disease may also significantly affect the gut microbiota, the intricate community of bacteria that lives within the gastrointestinal system. This extensive article intends to investigate the impact of COVID-19 on the gut microbiota, examining the underlying mechanisms, clinical implications, and potential therapeutic interventions. Understanding the complex interactions between COVID-19 and the gut microbiota will help us to gain valuable insights into the broader consequences of this viral infection on human health.

In this study, we evaluated how gut microbes associated with hepatopancreatic and gonadal expression genes impact on growth traits in different sex of M. rosenbergii. By comparing the relative abundance of gut microbes between the male (high weight gain, HiWG) and female (low weight gain, LoWG) animals, we have shown that at the phyla, family and genera level, the abundance of microbes existed significantly difference between both group. At the genera level, the abundance of Candidatus Hepatoplasma and unidentified Chloroplast lower in the LoWG animals than in the HiWG animals, and Lactobacillus and Ligilactobacillus have opposed trend. The abundance of Candidatus Hepatoplasma and unclassfied Chloroplast was associated with the growth traits in the HiWG group. The Lolium perenne microbial species belong to unclassfied Chloroplast genera have tight association with Ralstonia pickettii, both might association on Geobacter anodirecteducens abundance, which correlation with the expression of glutathione peroxidase and collagen, which were highly expressed in the hepatopancreas and gonads of HiWG group animals of M. rosenbergii and might promote growth and development. These associations were not detected in the female LoWG group.

Gut microbiota is a complex and dynamic ecosystem that influences various aspects of human health. Unfortunately, there is a lack of literature highlighting the importance of gut microbiome especially in diabetes management. This paper performs bibliometric analysis to establish the rising interest of researchers in this area and the importance of gut microbiota in diabetes management. Subsequently, the study performs a narrative review to provide an overview of the gut microbiota consisting of bacteria, archaea, fungi, and viruses, and its diversity, composition, and variation among individuals. The paper further discusses the role of the gut microbiota in different diseases, including Clostridium difficile infection, behavioral disorders, cancer, obesity, diabetes, atherosclerosis, and inflammatory bowel disease, among others. It emphasizes the link between gut dysbiosis (imbalanced gut microbiota) and the development of chronic metabolic disorders. Additionally, the paper discusses the factor negatively impacting the gut microbiota. The paper concludes by explaining the mechanistic abnormalities that link dysbiosis to type 2 diabetes, including changes in short-chain fatty acid production, amino acid metabolism, bile acid regulation, and the production of specific bacterial products. Thus, the paper highlights the importance of understanding gut microbiota and related mechanisms for developing therapeutic interventions targeting the gut microbiota.

Equine fecal microbiota transplantation (FMT) is an emerging therapy for restoring gut microbiome balance in horses. An imbalance in the gut microorganisms, known as dysbiosis, can cause inflammation and metabolic disruptions. FMT, which involves transferring gut bacteria from a healthy donor to a diseased recipient, has shown positive results in treating gastrointestinal diseases in horses, but is still largely limited to research purposes due to safety concerns and lack of understanding of its mechanisms. This paper aims to shed light on the possible mechanisms of FMT in horses and discuss future perspectives for its clinical application. Further research is needed to develop more effective and safer FMT techniques for horses.

Polyurethane (PU) is a polymer widely used by humans whose recycling is highly complex due his chemical structure, being limited to incineration or accumulation in landfills. Biodegradation by enzymes and microorganisms has been studied for decades as an effective method of biological decomposition. In this study, Tenebrio molitor larvae (T. molitor) were fed with polyurethane foams, which gut enzymes and microorganisms were capable of degrading the polymer by 35% in 17 days of treatment, producing a weight loss of 14% in the mealworm. Changes in T. molitor gut bacterial community and diversity were observed, which may be due to colonization of species associated with PU degradation. Physical and structural biodegradation in PU by T. molitor compared to virgin PU, was demonstrated by Fourier Transform InfraRed spectroscopy (FTIR), Thermal Gravimetric Analysis (TGA) and Scanning Electron Microphotography (SEM).

Background: Pharmacologic and non-pharmacologic treatments for stroke are essential but could be costly or harmful whereas probiotic has been a promising alternative. This scoping review aimed to synthesize the in vitro and in vivo evidence of probiotics on stroke-related neurological, biochemical, and histochemical outcomes. Method: We searched in PubMed, Embase, and Cochrane Central Register of Clinical up to May 7, 2021, and screened by two independent reviewers. We included the use of probiotics, prebiotics, and symbiotics both in vitro and in vivo for the prevention or treatment of the stroke-related model. Result: Of 6,293 articles, 4,990 passed the initial screen, of which 36 theme-related full-texts were assessed and 13 were included in this review. Probiotics could ameliorate the neurological deficit and show their property as an anti-inflammation and anti-oxidative stress. Histopathologically decreased loss of cerebral volume and inhibition of neuronal apoptosis were found. Conclusion: There are potential cognitive benefits of probiotic supplementation, especially among animal models, on decreasing cerebral volume, increasing neurological score, and decreasing the inflammatory response. However, further investigation is needed to validate these conclusions in various populations.

Species diversity in microbiome is a cutting-edge concept in metagenomic research. In this study, we propose a multifractal analysis for metagenomic research. From the chaos game representation (CGR) visualization of simulated and real metagenomes, we find that there exists self-similarity in the visualization of metagenomes. Then we compute the multifractal dimensions for simulated and real metagenomes. For simulated metagenomes, we also compute their diversity indices, such as species richness indices, Shannon’s diversity indices and Simpson’s diversity indices respectively for varying value of . Fom the Pearson correlation coefficients between their multifractal dimensions and traditional species diversity indices, we find that the correlation coefficients between the multifractal dimensions and species richness indices and Shannon diversity indices reach their maximums at respectively. The correlation coefficients between the multifractal dimensions and Simpson’s diversity indices reach their maximums at nearly. So the traditional diversity indices can be unified by the frame of multifractal analysis. These results coincided with the similar results in macrobial ecology. Finally, we apply our methods to real metagenomes of 100 infants’ gut microbiomes when they are newborn, 4 months and 12 months. Our results show that multifractal dimensions of infants’ gut microbiomes can discriminate the age difference.

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.