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Aim: Chronic alcoholics may have a reduced serum level of cyanocobalamin and there are scanty reports suggesting a role of ethanol-generated fine radicals. Thus, the aim of this study was to test novel fermented papaya antioxidant preparation (FPAP, Osato Res. Institute, Gifu Japan) on cyanocobalamin absorption in alcoholic chronic liver disease (CLD) patients. Methods: 30 patients with alcoholic CLD (>150g ethanol/day for at least 5 years) and 24 teetotallers underwent baseline chemistry and Dual Isotope Schilling test (DIST). During endoscopy, biopsy samples were taken from gastric antrum and body to assay: routine histology, malonyldialdehyde (MDA), vitamin E, GSH concentration and vitamin B12-Intrinsic Factor (IF) binding. Examinations were repeated after one week supplementation with FPAP 9g/day, Results: Plasma MDA level, lipid hydroperoxides, MDA and xanthine oxidase concentration in the gastric mucosa were higher in CLD than in healthy subjects (p<0.01) and significantly decreased after FPAP (p<0.05). Gastric mucosal GSH was depleted in CLD patients and partly recovered with FPAP (9<0.05 vs baseline). Although the CLD patients showed normal IF secretion in the gastric juice, they exhibited an impaired IF-cobalamin binding on the ex vivo study (p<0.001), Moreover, nearly 23% of them had an abnormal DIST. Both these failures reverted to normal after FPAP treatment (p<0.01 vs baseline). Conclusions: It can be postulated that the antioxidative action played by FPAP possibly due to its availability of substrates for GSH synthesis as welt as its effect on local oxidative burst from neutrophils, is able to recover a normal cobalamin absorption. [ABSTRACT FROM AUTHOR]

Human brain is the control system of body which helps in coordinating the function of every organ and maintaining homeostasis. A functioning brain receives information from the body and interprets information guiding the body's response to it. There is found to be an interaction between the brain and the intestinal flora of the body. Apart from known benefits of microbes such as digestion and host defense, the gut microbiome also impacts mental health. Stress is being the major cause of occurrence of various mental health problems. Neuroinflammation and neurodegeneration are the pathophysiological implications of stress as it disturbs the generation of neurons. Gut microbes have been found to help ease the effects of stress such as anxiety, depression but there is a negative consequence of their composition being altered in case of chronic stress or emotional trauma. Specific food supplements maintain the gut population as well as protects the brain from stress induced debilitating effects. Nutraceuticals providing nutrition to the microbiome and influence cognitive functions and development of brain can be referred as neuro-nutraceuticals. This review aims to highlight the multi-targeted action of nutraceuticals and gut-microbiota upon brain during stress and their specific effects on normal brain functioning and development. [ABSTRACT FROM AUTHOR]

Human gut microflora includes three enterotypes and composes the largest part of the whole microbiome. Because gut microflora play a crucial role in health and disease, knowing the microbial composition of the gut microbiome is an important task. Currently, the gut microbiome composition in the Kazakhstani population is poorly understood. Therefore, we studied the phylogenetic composition and types of the gut microbiome in Kazakhstani women and stratified the data by age. Female subjects were divided into three groups: six young (<44years old), eighteen middle-aged (50--70 years old), and six elderly (>90 years old). For the gut microbiome composition analysis, the 16S rDNA locus was amplified, ligated into high copy plasmid vectors, and sequenced. We observed that two gut microbiome types, Phyla Bacteroidetes and Firmicutes, were age independent. However, there were significant differences in species composition between groups that can be attributed to age. Fite highest species diversity occurred in the middle-aged group, which subsequently decreased in the elderly group. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis are characterized by abnormalities of both albumin and muscle protein turnover and anorexia which in turn contribute to cachexia. The main hemodynamic alteration in cirrhosis is caused by decreased albumin synthesis and turnover, which in turn lead to ineffective arterial blood, playing a significant role in development of decompensation and in the prognosis of these patients. Serum albumin might be corrected via administration of human albumin solution (HAS) but its use in all patients with decompensated cirrhosis is not always justified. The interest in therapeutic use of probiotics in these patients has increased during the last few years because of beneficial effects associated with correcting hypoalbuminemia and cachexia. This review aims to highlight potential of therapeutic use of probiotics in cirrhosis by revising the evidence-based results obtained in hepatic disorders. [ABSTRACT FROM AUTHOR]

The antioxidant and antigenotoxic properties of the probiotic consortium, including the strains Streptococcus thermophilus, Lactococcus lactis, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum, were investigated. According to the results o f our research the total antioxidant capacity (TAC) of the intact cells in the probiotic consortium was high - 15.3 mmol/ml, glutathione reductase activity was 0.004 U/ml, Superoxide dismutase activity was not revealed. The total antioxidant capacity of the cell lysates in the probiotic consortium is 11.1 mM/ml, glutathione reductase activity - 0,008 units/ml, superoxide dismutase activity - 0.24 U/mg. Co-incubation o f the epithelial cells with the probiotic consortium reduces the percentage o f damaged cells (DI - 0.6). [ABSTRACT FROM AUTHOR]

he aim of this study was to test for a potential anticarcinogenic effect of Celergen, a marine derivative devoid of traceable amounts of inorganic arsenic, on cell proliferation, cell cycle progression and apoptosis in the HepG2 human liver cancer cell line. Celergen significantly inhibited the proliferation of cancer cells in a dose-dependent manner while limiting the cell cycle progression at the G1 phase and significantly inducing apoptosis. Further examination showed that Celergen enhanced expression of the p21CIPl1WAF1, GADD153 genes and downregulated the c-myc gene. These results suggest that Celergen exerts promising chemopreventive properties to be further investigated. [ABSTRACT FROM AUTHOR]

Aims: To provide an epidemiologic interpretation of a suspected outbreak of food poisoning caused by Salmonella enterica subspecies enterica serovar Berta strains isolated from humans and from the leftovers of the implicated foods (cream, dairy-based desserts and eggs). Methods and Results: We have correlated the similarity between the strains through genotyping with Pulsed Field Gel Electrophoresis (PFGE), studying antimicrobial sensitivity patterns and epidemiological investigation. The clonal origin of the outbreak was confirmed by all laboratory tests. PFGE analysis of the restriction profiles obtained with XbaI and SpeI revealed a certainly correlation from the strains isolated from the various sources, while the antimicrobial sensitivity pattern was the same in all cases, with all strains sensitive to all antibiotics tested. Conclusions: Poor hygiene conditions in the facility concerned, lack of hygiene in food handling, high summer temperatures and positive cultures from asymptomatic staff could all be implicated in the infection, with food being the means through which it spread. Significance and Impact of the Study: This study describes the first outbreak of food poisoning caused by Salmonella enterica subspecies enterica serovar Berta ( Salmonella Berta) reported in Italy. It confirms the importance of correlating epidemiological investigations with genotyping and phenotyping to understand the dynamics of infection. [ABSTRACT FROM AUTHOR]

In view of the raising concern for gut fungal infection, the aim of the present research was to carry out a systematicin vitrostudy testing the antifungal activity and possible toxicity of a polygodial-anethole compound (Kolorex) in several strains ofCandida albicansand in other fungal pathogens.Thein vitrosusceptibility tests were carried out on 4 strains ofC. albicans(C. krusei, C. lipolytica, C. tropicalis, C. utilis),Aspergillus flavusandA. fumigatus. Cultures were also analyzed by varying medium, pH and inoculum size, and a time-course killing test was carried out.In the present study the polygodyal–anethole compound showed remarkablein vitroactivity against the most common fungi, which was significantly better than polygodyal alone. Moreover, such mixture compound was shown to exert its activity against a wide spectrum of fungi, includingC. lipolyticaandC. tropicalis, which required significantly higher MIC of polygodyal to be unfeasible in clinical application. The activity of the polygodyal–anethole compound was significantly better than polygodyal alone with high inoculum size and low pH. Moreover, it proved to exert a significantly faster biological activity against low inoculum.This study suggests that the mixture compound Kolorex has a very good profile of antifungal activity in terms of effectiveness and spectrum of action while being devoid of any significant toxicity. [ABSTRACT FROM AUTHOR]

Metals undergo redox cycling and there is increasing evidence of free radical generation and oxidative injury in the pathogenesis of liver injury and fibrosis in metal storage diseases. The aim of the present study was to test a natural hepatoprotective compound in metal-induced liver injury.Hepatocytes were isolated from Wistar rats by collagenase perfusion method and cultured as such and also withα-linolenic acid (LNA)-bovine serum albumin (BSA). Hepatocytes were then cultured with a graded dilution of PN-M001 (100 µg/mL and 200 µg/mL), which is a curcuma/absinthium-containing compound, or sylibin (100 µg/mL) dissolved in dimethyl sulfoxide for 10 min before the addition of metallic salts (iron, copper and vanadium). Lysosomal fractions were prepared for lysosome fragility tests in whichβ-galactosidase activity and lactate dehydrogenase (LDH) leakage were measured, as well as oxidative damage tests in the presence of hydrophilic and lipophilic free radical generators. Quenching activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) was also assessed.Malonildialdehyde accumulation in the medium showed a direct time-course increase with incubation time. Both PN-M001 and sylibin showed a significant protective effect against all challenge metal ions, as expressed by the half inhibition concentration (IC50) against lipid peroxidation. However, on a molar ratio, sylibin seemed to be more effective than PN-M001 in Fe-induced peroxidative damage (P < 0.05). Both test compounds, irrespective of the concentration, significantly reduced the LDH andβ-galactosidase concentration in the lysosomal fractions. As compared with untreated lysosomal fractions challenged with the two peroxide radicals generators, either PN-M001 or sylibin exerted significant protection However, PN-M001 was significantly better than sylibin in suppressing acid phosphatase enzyme activity. Both compounds showed comparable and significant DPPH radical-scavenging activity.These data support the potential clinical application of curcumin-containing compounds. [ABSTRACT FROM AUTHOR]

Experimental and clinical studies have shown that a novel symbiotic (known as SCM-III) exerts a beneficial effect on gut translocation and local and systemic inflammatory and microbial metabolic parameters. The present investigation was a preliminary trial on the effectiveness of SCM-III for irritable bowel syndrome (IBS).Sixty-eight consecutive adult patients with IBS who were free from lactose malabsorption, abdominal surgery, overt psychiatric disorders and ongoing psychotropic drug therapy or ethanol abuse were studied prospectively and divided into 2 groups that were comparable for age, gender, body size, education and pattern of presenting symptoms. The 2 groups were blindly given for 12 weeks either SCM-III 10 mL t.i.d or the same dosage of heat-inactivated symbiotic.Treatment with SCM-III was‘effective’ or‘very effective’ in more than 80% of the patients (P < 0.01 vs baseline values and control). Less than 5% reported‘not effective’ as the final evaluation compared with over 40% of patients in the control group. After 6 weeks of treatment, a significant improvement of pain and bloating was reported in the treatment group compared with control and baseline values. There was also a benefit for bowel habits, mostly for patients with constipation or alternating bowel habits. No overt clinical or biochemical adverse side-effects were recorded.Compared with baseline values and the control group, SCM-III resulted in a significant increase in lactobacilla, eubacteria and bifidobacteria, which suggests that some selected IBS patients could benefit substantially from symbiotics, but the treatment may need to be given on a cyclic schedule because of the temporary modification of the fecal flora. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present investigation was to test study benzodiazepines (BZDs) profile in patients with viral cirrhosis under different combinations of rifaximine and of a novel symbiotic. Methods: Our study groups consisted of 30 patients with a confirmed diagnosis of HCV-related Child B liver cirrhosis. Patients were randomly allocated into three groups: rifaximine 400 mg t.i.d. for 2 weeks; (B) SCM-III (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacteria in a ion- and vitamin-enriched medium, Named srl, Italy) 10 ml t.i.d. for 2 weeks; (C) rifaximine 400 mg t.i.d. for 1 week followed by SCM-III 10 ml t.i.d. for 5 weeks. At weekly interval, blood samples were withdrawn to test BZD-like substances, ammonia and endotoxin. Results: Rifaximine treatment brought about a significant early drop of BZDs (P<0.01 versus pre-treatment and versus control) till fourth week of observation when a gradual increase took place with return to pre-treatment values at the sixth week. Symbiotic treatment was comparably effective while given to patients but significantly elevated BZDs level were noted starting from the third week. Similar phenomena were noted for endotoxin and ammonia although symbiotic seemed more effective against endotoxin and rifaximine against ammonia increase. However, the sequential treatment rifaximine-symbiotic brought about a sustained normalization of BZDs, ammonia and endotoxin throughout the 6-week study. Conclusion: The present pilot study suggests that a rifaximine-symbiotic regimen could be an effective tool in compensated liver cirrhosis to limit some triggering factors of hepatic encephalopathy while being amenable to long-term use and devoid of significant side effects. [Copyright &y& Elsevier]

Issue/problem: The Italian National Health System has implemented a National Control Program for Salmonella in poultry populations in order to reduce the prevalence of infection. Starting from 2019, the control program has introduced health measures against Salmonella breeding flocks of Gallus gallus, positive to Salmonella Infantis, an emerging serotype at European level, and widespread along the entire poultry primary production chain. Description of the problem: Recent data from the European Union One Health 2019 Zoonoses Report published by EFSA, highlighted that most of the Salmonella isolates (70%) originated from broilers. Interestingly, Salmonella Infantis accounted for 29.7% of the total. Results: In the framework of the Italian Salmonella National Control Program the isolation of Salmonella spp. is carried out according to ISO 6579-1: 2017 from faeces, dust and boot socks. During the 2015-2020 period, testing in the Italian Regions Abruzzo and Molise was performed on 2,791 samples and 5,039 sample units. The percentage of samples positive to Salmonella spp. in Abruzzo and Molise was 16,9% and 10,1%, respectively. Out of 395 Salmonella spp. strains isolated, Salmonella Infantis was the most prevalent, representing the 54,9% and 61,9% for Abruzzo and Molise, respectively, followed by Salmonella Livingstone (18,4%) for Abruzzo and (14,4%) for Molise. Lessons: The record of Salmonella Infantis in the areas under study reflects the European trend highlighted by the EFSA 2019 Report and justifies the decision to increase the biosecurity measures in farms where this serotype is isolated and to proceed with destruction of positive animals according to the Regulation 1069/2009/EC. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome (SS) is an autoimmune disease and its management is palliative. There is no specific dietary protocol for SS patients. A gluten-free diet has been tested in SS patients with celiac disease (CD) and indicated modest improvements. Whether gluten-free diets per sè could alleviate autoimmune inflammatory processes in the salivary glands of SS patients with associated CD or even in SS patients without CD is an interesting hypothesis and warrants clinical studies. Hypokalemia in SS patients is among the most frequent sequelae of renal tubular acidosis. Supplementation with potassium (K)-rich diets can reduce inflammation and oxidative stress. K level in CD patients is highly abnormal at diagnosis and gluten-free diets help to normalize its serum level in CD patients. Furthermore, treatment of severe cases of SS requires concomitant glucocorticoid therapy and K supplementation. Results of two separate clinical trials in (i) patients with rheumatoid arthritis (RA) -a disease with similar pathology to SS- indicated that the enhanced serum cortisol followed K supplementation, and in (ii) celiac patients, serum K levels were normalized after the administration of a gluten-free diet. We reviewed the literature extensively on this topic to propose a hypothesis to address this problem and suggest a novel potential for K-rich, gluten-free diets in SS patients. Based on causal associations, we propose that higher K absorption and cortisol secretion following gluten-free diets accompanied by K-rich diets in SS patients with low serum potassium levels, may confer a higher therapeutic potential. Clinical trials are needed to test this hypothesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Long-standing overt ventriculomegaly in adults (LOVA) is a chronic form of hydrocephalus that can lead to cognitive deficits. Data on the cognitive profile of patients with LOVA and cognitive outcomes of endoscopic third ventriculostomy (ETV) are, however, scarce and mostly qualitative., Methods: Twenty-three consecutive patients with LOVA hydrocephalus underwent ETV surgery, and their cognitive status was assessed before surgery, immediately after surgery, and at the 5-month follow-up. Cognitive function was assessed using a neuropsychological battery measuring 6 cognitive domains: general cognitive status, attention/executive function, language, visuospatial skills, short-term memory, and long-term memory. Cognitive reserve was also estimated through a measure of premorbid IQ to assess its potential influence together with other clinical and demographic variables., Results: Patients with LOVA did not experience general cognitive decline but rather selective long-term memory (p < 0.001) and visuospatial skills (p = 0.001) deficits alone. Moreover, ETV surgery led to significant immediate postoperative improvement in both domains (p = 0.002 and p < 0.001 respectively), that persisted at follow-up (p < 0.001 for both). However, improvement was observed only in patients with higher premorbid IQ (p < 0.001), while the others did not improve (p > 0.532)., Conclusions: These findings confirm the effectiveness of ETV surgery and highlight the role of cognitive reserve in promoting plasticity of brain and cognitive functions thus fostering and predicting cognitive recovery.

Microbiome is an endocrine organ that refers to both the complicated biological system of microbial species that colonize our bodies and their genomes and surroundings. Recent studies confirm the connection between the microbiome and eye diseases, which are involved in the pathogenesis of eye diseases, including age-related macular disorders, diabetic retinopathy, glaucoma, retinitis pigmentosa, dry eye, and uveitis. The aim of this review is to investigate the microbiome in relation to eye health. First, a brief introduction of the characteristics of the gut microorganisms terms of composition and work, the role of dysbiosis, the gut microbiome and the eye microbiome in the progression of eye illnesses are highlighted, then the relationship among the microbiome and the function of the immune system and eye diseases, the role of inflammation and aging and the immune system, It has been reviewed and finally, the control and treatment goals of microbiome and eye diseases, the role of food factors and supplements, biotherapy and antibiotics in relation to microbiome and eye health have been reviewed., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Brucellosis is an economically important zoonotic disease affecting humans, livestock, and wildlife health globally and especially in Africa. Brucella abortus and B. melitensis have been isolated from human, livestock (cattle and goat), and wildlife (sable) in South Africa (SA) but with little knowledge of the population genomic structure of this pathogen in SA. As whole genome sequencing can assist to differentiate and trace the origin of outbreaks of Brucella spp. strains, the whole genomes of retrospective isolates (n = 19) from previous studies were sequenced. Sequences were analysed using average nucleotide identity (ANI), pangenomics, and whole genome single nucleotide polymorphism (wgSNP) to trace the geographical origin of cases of brucellosis circulating in human, cattle, goats, and sable from different provinces in SA. Pangenomics analysis of B. melitensis (n = 69) and B. abortus (n = 56) was conducted with 19 strains that included B. abortus from cattle (n = 3) and B. melitensis from a human (n = 1), cattle (n = 1), goat (n = 1), Rev1 vaccine strain (n = 1), and sable (n = 12). Pangenomics analysis of B. melitensis genomes, highlighted shared genes, that include 10 hypothetical proteins and genes that encodes for acetyl-coenzyme A synthetase (acs), and acylamidase (aam) amongst the sable genomes. The wgSNP analysis confirmed the B. melitensis isolated from human was more closely related to the goat from the Western Cape Province from the same outbreak than the B. melitensis cattle sample from different cases in the Gauteng Province. The B. melitensis sable strains could be distinguished from the African lineage, constituting their own African sub-clade. The sequenced B. abortus strains clustered in the C2 lineage that is closely related to the isolates from Mozambique and Zimbabwe. This study identified genetically diverse Brucella spp. among various hosts in SA. This study expands the limited known knowledge regarding the presence of B. melitensis in livestock and humans in SA, further building a foundation for future research on the distribution of the Brucella spp. worldwide and its evolutionary background., (© 2024. The Author(s).)

The nitrogen (N) cycle is the foundation of the biogeochemistry on Earth and plays a crucial role in global climate stability. It is one of the most important nutrient cycles in high-altitude lakes. The biogeochemistry of nitrogen is almost entirely dependent on redox reactions mediated by microorganisms. However, the nitrogen cycling of microbial communities in the high-altitude saline lakes of the Qinghai-Tibet Plateau (QTP), the world's "third pole" has not been investigated extensively. In this study, we used a metagenomic approach to investigate the microbial communities in four high-altitude pristine saline lakes in the Altun mountain on the QTP. We observed that Proteobacteria , Bacteroidota , and Actinobacteriota were dominant in these lakes. We reconstructed 1,593 bacterial MAGs and 8 archaeal MAGs, 1,060 of which were found to contain nitrogen cycle related genes. Our analysis revealed that nitrite reduction, nitrogen fixation, and assimilatory nitrate reduction processes might be active in the lakes. Denitrification might be a major mechanism driving the potential nitrogen loss, while nitrification might be inactive. A wide variety of microorganisms in the lake, dominated by Proteobacteria , participate together in the nitrogen cycle. The prevalence of the dominant taxon Yoonia in these lakes may be attributed to its well-established nitrogen functions and the coupled proton dynamics. This study is the first to systematically investigate the structure and nitrogen function of the microbial community in the high-altitude pristine saline lakes in the Altun mountain on the QTP. As such, it contributes to a better comprehension of biogeochemistry of high-altitude saline lakes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhao, Marotta, Xamxidin, Li, Xu, Hu and Wu.)

Background and Objective: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline., Methods: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites., Results: We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet., Conclusion: Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As the amount of metagenomic sequencing continues to increase, there is a growing need for tools that help biologists make sense of the data. Specifically, researchers are often interested in the potential of a microbial community to carry out a metabolic reaction, but this analysis requires knitting together multiple software tools into a complex pipeline. Thanos offers a user-friendly R package designed for the pathway-centric analysis and visualization of the functions encoded within metagenomic samples. It allows researchers to go beyond taxonomic profiles and find out, quantitatively, which pathways are prevalent in an environment, as well as comparing different environments in terms of their functional potential. The analysis is based on the sequencing depth of the genes of interest, either in the metagenome-assembled genomes (MAGs) or in the assembled reads (contigs), using a normalization strategy that enables comparison across samples. The package can import the data from multiple formats and offers functions for the visualization of the results as bar plots of the functional profile, box plots of compare functions across samples, and annotated pathway graphs. By streamlining the analysis of the functional potential encoded in microbial communities, Thanos can enable impactful discoveries in all the fields touched by metagenomics, from human health to the environmental sciences.

Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and all drugs can cause hepatotoxicity of varying degrees, including those for the treatment of inflammatory bowel diseases (IBD). The aim of this review is to illustrate the adverse effects on the liver of the various drugs used in the treatment of IBD, highlighting which drugs are safest to use based on current knowledge. The mechanism by which drugs cause hepatotoxicity is not fully understood. A possible cause is represented by the formation of toxic metabolites, which in some patients may be increased due to alterations in the enzymatic apparatus involved in drug metabolism. Various studies have shown that the drugs that can most frequently cause hepatotoxicity are immunosuppressants, while mesalazine and biological drugs are, for the most part, less associated with such complications. Therefore, it is possible to assume that in the future, biological therapies could become the first line for the treatment of IBD.

A 59-year-old man who had been presenting with a variety of neuropsychiatric symptoms for several weeks. Despite repeated visits to somatic emergencies, as well as a thorough work-up including complementary examinations and specialist opinions, no organic diagnosis was established. The patient was treated symptomatically with neuroleptics and benzodiazepines, which led to a significant improvement in symptoms., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved., Methods: This study represents the in augural analysis of the placebo's influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835., Results and Discussion: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among "healthy" gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium , Blautia , and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pepoyan, Marotta, Manvelyan, Galstyan, Stepanyan, Grigoryan, Grigoryan, Mikayelyan, Balayan, Harutyunyan, Mirzabekyan, Tsaturyan, Torok and Pepoyan.)

Campylobacteriosis, a prevalent foodborne gastrointestinal infection in Europe, is primarily caused by Campylobacter jejuni and Campylobacter coli , with rising global concerns over antimicrobial resistance in these species. This study comprehensively investigates 133 human-origin Campylobacter spp. strains (102 C. jejuni and 31 C. coli ) collected in Italy from 2013 to 2021. The predominant Multilocus Sequence Typing Clonal complexes (CCs) were ST-21 CC and ST-206 CC in C. jejuni and ST-828 CC in C. coli . Ciprofloxacin and tetracycline resistance, mainly attributed to GyrA (T86I) mutation and tet (O) presence, were prevalent, while erythromycin resistance was associated with 23S rRNA gene mutation (A2075G), particularly in C. coli exhibiting multidrug-resistant pattern CipTE. Notable disparities in virulence factors among strains were observed, with C. jejuni exhibiting a higher abundance compared to C. coli . Notably, specific C. jejuni sequence types, including ST-21, ST-5018, and ST-1263, demonstrated significantly elevated counts of virulence genes. This finding underscores the significance of considering both the species and strain-level variations in virulence factor profiles, shedding light on potential differences in the pathogenicity and clinical outcomes associated with distinct C. jejuni lineages. Campylobacter spp. plasmids were classified into three groups comprising pVir-like and pTet-like plasmids families, exhibiting diversity among Campylobacter spp. The study underscores the importance of early detection through Whole Genome Sequencing to identify potential emergent virulence, resistance/virulence plasmids, and new antimicrobial resistance markers. This approach provides actionable public health data, supporting the development of robust surveillance programs in Italy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Garcia-Fernandez, Janowicz, Marotta, Napoleoni, Arena, Primavilla, Pitti, Romantini, Tomei, Garofolo and Villa.)

As we age, our organ functions gradually decline. Circulating factors in the blood and the integrity of organ barriers can become dysfunctional, resulting in a condition known as leaky syndrome. This condition involves the unregulated exchange or leakage of components between organs. However, the triggers of leaky syndrome, as well as its role in aging-related disorders and illnesses, remain largely unknown. In this editorial, we discuss potential mechanisms that originate from the gut and resident microbes (microbiome) to contribute in leaky syndrome. Furthermore, we explore how the food we consume can impact the development of leaky syndrome, potentially influencing the biology of aging and challenges to diagnose the leaky gut condition accurately and clinically., Competing Interests: None of the authors report any other conflicts of interest related to this work. Francesco Marotta is affiliated to ReGenera R&D International for Aging Intervention. Dr. Yadav is Co-founder and Chief Scientific Officer of Postbiotics Inc and Dr. Jain is founder of MusB LLC, but their roles have no conflict and influence with the work presented in this manuscript. Dr. Leila Haghshenas is affiliated to the Department of Clinical Bioinformatics, Postdoc Association Member of Harvard Medical School, Boston, MA USA., (© 2023 Jain et al.)

In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. We identified metabolites associated with higher or lower risk of HF incidence, the associations that were not confounded by the other metabolites, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. We revealed the underlying relationships of the findings. For example, asparagine directly influenced glycine, and both were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids which are not synthesized in the human body and come directly from the diet. Metabolites may play a critical role in linking genetic background and lifestyle factors to HF progression. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates a mechanistic understanding of HF progression.

Campylobacter is one of the most common foodborne diseases worldwide with increasing rates of antibiotic resistance. Most cases of campylobacteriosis can be traced back to the consumption of poultry meat. Despite many efforts to reduce contamination in farms and in slaughterhouses, the persistence of this pathogen in poultry products remains a problem. This study aimed to evaluate the genetic diversity and antibiotic resistance of 542 C. jejuni and C. coli in Italian poultry, in the framework of two National Monitoring Programs. Genomes were screened for antibiotic resistance, virulence determinants and contextualized within a global collection of C. jejuni . ST2116, ST2863 and ST 832 were the most prevalent and significantly associated with Italian poultry. A worrying increase in resistance to quinolones, fluoroquinolones and tetracycline was observed in C. jejuni , while an increased occurrence of multidrug resistant (MDR) strains and strains resistant to macrolides was detected in C. coli . Low resistance rates were found for aminoglycosides. Molecular resistance determinants were consistent with the phenotypic resistance for tetracycline and quinolones. In silico analysis revealed 119 genes associated with virulence factors, with a notably higher prevalence of some genes in ST2863 genomes. This study highlights the increased resistance to macrolides and the emergence of MDR strains for C. coli , the genetic basis of AMR and the predominance of two genotypes among Campylobacter strains isolated from the Italian poultry farms.

Senotherapy, a promising therapeutic strategy, has drawn a lot attention recently due to its potential for combating cancer. Senotherapy refers to the targeting of senescent cells to restore tissue homeostasis and mitigate the deleterious effects associated with senescence. Senolytic drugs represent a promising avenue in cancer treatment, with the potential to target and modulate senescent cells to improve patient outcomes. The review highlights the intricate interplay between the senescence-associated secretory phenotype (SASP) and the tumor microenvironment, emphasizing the role of senescent cells in promoting chronic inflammation, immune evasion, and tumor-cell proliferation. It then explores the potential of senotherapy as a novel strategy for cancer therapy. This review addresses the emerging evidence on the combination of senotherapy with conventional cancer treatments, such as chemotherapy and immunotherapy.

This study aimed to identify the oral microbial signature of Kazakh female rheumatoid arthritis (RA) patients. A total of 75 female patients who met the American College of Rheumatology 2010 classification criteria for RA and 114 healthy volunteers were included in the study. Amplicons of the 16S rRNA gene were sequenced to analyze the microbial composition. We identified significant differences in bacterial diversity and abundance between the RA and control groups, as measured by Shannon ( p value = 0.0205) and Simpson ( p value = 0.00152) indices. The oral samples from RA patients had higher bacterial diversity than those from non-RA volunteers. The RA samples had a higher relative abundance of Prevotellaceae and Leptotrichiaceae , but a lower content of butyrate and propionate-producing bacteria compared to the control group. The samples from patients in remission had a higher abundance of Treponema sp. and Absconditabacteriales (SR1), whereas those with low disease activity had higher levels of Porphyromonas and those with high RA activity had higher levels of Staphylococcus. A positive correlation was found between the taxa Prevotella&#95;9 and serum levels of antibodies to cyclic citrullinated peptide (ACPA) and rheumatoid factor (RF). The predicted functional pattern of the ACPA+/RF- and ACPA+/RF+ seropositive groups was characterized by increased ascorbate metabolism, degradation of glycosaminoglycans, and reduced biodegradation of xenobiotics. These findings suggest that the functional pattern of the microflora should be considered when selecting a therapeutic strategy for RA in order to provide a personalized approach.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.

A total of 193 wild boars hunted in Tuscany, an Italian region with a high presence of wild ungulates, were examined to assess the occurrence of Campylobacter species in faeces, bile, liver and carcasses, with the aim of clarifying their contribution to human infection through the food chain. Campylobacter spp. were found in 44.56% of the animals, 42.62% of the faecal samples, 18.18% of the carcass samples, 4.81% of the liver tissues and 1.97% of the bile samples. The Campylobacter species genotypically identified were C. coli , C. lanienae , C. jejuni and C. hyointestinalis . The prevalent species transpired to be C. coli and C. lanienae , which were isolated from all the matrices; C. jejuni was present in faeces and liver, while C. hyointestinalis only in faeces. Identification was carried out by matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS) on 66 out of 100 isolates identified genotypically, and the technique yielded unsatisfactory results in the case of C. lanienae , which is responsible for sporadic human disease cases. The level of Campylobacter spp. contamination of meat and liver underlines the need to provide appropriate food safety information to hunters and consumers.

The liver is exposed to several harmful substances that bear the potential to cause excessive liver damage ranging from hepatitis and non-alcoholic fatty liver disease to extreme cases of liver cirrhosis and hepatocellular carcinoma. Liver ailments have been effectively treated from very old times with Chinese medicinal herbal formulations and later also applied by controlled trials in Japan. However, these traditional practices have been hardly well characterized in the past till in the last decades when more qualified studies have been carried out. Modern advances have given rise to specific molecular targets which are specifically good candidates for affecting the intricate mechanisms that play a role at the molecular level. These therapeutic regimens that mainly affect the progression of the disease by inhibiting the gene expression levels or by blocking essential molecular pathways or releasing cytokines may prove to play a vital role in minimizing the tissue damage. This review, therefore, tries to throw light upon the variation in the therapies for the treatment of benign and malignant liver disease from ancient times to the current date. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of benign chronic liver diseases as well as prevention and treatment of HCC is still warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Successful management of surgery in severe coagulation disorders depends on adequate replacement of the deficient factors from intervention until wound healing. Extended half-life (EHL) recombinant factor IX (rFIX) has been increasingly used in hemophilia B (HB) patients. Monitoring of blood levels of EHL rFIX allows to obtain pharmacokinetic (PK) parameters in order to optimize and personalize therapeutic scheme. We describe a case of a young male with severe HB who successfully underwent aortic valve repair. This is the first reported open-heart surgery in a patient with severe HB using EHL rFIX. The success was based on accurate PK evaluation and on meticulous preoperative planning and close cooperation among surgeons, hemophilia specialists, and laboratory team despite the long distance between hemophilia center and surgical clinic., (© 2023 S. Karger AG, Basel.)

Background: Nonalcoholic Fatty Liver Disease (NAFLD) is a widespread disease in the western world. It can develop into more serious pathological conditions (i.e. liver cirrhosis). Therefore, it is important to diagnose it in order to prevent this evolution. For diagnosis it is possible to use both imaging methods and biomarkers, such as the Triglycerides To High-Density Lipoprotein Cholesterol Ratio (TG/HDL-C). Aim of our study is to determine whether TG/HDL-C ratio is significantly associated with NAFLD and Metabolic Syndrome (MetS)., Methods: We recruited 231 patients, 131 with and 100 without NAFLD. The Body Mass Index had been calculated and different laboratory parameters had been obtained. TG/HDL-C ratio was calculated for each., Results: In our sample HDL-C was not significantly reduced in NAFLD group (P=0.49), but higher TG and TG/HDL-C ratio were significantly associated with NAFLD: in both P<0.001. According to receiver operating characteristic curve, the best cut-off of TG/HDL-C in NAFLD population was 1.64 (area under the curve [AUC] 0.675 [95% CI 0.604-0.746], P<0.001). TG/HDL-C higher ratio was significantly associated with MetS (P<0.001). The best cut-off of TG/HDL-C in patients with MetS was 2.48 (AUC 0.871 [95% CI 0.808-0.935], P<0.001)., Conclusions: We demonstrated that higher TG/HDL-C ratio is associated with NAFLD and MetS. Though nowadays TG/HDL-C ratio is not a criteria for NAFLD diagnosis, we believe that in the future it could be used as a reliable non-invasive marker in routine diagnostics of NAFLD.

The present study assessed the modulation of cecal microbiota and correlations with Campylobacter colonization and animal welfare status. For these purposes, we conducted a cross sectional study of the cecal microbiota from 187 broilers reared in 13 batches from 10 poultry farms by performing 16S rRNA sequencing (regions V3-4). The welfare of each batch was assessed using a simplified Welfare Quality® protocol, scoring higher in organic batches, compared to both antibiotic-free and conventional batches. The bioinformatics analyses were conducted in QIIME 2 and a linear discriminant analysis determined the association between microbiota and animals with different Campylobacter carriage status and welfare levels. In the microbiota from the subjects negative for Campylobacter or with high welfare scores, Bacteroidetes was the predominant phylum with the genus Megamonas significantly increased in abundance. A greater abundance of Parabacteroides, Phascolarctobacterium, Helicobacter in poultry negative for Campylobacter was also found at the genus level. Animals with the lowest welfare scores showed an increased abundance of Proteobacteria. The results suggested a different microbial composition and diversity in the analyzed groups., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)