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.

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.

Actually, the study aimed to manage and to analyse the results of the laboratory methods, using liver samples, preparing and analizing in pathology service. This mentioned, are known as routinally practice for hepatitis C diagnosis, which conduct to hepatic cirrhosis. In this study direction, chronic liver diseases stimulate a degree of hepatocyte injury. So previously mentioned modifications, alters thet affect the liver architecture and finally ends in cirrhosis are well analyse on microscopic preparates. Folowing morphological steps, it is possible to analyse normal and alterate liver structure, on colored preparates.

The study aimed to manage and to analyse the results of the laboratory tests, routinallypractice for hepatitis C diagnosis, using blood tests. Statistical analysis of this study results, was performed using the laboratory informatic system. The results of the study are substantial and intricate reffering to comparision between two methods concretlly ELISA method (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods and their results. Good to know our opinion that RT-PCR technique, it is considered proper for the diagnosis of HCV ( Hepatitis C virus).

Objectives: To compare the volumes and shapes of the coagulation zone (CZ) of a multi-probe RFA system (three RFA electrodes) and a single-probe MWA system from the same vendor in an ex-vivo bovine liver model. Material & Methods: A total of 48 CZs were obtained in bovine liver specimens with three different ablation system configurations (single-probe MWA vs. multi-probe RFA with 20 mm inter-probe distance [confluent CZ] vs. multi-probe RFA with 50 mm inter-probe distance [three individual CZ]) at 4-, 6-, 8-, and 10-min ablation time using a fixed ablation protocol. Ablation diameters were measured and ellipticity indices (EI) and volumes calculated. Calculations for all systems/configurations were compared. Results: Volumes and diameters increased with ablation time for all configurations. At 4- and 6-min ablation time volumes obtained with the RFA 50 mm setup, and at 8 and 10 min with the RFA 20 mm setup were the largest with 26.5 ± 4.1 mL, 38.1 ± 5.8 mL, 46.3 ± 4.9 mL, 48.4 ± 7.3 mL, respectively. The single-probe MWA could not reach the volumes of the RFA setups for any of the ablation times evaluated. EI were very similar and almost round for RFA 20 mm and single-probe MWA and differed significantly to the more ovoid ones for the RFA 50 mm configuration. Conclusion: The multi-probe RFA system employing three electrodes achieved significantly larger ablation volumes in both configurations (confluent CZ and three individual CZ) per time as compared to a single-probe MWA system in this ex-vivo bovine liver model.

Ascites is a term that describes a pathological accumulation of fluid in a peritoneal cavity. It is generally a rare occurrence in a pediatric population and is most commonly associated with liver failure and cirrhosis. In that case, a diuretic treatment is usually implemented to relieve the ascites as it forms in the mechanism of water retention and water leakage from the portal venous system due to portal hypertension. It is important to note however that many other issues may cause ascites in children. Those require a catered approach suited to the pathomechanism of ascites formation in those underlying conditions. That is why a complex diagnostic process ought to be run in pediatric patients with ascites to correctly identify a condition causing it and provide the patient with adequate and thorough care.

Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue, characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives The aim of study was to assess hepatic fibrosis and steatosis in SSc patients by transient elastography (TE). Methods Fifty-nine SSc patients, satisfying the 2013 ACR/EULAR classification criteria, were recruited. Clinical and laboratory findings, modified Rodnan skin score (mRSS), ac-tivity index, video-capillaroscopy, echocardiography, and lung function data were ana-lyzed. Liver stiffness (LS) was measured by transient elastography (TE), with 7 kPa used as the cut-off value for significant liver fibrosis and steatosis. Specifically, values ≥ 238 CAP ≤ 259 dB/m were considered consistent with mild steatosis (S1), 260 ≥ CAP ≤ 290 dB/m with moderate steatosis (S2) and ≥291 dB/m with severe steatosis (S3) Results The median age of patients was 51 years, with a median disease duration of 6 years. Median LS was 4.5 (2.9–8.3) kPa; 41 patients (69.5%) had no evidence of fibrosis (F=0), 16 (27.1%) displayed LS values between 5.2 and 7 kPa; only 2 patients (3.4%) had LS values >7 kPa (F3). The median CAP value for liver steatosis was 223 dB/m (IQR: 164–343). Overall, 39 patients (66.1%) did not show evidence of steatosis (CAP values <238 dB/m); 9 patients (15.2%) showed values consistent with mild (S1) steatosis (CAP value ≥238 ≤259 dB/m); 8 patients (13.5%) had moderate (S2) steatosis (CAP value ≥260 ≤290 dB/m); 3 patients (5.1%) were deemed to have severe steatosis (S3) due to CAP values ≥291 dB/m. Conclusions Only 3.4% of our patient population showed evidence of marked liver fibrosis, which is the same prevalence as that expected in the general population. Likewise, the prevalence of significant steatosis was low (5.1%) and depending on the same variables associated with fatty liver in the general population. TE was shown to be an easy and valuable method for detection and screening of liver fibrosis in SSc patients with no additional risk factors for liver disease.

Liver cancers give rise to a heavy burden of health care worldwide. Understanding the tumour microenvironment (TME) underpins the development of precision therapy. Single-cell RNA sequencing (scRNA-seq) technology has generated high-quality cell atlases of the TME, but its wider application faces enormous costs for various clinical circumstances. Fortunately, a variety of deconvolution algorithms can instead repurpose bulk RNA-seq data, alleviating the need for generating scRNA-seq datasets. In this study, we reviewed major public omics databases for relevance in this study and utilized 8 RNA-seq and 1 microarray datasets from clinical studies. To decipher the TME of liver cancer, we estimated the fractions of liver cell components by deconvoluting the samples with Cibersortx using three reference scRNA-seq atlases. We also confirmed that Cibersortx can accurately deconvolute cell types/subtypes of interest. Compared with non-tumorous liver, liver cancers showed multiple decreased cell types forming normal liver microarchitecture, as well as elevated cell types involved in fibrogenesis, abnormal angiogenesis and disturbed immune responses. Survival analysis shows that the fractions of five cell types/subtypes significantly correlated with patient outcomes, indicating potential therapeutic targets. Therefore, deconvolution of bulk RNA-seq data with scRNA-seq atlas references can be a useful tool to help understand the TME.

Fenugreek seeds are widely used in Asia and other places of the world for their nutritive and medicinal properties. In Asia, Fenugreek seeds are also widely recommended for the geriatric populations. Here, we evaluated for the first time the effect of fenugreek seed feed supplementation on the liver antioxidant defense systems in aging mice. The study was conducted on 12 months aged mice which were given fenugreek seed dietary supplement. We have evaluated the activities of various antioxidant defense enzymes like superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and estimated the phenolics and free radical scavenging properties in mice liver upon fenugreek supplementation. The estimation of SOD, GPx and GR activities in aged mice liver revealed a significant (P<0.01) difference among all the liver enzymes. Overall, this study reveals that fenugreek seed dietary supplementation has a positive effect in on the activities of the hepatic antioxidant defense enzymes in the aged mice.

COVID-19 breakout in Italy has caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection very few information are available about liver involvement in COVID-19 infection, that could possibly evocate a systemic disease targeting a lot of organs. Since now there are no reports of large series of histological evaluation of liver morphology in this setting. Knowledge of histological liver findings connected to clinical data is crucial in management of this disease.Post-mortem wedge liver biopsies from 48 patients died for COVID-19 infection were available from two main hospitals located in northern Italy, Lombardy; all sample were obtained during autopsies. No patient has a significant clinical complain of liver disease or signs of liver failure before and during hospitalization; for each of them laboratory data focused on liver were available. All liver samples showed minimal inflammation features; on the other side, many histological pictures compatible with vascular alterations were observed, characterized by portal vein braches number increase associated with lumen massive dilatation, partial or complete recent luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally severely enlarged and fibrotic. Our preliminary results concerning histological liver involvement in COVID-19 infection confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage; histopatological findings are highly suggestive for marked alteration of intrahepatic blood vessel network secondary to systemic alterations induced by virus that could target, besides lung parenchyma, cardiovascular system, coagulation cascade or endothelial layer of blood vessels.

The body of evidence available in paediatrics population is limited for making clinical decisions regarding pharmacotherapy optimization of tacrolimus. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in paediatric population. This was a longitudinal cohort study, with two-year follow-up of 77 patients under 18 who had liver transplant over the period 2009-2012 at the Paediatric Hospital J. P Garrahan. Tacrolimus levels from day 5 to 2-year post-transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) were performed in liver biopsies of both the donor and the recipient. Recipients frequency of CYP3A5 *1 expression was 37.1% and 32.2% for Donors. Patient who received an organ expresser showed lower Co/dose especially after 90 days post-surgery. The role of each polymorphism is different according to days after transplantation proceeds and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phase.

Introduction: Liver cirrhosis develops in about 10% of alcohol abusers. To date, a number of cells and cytokines have been identified, which are involved in induction of liver fibrotic processes. Nevertheless, the pathogenesis of liver cirrhosis has not been fully elucidated. The aim of the present study was to determine serum concentrations of afamin and adropin in patients with alcoholic liver cirrhosis and to define their correlation with the stage of disease. Materials and methods: The study included 99 patients with alcoholic cirrhosis from the region of Lublin, (Eastern Poland). Liver cirrhosis was diagnosed based on clinical features, history of heavy alcohol consumption, laboratory tests and abdominal ultrasonography. The control group consisted of 20 healthy individuals without liver disease who did not abuse alcohol. The serum afamin and adropin concentrations were determined using ELISA kits. Results: The concentration of afamin was found to be significantly lower in patients with compensated alcoholic liver cirrhosis, i.e. P-Ch B (85.1±40.6 μg/ml) and P-Ch C (56.4±32.3 μg/ml) individuals, as compared to the control group (135.9±43.6 μg/ml); p-value was <0.01 and <0.001, respectively. As far as adropin is concerned, a reverse relationship was demonstrated: the highest concentration was found in patients with P-Ch C (11.7±5.7 ng/ml) cirrhosis. Furthermore, the above concentration was significantly higher compared to patients with P-Ch A cirrhosis (7.2±2.8 ng/ml; p<0.05) and controls (7.5±2.6 ng/ml; p<0.05). Conclusions: The concentration of afamin decreases with the severity of alcoholic liver cirrhosis, which most likely results from impaired hepatic synthesis. Otherwise, the higher the stage of disease according to the Child-Pugh score, the higher the concentration of adropin.

Liver is structurally organized into zonation where LSECs endothelial cells play a crucial role during chronic liver injury and early stages of fibrosis. Fibrosis can be reversed if diagnosed early at molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in normal and diseased fibrotic human liver. DEG analysis is performed over LSECs and identified the top 20 expressed genes in periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells figured out OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, CTSL genes as expressed in DILI and NASH ECs populations. The connection between LSECs marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases.

Background Total serum bile acids (TSBA), liver-spleen scan and dynamic liver functional tests, in our case the antipyrine clearance (Ap Cl), have been long adopted. The aim of our study was that of assessing whether some diagnostic tests, scarcely performed due to the novel techniques implementation, were reliable diagnostic tools. Methods Data extracted from records of two well-matched for age and gender populations was retrospectively analysed. Specifically, 17 patients with biopsy-proven chronic hepatitis were confronted with 17 subjects suffering from liver cirrhosis. Clinical, laboratory and instrumental findings, such as the Child-Pugh classification, the number connection test for evaluating hepatic encephalopathy, prothrombin time, serum albumin levels, TSBA concentration, Ap Cl determination, abdominal ultrasound and liver-spleen scan imaging as well as endoscopy features were evaluated. Results Cirrhotics showed a median concentration of TSBA increased respect to that of patients with chronic hepatitis, independently from gender, 20.1 versus 12.24 micromol/L, P= 0.0054. The median AP Cl value of the patients with liver cirrhosis was reduced confronted with that of patients with chronic hepatitis, specifically, 13.92 opposed to 18.3 mcg Ap/dL, P= 0.045. Furthermore, the median liver-spleen scan score was higher in cirrhotics than in chronic hepatitis patients, i.e., 3.47 versus 1.47, P= 0.000. The AUROCs of TSBA levels and of the liver-spleen scan scores for differentiating patients with liver cirrhosis from those with chronic hepatitis were 0.82 and 0.96, respectively. When was applied a new predictive model, combining the previous ones, the AUROC to discriminate patients belonging to the two populations was 0.98. The best cut-off of the new index was 26, with a sensitivity and specificity of 100.00% and 82.35%, respectively, correctly classifying 91.18% of the patients. Discussion Both TSBA and liver-spleen scan were high discriminant as well as their combination, while Ap Cl showed some limitations as reliable diagnostic tool. TSBA and liver-spleen scan have been too soon and unnecessarily overlooked.

AIM Non-alcoholic　fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of the pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. METHODS One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. RESULTS Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not change significantly, but M2-BPGi, an index of fibrosis, decreased significantly. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

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.

Blisks subjected to rough machining for channel creation must undergo finishing processes, and such processes must achieve the required tolerance limits. A high-quality surface finish and predictable long tool life are critical for the finish milling of blisks. Accordingly, the aim of this study was to optimize parameters for the finish machining of an Inconel 718 alloy monolithic blisk. Ball-cone mills were used to machine the blade surface at a constant depth. A sensory tool holder was used to collect cutting force signals during machining, and a digital microscope was used to examine tool wear. The surface texture measuring instrument was used to measure blisk blade surface roughness to evaluate processing quality. This study manipulated two cutting parameters, namely cutting speed and feed per tooth, and investigated their effects. The relationship between cutting conditions and machining efficiency was analyzed. According to the experimental results, we identified a set of optimal parameters for marginal tool wear and fast cutting speeds and then estimated the corresponding tool life by using the derived parameters.

The described data set contains features from the machine control of a five-axis milling machine. The features were recorded during thirteen series productions. Each series production includes a changeover process in which the machine was set up for the production of a different product. In addition to the timestamps and the twenty recorded features derived from Numerical Control (NC) control variables, the data set also contains labels for the different production phases. For this purpose, up to 23 phases were assigned, which are based on a generalized milling process. The data set consists of thirteen .csv files, each representing a series production. The data set was recorded in a production company in the contract manufacturing sector for components with real series orders in ongoing industrial production.

A 57-year-old male with a history of hyperlipidemia and mild pulmonary hypertension presented for a left inguinal hernia repair. Preoperative electrocardiogram showed severe right axis deviation at 177 degrees and abnormal repolarization. Right ventricular hypertrophy secondary to pulmonary hypertension was the primary differential but was quickly ruled out due to the patient being asymptomatic and having great exercise tolerance. Dextrocardia was also ruled out due to normal progression on the precordial leads. The simultaneous severe right axis deviations of P, R, and T waves raised suspicion for erroneous lead placement. The repeat electrocardiogram confirmed the diagnosis.

Koalas (Phascolarctos cinereus) are one of Australia's most charismatic native small marsupial species. Unfortunately, populations of koalas are rapidly declining throughout Australia and they continue to face increasing pressure from a changing ecosystem. Negative stimulants in the environment can elicit stress responses through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Depending on the duration of the negative stimulant, the stress response can lead to either acute or chronic side effects, and is shown through the activation of the neuroendocrine stress system and the release of glucocorticoids (e.g., cortisol). Wild koalas entering clinical care face novel stressors that can be out of a wildlife carer's control. In this pilot study, we monitored physiological stress in three wild koalas at a wildlife rehabilitation centre in New South Wales, Australia. Acute and chronic stress was indexed non-invasively, with faecal samples taken to evaluate acute stress, and fur samples taken to evaluate chronic stress. Sampling occurred sporadically over four months, from the start of September 2018 to the end of December 2018. Results attempt to understand the stress response of koalas to negative stimulants in the environment by comparing faecal glucocorticoids on days where a known stressor was recorded with days where no known stressor was recorded. Furthermore, variations in faecal and fur glucocorticoids were compared between the three koalas in this study. To our knowledge, this is the first evidence of stress tracking of wild rescued koalas in a sanctuary. We suggest that further monitoring of baseline, acute and chronic stress will be needed to better understand how koalas respond to negative stimulants associated with clinical care.

The global energy crisis has lead researchers explore other sources of energy like wind, resulting in a wide acceptance of wind turbines. Vertical axis wind turbines (VAWT) more suitable for small scale application in urban conditions than their horizontal-axis counterparts. A Helical bladed VAWT would reduce the ripple effect when compared to Straight bladed VAWT. The effect of the blade helix angle on the aerodynamic performance of VAWT using 3D numerical simulations is studied. Turbulence modelled using 4-Equation transition SST k-w model. Three different helix angles of 60, 90 and 120 of a 3 bladed VAWT operating across different tip speed ratios were studied. The 60 helical bladed VAWT was found to perform better than all other helical bladed and straight bladed VAWT. Standard deviation of the moment coefficient generated by a blade plotted against 360 of azimuth rotation revealed that the ripple effect on the shaft produced by cyclic loading of the straight blade is considerably reduced upon introduction of helix angle, with 120 helical blade giving lowest standard deviation. The analysis has been done for the percentage of power generated by each quartile of flow and the contribution of each section of the blade. A comparative study was also conducted between different helical bladed VAWT and straight bladed VAWT. Flow feature analysis also revealed the reasons behind secondary peaks and the performance improvement when tip speed ratio increases. Wake structure analysis and flow contours were also studied for a better understanding of the flow field.

Liver is structurally organized into zonation where LSECs endothelial cells play a crucial role during chronic liver injury and early stages of fibrosis. Fibrosis can be reversed if diagnosed early at molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in normal and diseased fibrotic human liver. DGE analysis is performed over LSECs and identified the top 20 expressed genes in periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells figured out OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, CTSL genes as expressed in DILI and NASH ECs populations. The connection between LSECs marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases.

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. Because of organ shortages this treatment can only be applied to carefully selected patients according to clinical guidelines to minimize risk of recurrence. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging like radiology. With the help of these technologies laborious tasks like segmentation can be automated and workflow in radiology departments can be improved. Other roles include in depth pixel-wise analysis of lesions by radiomics or deep learning in order to find new imaging criteria that allow better prediction of treatment response or risk of recurrence. Liver transplant is an ideal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease and artificial intelligence could provide solutions for improving the management of liver transplant candidates to improve survival.

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.

Abstract: Role of gut microbiome in human health is becoming apparent. The major functional impact of gut microbiome is transmitted through the microbial metabolites that are produced in the gut and interact with host cells either in the local gut environment or get absorbed in the circulation to impact distant cells/organs. Short chain fatty acids (SCFAs) are the major microbial metabolites that are produced in the gut through fermentation of non-digestible fibers. SCFAs are known to function through various mechanism, however, their signaling through free-fatty acid receptor 2 and 3 (FFAR2/3; type of G-coupled protein receptors) is new therapeutic approach. FFAR2/3 are widely expression in diverse cell types in human and mice, and functions as sensors of SCFAs to change several physiological and cellular functions. FFAR2/3 modulates neurological signaling, energy metabolism, intestinal cellular homeostasis, immune response and hormone synthesis. FFAR2/3 functions through Gi and/or Gq signaling, that is mediated through specific structural features of SCFAs-FFAR2/3 bindings and modulating specific signaling pathway. In this review, we discussed the wide-spread expression and structural homologies between human and mice FFAR2/3, and their role in different human health conditions. This information can unlock opportunities to weigh the potential of FFAR2/3 as drug target to prevent human diseases.

Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, we speculate that the genetic makeup of CeD patients could elicit disease development through alterations in the intestinal microbiota. To evaluate potential causal relationships between gut microbiota and CeD, we performed a Two-Sample Mendelian Randomization analysis (2SMR). Exposure data were obtained from the raw results of a previous Genome Wide Association Study (GWAS) of gut microbiota, and outcome data from summary statistics of CeD GWAS and Immunochip studies. We have identified a number of putative associations between gut microbiota SNPs associated with CeD. Regarding bacterial composition, most of the associated SNPs are related to Firmicutes phylum, whose relative abundance has been previously reported to be altered in CeD patients. In terms of functional units, we have linked a number of SNPs to several bacterial metabolic pathways that seem to be related to CeD. Overall, this study represents the first 2SMR approach to elucidate the relationship between microbiome and CeD.

The tissue micro environment or milieu consists of a highly dynamic population of cellular and non-cellular components which constitute a complex regulatory network aimed at maintaining the organ homeostasis. In the modern medicine the discovery of miRNAs is undoubtedly a promising field of research and they are essential in orchestrating immune system logic and their release in the gut micro milieu can directly affect bacterial gene expression. Here, we briefly review the role of microRNAs, focuses on their role on immune system components in physiological and pathophysiological gut micro milieu.

It is of merit to study the appropriate amount of fiber to add to free-range chickens feed to improve the microbial diversity and gut health in times of plant fiber deprivation. OptiCell is a useful source of fiber as a type of eubiotic lignocellulose, and its positive effects on the growth performance and laying performance of chickens has already been proven. However, few researchers have researched the effects of adding OptiCell on the gut microbiota of chickens. In this research we added three different levels of OptiCell (0%, 2% and 4%) to the feed of caged and free-range Bian chickens from September to November, aiming to observe the effects of adding OptiCell and different feeding modes on the gut microbial diversity and gut health of chickens, and aiming to determine an appropriate amount of OptiCell. The results showed that adding OptiCell could increase the thickness of the cecum mucus layer and the abundance of Akkermansia and Faecalibacterium in caged chickens, and 4% OptiCell was optimum. In addition, adding OptiCell increased the microbial diversity and the abundance of the butyrate-producing bacteria Faecalibacterium and Roseburia of fee-range chickens. The α-diversity and the length of the small intestine with 2% OptiCell in free-range chickens were better than with 2% OptiCell in caged chickens. In addition, compared with caged chickens, the free-range chickens had longer small intestine and lower GLP-1. Taken together, an appropriate amount of OptiCell benefitted the microbial diversity and health of chickens; it was necessary to add dietary fiber to the feed of free-range chickens when plant fibers was lacking, and 2% OptiCell was found to be optimum.

Background The distinctive feature of liver fibrosis is the progressive replacement of healthy hepatic cells by extracellular matrix protein, which is abundant in collagen I and III with impaired matrix remodelling. The activation of myofibroblastic cells enhances a fibrogenic response of complex interactions of hepatic stellate cells, fibroblasts and inflammatory cells to produce excessive deposition of extracellular protein matrix. This process is activated by multiple fibrogenic mediators and cytokines such as TNF-α and IL-1ß with decrease in the anti-fibrogenic factor NF-ҡß. Mesenchymal stem cells (MSCs) represent a promising therapy for liver fibrosis giving more advanced regenerative influence when cultured with extrinsic or intrinsic proliferative factors, cytokines, anti-oxidants, growth factors, and hormones such as Melatonin (MT). However, previous studies showed conflicted findings concerning the therapeutic effects of adipose (AD) and bone marrow (BM)-MSCs, therefore, the present work aimed to accomplish a comparative and comprehensive study investigating the impact of MT pre-treatment on the immunomodulatory, anti-inflammatory and anti-apoptotic effects of AD and BM-MSCs and to critically analyse whether MT pre-treated both AD-MSCs and BM-MSCs reveal equal or different therapeutic and regenerative potentials in CCl4-injured liver of experimental rat models. Materials and methods Six groups of experimental rats were used with ten rats in each group; group I (control group), group II (CCl4-treated group), group III (CCl4 and BM-MSCs treated group), group IV (CCl4 and MT pre-treated BM-MSCs group), group V (CCl4 and AD-MSCs treated group) and group VI (CCl4 and MT pre-treated AD-MSCs group). Liver function tests, gene expression of inflammatory, fibrogenic, apoptotic and proliferative factors were analysed. Histological and immunohistochemical changes were assessed. Results The present study compared the capability of AD and BM-MSCs, with and without the pre-treatment of MT, to reduce hepatic fibrosis. Both types of MSCs improved hepatocyte function by reducing the serum levels of (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and total bilirubin (TBIL). In addition, the changes in the hepatocellular architecture including the hepatocytes, liver sinusoids, central veins, portal veins, biliary ducts and hepatic arteries showed decrease hepatocyte injury and cholestasis with reduction of inflammation, apoptosis and necrosis of the hepatic cells together with inhibition of liver tissue fibrosis. These results were augmented by the analysis of the expression of the anti-inflammatory cytokines TNFα and IL-1β, the anti-fibrogenic factor NF-ҡß, the apoptotic factor caspase-3 and the proliferative indicators antigen Ki-67 and proliferating cell nuclear antigen (PCNA). These findings were found statistically significant, with the best results in the rats received AD-MSCs pre-treated with MT, denoting better regenerative and therapeutic effects. Conclusion AD-MSCs, pre-treated with MT, are superior to BM-MSCs due to their better efficacy in improving hepatic fibrosis and promoting the therapeutic and regenerative capability of liver tissue. They represent a very significant tool for future stem cell use in tissue regeneration strategy for the treatment of liver diseases.

Background and Aims: The present study analyzed retrospectively the association between socioeconomic deprivation and graft and patient survival in a cohort of 2,568 adult recipients of a liver transplant between 1996 and 2022. Materials and methods: The primary exposure was a nationally validated socioeconomic deprivation index (DI) at census block level and ranking from 1-5, with higher ranks indicating more significant socioeconomic deprivation. Results: At a median (IQR) follow-up of 144.8 (204) months, the overall patient and graft survival rates were 92% and 90.4% at 1 year, 78.4% and 72.2% at 5 years, and 58% and 56.7% at 10 years. Recipients with a DI rank above the median (i.e., more deprived) had 1, 5, and 10-year patient and graft survival rates of 91% and 89.5%, 70.4% and 68.4%, 48% and 46.7%, respectively, versus 92% and 90.4%, 78.4% and 72.2%, and 58% and 56.7% for less deprived patients (log-rank p<0.001). More deprived patients had a higher risk of death (p<0.0001), hypertension (p<0.0001), obesity (p=0.02), diabetes mellitus (p=0.02), graft rejection (p<0.0001), chronic kidney dysfunction (p<0.0001), major cardiovascular events (p<0.0001) and de novo malignancies (p<0.0001) than less deprived recipients. The factors associated with the survival probability were younger donor and recipient ages (p=0.03 and 0.02, respectively), female recipient sex (p=0.04), absence of HCV (p<0.01), absence of HCC (p=0.02), absence of DM at transplantation (p=0.03) and 1 year (p=0.01), lower DI (p=0.02), lower MELD (0.02), shorter CIT (p=0.03), TAC (p=0.01), and EVR in the immunosuppressive regimen (p=0.02). Conclusions: Patients from more deprived areas have a higher risk of death after liver transplantation. Pre- and post-transplant socioeconomic risk profiling is warranted to better tailor care to patient’s needs and expectations.

Objective: To investigate the efficacy of a magnetic resonance imaging (MRI) radiomics model in predicting colorectal cancer liver metastasis (CRLM). Methods: A total of 120 patients who underwent baseline MRI examination at the Affiliated Hospital of North Sichuan Medical College from June 2016 to August 2022 and were pathologically confirmed to have colorectal cancer (CRC) were randomly divided into a training group and a validation group. The clinical risk factors and MRI data of all patients were collected. Univariate and multivariate analysis were used to screen the clinically independent risk factors for CRLM. The radiomic features of each sequence were extracted from oblique axial or axial fat-free T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the optimal radiomic features of each sequence. Logistic regression was used to establish a prediction model of each sequence (T2WI and DWI models), a combined radiomics model (M) integrating the features of T2WI and DWI sequences, and a combined imaging-clinical model (U) combining the radiomic features of each sequence with clinically independent risk factors. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the predictive performance of each model. Results: Among the 120 CRC patients enrolled, 57 had liver metastasis, and 63 did not. The tumor markers carcinoembryonic antigen and carbohydrate antigen 19-9 were clinically independent risk factors for CRLM. Three optimal radiomic features were screened from T2WI and DWI sequences through LASSO regression analysis, respectively. The AUC values of the T2WI, DWI, M, and U models were 0.811, 0.803, 0.824, and 0.899 in the training group and 0.795, 0.798, 0.813, and 0.889 in the validation group, respectively. The predictive performance of the combined models was better than that of the single-sequence models. The U model performed best at predicting CRLM. Conclusion: An MRI radiomics model based on CRC primary lesions can predict CRLM well. Our combined model integrating the radiomic features of each sequence and clinically independent risk factors had the best predictive performance.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD), is a widespread global health concern that affects around 25% of the global population. Its influence is expanding, and it is anticipated to overtake alcohol as the leading cause of liver failure and liver-related death worldwide. Unfortunately, there are no approved therapies for MASLD; as such, national and international regulatory health agencies undertook strategies and action plans designed to expedite the development of drugs for treatment of MASLD. A sedentary lifestyle and an unhealthy diet intake are important risk factors. Western countries have a greater estimated prevalence of MASLD partly due to lifestyle habits. Mitochondrial dysfunction is strongly linked to the development of MASLD. Further, it has been speculated that mitophagy, a type of mitochondrial quality control, may be impaired in MASLD. Thyroid hormone (TH) coordinates signals from the nuclear and mitochondrial genomes to control mitochondrial biogenesis and function in hepatocytes. Mitochondria are known TH targets and preclinical and clinical studies suggest that TH, thyroid receptor β (TR-β) analogs, and synthetic analogs specific to liver could be of therapeutic benefit in treating MASLD. In this review, we highlight how mitochondrial dysfunction contributes to development of MASLD, and how understanding the role of TH in improving mitochondrial function paved the way for innovative drug development programs of TH-based therapies targeting MASLD.

Background: Alcohol-associated Liver Disease (ALD) is the most common disorder of prolonged drinking. Mechanisms underlying cirrhosis in such patients remain unclear. MicroRNAs play regulatory role in several diseases, are affected by alcohol and may be important players in alcohol use disorders, such as cirrhosis. Methods: We investigated serum samples from heavy chronic alcohol users (80g/d (M) and 50g/d (F) for ≥10 years) that were available from our previously reported GenomALC study. A subset of drinkers with liver cirrhosis (cases, n=24) and those without significant liver disease (controls, n=23) were included. Healthy controls (HC, n=5) were volunteers in the study. Global microRNA profiling was performed using high-throughput real-time quantitative PCR to identify the microRNA signatures. Ingenuity Pathway Analysis software (IPA) was utilized to identify target mRNAs of significantly altered microRNAs and molecular pathways were analysed. Identified microRNAs were analysed for correlation with traditional liver disease biomarkers and risk gene variants previously reported from GenomALC genome-wide association study. Results: The expression of 81 and 21 microRNAs was significantly downregulated in cases compared to HC and controls, respectively (p<0.05, Ct >1.5-fold). Most microRNAs showed lower abundance in alcohol users compared with HC. Seven microRNAs (miR-16, miR-19a, miR-27a, miR-29b, miR-101, miR-130a, & miR-191) had a highly significant correlation (p<0.001) with INR, bilirubin and MELD score. Three microRNAs (miR-27a, miR-130a and miR-191) significantly predicted cases with AUC-ROC 0.8, 0.78 and 0.85, respectively (P<0.020), however, INR performed best (0.97, p<0.001). A different set of 6 microRNAs (miR-19a, miR-26a, miR-101, miR-151-3p, miR-221, & miR-301) showed positive correlation (ranging 0.32-0.51, p<0.05) with rs10433937:HSD17B13 gene variant, associated with risk of cirrhosis. IPA analysis revealed mRNA targets of the significantly altered microRNAs associated with cell death/necrosis, fibrosis and increased steatosis, particularly triglyceride metabolism related mRNA targets. Conclusions: MicroRNA signatures in drinkers distinguished those with liver cirrhosis from those without liver disease. We identified mRNA targets in liver functions that were enriched for disease pathogenesis pathways.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) to the liver. Although there are established criteria for LT in HCC, the evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.

Abstract Introduction Minimally invasive approaches to oncological liver resection is common in many hepatobiliary centres. This study aims to compare the key oncological and survival outcomes of patients with colorectal liver metastases (CRLM) undergoing laparoscopic or open resections using propensity score matching (PSM). Methods A single-centre retrospective study was performed using a prospective database of patients undergoing liver resection for CRLM between January 2016 and December 2019. Different co-variates were selected for matching using PSM. Pre-matching and post-matching analyses were compared. Surgical and survival outcomes were analysed. Results In total, 303 patients who met the inclusion criteria were identified: 214 underwent open liver resection (OLR) and 91 laparoscopic liver resection (LLR). LLR had a significantly reduced length of intensive treatment unit (ITU) and overall in-patient stay but longer pringle and operative times. In the unmatched cohort, the median overall and disease-free survival time was significantly longer in patients undergoing laparoscopic compared with open surgery. A PSM model demonstrated significantly reduced blood loss and length of hospital stay, with a significantly greater Pringle and operative time in the LLR group. Differences seen in overall and disease-free survival were lost with propensity score matching, possibly due to lack of bi-lobar disease within the minimally invasive group. Conclusion In selected patients with CRLM, LLR presents similar survival and oncological outcomes with the advantages of the short-term results associated with the laparoscopic approach.

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multi-targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia–reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 hours of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cyto-kines, oxidative stress, gene expression of apoptosis-related genes, TNF-alpha and Caspase 3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the Caspase 3 protein and a reduction in the TNF-alpha protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes and their combination represent a promising therapeutic proposal against liver IRI.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

Siam weed, scientifically known as Chromolaena odorata and belonging to the Asteraceae family, is a fast-growing plant with prolific seed production. Although it is a traditional medicinal plant, it has become an agricultural weed in Africa and Asia, posing a threat to biodiversity and causing environmental damage. Despite this, C. odorata is highly regarded as a medicinal herb in tropical Africa, with anticancer effects on breast, liver, and colorectal cancer. However, it is important to regulate the intake of the plant extract as it can have a hepatotoxic effect on liver cells at higher doses. Further research needs to be conducted on the plant extract, and proper orientation and knowledge of its oral daily administration are necessary. This review summarizes current scientific investigations using ethanolic and methanolic aqueous extracts of C. odorata leaves on various cancer cells, to uncover its potential as an anticancer agent. The investigations were sourced from online databases like Google Scholar, PubMed, and other online-based journals.

Nonalcoholic steatohepatitis (NASH), which is characterized by liver steatosis, inflammation and fibrosis, is the most severe variation of nonalcoholic fatty liver disease (NAFLD). This disease is a consequence of several metabolic alterations such as type 2 diabetes and dyslipidemia that trigger different pathways of cell dysfunction and systemic inflammation which ultimately affect the liver. Furthermore, those mechanisms activate a complex cascade of immune response after repeated cell aggression. In the liver cytokines and interleukins interact with network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), lymphocytes and hepatic stellate cells (HSC). These cells translate those signals into immune responses and pathologic hepatic changes during the development of NASH. In this scenario the development of fibrosis is the most important change since it is an adaptive mechanism that in the short time has the objective of repair the damaged tissue but after prolonged injury it progresses to parenchymal scarring, cellular dysfunction and finally to organ failure. Finally, since NASH is an important cause of liver cirrhosis; this review addresses the cellular pathways of fibrosis in the setting of NASH explained by the interaction between immune and hepatic cells.

Background and Objective: In the present study, the purpose was to compare the demographic, clinical and laboratory results of pediatric brucella cases who had liver involvement and who had no specific organ involvement. Material and Methods: The data of 248 patients between 2 and 18 years of age diagnosed with Brucellosis between July 2017 and August 2018 were analyzed retrospectively. The patients who had liver involvement and who did not have other specific organ involvement were compared in terms of presentation, physical examination findings, age, gender, hemogram, AST, ALT, GGT, ALP, bilirubines, sedimentation, CRP, clinical and laboratory findings, and culture and relapse rates. Results: No significant differences were detected between the patients who had liver involvement (n=92) and who did not have specific organ involvement (n=156) in terms of diagnosis age and gender. Loss of appetite, nausea and sensitive stomach were higher in the patients who had hepatic involvement, and weariness was determined to be more in the control group patients. In the patients who had hepatic involvement, the hemoglobin and platelet values were lower, and the sedimentation, CRP and blood culture growth were higher. The relapse rates were lower in patients who had liver involvement. Conclusion: In patients who have liver involvement, in addition to elevated hepatomegaly and transaminase levels, the growth rate of the acute-phase reactants and brucella is higher in blood culture; and the relapse rate is lower after treatment. Brucellosis must be considered in the differential diagnosis of hepatomegaly and transaminase elevation where brucellosis is seen endemically. We believe that early diagnosis of brucellosis is important in treatment response.

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis, published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial-mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

Background and Aim: Zinc plays a pivotal role in various zinc enzymes, resulting in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. It remains unknown whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development. Patients and Methods: Two hundred sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients) were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Results: Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p<0.001). According to the serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dl (p<0.001). Conclusion: Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dl.

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to end-stage of hepatocellular carcinoma and demolition of hepatic structures. EMT has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing complementary sequence of Smad transcription factor. Thus, this study evaluated the anti-fibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice. As shown in histological results, CCl₄ treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN treatment mice compared with CCl₄-injuried mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.

Many metabolic processes at the molecular level support both viral attack strategies and human defenses during Covid-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021-2023) from PubMed reporting the discovery of hub-nodes specific for the liver during covid-19, identifying 142 hub-nodes. They are highly connected proteins from which to get deep functional information on viral strategies when used as functional seeds. Therefore, we evaluated the functional and structural significance of each of them to endorse their reliable use as seeds. After filtering, the remaining 111 hubs were used to get by STRING an enriched interactome of 1111 nodes (13,494 interactions). It shows the viral strategy in the liver is to attack the entire cytoplasmic translational system, including ribosomes, to take control of protein bio-synthesis. We used the SARS2-Human-Proteome Interaction Database (33,791 interactions), de-signed by us with BioGRID data to implement a reverse-engineering process that identified human proteins actively interacting with viral proteins. The results show 57% of human liver proteins di-rectly involved in Covid, a strong impairment of the ribosome and spliceosome, an antiviral defense mechanism against cellular stress of the p53 system, and, surprisingly, a viral capacity for multiple protein attacks against single human proteins that reveal underlying evolutionary-topological molecular mechanisms. Viral behavior over time suggests different molecular strategies for different organs.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging lymphoma and gut microbiome investigation field.

Major depressive disorder (MDD) is one of life-threatening disorders that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Therefore, a possible mechanism is used to evaluate the antidepressant effect. Nowadays, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, has an antidepressive property. In vitro inhibitory effect on monoamine oxidase-A (MAO-A) enzyme was used to preliminarily screen the antidepressant effect of the O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks and daily administration of the OIS extract started from week 4. The mechanisms involved in antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in UCMS-induced mouse model via two possible pathways: (i) normalize the HPA-axis function by restoration of negative feedback (decreased FKBP5 and increased GR expressions) and reduction of glucocorticoid-related negative gene (SGK-1), (ii) improve neurogenesis by escalation of BDNF and CREB expression in the hippocampus and the frontal cortex. HPLC analysis of the extract showed the presence of All the results obtained from this study emphasize its potential as an effective and novel alternative treatment for MDD.

Objective: Several lines of evidence support a relationship between circadian rhythms disruption in the onset, course, and maintenance of mental disorders. Despite the study of circadian phenotypes promising a decent understanding of the pathophysiologic or etiologic mechanisms of psychiatric entities, several questions still need to be addressed. In this review, we aimed to synthesize the literature investigating chronobiologic theories and their associations with psychiatric entities. Methods: The Medline, Embase, PsycInfo, and Scopus databases were comprehensively and systematically searched and articles published between January 1990 and October 2019 were reviewed. Different combinations of the relevant keywords were polled. We first introduced molecular elements and mechanisms of the circadian system to promote a better understanding of the chronobiologic implications of mental disorders. Then, we comprehensively and systematically reviewed circadian system studies in mood disorders, schizophrenia, and anxiety disorders. Results: Although subject characteristics and study designs vary across studies, current research has demonstrated that circadian pathologies, including genetic and neurohumoral alterations, represent the neural substrates of the pathophysiology of many psychiatric disorders. Impaired HPA-axis function-related glucocorticoid rhythm and disrupted melatonin homeostasis have been prominently demonstrated in schizophrenia and other psychotic disorders, while alterations of molecular expressions of circadian rhythm genes including CLOCK, PER, and CRY have been reported to be involved in the pathogenesis of mood disorders. Discussion: Further translational work is needed to identify the causal relationship between circadian physiology abnormalities and mental disorders and related psychopathology, and to develop sound pharmacologic interventions.

In this paper, we define Ulisse Dini-type helicoidal hypersurface with spacelike axis in Minkowski 4-space ${\mathbb{E}}_1^4$ . We compute the Gaussian and the mean curvature of the hypersurface. Moreover, we obtain some special symmetry to the curvatures when they are flat and maximal.

Apart from their established role in embryonic development Nerve Growth Factors (NGFs) have diverse functions in the nervous system. Their role in integration of physiological functioning of the nervous system is now attracting attention. In the present analysis, we propose a novel paradigm about a novel role of NGFs: NGFs play imperative role in maintaining psychological integrity of an individual as a biological system. This function may be mediated through HPA-axis- operated homeostatic mechanisms; stress induced disruption of which may lead to psychiatric disorders. Current literature suggests existence of constitutive homeostatic regulatory mechanisms for NGFs disruption which may lead to pertinent and imperative behavioural effects. NGFs are known to play crucial role in endocrine regulation. This is especially true with the prototype ‘NGF’ and Brain Derived Neurotrophic Factor (BDNF). These moieties have been observed to play important function in maintaining neuro-endocrine homeostasis thereby having a profound impact on the psychological health of an individual. Role of NGFs and HPA-axis activation (in separate studies) in developing psychiatric disorders - especially those born of stress - have been reported. Literature suggests their unique interplay for producing a common effect which might be implicated in stress induced genesis of psychiatric disorders. This aspect, therefore, needs to be elucidated further as a disease etiogenesis model. This model may yield important insights into the biology of psychiatric disorders and may open ways for new therapeutic approaches.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Mast cells are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, mast cells act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. Mast cells originate from bone marrow progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating in heterogeneous tissue-specific subsets. Even though mast cell activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of mast cell biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand mast cell origin and differentiation as well as the phenotype and functions within different tissues, including the gut. This review recapitulates how single cell transcriptomic studies provided insight into mast cell development as well as into the functional role of intestinal MC subsets in health and disease.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

A bacterium known as Akkermansia muciniphila (AkkermansiaA. muciniphila) was detected in human feces in 2004. It is defined as a gram-negative, anaerobic, and mucin-degrading microbe belonging to the Verrucomicrobia species. Although the majority of A. muciniphila is found in the human intestinal tract playing a role in the gut microbiome, there are also smaller levels detected in breast milk and oral cavities as well as in the pancreas and appendix.Evidence suggests that having A. muciniphila present in the gut microbiome has positive effects on human health. As a result, A. muciniphila has been shown to have health benefits when taken as a dietary supplementation where it is considered a promising next-generation probiotic. However, the large-scale production of A. muciniphila remains a challenge due to its need for a stable environment. While culturing A. muciniphila in a mucin-based medium is one option, other strategies that use plate-based mediums have also been explored. Currently, both live and pasteurized forms of A. muciniphila are available on the market and shown to have promising outcomes in animal models. Additionally, researchers are investigating various prebiotics to increase the abundance of A. muciniphila in the human gut. This article presents a detailed summary of the phenotypic characteristics of A. muciniphila and its associations with various human health condition illnesses. Finally, the paper explores A. muciniphila's potential as an effective next-generation probiotic.

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

Coffee is one of the most widely consumed beverages in the world, with important repercussions on the health of the individual. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of it has also proven to be of fundamental importance for the development of new therapeutic strategies. In this narrative review, we thoroughly investigated the link between coffee consumption and its effects on the gut microbiota and their consequences on human health. We have selected the most significant articles published on this very interesting link, with the aim of going deeper in the light of the latest evidence more and more about the relationship that links coffee consumption and its repercussions on the composition of the gut microbiota and on human health.

Bacteria in the gut microbiome play an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. Gut microbiota communicates with the central nervous system (CNS) through the production of bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT) and histamine. A vast number of signals generated in the gastrointestinal tract (GIT) reaches the brain via afferent fibers of the vagus nerve (VN). Signals from the CNS are returned to entero-epithelial cells (EES) via efferent VN fibers and communicate with 100 to 500 million neurons in the submucosa and myenteric plexus of the gut wall, which is referred to as the enteric nervous system (ENS). Intercommunications between the gut and CNS regulate mood, cognitive behavior, and neuropsychiatric disorders such as autism, depression, and schizophrenia. The modulation, development, and renewal of nerves in the ENS, and changes in the gut microbiome alter the synthesis and degradation of neurotransmitters, which ultimately influence our mental health. The more we decipher the gut microbiome and understand its effect on neurotransmission, the closer we may get to the developing of novel therapeutic and psychobiotic compounds to improve cognitive functions and prevent mental disorders. In this review, the intricate control of entero-endocrine signaling and immune responses that keep the gut microbiome in a balanced state, and the influence that changing gut bacteria have on neuropsychiatric disorders are discussed.

Aquaculture is a fast-emerging food-producing sector in which fishery production plays an im-perative socio-economic role, providing ample resources and tremendous potential worldwide. However, aquatic animals are exposed to the deterioration of the ecological environment and in-fection outbreaks, which represent significant issues nowadays. One of the reasons for these threats is the excessive use of antibiotics and synthetic drugs that have harmful impacts on the aquatic atmosphere. It is not surprising that functional biotic feeds such as probiotics, prebiotics, postbiotics, and synbiotics have been developed as natural alternatives to sustain a healthy microbial envi-ronment in aquaculture. These functional feed additives possess several beneficial characteristics, including gut microbiota modulation, immune response reinforcement, resistance to pathogenic organisms, improved growth performance, and enhanced feed utilization in aquatic animals. Nevertheless, their mechanisms in modulating the immune system and gut microbiota in aquatic animals are largely unclear. This review discusses current research advancements to fill research gaps and promote effective and healthy aquaculture production.

The aim of the study was to investigate the association between maternal dietary iron intake during pregnancy and the gut microbiota characteristics of both the mother and neonate in a well-characterized cohort. A total of 95 mother-neonate dyads were included in our study, with basic information collected through questionnaires. A semi-quantitative Food Frequency Questionnaire (FFQ) was used to assess maternal dietary intake during pregnancy, and maternal dietary iron intake was categorized into &lt;20 mg/d and ≥20 mg/d groups. Fecal samples were collected from the mother in the third trimester and the neonate, allowing for assessment of the community profile and diversity of gut microbiota via 16S rRNA amplicon sequencing. Then, a comparison between different maternal dietary iron intake groups was conducted, adjusting for delivery mode (VD, vaginal delivery; CS, cesarean section) and other potential confounding factors. No significant differences in community profile and diversity were observed for the maternal gut microbiota in different dietary iron intake groups. In neonate fecal samples, the Shannon (P = 0.044) and Simpson (P = 0.010) diversity indices of the gut microbiota were higher in the maternal dietary iron intake ≥20 mg/d group, while Simpson diversity presented the same tendency in vaginal delivery (P = 0.041) after stratification. The relative abundance of the core genus Bifidobacterium showed a significant difference between groups (4.69 [1.19–12.77] vs. 13.98 [3.44–27.28]; P = 0.044). The abundance of Lactobacillus was different in the ≥20 mg/d group under both delivery modes (VD: beta = 2.9, w = 4.13; CS: beta = 2.77, w = 3.8). Our findings suggest that adequate dietary iron intake during pregnancy may promote beneficial bacterial colonization and increase the biodiversity of the neonate gut microbiota.

Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia. This opinion review also discusses the recent findings and clinical studies of the use of capsaicin in body weight control.

Cardiovascular disease (CVD), comprising heart and blood vessel disorders, persists as the foremost contributor to global morbidity and mortality. In modern times, the intricate composition of gut microbiota has garnered significant focus, particularly for its varying impact on diverse ailments. Perturbations in gut microbiota and consequent dysbiosis have demonstrated connections with the advancement and origin of CVD, including conditions like atherosclerosis, hypertension, and heart failure. This comprehensive review delves into the pivotal role of gut microbiota in maintaining cardiovascular well-being.

Background: Globally, about 3.5 billion people are affected by intestinal parasitic infections (IPIs). This study aimed to investigate the effects of IPIs on intestinal wall thickness and its potential association with hypertension in different genders. Methods: A total of 108 subjects, including 83 consecutive patients with symptomatic and laboratory-confirmed IPIs (male = 48; female = 35) and 25 healthy controls (male = 10; female = 15), were recruited. B-mode ultrasound grayscale and color images of the duodenum and colon were obtained with and without water contrast. Results: Patients with IPIs had a tendency towards greater duodenal wall thickness (DUOTHICK = 0.88 ± 0.73 cm) compared to controls (0.595 ± 0.089 cm), p = 0.056. Patients with IPIs also had significantly greater ascending colon wall thickness (ASCTHICK = 1.076 ± 0.29 cm) and descending colon wall thickness (DSCTHICK = 1.175 ± 0.366 cm) compared to controls (ASCTHICK = 0.6015 ± 0.1607 cm, DSCTHICK = 0.6223 ± 0.135 cm), p < 0.05. Men over 50 years had greater DSCTHICK (1.25 ± 0.434 cm) than post-menopausal women (0.986 ± 0.389 cm), p < 0.05. DSCTHICK significantly predicted diastolic blood pressure (β = -0.295, p < .05) and blood sodium level (β = -0.300, p < .05). Conclusion: We demonstrated the effects of IPIs on the intestinal microbiome causing intestinal wall cytoskeletal dysfunction, which led to the development of a "leaky gut syndrome."

Nutrigenomics is the study of the interaction of nutrition and genes, focusing on the influence of nutrients on the genome, proteome, and metabolome, and how nutrition affects human health. In the context of nutrigenomics, bioactive components are dietary ingredients that may transmit information from the external environment and alter gene expression in the cell, and hence the overall function of the organism. It is critical to consider food not only as a source of energy and essential nutrients necessary for life and growth, but also as a factor impacting health/disease, biochemical processes, biochemical pathway activation and affecting the diversity of the gut microbiome. Antimicrobial resistance in pathogenic and commensal microorganisms has emerged as a major public health concern due to emerging antimicrobial resistance genes in E. coli isolates from pig, cattle, chicken, and turkey meat, against tetracycline, streptomycin, and sulfonamides. Also, Salmonella spp. and Campylobacter spp. have shown antibiotic resistance at farms and slaughterhouses, and in animal-based food products. A correlation has been proven between a critical nutrient-responsive signaling system and catabolite control of gene expression, and a two-component signaling system that drives antibiotic resistance in E. faecalis, revealing a previously unknown integration between the nutritional status of the cell and intrinsic antibiotic resistance. Moreover, different nutrigenomic approaches can be applied to mitigate possible emergence of antimicrobial resistance against novel antibiotics. However, little progress has been achieved in converting nutrigenomics information into clinical advice, so far.

The gut microbiota plays a crucial role in maintaining host health and has a significant impact on human health and disease. In this study, we investigated the alpha diversity of gut microbiota in COVID-19 patients and analyzed the impact of COVID-19 variants, antibiotic treatment, type 2 diabetes (T2D), and metformin therapy on gut microbiota composition and diversity. We used a culture-based method to analyze the gut microbiota and calculated alpha-diversity using the Shannon H' and Simpson 1/D indices. We collected clinical data, such as length of hospital stay (LoS), C-reactive protein (CRP) levels, and neutrophil-to-lymphocyte ratio (NLR). We found that patients with T2D had significantly lower alpha-diversity than those without T2D. Antibiotic use was associated with a reduction in alpha-diversity, while metformin therapy was associated with an increase. We did not find significant differences in alpha-diversity between the Delta and Omicron groups. Length of hospital stay, CRP levels, and NLR showed weak to moderate correlations with alpha diversity. Our findings suggest that maintaining a diverse gut microbiota may benefit COVID-19 patients with T2D. Interventions aimed at preserving or restoring gut microbiota diversity, such as avoiding unnecessary antibiotic use and promoting metformin therapy, may improve patient outcomes.

The gut microbiome offers numerous advantages to the hosts, through a variety of physiological mechanisms like firming up gut integrity or shaping the intestinal epithelium. Studies showed 2172 species are identified and isolated from human beings, ordered into twelve different phyla, of which 93.5% belonged to Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria. Out of the 12, three phyla are identified. Human microbial communities are affected by the host external factors like dietary patterns, lifestyle factors, antibiotic usage, internal factors gender, host genotype, age and race. To analyze the dysbiosis and bacterial variation in different areas of District Faisalabad 10,000 individuals of age 25–35 years were recruited from the two different rural and urban localities. The oral swab and fecal sample were collected according to prescribed manner. The collected samples from demographically and geographically distinct regions of District Faisalabad were subjected to DNA extraction and quantification. The amplification of 16s rRNA was carried out by PCR and visualized through a transilluminator. The results revealed significant elevated, % abundance of fecal microbial profile Blautia spp, Firmicutes, Ruminococcaceae, in rural population however non-significant difference % abundance of total Bifido, E. coli, Faecali bacteria, total Lactobacillus were identified in both demographically distinct regions. The pathogenic Gamma Protebacteria, Fusobacterium, Campylobacter coli were not detected in both study areas. Out of five orally detected microbial profiles, elevated % abundance of Firmicutes was detected in rural population however non-significant difference was observed in % abundance of total Bifido and E. coli in both populations. Total Lactobacillus and Fusobacterium were not detected in oral sample of both urban and rural population. Conclusively, this research accomplished the potential effects of demographic and geographical induced dysbiosis in the normal microbiome of the oral cavity and intestine that might cause dysbiosis associated disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD=42; Ncontrols=50; NsubthreholdADHD=15; range age: 13-29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (P < 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that variation of a genus from the Ruminococcaceae family (Ruminococcaceae_UCG_004) is associated (after multiple testing correction) with inattention symptoms, and suggest a role of gut microbiota in ADHD pathophysiology.

The composition of bacteria in the gastrointestinal tract of piglets is easily affected by environmental changes, particularly during the weaning period. Compound strains of Lactobacillus reuteri and Lactobacillus salivarius were supplemented to piglets during pre- and post-weaning to determine their effects in improving the growth performance and ameliorating the diarrhea rate and stress caused by antioxidation in piglets. A larger number of L. reuteri and L. salivarius colonized the distal segment of the ileum and the total numbers of Lactobacillus spp. and Bifidobacterium were higher in the ileal mucous membrane and cecal lumen with probiotics supplementation. The numbers of antioxidative and immune molecules were increased in the plasma following compound bacteria (CL) supplementation, whereas cortisol and endotoxin levels were lower and growth hormone and insulin-like growth factor 1 were higher. Spearman’s and KEGG analysis of the bacterial operational taxonomic unit and antioxidative and immune indices and metabolic genes indicated that the body growth modulation by CL supplementation could be attributed to optimization of the intestinal bacterial composition. Collectively, these results suggest that supplementation with CL could reduce stress and improve the growth performance of piglets during weaning by optimizing the intestinal bacterial composition.

The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scan and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus. At a median (interquartile range) follow-up of 4.4 (3.8) years after transplantation, everolimus patients showed a reduced risk of recurrence versus tacrolimus (7.7% versus 16.9%; RR=0.45; P=0.002). At multivariable analysis, microvascular infiltration (HR=1.22; P<0.04) and a higher tumor grading (HR=1.27; P<0.04) were associated with higher recurrence rate while being within Milan criteria at transplant (HR=0.56; P<0.001), a successful pre-transplant downstaging (HR=0.63; P=0.01) and use of everolimus (HR=0.46; P<0.001) had a positive impact on the risk of post-transplant recurrence. EVR patients with earlier drug introduction (30 days; P<0.001), longer treatment duration (P<0.001), and higher drug exposure (5.9ng/mL; P<0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction of the relative risk of hepatocellular carcinoma recurrence, especially for advanced-stage patients and those with earlier drug administration, higher drug exposure, and longer time on treatment. These data advocate for early everolimus introduction after liver transplantation to reduce the attrition rate consequent to chronic immunosuppression.

We present our preliminary experience with transarterial radioembolization (TARE) with Yt-trium-90, and investigate the influence of additional treatments, injected activity, mean dose to the tumor on overall survival (OS). Our database was interrogated to retrieve patients who had undergone TARE with Yttrium-90 (90Y) glass or resin microspheres. The following information were searched: 1) type of pathology; 2) sex; 3) age; 4) administered activity; 5) mean dose to the tumor; 6) additional treatments; 7) OS. The OS of the different groups of patients were compared (p<0.05). A bivariate correlation (p<0.05) was used to investigate the association between injected activity and OS, and between mean dose to the tumor on OS. Thirty-nine patients were retrieved (Sex: 27 M, 12 F; mean age: 61.26 ± 14.95 years): 23 with hepatocellular carcinoma (HCC) and 16 with colorectal cancer (CRC) liver metastasis. Globally, patients with HCC demonstrated a sig-nificantly longer OS than those with CRC liver metastasis (22.66±19.11 vs. 10.41±8.75 months; p=0.022). Among patients with CRC liver metastasis, those receiving TARE and additional treatment demonstrated a longer OS than patients receiving only TARE (23.50±19.76 months vs. 8.54±5.31; p=0.018), there was a direct correlation between injected activity and OS (R=0.55, p=0.034) and between mean activity reaching the tumor and OS (R=0.812; p=0.008). Patients with HCC receiving TARE achieved a longer OS than those with CRC liver metastasis. Additional treatments, increasing injected activity and higher mean dose to the tumor seem beneficial for outcome, especially in patients with CRC liver metastases.

We conducted a hybrid-design study on a historical cohort of 359 adult recipients of a liver graft who received transplants between 1996 and 2002. The study aimed to identify predictors of survival and investigate the prevalence of co-morbidities among long-term survivors. The actuarial (95% CI) patient survival of the overall study cohort was 96% (94.6%-98.3%), 69% (64.2%-73.6%), 55% (49.8%-59.9%), 42.8% (37.6%-47.8%), and 34% (29.2%-38.9%) at 1, 5, 10, 15, and 20 years, respectively. The actuarial (95% CI) graft survival was 93.8% (91.6%-97.2%), 67.6% (62.2%-71.5%), 54.3% (49.6%-59.3%), 42.1% (37.3%-47.4%), and 33.8% (29.0%-38.4%) at 1, 5, 10, 15, and 20 years, respectively. The leading cause of death was hepatitis C virus recurrence (24.6%), followed by extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The Cox proportional hazards analysis revealed that several independent factors were associated with the survival probability. These factors include younger donor and recipient ages (p=0.001 and 0.004, respectively), female recipient sex (p<0.001), absence of HCV (p<0.01), absence of HCC (p=0.001), and absence of diabetes mellitus at one year (p<0.01). At the latest follow-up, the leading comorbidities in the long-term survivors were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. The Kaplan-Meier probability (95% CI) of complication-free survival was 65.4% (60.2%-70.3%), 38.4% (33.4%-43.7%), 17.8% (14.1%-22.2%), 7.2% (4.8%-10.5%), and 1.94% (0.85%-4.15%) at 1, 5, 10, 15, and 20 years, respectively. Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

The current management of colorectal cancer liver metastasis (CRCLM) patients involves a multidisciplinary approach with surgical resection remaining the primary curative option. The advances in liver surgery have improved outcomes, enabling more patients to undergo surgery successfully. In addition, the development of imaging software has improved the preoperative planning and patient selection for surgery and other interventions. Systemic therapies, such as targeted therapies and immunotherapies have enhanced the chances of complete resection. Targeted agents in combination with chemotherapy, have shown efficacy in downstaging tumors and increasing resectability.

This study aimed to evaluate the effects of a mixture of olive, laurel and rosemary leaf powders, on performance and egg quality, the oxidative state and biochemical, immune, and intestinal morphophysiological parameters of laying hens. One hundred Lohaman Brown hens (28 weeks old) were equally assigned to two groups (n. 50) corresponding to a basal control diet (CON) or the diet supplemented with 6g/kg feed of leaf powder mixture (LPM) containing olive, laurel and rosemary leaves (1:1:1), for 8 weeks. Egg traits, oxidative status, biochemical indices, immune response, cecal short chain fatty acids (SCFAs) and intestinal morphological characteristics were evaluated at the end of the experiment. The results indicated that body weight and egg quality parameters were not influenced by LPM. However, LPM improved (P<0.01) the oxidative status and the immune system, total protein (P<0.05) and HDL cholesterol (P<0.01) and decreased total cholesterol (P<0.01) and LDL cholesterol (P<0.05), as compared to the CON. Aspartate amino transferase (AST), alkaline phosphatase (ALP) and alanine amino transpherase were significantly better in the LPM than in the CON group. A significant increase (P<0.05) of SCFA content established in the caecum and in villi height and crypt depth in both duodenum and ileum LPM treated hens was observed.

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Aim: To investigate how much aerobic and resisted physical exercise affects the behavior of AST and ALT proteins in the NAFLD spectrum. Background: Non-alcoholic fatty liver disease (NAFLD) is a pathology resulting from the excessive accumulation of triglycerides in the liver. The pathophysiology of the disease comes from several mechanisms, among them, metabolic, environmental, and genetic. The measurement of liver enzymes, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) are essential to perform a differential diagnosis of NAFLD with other pathologies that affect the liver. The non-pharmacological treatment of NAFLD is based on aerobic and resisted physical exercise, and one of its aims is to reduce the inflammatory markers AST and ALT. Materials and Methods: Systematic review carried out in PubMed, Scopus, Embase, and Cochrane databases. Clinical trials that evaluated the effect of physical exercise on NAFLD on AST and ALT enzymes were included. Results: A total of 24 clinical trials met the inclusion criteria, with a sample size of 1141 participants, aged 20-82 years. The study protocol varied between aerobic exercise and resistance exercise with a weekly frequency between 2-6 times a week, a duration of 20-90 minutes for aerobics, and an intensity between 50-80% of peak VO2 and/or maximum HR for the resisted. Of the 24 studies included, only five showed improvements in both enzymes in the intervention group. Conclusion: Physical exercise cannot make significant changes in the behavior of AST and ALT liver parameters.

Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) presenting wide global dissemination and the pathogenic profile developed in infected individuals, which develop from nonspecific clinical conditions to severe forms, characterized by the promotion of significant lesions in different organs of the harborer, culminating in multiple organ dysfunction. To characterize, quantify, and compare the patterns of histopathological alterations in human liver samples from patients with yellow fever (YF), dengue fever (DF), and chikungunya fever (CF). Analytical cross-sectional study by histopathological analysis with 70 samples of liver patients, collected from 2000 to 2017, with confirmed laboratory diagnosis who died due to infection and complications by the YF, DF, and CF. Of the histopathological findings in human liver samples there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analyzed, among the arboviruses studied, the hepatic involvement in cases of YF showed greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis and apoptosis were classified as degree of tissue damage from severe to very severe. The pathological abnormalities associated with infection by YFV, DENV, and CHIKV showed predominance of changes in the midzonal area. We also noted that in among of the arboviruses studied, liver involvement in cases of YFV infection was more intense.

Abstract Aim: The study aimed to evaluate the clinical laboratory features of moderate and severe COVID-19 patients among a cohort of the Egyptian population. The study also aimed to assess the accuracy—sensitivity, specificity, and area under the curve (AUC) of various detected parameters in predicting the severity of COVID-19 infection. Patients and methods: One hundred diagnosed COVID-19 patients and fifty healthy participants in total were involved in current study. COVID-19 patients were categorized based on how severe their symptoms into two groups. Estimates were made for serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, lactate dehydrogenase (LDH) and C-reactive protein (CRP) as well as white blood cells (WBCs) count, lymphocytes count, and hemoglobin content (Hb) content. Results: COVID-19 patients displayed increased serum levels of liver enzymes and CRP as well as WBCs count when compared to healthy individuals. On the other hand, Hb content, lymphocytes count, and albumin level fell in all COVID-19 patients. The severe group showed a statistically significant rise in liver enzymes, WBCs, and CRP levels, compared with moderate group. WBCs and lymphocytes counts were closely correlated with age, ALT, LDH, and CRP in all cases. WBCs and lymphocytes counts also had a negative correlation with albumin Level. Additionally, WBCs count, lymphocytes count, LDH activity and CRP level have higher AUC in severe than in moderate cases. WBCs count, LDH activity and CRP level have AUC above 0.80 in the severe group. Conclusion: The current investigation found a significant correlation between WBCs count, lymphocytes count, CRP level and liver injury in COVID-19 patients. WBCs count, lymphocytes count, LDH activity and CRP level were effective indicators for determining the severity of COVID-19.

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient L-amino acid-defined high fat diet (CDHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports about the effects on mice of being fed CDAHFD for a long time, 1 to 3 months. However, the effect of this diet over a short period has been unknown. Therefore, we examined the effect of one week of feeding CDAHFD on the mouse liver. Feeding this diet for only one week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis and cirrhosis. Additionally, it was demonstrated that mitochondrial respiration is significantly impaired with severe oxidative stress in the liver by CDAHFD, associated with a decreasing mitochondrial DNA copy number and complexes-proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that one week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of the NASH in humans.