Hepatic consequences of COVID-19 infection. Lapping or biting?

The outbreak of coronavirus disease 2019 (COVID-19) starting last December in China placed emphasis on liver involvement during infection. This review discusses the underlying mechanisms linking COVID-19 to liver dysfunction, according to recent available information, while waiting further studies. The manifestations of liver damage are usually mild (moderately elevated serum aspartate aminotransferase activities), and generally asymptomatic. Few patients can still develop severe liver problems, and therapeutic options can be limited. Liver dysfunction may affect about one-third of the patients, with prevalence greater in men than women, and in elderly. Mechanisms of damage are complex and include direct cholangiocyte damage and other coexisting conditions such as the use of antiviral drugs, systemic inflammatory response, respiratory distress syndrome-induced hypoxia, sepsis, and multiple organ dysfunction. During new COVID-19 infections, liver injury may be observed. If liver involvement appears during COVID-19 infection, however, attention is required. This is particularly true if patients are older or have a pre-existing history of liver diseases. During COVID-19 infection, the onset of liver damage impairs the prognosis, and hospital stay is longer

Immunological aspects of the tumor microenvironment and epithelial-mesenchymal transition in gastric carcinogenesis

Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002–2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer

Gut microbiota between environment and genetic background in familial mediterranean fever (Fmf)

The gastrointestinal tract hosts the natural reservoir of microbiota since birth. The microbiota includes various bacteria that establish a progressively mutual relationship with the host. Of note, the composition of gut microbiota is rather individual-specific and, normally, depends on both the host genotype and environmental factors. The study of the bacterial profile in the gut demonstrates that dominant and minor phyla are present in the gastrointestinal tract with bacterial density gradually increasing in oro-aboral direction. The cross-talk between bacteria and host within the gut strongly contributes to the host metabolism, to structural and protective functions. Dysbiosis can develop following aging, diseases, inflammatory status, and antibiotic therapy. Growing evidences show a possible link between the microbiota and Familial Mediterranean Fever (FMF), through a shift of the relative abundance in microbial species. To which extent such perturbations of the microbiota are relevant in driving the phenotypic manifestations of FMF with respect to genetic background, remains to be further investigated

Fatty Acid Oxidation and Cardiovascular Risk during Menopause: A Mitochondrial Connection?

Menopause is a consequence of the normal aging process in women. This fact implies that the physiological and biochemical alterations resulting from menopause often blur with those from the aging process. It is thought that menopause in women presents a higher risk for cardiovascular disease although the precise mechanism is still under discussion. The postmenopause lipid profile is clearly altered, which can present a risk factor for cardiovascular disease. Due to the role of mitochondria in fatty acid oxidation, alterations of the lipid profile in the menopausal women will also influence mitochondrial fatty acid oxidation fluxes in several organs. In this paper, we propose that alterations of mitochondrial bioenergetics in the heart, consequence from normal aging and/or from the menopausal process, result in decreased fatty acid oxidation and accumulation of fatty acid intermediates in the cardiomyocyte cytosol, resulting in lipotoxicity and increasing the cardiovascular risk in the menopausal women

Malignant hypertension and hyperreninemia: Primary or secondary hypertension? A case report

Malignant hypertension is a rare condition characterized by severe hypertension and multi-organ ischemic damage. Marked activation of the renin-angiotensin system is observed in many patients, but its persistence over time is not known. We report a case of a 42-year-old woman who presented with severe hypertension and multi-organ damage. Initial evaluation showed an elevated value of direct renin concentration with normal plasma aldosterone concentration and a nodular lesion in the left adrenal gland. The differential diagnosis between the primary and secondary form of hypertension had to be questioned. Consequently, the patient was followed up for 20 months. Repeated checks showed a significant increase in renin levels with a normal aldosterone concentration and regression of organ damage. After 20 months, renin values returned within normal range. Hyperreninemia persisting over a long period of time has not been fully explained. Long-term follow-up allowed us to attribute malignant hypertension to de novo essential hypertension

Effects of temporary sacral nerve stimulation on gastrointestinal motility and function in patients with chronic refractory slow-transit constipation

Background: The efficacy of sacral nerve stimulation (SNS) on patients with chronic refractory slow-transit constipation is controversial and its mechanism of action on gastrointestinal motility and transit is not fully understood. The aim of this study was to document the effects of temporary SNS on the gastrointestinal and biliary tract motility and on gastrointestinal transit in patients with refractory slow-transit constipation. Methods: This was a prospective interventional study. Patients with slow-transit chronic constipation, unresponsive to any conservative treatment, were enrolled between January 2013 and December 2018. Patients’ quality of life [patient assessment of constipation quality of life (PAC-QOL) questionnaire], constipation scores (Cleveland Clinic Constipation Score) colonic transit time (CTT), orocecal transit time (OCTT), gastric and gallbladder kinetics, together with the assessment of the autonomic nerve function were evaluated before and during temporary SNS. Results: 14 patients (12 females, median age 38 years, range 24–42 years) had temporary SNS. The Cleveland Clinic Constipation Score did not change compared to baseline (23 ± 3 vs 21.4; p = 070). The PAC-QOL did not improve significantly during the stimulation period. Gallbladder/stomach motility (half-emptying time) did not change significantly before and after SNS. OCTT was delayed at baseline, as compared to standard internal normal values, and did not change during SNS. CTT did not improve significantly, although in two patients it decreased substantially from 97 to 53 h, and from 100 to 65 h. Conclusions: Temporary SNS did not have any effect on upper/lower gastrointestinal motility and transit in patients with severe constipation

Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Gallstones and Nonalcoholic Fatty Liver Disease

The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1), an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD) in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD

Bile acids and gpbar-1: Dynamic interaction involving genes, environment and gut microbiome

Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects

Mechanisms of the Epithelial-Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world's population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial-mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial-mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer