Diabetic nephropathy (DN) is one of the most perilous side effects of diabetes mellitus type 1 and type 2 (T1DM and T2DM).). It is known that sodium/glucose cotransporter 2 inhibitors (SGLT 2i) and glucagone like peptide-1 receptor agonists (GLP-1 RAs) have renoprotective effects, but the molecular mechanisms are still unknown. In clinical trials GLP-1 analogs exerted important impact on renal composite outcomes, primarily on macroalbuminuria, possibly through suppression of inflammation-related pathways, however enhancement of natriuresis and diuresis is also one of possible mechanisms of nephroprotection. Dapagliflozin, canagliflozin, and empagliflozin are SGLT2i drugs, useful in reducing hyperglycemia and in their potential renoprotective mechanisms, which include blood pressure control, body weight loss, intraglomerular pressure reduction, and a decrease in urinary proximal tubular injury biomarkers. In this review we have discussed the potential synergistic and/or additive effects of GLP 1 RA and SGLT2 inhibitors on the primary onset and progression of kidney disease, and the potential implications on current guidelines of diabetes type 2 management.

Liver fibrosis is a life-threatening disease, with challenging morbidity and mortality for healthcare systems worldwide. It imparts an enormous economic burden to societies, making continuous research and informational updates about its pathogenesis and treatment crucial. This review′s focus is on the current knowledge about the Wnt signaling pathway, serving as an important pathway in liver fibrosis development and activation of hepatic stellate cells (HSCs).

Drug-induced cholestasis represents a form of drug-induced liver disease that can lead to severe impairment of liver function. Numerous drugs have been shown to cause cholestasis and consequently bile duct toxicity. However, there is still lack of therapeutic tools that can prevent progression to advanced stages of liver injury. This review focuses on the various pathological mechanisms by which drugs express their hepatotoxic effects, as well as consequences of increased bile acid and toxin accumulation in the hepatocytes.

Metabolic dysfunction-associated fatty liver disease (commonly known as MAFLD) impacts global health in epidemic proportions, and the resulting morbidity, mortality and economic burden is enormous. While much attention has been given to metabolic syndrome and obesity as offending factors, a growing incidence of polypharmacy, especially in the elderly, has greatly increased the risk of drug-induced liver injury (DILI) in general, and drug-induced fatty liver disease (DIFLD) in particular. This review focuses on the contribution of DIFLD to DILI in terms of epidemiology, pathophysiology, the most common drugs associated with DIFLD, and treatment strategies.

(1) Background: With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The aim of our study was to study cell culture models of NAS and DIS and determine the effects of liraglutide (LIRA) in those models. (2) Methods: Huh7 cells were treated with oleic acid (OA), or amiodarone (AMD) to establish models of NAS and DIS, respectively. Cells were treated with LIRA and cell viability was assessed by MTT, lipid accumulation by Oil-Red-O staining and triglyceride assay, and intracellular signals involved in hepatosteatosis were quantitated by RT-PCR. (3) Results: After exposure to various OA and AMD concentrations, those that achieved 80% of cells viabilities were used in further experiments to establish NAS and DIS models using 0.5 mM OA and 20 µM AMD, respectively. In both models, LIRA increased cell viability (p < 0.01). Lipid accumulation was increased in both models, with microsteatotic pattern in DIS, and macrosteatotic pattern in NAS which corresponds to greater triglyceride accumulation in latter. LIRA ameliorated these changes (p < 0.001), and downregulated expression of lipogenic ACSL1, PPARγ, and SREBP-1c pathways in the liver (p < 0.01) (4) Conclusions: LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS.

Although hepatitis C virus (HCV) RNA may be eliminated from blood circulation by direct-acting antivirals (DAA) therapy as assessed by real-time polymerase chain reaction (PCR), HCV RNA can still be present in liver tissue, and this is known as occult HCV. There has been a lot of controversy surrounding the recurrence of hepatocellular carcinoma (HCC) after DAA treatment of hepatic cells infected with chronic HCV. One of the main risk factors that leads to de novo HCC is the chronicity of HCV in hepatic cells. There are many studies regarding the progression of HCV-infected hepatic cells to HCC. However, there is a lack of research on the different molecular mechanisms that lead to the progression of chronic HCV infection to HCC, as well as on the effect of HCV on the alteration of DNA ploidy, which eventually leads to a recurrence of HCC after DAA treatment. In this review article, we will address some risk factors that could lead to the development/recurrence of HCC after treatment of HCV with DAA therapy, such as the role of liver cirrhosis, the alteration of DNA ploidy, the reactivation of hepatitis B virus (HBV), the role of cytokines and the alteration of the immune system, concomitant non- alcoholic fatty liver disease (NAFLD), obesity, alcohol consumption and also occult HCV infection/co-infection. Clinicians should be cautious considering that full eradication of hepatocarcinogenesis cannot be successfully accomplished by anti-HCV treatment alone.

Background: Prescribing medications is one of the most common medical decisions that is made by primary care providers (PCPs). In the Republic of Croatia, PCPs hold a key position in prescribing and evaluating the medications that are provided for patients. Accordingly, providing advice for patients regarding the potential adverse drug reactions (ADRs) and drug-drug interactions (DDIs) is frequently the responsibility of the PCPs. The aim of the current study was to assess the knowledge, attitudes, and counseling practices of PCPs regarding drug interactions and adverse effects. Methods: After enrolling 195 PCPs that were selected at random, a survey was conducted while using an anonymous questionnaire that was created based on previously published studies, adjusted in a way that includes the most commonly prescribed medications in Croatia. Results: Of the 10 questions on knowledge about DDIs and ADRs, the median number of correct responses by PCPs was 5 (interquartile range 4 to 7). More than half of respondents (56%) agreed with the claim that knowledge of drug side effects facilitated their work in family medicine. Almost all of the respondents (92.8%) explained side effects and drug interactions to special groups of patients (pregnant women, elderly patients etc.). Conclusion: The results show a need for additional education in the field of drug prescribing. However, PCPs were aware of the importance of counseling practices about adverse drug reactions and interactions and counseling practices among special patients populations are satisfactory.

Background and Objectives: Peptic ulcer disease is a chronic disease affecting up to 10% of the world’s population. Proton pump inhibitors, such as lansoprazole are the gold standard in the treatment of ulcer disease. However, various studies have shown the effectiveness of garlic oil extracts in the treatment of ulcer disease. A cellular model can be established in the human gastric cell line by sodium taurocholate. The aim of this study was to explore the effects of garlic oil extracts pretreatment and LPZ addition in the cell culture model of peptic ulcer disease by examining oxidative stress and F-actin distribution. Materials and Methods: Evaluation was performed by determination of glutathione and prostaglandin E2 concentrations by ELISA; human gastric cell line proliferation by cell counting; expression of ATP-binding cassette, sub-family G, member 2; nuclear factor kappa B subunit 2 by RT PCR; and F-actin cytoskeleton visualization by semi-quantification of Rhodamine Phalloidin stain. Results: Our results showed significant reduction of cell damage after sodium taurocholate incubation when the gastric cells were pretreated with lansoprazole (p < 0.001) and increasing concentrations of garlic oil extracts (p < 0.001). Pretreatment with lansoprazole and different concentrations of garlic oil extracts increased prostaglandin E2 and glutathione concentrations in the cell culture model of peptic ulcer disease (p < 0.001). Positive correlation of nuclear factor kappa B subunit 2 (p < 0.01) with lansoprazole and garlic oil extracts pretreatment was seen, while ATP-binding cassette, sub-family G, member 2 expression was not changed. Treatment with sodium taurocholate as oxidative stress on F actin structure was less pronounced, although the highest concentration of garlic oil extracts led to a statistically significant increase of total amount of F-actin (p < 0.001). Conclusions: Hence, pretreatment with garlic oil extracts had gastroprotective effect in the cell model of peptic ulcer disease. However, further experiments are needed to fully elucidate the mechanism of this protective role.