Non-alcoholic fatty liver disease (NAFLD), or metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by high global incidence and prevalence, a tight association with common metabolic comorbidities, and a substantial risk of progression and associated mortality. Despite the increasingly high medical and socioeconomic burden of NAFLD, the lack of approved pharmacotherapy regimens remains an unsolved issue. In this paper, we aimed to provide an update on the rapidly changing therapeutic landscape and highlight the major novel approaches to the treatment of this disease. In addition to describing the biomolecules and pathways identified as upcoming pharmacological targets for NAFLD, we reviewed the current status of drug discovery and development pipeline with a special focus on recent evidence from clinical trials.

The effects of the selective sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin in low dose on cardiac function were investigated in normoglycemic rats. Cardiac parameters were measured by intracardiac catheterization 30 min after intravenous application of empagliflozin to healthy animals. Empagliflozin increased the ventricular systolic pressure, mean pressure, and the max dP/dt (p < 0.05). Similarly, treatment with empagliflozin (1 mg/kg, p.o.) for one week increased the cardiac output, stroke volume, and fractional shortening (p < 0.05). Myocardial infarction (MI) was induced by ligation of the left coronary artery. On day 7 post MI, empagliflozin (1 mg/kg, p.o.) improved the systolic heart function as shown by the global longitudinal strain (−21.0 ± 1.1% vs. −16.6 ± 0.7% in vehicle; p < 0.05). In peri-infarct tissues, empagliflozin decreased the protein expression of matrix metalloproteinase 9 (MMP9) and favorably regulated the cardiac transporters sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA2a) and sodium hydrogen exchanger 1 (NHE1). In H9c2 cardiac cells, empagliflozin decreased the MMP2,9 activity and prevented apoptosis. Empagliflozin did not alter the arterial stiffness, blood pressure, markers of fibrosis, and necroptosis. Altogether, short-term treatment with low-dose empagliflozin increased the cardiac contractility in normoglycemic rats and improved the systolic heart function in the early phase after MI. These effects are attributed to a down-regulation of MMP9 and NHE1, and an up-regulation of SERCA2a. This study is of clinical importance because it suggests that a low-dose treatment option with empagliflozin may improve cardiovascular outcomes post-MI. Down-regulation of MMPs could be relevant to many remodeling processes including cancer disease.

Alzheimer’s disease and cerebral ischemia are among the many causative neurodegenerative diseases that lead to disabilities in the middle-aged and elderly population. There are no effective disease-preventing therapies for these pathologies. Recent in vitro and in vivo studies have revealed the TRPC6 channel to be a promising molecular target for the development of neuroprotective agents. TRPC6 channel is a non-selective cation plasma membrane channel that is permeable to Ca²⁺. Its Ca²⁺-dependent pharmacological effect is associated with the stabilization and protection of excitatory synapses. Downregulation as well as upregulation of TRPC6 channel functions have been observed in Alzheimer’s disease and brain ischemia models. Thus, in order to protect neurons from Alzheimer’s disease and cerebral ischemia, proper TRPC6 channels modulators have to be used. TRPC6 channels modulators are an emerging research field. New chemical structures modulating the activity of TRPC6 channels are being currently discovered. The recent publication of the cryo-EM structure of TRPC6 channels should speed up the discovery process even more. This review summarizes the currently available information about potential drug candidates that may be used as basic structures to develop selective, highly potent TRPC6 channel modulators to treat neurodegenerative disorders, such as Alzheimer’s disease and cerebral ischemia.

Aim:localization of the new nomenclature of steatotic liver disease in Russian clinical practice.Key points.In 2023, international consensus decided to introduce a new nomenclature for steatotic liver disease. The article discusses the reasons for the change in nomenclature and the new terms adopted: steatotic liver disease, metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol associated steatotic liver disease. Adapting new terms to Russian healthcare poses a certain problem. The results of voting by Russian doctors on the introduction of new terms and their optimal translation are presented. A comparison of existing classifiers with new terms was carried out and the formulation of diagnoses was discussed taking into account the new nomenclature.Conclusions.Adaptation and implementation of new nomenclature into clinical practice is an important and complex task, in which it is necessary to maintain a balance between a progressive concept and the interests of practical healthcare.

Aim. The clinical guidelines are intended to provide information support for making decisions by gastroenterologists, general practitioners and internists that will improve the quality of medical care for patients with non-alcoholic fatty liver disease, taking into account the latest clinical data and principles of evidence-based medicine. Key points. Clinical guidelines contain information about current views on etiology, risk factors and pathogenesis of nonalcoholic fatty liver disease, peculiarities of its clinical course. Also given recommendations provide information on current methods of laboratory and instrumental diagnostics, invasive and non-invasive tools for nonalcoholic fatty liver disease and its clinical phenotypes assessment, approaches to its treatment, considering the presence of comorbidities, features of dispensary monitoring and prophylaxis. The information is illustrated with algorithms of differential diagnosis and physician's actions. In addition, there is information for the patient and criteria for assessing the quality of medical care. Conclusion. Awareness of specialists in the issues of diagnosis, treatment and follow-up of patients with nonalcoholic fatty liver disease contributes to the timely diagnosis and initiation of treatment, which in the long term will significantly affect their prognosis and quality of life.