The cellular mechanisms and signaling network that guide the cardiac disease pathophysiology are inextricably intertwined, which explains the current scarcity of effective therapy and to date remains the greatest challenge in state-of-the-art cardiovascular medicine. Accordingly, a novel concept has emerged in which cardiomyocytes are the centerpiece of therapeutic targeting, with dysregulated mitochondria as a critical point of intervention. Mitochondrial dysfunction pluralism seeks a multi-faceted molecule, such as renalase, to simultaneously combat the pathophysiologic heterogeneity of mitochondria-induced cardiomyocyte injury. This review provides some original perspectives and, for the first time, discusses the functionality spectrum of renalase for mitochondrial dysfunction improvement within cardiac disease, including its ability to preserve mitochondrial integrity and dynamics by suppressing mitochondrial ΔΨm collapse; overall ATP content amelioration; a rise of mtDNA copy numbers; upregulation of mitochondrial genes involved in oxidative phosphorylation and cellular vitality promotion; mitochondrial fission inhibition; NAD⁺ supplementation; sirtuin upregulation; and anti-oxidant, anti-apoptotic, and anti-inflammatory traits. If verified that renalase, due to its multi-faceted nature, behaves like the “guardian of mitochondria” by thwarting pernicious mitochondrial dysfunction effects and exerting therapeutic potential to target mitochondrial abnormalities in failing hearts, it may provide large-scale benefits for cardiac disease patients, regardless of the underlying causes.

Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

The hallmark of the coronavirus disease 2019 (COVID‐19) pathophysiology was reported to be an inappropriate and uncontrolled immune response, evidenced by activated macrophages, and a robust surge of proinflammatory cytokines, followed by the release of reactive oxygen species, that synergistically result in acute respiratory distress syndrome, fibroproliferative lung response, and possibly even death. For these reasons, all identified risk factors and pathophysiological processes of COVID‐19, which are feasible for the prevention and treatment, should be addressed in a timely manner. Accordingly, the evolving anti‐inflammatory and antifibrotic therapy for severe COVID‐19 and hindering post‐COVID‐19 fibrosis development should be comprehensively investigated. Experimental evidence indicates that renalase, a novel amino‐oxidase, derived from the kidneys, exhibits remarkable organ protection, robustly addressing the most powerful pathways of cell trauma: inflammation and oxidative stress, necrosis, and apoptosis. As demonstrated, systemic renalase administration also significantly alleviates experimentally induced organ fibrosis and prevents adverse remodeling. The recognition that renalase exerts cytoprotection via sirtuins activation, by raising their NAD⁺ levels, provides a “proof of principle” for renalase being a biologically impressive molecule that favors cell protection and survival and maybe involved in the pathogenesis of COVID‐19. This premise supports the rationale that renalase’s timely supplementation may prove valuable for pathologic conditions, such as cytokine storm and related acute respiratory distress syndrome. Therefore, the aim for this review is to acknowledge the scientific rationale for renalase employment in the experimental model of COVID‐19, targeting the acute phase mechanisms and halting fibrosis progression, based on its proposed molecular pathways. Novel therapies for COVID‐19 seek to exploit renalase’s multiple and distinctive cytoprotective mechanisms; therefore, this review should be acknowledged as the thorough groundwork for subsequent research of renalase’s employment in the experimental models of COVID‐19.

Background and Objectives: Diabetic gastroenteropathy (DG) is a common complication of diabetes mellitus type 2. Interstitial cells are non-neural cells of mesenchymal origin inserted between nerve elements and smooth muscle cells, necessary for normal function and peristaltic contractions in the gastrointestinal (GI) tract. There are at least two types of interstitial cells within the GI muscle layer—interstitial cells of Cajal (ICC) and interstitial platelet-derived growth factor receptor α-positive cells (IPC). The mechanism of diabetic gastroenteropathy is unclear, and interstitial cells disorders caused by metabolic changes in diabetes mellitus (DM) could explain the symptoms of DG (slow intestinal transit, constipation, fecal incontinence). The aim of this study was to identify PDGFRα and c-kit immunoreactive cells in the colon of rats with streptozotocin–nicotinamide-induced diabetes mellitus type 2, as well as to determine their distribution in relation to smooth muscle cells and enteric nerve structures. Materials and Methods: Male Wistar rats were used, and diabetes type 2 was induced by an intraperitoneal injection of streptozotocin, immediately after intraperitoneal application of nicotinamide. The colon specimens were exposed to PDGFRα and anti-c-kit antibodies to investigate interstitial cells; enteric neurons and smooth muscle cells were immunohistochemically labeled with NF-M and desmin antibodies. Results: Significant loss of the intramuscular ICC, myenteric ICC, and loss of their connection in intramuscular linear arrays and around the ganglion of the myenteric plexus were observed with no changes in nerve fiber distribution in the colon of rats with diabetes mellitus type 2. IPC were rarely present within the colon muscle layer with densely distributed PDGFRα+ cells in the colon mucosa and submucosa of both experimental groups. In summary, a decrease in intramuscular ICC, discontinuities and breakdown of contacts between myenteric ICC without changes in IPC and nerve fibers distribution were observed in the colon of streptozotocin/nicotinamide-induced diabetes type 2 rats.

Intense physical activity imposes substantial oxidative, metabolic, and immunological stress on the human body. It is often accompanied by reductions in plasma glutamine levels, making this amino acid conditionally essential. Glutamine plays a vital role in energy production, nitrogen transport, acid–base balance, antioxidant defense, and immune function. It is required in the biosynthesis of neurotransmitters, nucleotides, nicotinamide-derived coenzymes, glutathione, and hexosamines, making it a candidate for supporting exercise recovery. In addition, glutamine may support key mechanisms involved in muscle adaptation and recovery during exercise-induced stress by contributing to redox balance, energy sensing, anabolic signaling, intestinal barrier integrity, and immune function. This narrative review aims to synthesize biochemical mechanisms underlying glutamine effects relevant to exercise and evaluate preclinical and clinical findings on supplementation outcomes, with emphasis on timing strategies. Preclinical findings demonstrate that glutamine can modulate protein synthesis, reduce oxidative stress, improve intestinal integrity, and attenuate immune and inflammatory disturbances. Limited preclinical data suggest that post-exercise supplementation may better resolve muscle and organ damage. Clinical trials, however, report heterogeneous outcomes: several studies show improvements in markers of intestinal permeability and intestinal epithelial damage, oxidative stress, muscle damage, and inflammation, whereas others report minimal or no effect, including limited influence on performance outcomes. Variability in timing protocols, participant characteristics, and measured endpoints contributes to inconsistent findings. Overall, glutamine demonstrates several biologically plausible mechanisms that could support recovery and overall health in active individuals, athletes, and specific clinical populations. However, current evidence remains insufficient to determine clear supplementation benefits or define an optimal timing strategy. Future research using standardized protocols and integrated biochemical and functional endpoints is needed to clarify timing effects. Until such evidence emerges, recommendations should remain individualized, considering athlete-specific needs.

Anoctamin 1 (ANO1, TMEM16A) is a transmembrane protein belonging to the ANO family, with a role in the formation of calcium-activated chloride channels (CaCC). It is included in the regulation of physiological processes such as muscle contraction, gastrointestinal motility, secretion, and electrical excitability. Also, recent data suggest that ANO1 is a specific marker for interstitial cells of Cajal (ICC). The aim of the paper was to examine the spatial and temporal distribution of ANO1 in the human stomach, small intestine, and large intestine during embryofetal development as a potential marker for the differentiation of ICC and smooth muscle cells. As a material, we used 2 embryos and samples from 21 fetuses. The tissue samples were routinely processed into paraffin blocks, and 5 µm-thick sections were immunostained for ANO1. Our results show that ANO1 appears during embryonic development (8th week), and its expression continues through the fetal stages. Epithelial, endothelial and ICC cells consistently expressed ANO1 in all examined samples. Smooth muscle cells showed strong expression in muscularis propria, however by the 25th week this immunopositivity was absent from outer muscle layers in stomach and large intestine. In conclusion, ANO1 can be considered as a reliable marker for following the differentiation of SMC and ICC during embryonic and fetal development.