Dry eye disease (DED) is a multifactorial disorder of the lacrimal system and ocular surface, characterized by a deficiency in the quality and/or quantity of the tear fluid. The multifactorial nature of DED encompasses a number of interconnected underlying pathologies, including loss of homeostasis, instability and hyperosmolarity of the tears, and the induction and propagation of detrimental inflammatory responses in the eyes, which finally results in the development of neurosensory dysfunction and visual disruption. Dryness, grittiness, scratchiness, discomfort, inflammation, burning, watering, ocular fatigue, pain, and decreased functional visual acuity are common symptoms of DED. Eye dysfunction drastically attenuates patients’ quality of life. Accordingly, a better understanding of the pathogenic processes that regulate the development and progression of DED is crucially important for the establishment of new and more effective DED-related treatment approaches, which would significantly improve the quality of life of DED patients. Since the process of osmoregulation, which guards the ocular surface epithelia and maintains normal vision, is affected when the osmolarity of the tears is greater than that of the epithelial cells, tear hyperosmolarity (THO) is considered an initial, important step in the development, progression, and aggravation of DED. In order to delineate the role of THO in the pathogenesis of DED, in this review article, we summarize current knowledge related to the molecular mechanisms responsible for the development of THO-induced pathological changes in the eyes of DED patients, and we briefly discuss the therapeutic potential of hypo-osmotic eye drops in DED treatment.

Breast cancer is characterized by the uncontrolled proliferation of breast cells, with a high incidence reported in 2020 to have affected over 2 million women. In recent years, the conventional methods of treating breast cancer have involved radiotherapy and chemotherapy. However, the emergence of CDK4/6 inhibitors has shown potential as a promising cancer therapy. Cyclin-dependent kinases (CDK) inhibitors are a class of molecules that impede the formation of an active kinase complex, thereby hindering its activity and consequently halting the progression of the cell cycle. It was discovered that they have a significant impact on impeding the progression of the cancer. This is evident with the Food and Drug Administration’s approval of drugs such as palbociclib, ribociclib, and abemaciclib for hormone receptor-positive metastatic breast cancer in combination with specific endocrine therapies. In spite of enormous success in breast cancer treatment, certain obstacles have emerged, such as therapy resistance, side effects, and most of all, cardiotoxicity. Some of these drawbacks have been successfully overcome by dosage reduction, different combinations of the drugs, and the assessment of each patient’s condition and suitability prior to treatment. Yet other drawbacks still require tenacious research, especially certain cases of cardiotoxicities. This article delves into the biological mechanisms of CDK4/6 in the cell cycle and cancer, as well as the clinical advantages and most common adverse events (AEs) associated with CDK4/6 inhibitors. The primary objective of this review is to provide a comprehensive analysis of cardiotoxic AEs and elucidate the underlying pathophysiological mechanisms responsible for the cardiotoxicity of CDK4/6 inhibitors.

Inflammatory diseases are a group of debilitating disorders with varying degrees of long-lasting functional impairment of targeted system. New therapeutic agents that will attenuate on-going inflammation and, at the same time, promote regeneration of injured organ are urgently needed for the treatment of autoimmune and inflammatory disorders. During the last decade numerous studies have demonstrated that crucial therapeutic benefits of mesenchymal stem cells (MSCs) in inflammatory diseases are based on the effects of MSC-produced paracrine mediators and not on the activity of engrafted cells themselves. Thus, to overcome the limitations of stem cell transplantation, MSC-derived extracellular vesicles (MSC-EVs) have been rigorously investigated, as a promising cell-free pharmaceutical component. In this review, we focus on the mechanisms of MSC-EV covering the current knowledge on their potential therapeutic applications for immune-mediated diseases.

Cancer patients represent a growing population with drastically difficult care and a lowered quality of life, especially due to the heightened risk of vast complications. Thus, it is well established so far that one of the most prominent complications in individuals with cancer is venous thromboembolism. Since there are various improved methods for screening and diagnosing cancer and its complications, the incidence of cancer-associated thrombosis has been on the rise in recent years. Therefore, the high mortality and morbidity rates among these patients are not a surprise. Consequently, there is an excruciating need for understanding the mechanisms behind this complex process, as well as the imperative for adequate analysis and application of the most suitable steps for cancer-associated thrombosis prevention. There are various and numerous mechanisms offering potential answers to cancer-associated thrombosis, some of which have already been elucidated in various preclinical and clinical scenarios, yet further and more elaborate studies are crucial to understanding and preventing this complex and harsh clinical entity. This article elaborates on the growing incidence, mortality, morbidity, and risk factors of cancer-associated thrombosis while emphasizing the pathophysiological mechanisms in the light of various types of cancer in patients and summarizes the most novel therapy and prevention guidelines recommendations.

The increasing and global distribution of microplastics and nanoplastics (MPs/NPs) in the environment has led to concern about their potential influence on human health, especially on the gastrointestinal tract, as well as the brain. MPs/NPs could traverse epithelial and endothelial barriers, disrupt the gut microbiota, and perturb the microbiota–gut–brain axis, leading to systemic inflammation and possibly extending neurodegenerative processes. Experimental models now demonstrate that MPs/NPs reprogram nuclear and mitochondrial epigenetics—DNA methylation, histone modifications, non-coding RNAs, and mitochondrial DNA regulation—in gut, immune, and neural cells with downstream effects on synaptic function, neuronal survival, and protein aggregation. This mechanistic narrative review integrates preclinical and emerging human evidence of how MPs/NPs compromise intestinal barrier integrity, modulate gut microbiota composition, affect the blood–brain barrier, and converge on oxidative stress, neuroinflammatory signaling, and cell death pathways within the central nervous system across key neurodegenerative diseases. Overall, the review offers an integrated model in which environmental exposure to chronic MPs/NPs disrupts the microbiota–gut–brain axis and drives concurrent nuclear and mitochondrial epigenetic remodeling, lowering the threshold for neurodegeneration in susceptible individuals, while outlining candidate mechanistic readouts that require exposure-specific validation in human-relevant models and longitudinal cohorts.

Immune Checkpoint Inhibitors (ICIs) are monoclonal antibodies that block inhibitory immune targets, such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L). Pembrolizumab targets the PD-1 receptor of lymphocytes in lung cancer treatment. ICI checkpoint blockade enhances immunity against cancer cells. However, loss of immunoregulatory control can cause autoimmune reactions in various organs, leading to immune-related adverse events (irAEs). The most common irAE is ICIs-induced colitis, which usually develops 6–8 weeks after ICI initiation and can involve any part of the gastrointestinal system. Herein, we report a presentation of pembrolizumab-induced colitis in a female patient with metastatic lung cancer and review the most recent findings in the model of checkpoint-induced colitis. It was interesting to learn that the colon mucosa may show normal macroscopic findings, but microscopically, immunotherapy-induced autoimmune colitis could be present. Additionally, patients with grade 2 or higher symptoms should have a colonoscopy, receive systemic corticosteroids as treatment, and, based on their response, receive biologic therapy. Here, we present a case report of in a 45-year-old female who has been a smoker for 25 years, without comorbidities, and with metastatic lung cancer who developed colitis after the seventh cycle of pembrolizumab. This case presentation highlights the importance of early recognition and appropriate intervention in order to prevent permanent interruption of treatment with checkpoint inhibitors, as well as prevention of colitis complications.