Extracellular vesicle-mediated drug delivery in breast cancer theranostics.

Breast cancer (BC) continues to be a significant global challenge due to drug resistance and severe side effects. The increasing prevalence is alarming, requiring new therapeutic approaches to address these challenges. At this point, Extracellular vesicles (EVs), specifically small endosome-released nanometer-sized EVs (SEVs) or exosomes, have been explored by literature as potential theranostics. Therefore, this review aims to highlight the therapeutic potential of exosomes in BC, focusing on their advantages in drug delivery and their ability to mitigate metastasis. Following the review, we identified exosomes' potential in combination therapies, serving as miRNA carriers and contributing to improved anti-tumor effects. This is evident in clinical trials investigating exosomes in BC, which have shown their ability to boost chemotherapy efficacy by delivering drugs like paclitaxel (PTX) and doxorubicin (DOX). However, the translation of EVs into BC therapy is hindered by various challenges. These challenges include the heterogeneity of EVs, the selection of the appropriate parent cell, the loading procedures, and determining the optimal administration routes. Despite the promising therapeutic potential of EVs, these obstacles must be addressed to realize their benefits in BC treatment.

The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy.

INTRODUCTION: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. METHODS: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. RESULTS: Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA. CONCLUSION: The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.

The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review.

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs.

RNA in cardiovascular disease: A new frontier of personalized medicine.

Personalized medicine has witnessed remarkable progress with the emergence of RNA therapy, offering new possibilities for the treatment of various diseases, and in particular in the context of cardiovascular disease (CVD). The ability to target the human genome through RNA manipulation offers great potential not only in the treatment of cardiac pathologies but also in their diagnosis and prevention, notably in cases of hyperlipidemia and myocardial infarctions. While only a few RNA-based treatments have entered clinical trials or obtained approval from the US Food and Drug Administration, the growing body of research on this subject is promising. However, the development of RNA therapies faces several challenges that must be overcome. These include the efficient delivery of drugs into cells, the potential for immunogenic responses, and safety. Resolving these obstacles is crucial to advance the development of RNA therapies. This review explores the newest developments in medical studies, treatment plans, and results related to RNA therapies for heart disease. Furthermore, it discusses the exciting possibilities and difficulties in this innovative area of research.

CLINICAL AND EPIDEMIOLOGICAL FEATURES OF COVID-19 IN CHILDREN FOR THE PERIOD 2020-2022.

OBJECTIVE: The aim: To investigate the epidemiological and clinical characteristics of COVID-19 in children for the period 2020-2022. PATIENTS AND METHODS: Materials and methods: A retrospective analysis of 1144 case histories of children who were hospitalized at the St. Zinaida Children's Clinical Hospital (Sumy, Ukraine) for coronavirus disease for 2020-2022 was carried out. The observed patients were divided into 3 groups corresponding to the 3 waves of the pandemic: group 1 - 120 children, group 2 - 311 children, and group 3 - 713. The diagnosis of COVID-19 was established based on clinical, medical histories, laboratory and instrumental data. The etiology of coronavirus disease was determined based on the detection of antigens of the SARS-CoV-2 virus using PCR reverse transcription of a nasopharyngeal swab. RESULTS: Results: An analysis of the clinical and epidemiological indicators of children who were treated for COVID-19 during 2020-2022 was conducted, depending on the outbreak of the pandemic. The frequency of lesions in children of different age groups was determined, and the main clinical symptoms and the frequency of complications in the form of pneumonia during different waves of COVID-19 were determined. CONCLUSION: Conclusions: The incidence of coronavirus infection was mainly observed in children of the younger group (0-5 years). A more severe course of the disease and a higher frequency of complications in the form of pneumonia in children were determined during the 3rd wave of the COVID-19 pandemic.