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.

STRUCTURAL CHANGES OF LONG TUBULAR BONES OF MATURE RATS UNDER THE HYPERGLYCEMIA.

OBJECTIVE: The aim: To evaluate morphological changes in long tubular bones of mature rats under the influence of experimental hyperglycemia. PATIENTS AND METHODS: Materials and methods: The study was conducted on 140 nonlinear white male rats divided into two groups. The experimental group included rats that were introduced into a state of hyperglycemia by a single intraperitoneal injection of an alloxan dihydrate solution at a dose of 150 mg / kg body weight in 0.9% sodium chloride. The control group included rats that were injected with a similar volume of 0.9% sodium chloride one time intraperitoneally. The animals were taken out of the experiment on the 2nd, 30th, 60th, 90th, 120th, 150th and 180th day. Right and left femur and humerus were studied by morphometric and histological methods. RESULTS: Results: Under conditions of prolonged uncontrolled hyperglycemia in mature rats, there is a slowdown in the growth rate of length and thickness of femur and humerus. This is indicated by a significant decrease in the length of bone and its diaphyses, as well as by a decrease in the cross-sectional area of the diaphysis, the width of the proximal and distal epiphyses, starting from 120 and 90 days of the experiment, respectively. The relative area of trabecular tissue, thickness of trabeculae and epiphyseal cartilage decreases in comparison with animals of the control group. The diameter of osteons and their channels increases in cortical tissue. Changes in the microarchitecture of the trabecular and cortical compartments of femur and humerus under conditions of hyperglycemia are similar and are characterized by a reduced bone mass, bone disorder progression and remodeling disorders. CONCLUSION: Conclusions: Prolonged uncontrolled experimental hyperglycemia leads to slow growth of femur and humerus in mature rats, which is accompanied by an increase in microarchitecture disorder of the trabecular and cortical compartments, causing miniaturization of bones and, consequently, violation of their biomechanical properties and increased risk of fractures.

The nomogram technique for determining the prescription of death coming by the content of acid phosphatase in the muscle tissue.

Criminologists and medical examiners in practice are interested in the existence of reliable, stable criteria that would allow to unambiguously interpret certain post-mortem phenomena observed in the body, and which would allow to determine the age of death. AIM: The aim of the study was to study the postmortem patterns of acid phosphatase in muscle tissue (MT) of various types to improve the accuracy of determining the age of death. MATERIALS AND METHODS: Determination of acid phosphatase content is performed in homogenates of myocardial, esophageal, diaphragm and intercostal muscles in the early postmortem period (PMP) (3-13 hours after death) in 30 human corpses. MT sampling was performed in the conditions of sectional biopsy with the use of special tools, preparation of MT homogenates - according to the standard method with subsequent determination of MT phosphatase content in MT homogenates by kinetic method. RESULTS: Analysis of postmortem changes in the content of acid phosphatase in MT depending on the time periods of the determining the age of death revealed that after 3 hours from the moment of death its content was the highest in a myocardium, the smallest - in MT of intercostal muscles (accordingly - 3,475±0,057 units/g and 2,662±0,028 units/g, p <0,001). The general pattern of acid phosphatase content in MT of different types was characterized by an increase in the content with increasing the age of death terms. In addition, the time series of changes in the acid phosphatase content obtained by us became the basis for substantiating the quantitative time dependences and constructing appropriate nomograms for forensic diagnosis of determining the age of death by the acid phosphatase content in MT. CONCLUSIONS: It is proved that the content of acid phosphatase naturally (and nonlinearly) changed in all studied homogenates of MT, but the initial and final level of acid phosphatase, depending on the type of MT differs. In addition, the dynamics of changes in the content of acid phosphatase in the time period 3÷13 hours. from the moment of death, depending on the type of MT, also varies. The quantitative analytical and graphical dependences of the change in the content of acid phosphatase in MT in the early PMP revealed in the study allowed to substantiate the corresponding nomograms.