Acta Naturae

As а model organism, the fruit fly (Drosophila melanogaster) has assumed a leading position in modern biological research. The Drosophila genetic system has a number of advantages making it a key model in investigating the molecular mechanisms of metazoan developmental processes. Over the past two decades, significant progress has been made in understanding the molecular mechanisms regulating Drosophila hematopoiesis. This review discusses the major advances in investigating the molecular mechanisms involved in maintaining the population of multipotent progenitor cells and their differentiation into mature hemocytes in the hematopoietic organ of the Drosophila larva. The use of the Drosophila hematopoietic organ as a model system for hematopoiesis has allowed to characterize the complex interactions between signaling pathways and transcription factors in regulating the maintenance and differentiation of progenitor cells through the signals from the hematopoietic niche, autocrine and paracrine signals, and the signals emanated by differentiated cells.

Anatomical visualization and molecular typing of tumor tissue of regional metastatic lymph nodes (mALN) in patients with breast cancer, it is an important clinical problem in modern oncology. According to the results of previous studies, the [99mTc]Tc-(HE)3-G3 has proven itself as a promising diagnostic agent that allows differentiating the status of the HER2/neu receptor of a primary breast tumor (p<0.05, Mann-Whitney test). In this regard, the purpose of this study is to explore the possibilities of using [99mTc]Tc-(HE)3-G3 to type the status of HER2/neu in patients with breast cancer. The study was conducted on clinical material including 20 patients with breast cancer (T2-4N1-3M0-1) before the  systemic therapy (10 patients with overexpression of HER2/neu in metastases of axillary lymph nodes and 10 patients with negative) who underwent SPECT/CT scan 4 hours after injection of [99mTc]Tc-(HE)3-G3. Morphological and immunohistochemical studies of tumor tissue of metastatic axillary lymph nodes were performed in all patients with an assessment of HER2/neu status. Based on the results of our analysis, we found that the use of the mALN -to-contralateral and mALN-to-LDM ratios 4 hours after injection of [99mTc]Tc-(HE)3-G3 should be considered for typing the status of HER2/neu in mALN in breast cancer patients (p<0.05, Mann-Whitney test). At the same time, for the low/background parameter, the sensitivity and specificity indicators were 80% with a threshold value > 12.25.

The effects of the antioxidant dihydroquercetin (DHQ) were studied in a model of pulmonary fibrosis. DHQ penetration into the lesion was facilitated by encapsulation into liposomes. Pulmonary fibrosis was modeled in rats by intratracheal injection of bleomycin. For the first 7 days, the rats in the treatment group received a liposomal emulsion with DHQ, while in the comparator group rats received saline. In the control group, intact rats did not receive any exposure. Thirty days after the initiation, lung function and the pathological lesion volume were assessed by 7T 1H MRI and the lungs were taken for histologic examination. The proportion of fibrous tissue was counted by Masson’s trichrome staining. Both experimental groups were characterized by a significant functional pulmonary deficiency, with low mortality and a small lesion area. In the rats treated with DHQ, the distribution of fibrous tissue was significantly altered. Significantly more fibrous tissue was found in the center of the lesion, while significantly less was in the interstitial space of alveoli. Lung density at the same time was lower in the treated lungs. Dihydroquercetin encapsulated in liposomes affects the mechanisms of bleomycin-induced pulmonary fibrosis progression in rats. While accelerated fibrosis of the lesion can restrict inflammatory processes, delayed fibrosis of the interstitium can further improve the functional state of the lungs.

Today, in preclinical studies, optical bioimaging based on luminescence and fluorescence is indispensable in studying the development of neoplastic transformations, the proliferative activity of the tumor, its metastatic potential, as well as the therapeutic effect of antitumor agents. In order to expand the capabilities of optical imaging, sensors based on the bioluminescence resonance energy transfer (BRET) mechanism and, therefore, independent of an external light source are being developed. A targeted nanoplatform based on HER2-specific liposomes whose internal environment contains a genetically encoded BRET sensor was developed in this study to visualize deep-seated tumors characterized by overexpression of human epidermal growth factor receptor type 2 (HER2). The BRET sensor is a hybrid protein consisting of the highly catalytic luciferase NanoLuc (an energy donor) and a LSSmKate1 red fluorescent protein with a large Stokes shift (an energy acceptor). During the bioimaging of disseminated intraperitoneal tumors formed by HER2-positive SKOV3.ip1cells of serous ovarian cystadenocarcinoma, it was shown that the developed system is applicable in detecting deep-seated tumors of a certain molecular profile. The developed system can become an efficient platform for optimizing preclinical studies of novel targeted drugs.