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Neurodegenerative diseases pose a significant health challenge for the elderly. The escalating presence of toxic metals and chemicals in the environment is a potential contributor to central nervous system dysfunction and the onset of neurodegenerative conditions. Transition metals play a crucial role in various pathophysiological mechanisms associated with prevalent neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Given the ubiquitous exposure to metals from diverse sources in everyday life, the workplace, and the environment, most of the population faces regular contact with different forms of these metals. Disturbances in the levels and homeostasis of certain transition metals are closely linked to the manifestation of neurodegenerative disorders. Oxidative damage further exacerbates the progression of neurological consequences. Presently, there exists no curative therapy for individuals afflicted by neurodegenerative diseases, with treatment approaches primarily focusing on alleviating pathological symptoms. Within the realm of biologically active compounds derived from plants, flavonoids and curcuminoids stand out for their extensively documented antioxidant, antiplatelet, and neuroprotective properties. The utilization of these compounds holds the potential to formulate highly effective therapeutic strategies for managing neurodegenerative diseases. This review provides a comprehensive overview of the impact of abnormal metal levels, particularly copper, iron, and zinc, on the initiation and progression of neurodegenerative diseases. Additionally, it aims to elucidate the potential of fisetin and curcumin to inhibit or decelerate the neurodegenerative process.

Mycobacterium tuberculosis infection remains a major cause of global morbidity and mortality due to the increase of antibiotics resistance. Dual/multi-target drug discovery is a promising approach to overcome bacterial resistance. In this study, we built ligand-based pharmacophore models and performed pharmacophore screening in order to identify hit compounds targeting simultaneously two enzymes—M. tuberculosis leucyl-tRNA synthetase (LeuRS) and methionyl-tRNA synthetase (MetRS). In vitro aminoacylation assay revealed five compounds from different chemical classes inhibiting both enzymes. Among them the most active compound—3-(3-chloro-4-methoxy-phenyl)-5-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-3H-[1,2,3]triazol-4-ylamine (1) inhibits mycobacterial LeuRS and MetRS with IC50 values of 13 µM and 13.8 µM, respectively. Molecular modeling study indicated that compound 1 has similar binding mode with the active sites of both aminoacyl-tRNA synthetases and can be valuable compound for further chemical optimization in order to find promising antituberculosis agents.

The Coenobitidae (Decapoda, Anomura, Paguroidea) is a taxon of hermit crabs that includes two genera with a fully terrestrial life style as adults. Previous studies have shown that Coenobitidae have evolved a sense of spatial odor localization that is behaviorally highly relevant. Here, we examined the central olfactory pathway of these animals by analyzing central projections of the antennular nerve of Coenobita clypeatus, combining backfilling of the nerve with dextran-coupled dye, Golgi impregnations and three-dimensional reconstruction of the primary olfactory center, the antennular lobe. The principal pattern of putative olfactory sensory afferents in C. clypeatus is in many aspects similar to what have been established for aquatic decapod crustaceans, such as the spiny lobster Panulirus argus. However, there are also obvious differences that may, or may not represent adaptations related to a terrestrial lifestyle. In C. clypeatus, the antennular lobe dominates the deutocerebrum, having more than one thousand allantoid-shaped subunits. We observed two distinct patterns of sensory neuron innervation: putative olfactory afferents from the aesthetascs either supply the cap/subcap region of the subunits or they extend through its full depth. Our data also demonstrate that any one sensory axon can supply input to several subunits. Putative chemosensory (non-aesthetasc) and mechanosensory axons represent a different pathway and innervate the lateral and median antennular neuropils. Hence, we suggest that the chemosensory input in C. clypeatus might be represented via a dual pathway: aesthetascs target the antennular lobe, and bimodal sensilla target the lateral antennular neuropil and median antennular neuropil. The present data is compared to related findings in other decapod crustaceans.

Повоєнне відновлення економіки вимагає перегляду пріоритетів розвитку та пошуку компромісу між економічними, соціальними й екологічними пріоритетами розвитку, які в сукупності мають забезпечити сталий розвиток суспільства. Метою дослідження є вивчення сутності «зелених» фінансів у контексті сталого розвитку на засадах «зеленої» економіки та необхідності повоєнного відновлення України. Для досягнення мети виконано такі завдання: проведено аналіз підходів до розуміння сутності «зелених» фінансів на основі надбань вітчизняної та іноземної літератури, визначено інституційно-організаційне забезпечення «зелених» фінансів в Україні, систематизовано фінансові інструменти «зелених» фінансів.У дослідженні використано такі методи: діалектичний та історичний – для дослідження еволюції̈  «зелених» фінансів, їхніх фінансових інструментів; індукції та дедукції, системний підхід – для визначення сутності «зелених» фінансів та основних їх аспектів; порівняльний метод – для дослідження активності «зеленого» фінансування в країнах ОЕСР та ін.Досліджено інституційно-організаційне забезпечення «зелених» фінансів на основі функціонування фіскальних і квазіфіскальних інструментів, які реалізують у сучасній фіскальній системі: екологічного податку, рентної плати в частині використання природних ресурсів, «зелених» облігацій. Визначено недостатньо використаний в Україні потенціал фіскальних і квазіфіскальних інструментів порівняно з міжнародним досвідом, у тому числі на ринках, що розвиваються. Побудовано авторську структурно-логічну схему формування та розміщення публічних фінансових ресурсів для потреб «зеленої» економіки. Рекомендовано повоєнне відновлення України здійснювати на засадах «зелених» фінансів, що можливо реалізувати за такими напрямами: підвищення суспільної поінформованості щодо «зелених» фінансів та впровадження екологічної грамотності населення, запровадження прогресивних ставок екологічного податку та рентної плати тощо; перегляд підходів до формування бюджету й унесення надходжень екологічних податків до спецфонду бюджетів; забезпечення диверсифікації фінансування для реалізації проєктів екологічного спрямування; створення передумов для запровадження ринку зелених облігацій, емітентами яких будуть держава, місцеві органи влади та суб’єкти господарювання тощо.

The complex interactions between cancer and host cells are far from being fully elucidated. Assessment of Th 1 /Th 2 /Th 3 /Tr 1 balance is an interesting approach to explain immunological disturbances in lymphomas. The aim of our study was to assess mRNA for pro- and anti-inflammatory cytokines in T-cells in 20 children with Hodgkin- and non-Hodgkin lymphomas. CD4 + and CD8 + cells were isolated from whole peripheral blood and four different cytokine mRNA levels (IFN-γ, IL-10, IL-4, TGF-β) were determined by real-time PCR technique. Comparing to the control group, we found lower expression of mRNA for IFN-gamma in CD4 + cells at the time of lymphoma diagnosis. It may be one of the pathogenetic mechanisms of impaired immunity in these patients.

The development of immunotherapy in hematologic malignancies has been observed in the last few years. One of the approaches is the use of cancer vaccines based on leukemia-derived dendritic cells (DC). Recent studies from our laboratory and other laboratories have shown that CD40 stimulation improves leukemia cells immunogenicity and generates an antitumor immune response. The design of future cancer vaccines requires the knowledge concerning the function of dendritic cells including antigen processing. The aim of our present study was the assessment of antigen-processing machinery (APM) components in acute lymphoblastic leukemia (ALL) cells before and after CD40 stimulation at messenger RNA (mRNA) level. Twenty-five children with ALL were enrolled into the study. Leukemic cells were stimulated (or not) with CD40L and IL-4. Elements of the antigen-processing machinery (MB1, LMP2, LMP7, LMP10, TAP1, TAP2, calnexin, calreticulin, tapasin, ERp57, zeta, delta) were determined by real-time PCR technique. The expression of important costimulatory and adhesion molecules considered as DC markers (CD40, CD54, CD80, CD83, CD86) were determined at the mRNA (PCR) and protein (flow cytometry) levels. The following are the results of our study: (1) We noted an upregulation of all costimulatory and adhesion molecules at the mRNA and protein levels in ALL cells after the culture; (2) the significant rise in expression of nearly all APM components after CD40 stimulation was observed. This confirms specific stimulation of the antigen-processing system in ALL cells by CD40L. Future work should focus on the clinical significance of these findings for immunotherapy in leukemias.

The use of cancer vaccines based on dendritic cells (DC) presenting tumor antigens can be a promising tool in the treatment of leukemia. The functional characteristics of leukemia derived DC is still to be elucidated. CD40 promotes survival, proliferation and differentiation of normal B cells. CD40 triggering was used to enhance the poor antigen-presenting capacity of leukemic B-cells. Since it is still unclear whether CD40 ligation drives neoplastic B-cells to apoptosis or not, we assessed the mRNA expression of FLICE, FAS, FADD and TRADD - important components of apoptosis machinery, using real-time PCR in acute lymphoblastic leukemia cells before and after CD40 and IL-4 stimulation. ALL cells stimulated with CD40L/IL-4 expressed dendritic cell phenotype at mRNA and protein levels (upregulation of main costimulatory and adhesion molecules noted in real-time RT PCR and flow cytometry); they also expressed higher amounts of mRNA for FLICE, TRADD and FADD after CD40L/IL-4 stimulation. However differences statistically significant comparing cells cultured with CD40L/IL-4 and medium alone regarded only FLICE. Concluding, we showed upregulation of important elements of apoptosis at mRNA level in ALL cells after CD40 ligation.

The complex interactions between cancer and host cells are far from being fully elucidated. Assessment of Th1/Th2/Th3/Tr1 balance is an interesting approach to explain immunological disturbances in lymphomas. The aim of our study was to assess mRNA for pro- and anti-inflammatory cytokines in T-cells in 20 children with Hodgkin- and non-Hodgkin lymphomas. CD4+ and CD8+ cells were isolated from whole peripheral blood and four different cytokine mRNA levels (IFN-gamma, IL-10, IL-4, TGF-beta) were determined by real-time PCR technique. Comparing to the control group, we found lower expression of mRNA for IFN-gamma in CD4+ cells at the time of lymphoma diagnosis. It may be one of the pathogenetic mechanisms of impaired immunity in these patients.