The development of age-related diseases and immune system dysfunction are associated with accumulation of senescent cells characterized by a senescent-associated secretory phenotype (SASP). It is widely recognized as a key mechanism of pathologies in the elderly that increase the risk of cardiovascular, neurodegenerative, autoimmune, and cancer diseases, reducing the effectiveness of vaccinations, which increases the burden on the health care system. Research the mechanisms of immunosenescence offers new approaches for the prevention and therapy of age-related diseases. In this study, immune cells aging were measured using a senescence-associated beta-galactosidase (SA-β-Gal) assay by FACS. The number of SA-β-Gal^high CD3+ Т-cells significantly increases in peripheral blood of aged donors (>60 y.o.) compared with 20-30 y.o. The most dramatic differences in the number of senescent cells were observed in CD8+ T-cells, while the differences were less pronounced in CD4+ T cells. In agreement with previously published data SA-β-Gal^high lymphocytes express p16 and p21 (cell cycle arrest proteins). Further verification by secretion of SASP inflammatory cytokines, extra-nuclear localization of HMGB1, histone H2AX phosphorylation (γH2AX) and functional tests will confirm senescent status of SA-β-Gal^high T-cells. A comparative study of Macaca fascicularis samples of different ages, including very old, 20-30-year-old animals, will contribute for uncovering the conservative aging mechanisms in primates. This research will facilitate establishing a convenient model for testing small molecules and FDA-approved substances as potential anti-aging drugs and will serve as a basis for the development of new effective solutions to support active and healthy longevity. Study supported by Russian Science Foundation https://rscf.ru/project/23-15-00443.

Nanomedicine has witnessed remarkable progress, utilizing nano and microcarriers for treating diverse diseases. Enhancing the effectiveness of drugs through nanocarriers has been extensively researched in laboratories and clinical settings. Nanocarriers provide advantages such as protection of bioactive molecules, controlled release profiles, and targeted accumulation in specific tissues by leveraging enhanced permeability effects. However, achieving tissue-specific targeting often requires additional modifications to the carrier surface, increasing production costs and complexity. Moreover, the inherent tissue-specificity of carriers remains poorly understood and demands further exploration.

Many studies on nanocarriers rely on two-dimensional monolayer cell cultures, which do not faithfully replicate the complex three-dimensional networks present in the tumor microenvironment. Consequently, investigating carrier interactions within 2D cultures may yield unreliable results. To address this limitation, it is crucial to culture human cells in three dimensions, mimicking tissue-specific properties such as intercellular space, tissue stiffness, cell size, phagocytic function, receptor expression, and chemical gradients. Assessing the passage and uptake of nano and microcarriers within three-dimensional multicellular tumor spheroids can provide more accurate insights into the key parameters governing nanocarrier-cell interactions.

In this study, we explored the uptake and passage of polymeric carriers within cellular spheroids, with a focus on their behavior within complex three-dimensional cell systems. The carriers were constructed using a CaCO3 core and tannic acid/polyarginine-polyarginine/tannic acid. We investigated a wide range of carrier properties, including size (ranging from 300 to 1000 nm), charge (ranging from -19 to +24 mV), and stiffness (polymeric capsules and core-shell structures). To assess nanocarrier uptake and passage, we employed a combination of fluorescent microscopy and flow cytometry, enabling us to detect carriers in distinct zones of the cellular spheroids: the necrotic core, static zone, and proliferation zone, within 4T1 and L929 cell cultures. Through fluorescent microscopy, we determined carrier positions within normal and cancer spheroids, while flow cytometry facilitated the determination of their cellular and intercellular localization. Our innovative analytical method provided valuable insights into the essential aspects of carrier interactions within three-dimensional cellular systems. By utilizing three-dimensional cell cultures and employing comprehensive analytical techniques, our study significantly advances our understanding of polymeric carrier behavior within intricate cellular environments. The findings hold promising implications for the development of targeted drug delivery systems and pave the way for future advancements in the field of nanomedicine.

The inert gas xenon (Xe) is used in medicine as a safe and high-quality anesthetic during complex surgical interventions, as well as an antipsychotic agent. Sports medicine publications have described the properties of xenon in the recovery processes after prolonged physical training when used in xenon/oxygen (Xe/O₂) inhalations. Since 2014, xenon is in the World Anti-Doping Agency Prohibited List, in accordance with article S2 “Peptide hormones, growth factors, similar substances and mimetics” 1.2 “Hypoxia-inducible factor (HIF) activators”. MicroRNAs involved in the regulation of the HIF-signaling can be the markers to indirect determination of the abuse of HIF-activators. The aim of our work was to identify potential marker microRNAs, the alteration in expression of which could reveal the abuse of Xe in cases where the direct determination of this substance becomes practically impossible, for example, after the expiration of Xe excretion from the body. Clinical blood test were carried out on analyser SysmexXN-1000 (Germany). Isolation of miRNAs from blood plasma samples was performed using the PAXgene Blood miRNA Kit (Qiagen, USA). RT-qPCR was performed using miRCURY LNA SYBR Green PCR Kits and panels for studying the expression profiles of mature microRNAs of miRCURY LNA miRNA Focus PCR Panel (Qiagen, USA). Reference genes are included in the used panel. Statistical processing of the results was carried out using Bio-Rad CFX Maestro 3.0 software (USA). After five daily Xe/O₂ (25:75 v/v) inhalations for 30 minutes, the activation of erythropoesis, including an increase in the number of erythrocytes, an increase in hemoglobin concentration, etc., was determined. Simultaneously, the alterations in the expression profile of microRNAs circulating in blood plasma were observed. We found that the expression of hsa-miR-378a-3p in the blood plasma of volunteers after Xe/O₂ inhalation increases approximately 70 times (p<0.05) and is not detrmined at all in some volunteers before the inhalations. Thus, hsa-miR-378a-3p can be recomended as a potential candidate for the role of a marker of abuse of Xe in doping control.

The combination of an anticancer Pt drug and another coadjutant molecule with different biological targets is a promising therapeutic strategy. Octahedral Pt(IV) complexes allow to combine cisplatin-like moieties and a second anticancer agent in a single molecule to obtain potential bifunctional antiproliferative prodrugs. Indeed, in the hypoxic and reducing tumor environment Pt(IV) complexes are activated by a two-electron reduction to form an active Pt(II) metabolite with concomitant loss of the second agent, when linked to the metal in axial position. The natural anthranoid rhein or cassic acid has several pharmacological effects and exerts anticancer effects by modulating cellular proliferation, apoptosis, migration, and invasion. Moreover, it can inhibit in vivo glioma tumor progression. For this reason, cisplatin-based Pt(IV) derivatives were synthesized by differently linking rhein to the metal. The complexes proved to be similar to or more potent than cisplatin and rhein, and temozolomide (reference drug) on glioblastoma cells. The Pt(IV) complexes caused a significant decrease in the motility of cells, which can be related to inhibition of matrix metalloproteinases.

Chamaecyparis lawsoniana (A.Murray bis) Parl., known as Port Orford cedar or Lawson cypress and Thuja plicata Donn ex D.Don, also called giant arborvitae, are a species of the Cupressaceae family. Multiple significant biological activities of C. lawsoniana and T. plicata essential oils have been widely investigated, but their genotoxic and/or antigenotoxic properties are not well established. In the present study, two in vitro antioxidant assays were performed to assess the possible DNA protective activity of five different concentrations (0.19, 0.38, 0.75, 1.5, and 3%) of essential oils against oxidative damage induced by hydroxyl and peroxyl radicals. According to the obtained results, both essential oils have a remarkable DNA protective activity against hydroxyl and peroxyl radicals induced DNA damage. These findings confirm that C. lawsoniana and T. plicata essential oils in tested concentrations could be valuable candidates for medicinal and pharmaceutical applications.

Back ground -Bombax Malabaricum DC. is known as the red silk cotton tree, found in tropical America, Eastern Himalayas to South-East Asia. According to Charak Samhita, Bombax Malabaricum is among the top ten antiseptic, and tissue regenerator. While, according to another classical literature Sushrut Samhita, Bombax Malabaricum stem bark is useful in acne, hemorrhagic disorders, wound healing, and in burns. The trunk of plant bears prickles. The stem bark has been studied for its effect on acne. However, very limited work has been carried out for evaluating antioxidant and free radical scavenging potential of Bombax Malabaricum prickles. Objective -So, we were aimed to analyze the antioxidant potential and phytochemical screening of methanol extract of prickles of Bombax Malabaricum. Methods- Antioxidant & free radical scavenging potential was measured by DPPH, nitric oxide, hydrogen peroxide radical scavenging and reducing power assay. Phytochemical screening was performed as per standard literature. Results-Based on DPPH, nitric oxide, and hydroxyl radical scavenging activity, prickle extract showed strong scavenging activity with an IC₅₀ value of 35.30 ± 1.11 µg/ml, 16.33 ± 1.05 µg/ml. & 41.73 ± 1.17 µg/ml, respectively. Curcumin & ascorbic acid were used as standard. Phytochemical screening revealed the presence of phenol, tannin, flavonoids, saponins, carbohydrates, and triterpenoids. Conclusion -Thus, methanol extract of prickles of Bombax malabaricum DC. scavenged different free radicals efficiently, which might be due to the presence of tannins, & polyphenols. Further research can be done for isolation & characterization of phytochemicals.

The objective of this research was to assess the phytochemical profile, total phenolic and flavonoid contents, and antioxidant potential of extracts obtained from the leaves of Stachys mouretii. The plant material was collected from the Talasemtane National Park in the Ouazzane region of Morocco in April 2018. The leaves were dried, crushed, and subjected to sequential extraction using hexane, ethyl acetate, and methanol. The antioxidant activity of the ethyl acetate and methanol extracts was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, ferric reducing antioxidant power (FRAP) assay, and total antioxidant capacity method. The Folin-Ciocalteu method and the aluminum chloride (AlCl₃) colorimetric assay were employed to measure the total phenolic and flavonoid contents, respectively. The qualitative phytochemical screening of the Stachys mouretii leaf extracts indicated the presence of various bioactive phytoconstituents, such as flavonoids, sterols/steroids, terpenes/terpenoids, and polyphenols. The methanol extract displayed higher DPPH scavenging activity than the ethyl acetate extract. However, both ethyl acetate and methanol extracts exhibited greater antioxidant activity than Butylated Hydroxy Toluene (BHT) in the total antioxidant capacity determination. The ethyl acetate extract showed a significant amount of total phenolic and flavonoid contents. These findings provide a basis for further exploration of the medicinal potential of Stachys mouretii and for the isolation and purification of antioxidant compounds from this plant species.

Despite the use of available pharmaceutical drugs, high rates of metabolic diseases and cardiovascular disorders are alarming. This calls for alternative therapies that can attenuate these complications. Therefore, we investigated the beneficial effects of okra on glycaemic control in pre-diabetes and type 2 diabetes mellitus (T2D). MEDLINE and Scopus were searched for relevant studies. Search followed an updated preferred reporting items for systematic review and meta-analysis. Collected data were analysed using Review Manager version 5.4 and reported as mean difference and 95% confidence intervals (CI). Eight clinical studies, including 331 patients with pre-diabetes and T2D, were eligible. Our findings showed that okra treatment reduced the levels of fasting blood glucose, mean difference (MD) = −14.63 mg/dL; 95% CI (-25.25, −4.00, p = 0.007); I² = 33%, p = 0.17 compared to placebo. Glycated hemoglobin, however, did not differ significantly between the groups: MD = 0.01%; 95%CI (-0.51, 0.54, p = 0.96); I² = 43%, p = 0.28. This study revealed an improved glycemic control following okra treatment pre-diabetes and T2D patients. The findings suggest that okra may be used as a supplemental dietary nutrient, especially in pre-diabetic and T2D patients due to its potential to regulate hyperglycemia.

Human Transferrin is a biochemical marker of iron status in the body. Transferrin (TF) is responsible for the transport of iron through the blood to various tissues. It is a blood plasma glycoprotein that plays a central role in iron metabolism. Members of the transferrin family are mostly monomeric glycoproteins, consisting of two lobes capable of binding ferric ions. When the binding sites are empty, transferrin is called apo-transferrin, as opposed to holo-transferrin, when the binding sites are occupied. The aim of this work is to determine the binding constant, number of binding sites and the binding mechanism between Olanzapine (OLZ) and TF by spectroscopic methods (fluorescence and absorption measurements). Results showed that Olanzapine reacts with transferrin and forms a TF-OLZ complex. The binding of olanzapine to transferrin is a spontaneous process. According to the calculated quenching constants, it appears that the quenching mechanism, which involves the formation of a complex, was found to be static. The main interactions between olanzapine and transferrin are hydrogen bonding and weak van der Waals forces.

The research delves into quinazolinone derivatives, a significant class of heterocyclic compounds. With a resilient quinazolinone nucleus, these derivatives have been explored for their pharmacological potential. Computational docking studies reveal their promise as DNA gyrase inhibitors, with compound (Nitro substituent) displaying a notable -8.3 kcal/mol docking score. Binding energy analyses and receptor interactions highlight their potential . The study's core involves synthesizing Quinazolin-4(3H)-one derivatives with variations at the 6th position. NMR and IR spectral data confirm distinctive structural characteristics. These derivatives exhibit potent antimicrobial activity against gram-positive and gram-negative bacteria, including E. coli, S. typhi, B. subtilis, and S. aureus. Notably, nitro-substituted derivatives demonstrate substantial antibacterial efficacy, indicating a promising avenue for future antimicrobial drug development. Overall, the research underscores the diverse and promising applications of quinazolinone derivatives in pharmacology and therapeutic interventions.