Gruznova, Olga Alexandrovna

Gruznov D.V., Gruznova O.A., Sokhlikov A.B., Chesnokova I.P.

Aspergillosis of bees is an infectious disease of bee brood and adult bees caused by fungi of the Aspergillus genus. These fungi live and are reproduced in soil, feeding on plant material, including the stamens and nectary of flowers. The causative agents are brought into hives by bees carrying nectar and pollen. Once inside, they grow on honeycomb, bee bread, larvae, pupae, and adult bees under favorable conditions. Aspergillosis is a zooanthroponosis, causing significant economic damage to beekeeping and potentially posing a risk to consumers of bee-derived products. Therefore, important tasks are the selection of preparations that meet the requirements of the industry and the development of effective regimens and applications. This paper presents the results of laboratory and apiary trials of oxygen-containing preparations for the disinfection of bee-keeping facilities (hives, frames, equipment) in cases of aspergillosis. Based on the data obtained, effective regimes of their use are recommended.

Shcherbakova G.S., Popov N.I., Shuteeva E.N., Kuvshinchikov N.N., Pirozhikhin V.A., Gruznova O.A., Gruznov D.V.

The work presents the results of a study on a new disinfectant known as “Aseptobrom” for use in veterinary medicine. It contains didecyldimethylammonium bromide and alcohols as active substances. The laboratory trials showed that the disinfectant had significant antimicrobial activity against Escherichia coli (strain 1257), Staphylococcus aureus (strain 209-P) and Mycobacterium (strain terrae). As a result, it was found that S. aureus was more sensitive than E. coli. When rough, moisture-absorbing surfaces were contaminated with E. coli, disinfection was achieved with a 1% solution (3-hour exposure, disinfectant consumption rate – 0.5 L/m2). In case of contamination with staphylococcus, a 0.4% solution was used. Other specified parameters were not changed. To destroy Mycobacterium, a concentration of 6.0% was required with an exposure of 24 h. Moreover, the disinfectant was applied twice with an interval of 60 min. The consumption rate of the preparation for each irrigation was 0.5 L/m2. A study of the corrosion properties of the preparation showed that, in comparison with sodium hydroxide, it has a slight corrosive effect on metal surfaces, in particular on stainless steel and iron test plates.

Tyubaeva P.M., Varyan I.A., Romanov R.R., Merzlikin V.A., Gruznova O.A., Gruznov D.V., Popov N.I., Shcherbakova G.S., Shuteeva E.N., Chesnokova I.P., Lobanov A.V., Olkhov A.A.

This work is devoted to the creation of biocompatible fibrous materials with a high antimicrobial effect based on poly-3-hydroxybutyrate (PHB) and chlorophyll (Chl). The data obtained show the possibility of obtaining fibrous materials from PHB and Chl by electrospinning methods. The obtained electrospun matrices were investigated by the SEM, DSC and FTIR methods. Various key properties of the matrices were evaluated, including hydrophilicity and mechanical strength, as well as photodynamic and light-dependent antimicrobial effects against the conditionally pathogenic microorganism Staphylococcus aureus. The results demonstrate a significant improvement in electrospinning properties for a concentration of 0.5% Chl and a reduction in fiber formation defects, as well as an increase in the strength of nonwovens. It was found that the antimicrobial potential of Chl-PHB (with concentrations of Chl of 1.25 and 1.5%) is higher than that of Chl in free form. It was also determined that irradiation increases the inhibitory effect of Chl, both in free form and in the form of a complex with a polymer.

Gruznov D.V., Gruznova O.A., Sokhlikov A.B., Lobanov A.V., Chesnokova I.P.

Natural bee honey can change its physicochemical and biological properties during storage. Literature data on long-term storage of honey at low temperatures (from 0 to -20 °C) indicate that this ensures the stability of some physicochemical parameters. Despite the potential benefits of these temperature regimes for practical use, it is important to consider their potential negative effects on honey quality. The aim of this study was to investigate the influence of various temperature conditions on the physicochemical and biochemical parameters of linden, buckwheat, and sunflower honeys during storage for 12 months. For the first time, a wide range of physicochemical parameters of honey samples was analyzed before and during storage for 12 months at temperatures of 18, 10, 5, 0, -5, -10 and -18 (±2) °C. The evaluation of the physicochemical parameters before storage demonstrated that the samples fully complied with the Interstate Standards. Throughout the storage period, the HMF level remained stable at -18 °C, whereas it significantly increased at higher temperatures; for example, after 12 months at 18 °C, the increase ranged from 472.5% to 488.1%, depending on the botanical origin of the honey. However, maximum permissible concentration – MPC (25 mg/kg) was not exceeded. A decrease in the activity of diastase, D-glucose-1-oxidase and catalase was observed at all temperature conditions already during the first month of storage. Minimal changes were observed at 0 and 5 °C. Hydrogen peroxide (H2O2) remained stable in this temperature range. Moisture content, total mass fraction of reducing sugars, and acidity did not change significantly in all samples. An antimicrobial study using test cultures found that honey stored at 5 and 0 °C had the greatest inhibitory effect. The data obtained demonstrates that the optimal temperature range for 12-month storage of honey is between 5 and 0 °C. These findings can be used as supplementary guidance when making amendments to regulatory documents governing storage requirements for this product.

Gruznov D., Gruznova O., Sokhlikov A., Lobanov A.

Natural honey can change its physicochemical and biological properties during storage. According to State Standard 19792-2017, honey should be stored at ≤ 20°C. Some publications promote long-term storage of honey at temperatures between 0 and –20°C that preserves its physicochemical parameters, especially the content of hydroxymethylfurfural. Promising as they seem, such temperature modes may affect other physicochemical parameters of honey. The research objective was to study the effect of different temperature conditions on various honey samples and their physicochemical and biological parameters during long-term storage. The study applied standard and authentic research methods to fresh linden, buckwheat, and sunflower honey samples obtained from Rostov, Volgograd, Kursk, Voronezh, Saratov, and Krasnodar regions. They were stored in heat, cold, and moisture test chambers M-60/100-500 for 12 months. Hydroxymethylfurfural proved stable at –18°C for 12 months. After 12 months at 18°C, it showed a sharp increase of 472.5–488.1%. The activity of enzymic diastase, D-glucose-1-oxidase, and catalase occurred at all temperature modes after 1 month of storage. At 0–5°C, the changes were minimal: hydrogen peroxide (H2O2) remained stable, and its concentration decreased by ≤ 12.2% after 12 months of storage. Moisture, mass fraction of reducing sugars, and acidity remained stable in all samples. An antimicrobial test by Escherichia coli (strain 1257), Staphylococcus aureus (strain 209-P), and Bacillus cereus (strain 96) showed that the best inhibiting properties belonged to the samples of linden and buckwheat honey stored at 5 and 0°C for 12 months. The optimal temperatures for long-term honey storage were in the range between 5 and 0°C. The results obtained can be used in updated honey storage standards.

Gruznov D.V., Gruznova O.A., Popov N.I., Alieva Z.E., Shcherbakova G.S., Kitushina E.V., Ovcharenko E.N., Gololobova E.G., Klimenko I.V., Lobanov A.V., Melnikov M.Y.

Gruznov D.V., Smirnov A.M., Sokhlikov A.B., Luganskiy S.N., Gruznova O.A.

Ascospherosis of bees is an infectious disease that leads to the death of bee colonies and causes serious economic damage to the beekeeping industry. The purpose of this work is to develop disinfection regimes for beekeeping objects using effective and environmentally friendly preparations of domestic production that don’t contaminate commercial products. The studies were carried out in accordance with well-known instructions, methodological requirements and methods. Based on literature data, a number of preparations that meet the above requirements were selected. Based on the results of laboratory studies and apiary tests of selected preparations, effective regimes were selected that ensure reliable disinfection of beekeeping objects in case of ascospherosis of bees.

Gruznov D.V., Gruznova O.A., Chesnokova I.P., Plaksina L.F., Lobanov A.V., Shcherbakova G.S.

The increase in the number of antibiotic-resistant strains of microorganisms is becoming more widespread. Metalloporphyrins are promising and modern antimicrobial agents. The most well-known representatives of metalloporphyrins are chlorophyll (Chl) and hemin. This paper presents the results of studies on the effectiveness of Chl and hemin complexes with poly-N -vinylpyrrolidone (PVP) as an antimicrobial agent against Staphylococcus aureus and Escherichia coli. The method for preparing polymeric forms of Chl and hemin is presented. The binding constants of these substances to the polymer were calculated, which were 0.5×105 L/mol for Chl and 3.3×104 L/mol for hemin. Experimental data on the release of substances from the polymeric matrix were obtained. It was found that the complete release of Chl from PVP was observed after 13 h, and hemin – after 10 h. The data on the comparative antimicrobial effect of substances in free and polymeric form were obtained in a microbiological test. Further these results can be used in the development of medicines against microbial infections.

Gruznov D.V., Gruznova O.A., Lobanov A.V., Sokhlikov A.B., Shcherbakova G.S., Stepanova S.P., Popov N.I.

The chemical composition and antibacterial activity of heather honey (Calluna vulgaris) subjected to heat treatment at 35–40°C for 12 h are studied. The temperature range (38–40°C) at which the H2O2 concentration and D-glucose-1-oxidase activity decrease and the 5-hydroxymethylfurfural content increases is identified. The degree of chemical changes is directly proportional to the temperature and time of thermal exposure. The correlation between changes in the chemical composition and antibacterial activity of honey against the Escherichia coli (strain 1257), Staphylococcus aureus (strain 209-P), and Bacillus cereus (strain 96) test microorganisms is established. The obtained results show that heating the honey to 37°C even for 12 h does not cause undesirable changes in its chemical composition or decrease in antibacterial activity. Thus, this temperature regime can be considered gentler and recommended for use in the heat treatment of this food product.

Gruznov D.V., Gruznova O.A., Lobanov A.V., Shcherbakova G.S., Chesnokova I.P.

The increase in the number of microorganism strains with resistance to anti-bacterial and disinfecting agents is getting more and more prevalent and has become an issue when treating the human and animals diseases and carrying out measures for disinfection treatment. This problem can be solved by using photodynamic and light-independent therapy. In both areas, metalloporphyrins have been successfully used for many years. One of the most famous representatives of porphyrins is chlorophyll (Chl). This work aims to develop of Chl polymeric form by incorporation in poly(lactic acid) (PLA) and study its inhibitory effect against Staphylococcus aureus and Escherichia coli, which are known as contaminants of the mucous and skin epithelium of humans and animals. The preparation method of Chl polymeric form is presented. The degree of Chl incorporation into PLA was more than 98%. The assessment of antimicrobial activity was carried out by measuring the inhibition zone diameters after bacterial incubation for 24–96 h. It was shown that Chl and Chl-PLA at a dosage of 75 µg inhibited S. aureus significantly. The exclusively bacteriostatic effect on E. coli was observed. These results can be used in the development of dosage forms and disinfectants.

Shcherbakova G.S., Gruznov D.V., Gruznova O.A., Popov N.I., Pirozhikhin V.A.

The stability of work solutions of domestic disinfectants “STEROX vet” and “Biolok” of different concentrations (0.1%, 0.5% and 1%) was examined by electronic absorption spectroscopy. The study was conducted between July and September 2023. When stored according to manufacturer requirements, the changes in the content of the work solution components were found to be directly dependent on the dilution degree. At a concentration of 1.0%, the level of active substance (N,N-bis(3-aminopropyl)-dodecylamine) remained virtually unchanged. Based on the data obtained, it is recommended to prepare work solutions of lower concentrations immediately before using. In addition, effective disinfection modes and efficacious concentrations for these products were determined in relation to sanitary-indicative microorganisms of different resistance groups to the chemical disinfectants.

Gruznov D.V., Gruznova O.A., Popov N.I., Shcherbakova G.S., Shuteeva E.N., Konyashkina A.V., Chesnokova I.P., Plaksina L.F., Lobanov A.V.

Gruznov D.V., Gruznova O.A., Popov N.I., Alieva Z.E., Stepanova S.P., Shcherbakova G.S., Kitushina E.V., Tyubaeva P.M., Varyan I.A., Olkhov A.A., Popov A.A., Klimenko I.V., Lobanov A.V.

Zhunina O.A., Yabbarov N.G., Grechko A.V., Starodubova A.V., Ivanova E., Nikiforov N.G., Orekhov A.N.

Mitochondrial dysfunction is known to be associated with a wide range of human pathologies, such as cancer, metabolic, and cardiovascular diseases. One of the possible ways of mitochondrial involvement in the cellular damage is excessive production of reactive oxygen and nitrogen species (ROS and RNS) that cannot be effectively neutralized by existing antioxidant systems. In mitochondria, ROS and RNS can contribute to protein and mitochondrial DNA (mtDNA) damage causing failure of enzymatic chains and mutations that can impair mitochondrial function. These processes further lead to abnormal cell signaling, premature cell senescence, initiation of inflammation, and apoptosis. Recent studies have identified numerous mtDNA mutations associated with different human pathologies. Some of them result in imbalanced oxidative phosphorylation, while others affect mitochondrial protein synthesis. In this review, we discuss the role of mtDNA mutations in cancer, diabetes, cardiovascular diseases, and atherosclerosis. We provide a list of currently described mtDNA mutations associated with each pathology and discuss the possible future perspective of the research.

Sokol M.B., Faustova M.R., Nikolskaya E.D., Zhunina O.A., Fomicheva M.V., Petrov R.V., Yabbarov N.G.

New high-molecular-weight contrast agents based on polyamidoamine (PAMAM) dendrimers for targeted imaging of malignant tumors characterized by overexpression of human epidermal growth factor receptor (EGFR) and human alpha-fetoprotein receptor (RECAF) were designed. Conjugates of second (G2) and third (G3) generation polyamidoamine dendrimers with 1,4,7,10-tetraazocyclodecane-1,4,7,10-tetraacetic acid (DOTA) were obtained. The quantitative composition of the conjugates was determined by 1 HNMR spectroscopy. It was shown that four out of the 16 terminal NH 2 groups in G2-DOTA and nine out of the 32 groups in G3-DOTA were modified with DOTA. The morphology, size, and charge of the synthesized macromolecules were characterized by dynamic light scattering and electrophoresis. Gadolinium(III) was loaded into the conjugates and the Gd content was determined by atomic emission spectroscopy. For increasing the selectivity of accumulation in the tumor cells, two recombinant proteins able to bind selectively to EGFR and RECAF, namely, human recombinant epidermal growth factor (rEGF) and human recombinant 3rd domain of alpha-fetoprotein (3dAFPpG), were conjugated with G2 and G3 dendrimers. The conjugates containing vector molecules were mainly accumulated via clathrin-dependent endocytosis, whereas G2-DOTA and G3-DOTA were absorbed via caveolin-dependent endocytosis and macropinocytosis. The dendrimer conjugates with vector molecules were intensely accumulated in A549 cells characterized by high expression of EGFR (Herl) and RECAF, whereas the accumulation of conjugates in the control K562 cells (with low expression of Her1) and in the CD14 − population of human unstimulated mononuclear white blood cells was insignificant. The 3dAFPpG-conjugated dendrimers were partly recycled. All synthesized conjugates had a rather low toxicity in the range of 350–450 µmol L −1 (IC 50 ).

Wang Z., Sun W., Zhang K., Ke X., Wang Z.

Li J., Hou Y., Wu H., Chen C., Fu X., Liu J., Li L., Shang S., Deng G.

Nazarnezhad S., Gorgani S., Hosseini S.A., Azari Z., Baino F.

Sharma S.

Junco M., Ventura C., Santiago Valtierra F.X., Maldonado E.N.

Cancer metabolism is sustained both by enhanced aerobic glycolysis, characteristic of the Warburg phenotype, and oxidative metabolism. Cell survival and proliferation depends on a dynamic equilibrium between mitochondrial function and glycolysis, which is heterogeneous between tumors and even within the same tumor. During oxidative phosphorylation, electrons from NADH and FADH2 originated in the tricarboxylic acid cycle flow through complexes of the electron transport chain. Single electron leaks at specific complexes of the electron transport chain generate reactive oxygen species (ROS). ROS are a concentration-dependent double-edged sword that plays multifaceted roles in cancer metabolism. ROS serve either as signaling molecules favoring cellular homeostasis and proliferation or damage DNA, protein and lipids, causing cell death. Several aspects of ROS biology still remain unsolved. Among the unknowns are the actual levels at which ROS become cytotoxic and if toxicity depends on specific ROS species or if it is caused by a cumulative effect of all of them. In this review, we describe mechanisms of mitochondrial ROS production, detoxification, ROS-induced cytotoxicity, and the use of antioxidants in cancer treatment. We also provide updated information about critical questions on the biology of ROS on cancer metabolism and discuss dogmas that lack adequate experimental demonstration. Overall, this review brings a comprehensive perspective of ROS as drivers of cancer progression, inducers of cell death, and the potential use of antioxidants as anticancer therapy.

Jia G., Jiang Y., Li X.

Traditional chemotherapy is often accompanied by off-target toxicity, resulting in adverse side effects and driving the development of targeted therapies. Targeted drug conjugates (TDCs) typically comprise targeting ligands, such as specific antibodies, peptides, or small molecules, attached to a cytotoxic agent via a chemical linker. In this study, we briefly discussed the molecular aspects of the key components of TDCs and the mechanisms by which these key factors exert their activity. Moreover, we reviewed FDA-approved TDCs and promising candidates in clinical trials and discussed current challenges and future directions for TDC development, providing insights for the research and development of novel cancer therapeutics using TDCs. TDCs combine the advantages of highly specific targeting and a potent killing effect, enabling accurate and efficient cancer cell elimination. Food and Drug Administration (FDA)-approved antibody-drug conjugates (ADCs) have shown good efficacy in treating various cancers; however, they still present limitations such as immunogenicity, hematotoxicity, and complex pharmacokinetics. Smaller peptide-drug conjugates (PDCs) and small molecule-drug conjugates (SMDCs) may combine the advantages of ADCs while overcoming some of their limitations, thereby presenting more efficacious and safer alternatives. TDCs enhance the therapeutic effects of cytotoxic agents and reduce their adverse effects. However, tumor heterogeneity, limited transmembrane permeability, and drug resistance pose significant challenges for TDCs, potentially affecting their therapeutic efficacy. Nevertheless, TDCs are a promising therapeutic approach for cancer treatment, achieving precise drug delivery while minimizing toxicity and side effects on normal cells.

Tyubaeva P.M., Varyan I.A., Romanov R.R., Merzlikin V.A., Gruznova O.A., Gruznov D.V., Popov N.I., Shcherbakova G.S., Shuteeva E.N., Chesnokova I.P., Lobanov A.V., Olkhov A.A.

This work is devoted to the creation of biocompatible fibrous materials with a high antimicrobial effect based on poly-3-hydroxybutyrate (PHB) and chlorophyll (Chl). The data obtained show the possibility of obtaining fibrous materials from PHB and Chl by electrospinning methods. The obtained electrospun matrices were investigated by the SEM, DSC and FTIR methods. Various key properties of the matrices were evaluated, including hydrophilicity and mechanical strength, as well as photodynamic and light-dependent antimicrobial effects against the conditionally pathogenic microorganism Staphylococcus aureus. The results demonstrate a significant improvement in electrospinning properties for a concentration of 0.5% Chl and a reduction in fiber formation defects, as well as an increase in the strength of nonwovens. It was found that the antimicrobial potential of Chl-PHB (with concentrations of Chl of 1.25 and 1.5%) is higher than that of Chl in free form. It was also determined that irradiation increases the inhibitory effect of Chl, both in free form and in the form of a complex with a polymer.

Pal S., Firdous S.M.

Cancer is a multifaceted disease characterized by the gradual accumulation of genetic and epigenetic alterations within cells, leading to uncontrolled cell growth and invasive behavior. The intricate interplay between environmental factors, such as exposure to carcinogens, and the molecular cascades governing cell growth, differentiation, and survival contributes to cancer’s development and progression. This review offers a comprehensive overview of key molecular targets and their roles in cancer development. Peroxisome proliferator-activated receptors are implicated in various cancers due to their role in regulating lipid metabolism, inflammation, and cell proliferation. Nuclear factor erythroid 2-related factor 2 protects cells from oxidative damage but can also promote tumor cell survival. Cytochrome P450 1B1 metabolizes exogenous and endogenous substances, and its increased expression is observed in several cancers. The constitutive androstane receptor regulates gene expression, and its dysregulation can lead to liver cancer. Transforming growth factor-beta 2 is involved in the development and progression of various cancers by dysregulating cell proliferation, differentiation, and migration. Chelation treatment has been investigated for removing heavy metals, while genetically altered immune cells show promise in treating specific cancers. Metal–organic frameworks and fibronectin targeting represent new directions in cancer treatment. While some heavy metals, such as arsenic, chromium, nickel, and cadmium, are known to have carcinogenic properties, others, like zinc, Copper, gold, bismuth, and silver, have many uses that highlight their potential as effective cancer control tactics. There are a variety of heavy metal-based technologies that show potential for improving cancer treatment methods, including targeted drug delivery, improved radiation, and diagnostic tools.

Xiong W., Xu K., Sun J.K., Liu S., Zhao B., Shi J., Herrup K., Chow H., Lu L., Li J.

AbstractMaintaining mitochondrial homeostasis is crucial for cell survival and organismal health, as evidenced by the links between mitochondrial dysfunction and various diseases, including Alzheimer’s disease (AD). Here, we report that lncMtDloop, a non-coding RNA of unknown function encoded within the D-loop region of the mitochondrial genome, maintains mitochondrial RNA levels and function with age. lncMtDloop expression is decreased in the brains of both human AD patients and 3xTg AD mouse models. Furthermore, lncMtDloop binds to mitochondrial transcription factor A (TFAM), facilitates TFAM recruitment to mtDNA promoters, and increases mitochondrial transcription. To allow lncMtDloop transport into mitochondria via the PNPASE-dependent trafficking pathway, we fused the 3’UTR localization sequence of mitochondrial ribosomal protein S12 (MRPS12) to its terminal end, generating a specified stem-loop structure. Introducing this allotropic lncMtDloop into AD model mice significantly improved mitochondrial function and morphology, and ameliorated AD-like pathology and behavioral deficits of AD model mice. Taken together, these data provide insights into lncMtDloop as a regulator of mitochondrial transcription and its contribution to Alzheimer’s pathogenesis

Salis Torres A., Lee J., Caporali A., Semple R.K., Horrocks M.H., MacRae V.E.

Individuals diagnosed with Parkinson’s disease (PD) often exhibit heightened susceptibility to cardiac dysfunction, reflecting a complex interaction between these conditions. The involvement of mitochondrial dysfunction in the development and progression of cardiac dysfunction and PD suggests a plausible commonality in some aspects of their molecular pathogenesis, potentially contributing to the prevalence of cardiac issues in PD. Mitochondria, crucial organelles responsible for energy production and cellular regulation, play important roles in tissues with high energetic demands, such as neurons and cardiac cells. Mitochondrial dysfunction can occur in different and non-mutually exclusive ways; however, some mechanisms include alterations in mitochondrial dynamics, compromised bioenergetics, biogenesis deficits, oxidative stress, impaired mitophagy, and disrupted calcium balance. It is plausible that these factors contribute to the increased prevalence of cardiac dysfunction in PD, suggesting mitochondrial health as a potential target for therapeutic intervention. This review provides an overview of the physiological mechanisms underlying mitochondrial quality control systems. It summarises the diverse roles of mitochondria in brain and heart function, highlighting shared pathways potentially exhibiting dysfunction and driving cardiac comorbidities in PD. By highlighting strategies to mitigate dysfunction associated with mitochondrial impairment in cardiac and neural tissues, our review aims to provide new perspectives on therapeutic approaches.

Demyashkin G., Parshenkov M., Koryakin S., Skovorodko P., Shchekin V., Yakimenko V., Uruskhanova Z., Ugurchieva D., Pugacheva E., Ivanov S., Shegay P., Kaprin A.

Background: Radiation-induced liver disease (RILD) is a severe complication arising from radiotherapy, particularly when treating abdominal malignancies such as hepatocellular carcinoma. The liver’s critical role in systemic metabolism and its proximity to other abdominal organs make it highly susceptible to radiation-induced damage. This vulnerability significantly limits the maximum safe therapeutic dose of radiation, thereby constraining the overall efficacy of radiotherapy. Among the various modalities, electron beam therapy has gained attention due to its ability to precisely target tumors while minimizing exposure to surrounding healthy tissues. However, despite its advantages, the long-term impacts of electron beam exposure on liver tissue remain inadequately understood, particularly concerning chronic injury and fibrosis driven by sustained oxidative stress. Objectives: to investigate the molecular and cellular mechanisms underlying the radioprotective effects of vitamin C in a model of radiation-induced liver disease. Methods: Male Wistar rats (n = 120) were randomly assigned to four groups: control, fractionated local electron irradiation (30 Gy), pre-treatment with vitamin C before irradiation, and vitamin C alone. The study evaluated the effects of electron beam radiation and vitamin C on liver tissue through a comprehensive approach, including biochemical analysis of serum enzymes (ALT, AST, ALP, and bilirubin), cytokine levels (IL-1β, IL-6, IL-10, and TNF-α), and oxidative stress markers (MDA and SOD). Histological and morphometric analyses were conducted on liver tissue samples collected at 7, 30, 60, and 90 days, which involved standard staining techniques and advanced imaging, including light and electron microscopy. Gene expression of Bax, Bcl-2, and caspase-3 was analyzed using real-time PCR. Results: The present study demonstrated that fractional local electron irradiation led to significant reductions in body weight and liver mass, as well as marked increases in biochemical markers of liver damage (ALT, AST, ALP, and bilirubin), inflammatory cytokines (IL-1β, IL-6, and TNF-α), and oxidative stress markers (MDA) in the irradiated group. These changes were accompanied by substantial histopathological alterations, including hepatocyte degeneration, fibrosis, and disrupted microvascular circulation. Pre-treatment with vitamin C partially mitigated these effects, reducing the severity of the liver damage, oxidative stress, and inflammation, and preserving a more favorable balance between hepatocyte proliferation and apoptosis. Overall, the results highlight the potential protective role of vitamin C in reducing radiation-induced liver injury, although the long-term benefits require further investigation. Conclusions: The present study highlights vitamin C’s potential as a radioprotective agent against electron beam-induced liver damage. It effectively reduced oxidative stress, apoptosis, and inflammation, particularly in preventing the progression of radiation-induced liver fibrosis. These findings suggest that vitamin C could enhance radiotherapy outcomes by minimizing liver damage, warranting further exploration into its broader clinical applications.

Qu Y., Meng B., Cai S., Yang B., He Y., Fu C., Li X., Li P., Cao Z., Mao X., Teng W., Shi S.

Over 50 billion cells undergo apoptosis each day in an adult human to maintain tissue homeostasis by eliminating damaged or unwanted cells. Apoptotic deficiency can lead to age-related diseases with reduced apoptotic metabolites. However, whether apoptotic metabolism regulates aging is unclear. Here, we show that aging mice and apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) mice exhibit decreased apoptotic levels along with increased aging phenotypes in the skeletal bones, which can be rescued by the treatment with apoptosis inducer staurosporine (STS) and stem cell-derived apoptotic vesicles (apoVs). Moreover, embryonic stem cells (ESC)-apoVs can significantly reduce senescent hallmarks and mtDNA leakage to rejuvenate aging bone marrow mesenchymal stem cells (MSCs) and ameliorate senile osteoporosis when compared to MSC-apoVs. Mechanistically, ESC-apoVs use TCOF1 to upregulate mitochondrial protein transcription, resulting in FLVCR1-mediated mitochondrial functional homeostasis. Taken together, this study reveals a previously unknown role of apoptotic metabolites in ameliorating bone aging phenotypes and the unique role of TCOF1/FLVCR1 in maintaining mitochondrial homeostasis.

Borlan R., Tudor M., Soritau O., Florea A., Pall E., Pop B., Maniu D., Astilean S., Focsan M.

Gruznov D.V., Gruznova O.A., Sokhlikov A.B., Lobanov A.V., Chesnokova I.P.

Natural bee honey can change its physicochemical and biological properties during storage. Literature data on long-term storage of honey at low temperatures (from 0 to -20 °C) indicate that this ensures the stability of some physicochemical parameters. Despite the potential benefits of these temperature regimes for practical use, it is important to consider their potential negative effects on honey quality. The aim of this study was to investigate the influence of various temperature conditions on the physicochemical and biochemical parameters of linden, buckwheat, and sunflower honeys during storage for 12 months. For the first time, a wide range of physicochemical parameters of honey samples was analyzed before and during storage for 12 months at temperatures of 18, 10, 5, 0, -5, -10 and -18 (±2) °C. The evaluation of the physicochemical parameters before storage demonstrated that the samples fully complied with the Interstate Standards. Throughout the storage period, the HMF level remained stable at -18 °C, whereas it significantly increased at higher temperatures; for example, after 12 months at 18 °C, the increase ranged from 472.5% to 488.1%, depending on the botanical origin of the honey. However, maximum permissible concentration – MPC (25 mg/kg) was not exceeded. A decrease in the activity of diastase, D-glucose-1-oxidase and catalase was observed at all temperature conditions already during the first month of storage. Minimal changes were observed at 0 and 5 °C. Hydrogen peroxide (H2O2) remained stable in this temperature range. Moisture content, total mass fraction of reducing sugars, and acidity did not change significantly in all samples. An antimicrobial study using test cultures found that honey stored at 5 and 0 °C had the greatest inhibitory effect. The data obtained demonstrates that the optimal temperature range for 12-month storage of honey is between 5 and 0 °C. These findings can be used as supplementary guidance when making amendments to regulatory documents governing storage requirements for this product.

Liang R., Zhu L., Huang Y., Chen J., Tang Q.

As one of the most vital organelles within biological cells, mitochondria hold an irreplaceable status and play crucial roles in various diseases. Research and therapies targeting mitochondria have achieved significant progress in numerous conditions. Throughout an organism’s lifespan, mitochondrial dynamics persist continuously, and due to their inherent characteristics and various external factors, mitochondria are highly susceptible to damage. This susceptibility is particularly evident during aging, where the decline in biological function is closely intertwined with mitochondrial dysfunction. Despite being an ancient and enigmatic organelle, much remains unknown about mitochondria. Here, we will explore the past and present knowledge of mitochondria, providing a comprehensive review of their intrinsic properties and interactions with nuclear DNA, as well as the challenges and impacts they face during the aging process.

Williams L., Holzer V.J., Nickelsen J., Hatton F.L., Mele E.

Mendonça I., Silva D., Conde T., Maurício T., Cardoso H., Pereira H., Bartolomeu M., Vieira C., Domingues M.R., Almeida A.

Antibacterial resistance causes around 1.27 million deaths annually around the globe and has been recognized as a top 3 priority health threat. Antimicrobial photodynamic therapy (aPDT) is considered a promising alternative to conventional antibiotic treatments. Algal lipid extracts have shown antibacterial effects when used as photosensitizers (PSs) in aPDT. In this work we assessed the photodynamic efficiency of lipidic extracts of microalgae belonging to different phyla (Bacillariophyta, Chlorophyta, Cyanobacteria, Haptophyta, Ochrophyta and Rhodophyta). All the extracts (at 1 mg mL

Gonçalves A.S., Leitão M.M., Fernandes J.R., Saavedra M.J., Pereira C., Simões M., Borges A.

Staphylococcus aureus is characterized by its high resistance to conventional antibiotics, particularly methicillin-resistant (MRSA) strains, making it a predominant pathogen in acute and chronic wound infections. The persistence of acute S. aureus wound infections poses a threat by increasing the incidence of their chronicity. This study investigated the potential of photodynamic activation using phytochemical-antibiotic combinations to eliminate S. aureus under conditions representative of acute wound infections, aiming to mitigate the risk of chronicity. The strategy applied takes advantage of the promising antibacterial and photosensitising properties of phytochemicals, and their ability to act as antibiotic adjuvants. The antibacterial activity of selected phytochemicals (berberine, curcumin, farnesol, gallic acid, and quercetin; 6.25-1000 μg/mL) and antibiotics (ciprofloxacin, tetracycline, fusidic acid, oxacillin, gentamicin, mupirocin, methicillin, and tobramycin; 0.0625-1024 μg/mL) was screened individually and in combination against two S. aureus clinical strains (methicillin-resistant and -susceptible-MRSA and MSSA). The photodynamic activity of the phytochemicals was assessed using a light-emitting diode (LED) system with blue (420 nm) or UV-A (365 nm) variants, at 30 mW/cm

Abdelshafy A.M., Neetoo H., Al-Asmari F.

Hydrogen peroxide (H2O2) is a well-known agent with a broad-spectrum antimicrobial activity against pathogenic bacteria, fungi, and viruses. It is a colorless liquid and commercially available in aqueous solution over a wide concentration range. It has been extensively used in the food industry by virtue of its strong oxidizing property and its ability to cause cellular oxidative damage in microbial cells. This review comprehensively documents recent research on the antimicrobial activity of H2O2 against organisms of concern for the food industry, as well as its effect against SARS-CoV-2 responsible for the COVID-19 pandemic. In addition, factors affecting the antimicrobial effectiveness of H2O2, different applications of H2O2 as a sanitizer or disinfectant in the food industry as well as safety concerns associated with H2O2 are discussed. Finally, recent efforts in enhancing the antimicrobial efficacy of H2O2 are also outlined.

Gruznov D.V., Gruznova O.A., Chesnokova I.P., Plaksina L.F., Lobanov A.V., Shcherbakova G.S.

The increase in the number of antibiotic-resistant strains of microorganisms is becoming more widespread. Metalloporphyrins are promising and modern antimicrobial agents. The most well-known representatives of metalloporphyrins are chlorophyll (Chl) and hemin. This paper presents the results of studies on the effectiveness of Chl and hemin complexes with poly-N -vinylpyrrolidone (PVP) as an antimicrobial agent against Staphylococcus aureus and Escherichia coli. The method for preparing polymeric forms of Chl and hemin is presented. The binding constants of these substances to the polymer were calculated, which were 0.5×105 L/mol for Chl and 3.3×104 L/mol for hemin. Experimental data on the release of substances from the polymeric matrix were obtained. It was found that the complete release of Chl from PVP was observed after 13 h, and hemin – after 10 h. The data on the comparative antimicrobial effect of substances in free and polymeric form were obtained in a microbiological test. Further these results can be used in the development of medicines against microbial infections.

Marioni J., Mugas M.L., Martinez F., Romero B., Gómez T.I., Lingua G., Konigheim B., Núñez Montoya S.C.

Antimicrobial Photodynamic Therapy (aPDT) has demonstrated effectiveness against various Candida biofilms, typical resistant to conventional treatments. Some strategies have shown to enhance the photoactivity of some photosensitizers (PS), such as the use of a multiple irradiation scheme or the combination with drugs that improve the penetration of the PS through the microbial membrane. Having demonstrated the photodynamic antibiofilm activity of some natural anthraquinones (AQs), we selected rubiadin 1-methyl ether (R-1ME) that showed a low photo-reduction percentage (%R) on the biofilm mass, with the aim to improve its effect. Experimental in vitro photo-stimulation protocols have been developed, which include successive light exposures and the combination of this AQ with a commonly used antifungal such as Amphotericin B (AmB). The biofilms reduction was quantified by Crystal Violet staining. Reactive oxygen and nitrosative species were observed as action mechanism, alongside an assessment of antioxidant response through superoxide dismutase enzyme activation and total antioxidant system capacity. Applying R-1ME to C. tropicalis biofilms with sequential 15-min irradiation sessions at varied incubation intervals (0, 3, 6, 24, 27, and 30 h) yielded a substantial photo-reduction (62.9 %R) on biofilm mass, even halving the bioactive concentration of R-1ME. Moreover, combining R-1ME with AmB under this irradiation pattern produced an even greater impact (82 %R) at concentrations below the Minimal Inhibitory Concentration. Evident redox imbalances in the biofilm were linked to this photosensitized activity. A new strategy was found to improve the activity of a natural PS on fungal biofilms, by combining it with antifungal drugs, under a staged irradiation scheme, which, in turn, required low doses of the PS and the antifungal to achieve this improved photo-reduction.

Wang S., Qiu Y., Zhu F.

Manuka honey (MH) is a highly prized natural product from the nectar of Leptospermum scoparium flowers. Increased competition on the global market drives MH product innovations. This review updates comparative and non-comparative studies to highlight nutritional, therapeutic, bioengineering, and cosmetic values of MH. MH is a good source of phenolics and unique chemical compounds, such as methylglyoxal, dihydroxyacetone, leptosperin glyoxal, methylsyringate and leptosin. Based on the evidence from in vitro, in vivo and clinical studies, multifunctional bioactive compounds of MH have exhibited anti-oxidative, anti-inflammatory, immunomodulatory, anti-microbial, and anti-cancer activities. There are controversial topics related to MH, such as MH grading, safety/efficacy, implied benefits, and maximum levels of contaminants concerned. Artificial intelligence can optimize MH studies related to chemical analysis, toxicity prediction, multi-functional mechanism exploration and product innovation.

Scott J.W., Steel J.J.

ABSTRACT There are places on earth that are considered to possess extreme physico-chemical characteristics as they relate to life. Surprisingly, there are microbes that have adapted various strategies that enable them to form robust communities in these environments. The microbes that live in these environments, called extremophiles, are described as being thermophilic, psychrophilic, halophilic, acidophilic, alkaliphilic, barophilic, and so on. Given that extremophiles were not discovered until relatively recently due to a view point that the environments in which they inhabited were not conducive to life, it is reasonable to conclude that the concept of extremophiles may be hard to grasp for students. Herein is described a laboratory exercise adapted from laboratory exercises that use mesophilic catalase enzymes to illustrate the influence of physico-chemical parameters on enzyme activity. Catalase is an enzyme that accelerates the degradation of hydrogen peroxide to water and oxygen gas. In addition to mesophilic catalases, the catalase from Pyrobaculum calidifontis , a hyperthermophile with an optimal growth temperature of 90°C, is used to highlight the adaptation of an enzyme to an extreme environment. A visual comparison of bubble production by the hyperthermophilic and mesophilic enzymes after heating at high temperatures dramatically illustrates differences in thermostability that will likely reinforce concepts that are given in a pre-laboratory lecture that discusses not only the extremophiles themselves but also their applications in biotechnology and possible role in the field of astrobiology.

Tyubaeva P.M., Varyan I.A., Nikolskaya E.D., Yabbarov N.G., Chirkina M.V., Sokol M.B., Mollaeva M.R., Yurina L.V., Vasilyeva A.D., Rosenfeld M.A., Obydennyi S.I., Chabin I.A., Popov A.A.

Electrospun biomimetic materials based on polyester of natural origin poly-3-hudroxybutyrate (PHB) modified with hemin (Hmi) and fibrinogen (Fbg) represent a great interest and are potentially applicable in various fields. Here, we describe formulation of the new fibrous PHB-Fbg and PHB-Hmi-Fbg materials with complex structure for biomedical application. The average diameter of the fibers was 3.5 μm and 1.8 μm respectively. Hmi presence increased porosity from 80 % to 94 %, significantly reduced the number of defects, ensured the formation of a larger number of open pores, and improved mechanical properties. Hmi presence significantly improved the molding properties of the material. Hmi facilitated effective Fbg adsorption on the of the PHB wound-healing material, ensuring uniform localization of the protein on the surface of the fibers. Next, we evaluated cytocompatibility, cell behavior, and open wound healing in mice. The results demonstrated that PHB-Fbg and PHB-Hmi-Fbg electrospun materials had pronounced properties and may be promising for early-stage wound healing - the PHB-Hmi-Fbg sample accelerated wound closure by 35 % on the 3rd day, and PHB-Hmi showed 45 % more effective wound closure on the 15th day.

Bush D.S., Calla B., Berenbaum M.R.

AbstractAspergillus fungi are ubiquitous inhabitants of colonies of the western honey bee (Apis mellifera), where they interact with bees in associations ranging from parasitism to possible mutualism. Aspergillus Flavi fungi are frequently found in bee bread (pollen processed for longterm storage) and are thought to contribute to food preparation, processing, preservation, and digestion. Conditions in the hive are challenging for fungi due, in part, to xeric and acidic properties of bee bread and the omnipresence of propolis, an antimicrobial product manufactured by bees from plant resins. We used quantitative and qualitative assays to determine whether A. flavus isolated from bee bread demonstrates tolerance for hive environmental conditions in terms of temperature, pH, osmotic pressure, and propolis exposure. Comparisons made use of three strains of A. flavus: a fungal biocontrol product not known from beehives (AF36), a strain isolated from bee bread (AFBB) in hives from central Illinois, and a pathogenic strain from a honey bee colony displaying symptoms of stonebrood (AFPA). Strain AFBB displayed higher tolerance of acidic conditions, low matric potential (simulating xeric substrate), and propolis exposure than did other strains. A genomic comparison between this new strain and the reference NRRL‐3357 showed that AFBB, like AF36, might be blocked from carrying out aflatoxin biosynthesis. Sequence comparisons also revealed several missense variants in genes that encode proteins regulating osmotolerance and osmotic pressure in Aspergillus spp., including SakA, SskB, GfdA, and TcsB/Sln1. Collectively, results of our laboratory assays and genetic analyses are consistent with the suggestion that the strain isolated from bee bread is adapted to the bee bread environment and may have persisted due to a coevolutionary relationship between Aspergillus and A. mellifera. This finding bolsters recent concerns about the effects of fungicide use near bee colonies and broadens the ecological importance of highly adaptable fungal strains.

Gruznov D.V., Gruznova O.A., Lobanov A.V., Sokhlikov A.B., Shcherbakova G.S., Stepanova S.P., Popov N.I.

The chemical composition and antibacterial activity of heather honey (Calluna vulgaris) subjected to heat treatment at 35–40°C for 12 h are studied. The temperature range (38–40°C) at which the H2O2 concentration and D-glucose-1-oxidase activity decrease and the 5-hydroxymethylfurfural content increases is identified. The degree of chemical changes is directly proportional to the temperature and time of thermal exposure. The correlation between changes in the chemical composition and antibacterial activity of honey against the Escherichia coli (strain 1257), Staphylococcus aureus (strain 209-P), and Bacillus cereus (strain 96) test microorganisms is established. The obtained results show that heating the honey to 37°C even for 12 h does not cause undesirable changes in its chemical composition or decrease in antibacterial activity. Thus, this temperature regime can be considered gentler and recommended for use in the heat treatment of this food product.

Carter C., Kahai R., Cunningham J., Kilduff J., Hough N., Baxter C., Connell D., Shah A.

This collaborative article presents a review of chronic pulmonary aspergillosis (CPA) from the perspective of a multidisciplinary team comprising of respiratory physicians, radiologists, mycologists, dietitians, pharmacists, physiotherapists and palliative care specialists. The review synthesises current knowledge on CPA, emphasising the intricate interplay between clinical, radiological, and microbiological aspects. We highlight the importance of assessing each patient as multidisciplinary team to ensure personalised treatment strategies and a holistic approach to patient care.

Gruznov D.V., Gruznova O.A., Lobanov A.V., Shcherbakova G.S., Chesnokova I.P.

The increase in the number of microorganism strains with resistance to anti-bacterial and disinfecting agents is getting more and more prevalent and has become an issue when treating the human and animals diseases and carrying out measures for disinfection treatment. This problem can be solved by using photodynamic and light-independent therapy. In both areas, metalloporphyrins have been successfully used for many years. One of the most famous representatives of porphyrins is chlorophyll (Chl). This work aims to develop of Chl polymeric form by incorporation in poly(lactic acid) (PLA) and study its inhibitory effect against Staphylococcus aureus and Escherichia coli, which are known as contaminants of the mucous and skin epithelium of humans and animals. The preparation method of Chl polymeric form is presented. The degree of Chl incorporation into PLA was more than 98%. The assessment of antimicrobial activity was carried out by measuring the inhibition zone diameters after bacterial incubation for 24–96 h. It was shown that Chl and Chl-PLA at a dosage of 75 µg inhibited S. aureus significantly. The exclusively bacteriostatic effect on E. coli was observed. These results can be used in the development of dosage forms and disinfectants.

Asbell P.A., Sanfilippo C.M., DeCory H.H.

Antibiotic resistance in bacterial ocular infections is of significant clinical concern and may affect treatment outcomes. We report on in vitro antibiotic susceptibility rates and trends among conjunctival-sourced isolates collected in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) surveillance study. A total of 2214 conjunctival isolates (918 Staphylococcus aureus, 589 coagulase negative staphylococci [CoNS], 194 Streptococcus pneumoniae, 171 Pseudomonas aeruginosa, and 342 Haemophilus influenzae) obtained between 2009-2021 were analyzed. Staphylococci were commonly resistant to azithromycin (≥54.8%) and oxacillin (≥29.3%). Resistance among S. pneumoniae isolates was notable for azithromycin (34.0%) and penicillin (28.9%), while P. aeruginosa and H. influenzae isolates were highly susceptible to most tested antibiotics. Methicillin-resistant staphylococci demonstrated greater concurrent resistance to other antibiotics than methicillin-susceptible isolates and exhibited high rates of multidrug resistance (≥74.0%). Among staphylococci, antibiotic resistance increased with patient age, and there were small decreases in resistance to several drugs over the 13-year period. These findings indicate that resistance to antibiotics routinely used in ophthalmic practice remains high among conjunctival isolates.

Park B., Shim T.S., Jo K., Won E.J., Kim M., Sung H.

Amikacin is a first-line drug that must be evaluated when performing an antimycobacterial susceptibility test (AST) for Mycobacterium avium complex (MAC). However, the presence of sporadic trailing growth in MAC makes determining the precise point for reading its minimal inhibitory concentration (MIC) challenging. Susceptibility was re-tested for 134 MAC clinical isolates using the Sensititre SLOMYCOI panel, the rrs gene was sequenced, and amikacin exposure history was investigated. The MIC50, MIC90, and the epidemiological cut-off value (ECOFF) were calculated using the EUCAST method. After re-testing and ignoring trailing growth, of the 22 M. intracellulare isolates originally classified as resistant to amikacin according to the CLSI guideline, 10 strains were reclassified as intermediate and four as susceptible. Similarly, from the seven resistant M. avium strains, one was reclassified as intermediate and four as susceptible. No rrs gene mutations were detected in any isolates, including resistant strains. When ignoring trailing growth, the calculated MIC50, MIC90, and ECOFF values closely aligned with the EUCAST MIC distribution. To maintain the current CLSI breakpoint, trailing growth should be ignored when reading the amikacin MIC of MAC. To read the MIC at complete bacterial inhibition, the CLSI breakpoint needs to be raised.