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BDNF improves the survival of mesenchymal stem cells cultured on pre-structured gelatin material containing strontium and calcium phosphates for bone regeneration.

INTRODUCTION: The treatment of osteoporotic fractures is still challenging and may be improved using materials for bone regeneration, such as pre-structured gelatin with calcium and strontium phosphates (PPGC+S), combined with brain-derived neurotrophic factor (BDNF). Recently, it was shown that PPGC+S stimulates bone formation, and BDNF improves cell survival. This study aimed to analyze the combined effect of PPGC+S and BDNF on the survival of mesenchymal stem cells (MSCs) from osteoporotic and non-osteoporotic female donors. METHODS: In our study, cells were seeded on PPGC+S plates with th

Корреляция физико-химических свойств с антиоксидантной активностью в фенолах и тиофенолах.

Окисляющий стресс, связанный с чрезмерным производством реактивных видов кислорода и азота (ROS, RNS), способствует развитию и развитию многих заболеваний, таких, как старение, сердечно-сосудистые заболевания, болезнь Альцгеймера, болезнь Паркинсона, диабет, рак, предэклампсия или множественный склероз. В то время как фенолы и полифенолы являются наиболее изученными структурно схожими соединениями антиоксидантов, такими, как анилины или тиофенолины, периодически анализируются, несмотря на их радикальный потенциал сбора. В ходе этой работы проводится оценка воздействия структурных особенностей

Бенефициарное воздействие Омега-3 Жировых кислот на ожирение и связанные с ним метаболические и хронические воспаленные заболевания.

Известно, что омега-3 полинунасыщенные жирные кислоты (N-3 PUFA) помогают решить проблему воспаления посредством создания антивоспалительных эйкосаноидов и специализированных посредников по восстановлению, включая резолвинов, защитных сооружений и мареинов. Благодаря привязке к рецептору GPR120/FFAR4 они оказывают благоприятное воздействие в результате фосфолипидной реконструкции мембраны, повреждения воспалительных сигнальных молекул, последующего ингибирования NF-ИВ и воспаления активации, а также уменьшения окислительного стресса. Ожирение, хроническое воспалительное заболевание, которое пр

Paeoniflorin Ameliorates BiPN by Reducing IL6 Levels and Regulating PARKIN-Mediated Mitochondrial Autophagy.

BACKGROUND: Bortezomib-induced peripheral neuropathy (BiPN) is a common complication of multiple myeloma (MM) treatment that seriously affects the quality of life of patients. The purpose of the present study was to explore the therapeutic effect of paeoniflorin on BiPN and its possible mechanism. METHODS: ELISA was used to measure the level of interleukin-6 (IL6) in the plasma of MM patients, and bioinformatics analysis was used to predict the mechanism underlying the effect of paeoniflorin on peripheral neuropathy. Cell and animal models of BiPN were constructed to evaluate mitochondrial fu

Radiotherapy-induced oxidative stress and fibrosis in breast cancer are suppressed by vactosertib, a novel, orally bioavailable TGF-β/ALK5 inhibitor.

Radio-resistance resulting from radiotherapy-induced fibrosis is a major clinical obstacle in breast cancer treatment because it typically leads to cancer recurrence, treatment failure, and patient death. Transforming growth factor-β (TGF-β) is a key signal messenger in fibrosis, which plays an important role in radiation-induced fibrosis and cancer stem cell (CSC) development, may be mediated through the generation of oxidative stress. This study was conducted to confirm the efficacy of vactosertib, a TGF-β/ALK5 inhibitor, as a potent inhibitor in radiation-induced oxidative stress generation

Ascorbic Acid Sensitizes Colorectal Carcinoma to the Cytotoxicity of Arsenic Trioxide via Promoting Reactive Oxygen Species-Dependent Apoptosis and Pyroptosis.

Arsenic trioxide (ATO) is an effective therapeutic agent against acute promyelocytic leukemia (APL); however, its anti-tumor effect on solid tumors such as colorectal cancer (CRC) is still in debate. Ascorbic acid (AA) also produces a selective cytotoxic activity against tumor cells. Here, we exploit the potential benefit of ATO/AA combination in generating cytotoxicity to CRC cells, which may lay the groundwork for the potential combinational chemotherapy of CRCs. According to the results, we found that ATO and AA effectively inhibited the viability of human CRC cells in a synergistic manner.

Токсичность тяжелых металлов в клиническом и экологическом здравоохранении: источники, механизмы, диагностика и научно обоснованное управление ртутью, свинцом, кадмием и арсеником.

Тяжелые металлы, включая ртуть (Hg), свинец (Pb), кадмий (Cd) и мышьяк (As), по-прежнему остаются значительными глобальными токсинами в силу их экологической стойкости, широкомасштабного антропогенного высвобождения и серьезного биологического воздействия. Этот обзор укрепляет нынешнее понимание их природных и промышленных источников, круговорота окружающей среды, маршрутов воздействия на человека и факторов уязвимости на уровне населения. Она охватывает их токсикокинетику и токсикодинамику, делая акцент на специфических для каждого вида механизмах поглощения, распределения и травмирования, вк

Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting.

BACKGROUND: Muscle wasting, a prominent feature of cancer cachexia, is mainly caused by sustained protein hypercatabolism. The enhanced muscle protein degradation rates rely on the activity of different proteolytic systems, although the Adenosine triphosphate (ATP)-ubiquitin-proteasome-dependent pathway and autophagy have been shown to play a pivotal role. Bortezomib is a potent reversible and selective proteasome and NF-κB inhibitor approved for the clinical use, which has been shown to be effective in preventing muscle wasting in different catabolic conditions. The aim of the present study h

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… branched‐chain amino acid‐preferring, and small‐neutral amino acid‐preferring activities. 5 Several chemical compounds able to inhibit proteasome activity have been described including peptide analogues of substrates with different C‐terminal groups such as aldehydes, epoxyketones, boronic acids, and vinyl sulfones …

Human isoprenoid synthase enzymes as therapeutic targets.

In the human body, the complex biochemical network known as the mevalonate pathway is responsible for the biosynthesis of all isoprenoids, which consists of a vast array of metabolites that are vital for proper cellular functions. Two key isoprenoids, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are responsible for the post-translational prenylation of small GTP-binding proteins, and serve as the biosynthetic precursors to numerous other biomolecules. The down-stream metabolite of FPP and GGPP is squalene, the precursor to steroids, bile acids, lipoproteins, and vitamin

Review of the Longitudinal Management of Autoimmune Encephalitis, Potential Biomarkers, and Novel Therapeutics.

Purpose of reviewIncreasing awareness and earlier diagnosis of autoimmune encephalitis (AE) have led to a greater number of patients being cared for longitudinally by neurologists. Although many neurologists are now familiar with the general approach to diagnosis and acute immunosuppression, this review aims to provide neurologists with guidance related to management beyond the acute phase of disease, including long-term immunosuppression, monitoring, potential biomarkers of disease activity, outcome measures, and symptom management.Recent findingsObservational studies in AE have demonstrated

Açai Berry Attenuates Cyclophosphamide-Induced Damage in Genitourinary Axis-Modulating Nrf-2/HO-1 Pathways.

Cyclophosphamide (CYP) is used to treat different malignancies and autoimmune disorders in men. This chemotherapy frequently reduces tumors, which is beneficial, but also causes infertility because of severe oxidative stress, inflammation, and apoptosis in the bladder and testes brought on by its metabolite, acrolein. The goal of this study was to assess the efficacy of a novel food, açai berry, in preventing CYP-induced damage in the bladder and testes.MethodsCYP was administered intraperitoneally once during the experiment at a dose of 200 mg/kg body weight diluted in 10 mL/kg b.w. of water.

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of appro

Moving Beyond G-CSF Mobilization-Learning From a 15-Year Experience of Different Stem Cell Mobilization Regimens in Multiple Myeloma.

BackgroundStem-cell mobilization in multiple myeloma is usually done with G-CSF with or without Cyclophosphamide (Cy) based chemotherapy/Plerixafor. Pre-clinical data suggest the role of proteasome inhibitors in mobilization. We previously reported that Bortezomib (Bort) when added to a Cy-based regimen had a better stem-cell yield. Consequent to favorable results with Bort + Cy-G-CSF, we used Bortezomib with G-CSF too. Hence, four different mobilization regimens were used-Bort + G-CSF (Group-1); G-CSF + Plerixafor (Group-2); Bort - Cy-G-CSF (Group-3); Cy + G-CSF (Group-4). We report here our

Septic Hyperinflammation-Is There a Role for Extracorporeal Blood Purification Techniques?

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cy

Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation.

P-selectin is a membrane glycoprotein and a member of the selectin family of cell adhesion molecules. It is prestored in α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly expressed on their surfaces upon activation during the course of an inflammatory response. Although a critical component of the innate immune system, the interaction of P-selectin with its cognate ligand, P-selectin glycoprotein ligand 1 (PSGL-1) may mediate maladaptive events central to the pathophysiology of venous thromboembolism, cardiovascular disease, stroke, metabolic syndrome, and si

The Production Processes and Biological Effects of Intravenous Immunoglobulin.

Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it ca

PPARs in Irradiation-Induced Gastrointestinal Toxicity.

The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment are well established, many patients experience distressing complications due to injury to normal tissue. These side effects are related to inflammatory processes, and they decrease therapeutic benefit by increasing the overall treatment time. Emerging evidence indicates that PPARs and their ligands are important in the modulation of immune and inflammatory reactions. This paper discusses the effects of abdominal irradiation on PPARs, their role and functions in i

Novel intriguing strategies attenuating to sarcopenia.

Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to pre

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… There are several chemical classes of compounds that inhibit proteasomal activity, including peptide analogs of substrates with different C-terminal groups, such as aldehydes, epoxyketones, boronic acids, and vinyl sulfones [ 90 ]. …

DNA Binding, DNA Photocleavage, Molecular Docking Studies and Photo-Induced Effect on Melanoma Cells of 2-Methyl-3-OR Quinazolinone Derivatives.

Thirty 2-methyl-quinazolinone fussed hydroxamic acids (3-OH) and their 3-OEt and 3-OBn derivatives were evaluated for their affinity towards calf-thymus (CT) DNA using UV-vis absorption, viscosity and fluorescence spectroscopy. DNA photocleavage activity was assessed by incubating the compounds with plasmid DNA followed by UV-A and visible light irradiation, which enabled identification of the most potent derivatives active at concentrations of 100 nΜ and 10 μΜ, respectively. Mechanistic studies on the most active compounds indicated the formation of oxygen radical species and a decrease in ef

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… Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells Int. J. Mol. Sci. 2023 24 1834 10.3390/ijms24031834 36768159 PMC9915714 59. Panagopoulos A. Alipranti K. Mylona K. Paisidis P. Rizos S. …

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-7.

Breakthroughs in Medicinal Chemistry [...].