Pronounced Anti-inflammatory Effect Research Articles

Study of anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats

Introduction: The combination treatment of patients with dentition problems including endodontic-periodontal lesions (EPL) is known to widely involve anti-inflammatory drugs, including non-steroidal anti-inflammatory agents, and antimicrobial drugs, in particular antibiotics and antiseptics, from which the former often lead to the development of gastro- and neuropathy, lesions of kidneys and liver, as well as the cardiovascular system, and the latter, in addition to serious side effects, lead to the development of steady resistance of pathogenic microorganisms and dysbacteriosis. This necessitates search for and development of new molecules with a wide range of therapeutic effects aimed to block the infectious and inflammatory process and to restore the functional ability of teeth in EPLs as much as possible (depending on a lesion severity). The aim of the study was to examine the anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats. Materials and Methods: EPL simulation in experiments on the anesthetized rats was conducted in the following way: first, the pulp cavity of lower incisors was opened and left exposed to infection; then periodontal inflammation was induced using a ligature. Thirty days later, EPL developed in the animals. An N-isopropenylimidazole zinc metal complex derivative (laboratory code Pilim-1, prepared in form of gel), reference drug Metrogyl Denta® (M-D, dental gel), as well as the combination Pilim-1 + M-D were applied daily for 14 days on the lower incisors and appropriate gums, and also placed in the gingival pockets and pulp cavities, with pulp partially removed beforehands. After euthanasia of the animals on the 15th day of the experiments, gingival homogenates were assayed for the activity of elastase, urease, catalase, the level of malondialdehyde, and the antioxidant-prooxidant index was calculated, while pulp homogenates were assayed for the activity of elastase, urease, alkaline and acidic phosphatases, and the mineralizing index was calculated. Results and Discussion: In the gum in EPL, Pilim-1 and, especially, the combination Pilim-1+M-D more significantly than M-D have a pronounced anti-inflammatory, antioxidant and antimicrobial (reduce a microbial content level) effects. In the pulp in EPL, Pilim-1 and, to a greater extent, the combination Pilim-1 + M-D in a more pronounced way than M-D have anti-inflammatory, antimicrobial (reduce a microbial content level) and mineralizing effects. In the therapeutic action mechanisms of Pilim-1 and, especially, the combination Pilim-1 + M-D in EPL conditions, their ability to have an antihypoxic effect and an inhibitory effect on cyclooxygenase and 5-lipoxygenase is likely to play a very important role, in addition to their identified effect on the examined metabolic processes. Besides, a certain role may be played by the presence of zinc and imidazole in the structure of Pilim-1, as they have a wide range of biological activity. Conclusion: The presented results of studying Pilim-1 and its combination with M-D indicate their high therapeutic efficiency, especially when using the latter in the experimental EPL in rats, which makes it possible to consider Pilim-1 and Pilim-1 + M-D as potential therapeutic agents to treat EPL.

Ototoxicity-Alleviating and Cytoprotective Allomelanin Nanomedicine for Efficient Sensorineural Hearing Loss Treatment.

Sensorineural hearing loss (SNHL) represents a significant clinical challenge, predominantly attributed to oxidative stress-related mechanisms. In this work, we report an innovative antioxidant strategy for mitigating SNHL, utilizing synthetically engineered allomelanin nanoparticles (AMNPs). Empirical evidence elucidates AMNPs' profound capability in free radical neutralization, substantiated by a significant decrement in reactive oxygen species (ROS) levels within HEI-OC1 auditory cells exposure to cisplatin or hydrogen peroxide (H2O2). Comparative analyses reveal that AMNPs afford protection against cisplatin-induced and noise-induced auditory impairments, mirroring the effect of dexamethasone (DEX), a standard pharmacological treatment for acute SNHL. AMNPs exhibit notable cytoprotective properties for auditory hair cells (HCs), effectively preventing ototoxicity from cisplatin or H2O2 exposure, as confirmed by both in vitro assays and cultured organ of Corti studies. Further in vivo research corroborates AMNPs' ability to reverse auditory brainstem response (ABR) threshold shifts resulting from acoustic injury, concurrently reducing HCs loss, ribbon synapse depletion, and spiral ganglion neuron degeneration. The therapeutic benefits of AMNPs are attributed to mitigating oxidative stress and inflammation within the cochlea, with transcriptome analysis indicating downregulated gene expression related to these processes post-AMNPs treatment. The pronounced antioxidative and anti-inflammatory effects of AMNPs position them as a promising alternative to DEX for SNHL treatment.

Modulatory effects of Enteromorpha prolifera powder and its enzymatic hydrolysate on growth performance, antioxidant capacity, and non-specific immunity of Trachinotus ovatus

The excessive proliferation of the genus Enteromorpha serves as the primary catalyst for the occurrence of red tides. Nonetheless, this genus is abundant in sulfated polysaccharides, phenolic compounds, peptides, and alkaloids, which exhibit remarkable efficacy in antioxidation, anti-inflammation, and immune response modulation. Consequently, Enteromorpha-derived products hold promising application prospects as aquatic feed additives. The primary objective of this study was to evaluate the impact of E. prolifera powder (EPM) and its enzymatic hydrolysate (EPH) on the growth, antioxidant capacity, intestinal morphology, and immunity of juvenile Trachinotus ovatus. Four isonitrogenous and isolipidic diets were formulated with varying levels of Enteromorpha products: 0 % (Control), 0.1 % EPH (EPH0.1), 0.3 % EPH (EPH0.3), and 3 % EPM, and were administered to juvenile T. ovatus for eight weeks. The findings revealed that growth performance in the EPH0.3 and EPM groups surpassed that of the control group, concomitant with increased feed intake and elongated intestinal villi. Notably, Enteromorpha-derived products supplementation significantly bolstered the antioxidant capacity of T. ovatus through activation of the Nrf2-Keap1 signaling pathway, leading to elevations in antioxidant enzymes such as SOD and CAT, as well as T-AOC. Conversely, MDA levels were conspicuously reduced in the Enteromorpha-treated groups. Moreover, Enteromorpha-derived products supplementation exhibited pronounced anti-inflammatory effects, marked by the downregulation of proinflammatory cytokine expression and upregulation of anti-inflammatory cytokines, along with decreased apoptotic gene expression. These observations highlight the potential anti-inflammatory properties of EPM and EPH, which may contribute to the preservation of hepatic tissue health and homeostasis. In summary, the optimal growth performance and antioxidant capacity were achieved with 0.3 % EPH supplementation, indicating the efficacy of this concentration in promoting the overall wellbeing of T. ovatus. Remarkably, the employment of processing methodologies, notably enzymatic hydrolysis, has not only facilitated the manifestation but also potentially augmented the inherent beneficial attributes traditionally ascribed to EPM. Furthermore, this refinement process has enabled a reduction in the inclusion rate of EPM within feed formulations, thereby enhancing cost-effectiveness. Consequently, Enteromorpha-derived products emerge as highly promising candidates for aquatic feed additives, with the potential to mitigate the economic burdens imposed by red tide management strategies. Their utilization represents a strategic approach towards sustainable aquaculture practices.

Mesenchymal stromal cells restrain the Th17 cell response via L-amino-acid oxidase within lymph nodes

Mesenchymal stromal/stem cells (MSC) have emerged as a promising therapeutic avenue for treating autoimmune diseases, eliciting considerable interest and discussion regarding their underlying mechanisms. This study revealed the distinctive ability of human umbilical cord MSC to aggregate within the lymph nodes of mice afflicted with autoimmune diseases, but this phenomenon was not observed in healthy mice. The specific distribution is driven by the heightened expression of the CCL21-CCR7 axis in mice with autoimmune diseases, facilitating the targeted homing of MSC to the lymph nodes. Within the lymph nodes, MSC exhibit a remarkable capacity to modulate Th17 cell function, exerting a pronounced anti-inflammatory effect. Transplanted MSC stimulates the secretion of L-amino-acid oxidase (LAAO), a response triggered by elevated levels of tumor necrosis factor-α (TNF-α) in mice with autoimmune diseases through the NF-κB pathway. The presence of LAAO is indispensable for the efficacy of MSC, as it significantly contributes to the inhibition of Th17 cells. Furthermore, LAAO-derived indole-3-pyruvic acid (I3P) serves as a potent suppressor of Th17 cells by activating the aryl hydrocarbon receptor (AHR) pathway. These findings advance our understanding of the global immunomodulatory effects exerted by MSC, providing valuable information for optimizing therapeutic outcomes.

The preventive effects of native probiotic and postbiotic on inflammation and oxidative stress in DSS-induced colitis with normal diet: Which of these agents may offer greater advantages?

BackgroundMaintaining a well-rounded and healthy diet is essential to promote the well-being and optimal performance of the body, especially for those suffering from Inflammatory Bowel Disease (IBD). The objective of this study is to examine whether probiotics and postbiotics can modulate oxidative stress and inflammation, and to evaluate the properties of these compounds. MethodsA total of eighty eight strains of Lactobacillus and Bifidobacterium were assessed for their antioxidant activities. C57BL/6 mice were allocated into four groups: normal diet (ND) + PBS, ND + DSS, ND + DSS + 10⁹ cfu/ml of probiotics, and ND + DSS + 10⁹ cfu/ml of postbiotics. Biochemical antioxidant assays, along with colitis indices, were evaluated. The ELISA assay was conducted to measure oxidant/antioxidant properties and cytokines. Additionally, the genes enrolled in NF-kB and Nrf2 signaling pathways was analyzed. ResultsIn comparison to the groups exposed to DSS alone, mice that received our native agents in addition to DSS demonstrated an improvement in the negative effects induced by DSS on DAI and pathological scores, as well as on colon length and body weight. The levels of cytokines and antioxidant markers have also been normalized following the administration of our native agents, along with molecular markers. It should also be noted that our native postbiotic was able to develop more pronounced and significant anti-inflammatory and antioxidant effects in comparison to the probiotic strains. ConclusionIn this study, our native postbiotic has demonstrated a more pronounced ability to exhibit antioxidant and anti-inflammatory effects. This finding is particularly important for individuals with impaired immune function, for whom the use of live bacteria could be risky. Therefore, the utilization of agents like probiotics and postbiotics, which come with minimal side effects in compared to chemical drugs, could be essential in managing symptoms in IBD patients.

Phillyrin: A potential therapeutic agent for osteoarthritis via modulation of NF-κB and Nrf2 signaling pathways

Osteoarthritis (OA) is the predominant cause of disability among elderly people worldwide and is characterized by cartilage degeneration and excessive bone formation. Phillyrin, derived from forsythia, is a key extract renowned for its pronounced antibacterial and anti-inflammatory effects. Forsythia, deeply integrated into traditional Oriental medicine, has historically been utilized for its various pharmacological effects, including antibacterial, anti-inflammatory, and hepato-protective properties. Nevertheless, the anti-inflammatory impact of phillyrin on the progression of osteoarthritis remains enigmatic. The objective of this research was to assess the anti-inflammatory and anti-aging properties of phillyrin in mouse chondrocytes induced by IL-1β, as well as to elucidate the fundamental mechanisms underlying the phenomenon at play. Additionally, the investigation extends to observing the impact of phillyrin by establishing a murine osteoarthritic model. The ultimate goal was to identify phillyrin as a potential antiosteoarthritic agent. This investigation employs a multifaceted approach. Initially, key action targets of phillyrin, along with its probable action pathways, were identified by molecular docking and network pharmacological techniques. These findings were subsequently confirmed through both in vivo and in vitro studies. Network pharmacological analysis revealed NFE2L2 (NRF2), NFKB1, TLR4, and SERPING1 as pivotal candidate targets for the treatment of osteoarthritis with phillyrin. Molecular docking revealed hydrogen bond interactions between phillyrin and Arg415, Arg483, Ser508, and Asn387 on the Nrf2 receptor, while electrostatic interactions occurred with residues Arg415 and Arg380. Experiments conducted in vitro indicated that phillyrin preconditioning hindered the IL-1β-induced expression of proinflammatory factors which included TNF-α, COX-2, IL-6, and iNOS. Furthermore, phillyrin counteracts the IL-1β-induced degradation of aggrecan and collagen II within the extracellular matrix (ECM). This protective action is caused by the inhibition of the NF-κB pathway by phillyrin. Additionally, the mitigation of chondrocyte aging by phillyrin was observed. Our investigation revealed that phillyrin mitigates inflammation and counteracts cartilage degeneration in osteoarthritis (OA) patients by suppressing inflammation in chondrocytes and impeding aging through suppression of the NF-κB pathway.

Effect of interval hypoxytherapy on the immune status of hypertensive patients

In recent years, the role of sluggish nonspecific inflammation in the pathogenesis of hypertension has been proven. Oxidative stress that develops in hypertension leads to damage of endothelial glycocalyx with impaired barrier and adaptive functions of endothelium. Activation of transcription factor NF-kB leads to increased synthesis of free oxygen radicals, adhesion molecules (VCAM-1, ICAM-1, P-selectin, E-selectin) and proinflammatory cytokines (TNFα, IL-1, IL-6), triggering the inflammatory process in the endothelium. Modern antihypertensive drugs, affecting various pathogenetic mechanisms of arterial hypertension development, do not fully affect the immune component of arterial hypertension. Therefore, the search for various methods affecting the immunologic reactivity of hypertensive patients remains relevant in our time. The aim of the study was to reveal the effect of interval hypoxytherapy on the state of immunologic reactivity of patients with hypertension stage I. One hundred seventy male patients of 30-45 years old (mean age 38.36±1.64 years) with hypertension stage I (n = 170) who underwent combined treatment including drug therapy and normobaric interval hypoxic therapy in hypoxia-normoxia mode (oxygen content in hypoxic gas mixture was 20.9%) were examined. Indices of redox status and immunologic reactivity before and after interval hypoxytherapy were studied. Having a significant antioxidant effect, interval hypoxytherapy led to the subsidence of oxidative stress, which was indicated by an increase in the activity of superoxide dismutase and glutathione peroxidase in blood erythrocytes and a decrease in the content of malonic dialdehyde in blood as a result of a decrease in the generation of free oxygen radicals and suppression of lipid peroxidation processes. Interval hypoxytherapy resulted in a statistically significant increase in the initially decreased content of CD3+T lymphocytes (p 0.05), CD3+CD4+T lymphocytes (p 0.02), CD3+CD8+T lymphocytes (p 0.02). Initially increased number of B-lymphocytes CD19+, CD16+ lymphocytes, CD95+ lymphocytes significantly decreased. An important result of interval hypoxytherapy was a pronounced anti-inflammatory effect: statistically significant decrease in the content of pro-inflammatory interleukins IL-1β (p 0.02), IL-6 (p 0.01) and increase in the content of anti-inflammatory cytokines IL-4 (p 0.005) and IL-10 (p 0.005), which led to the subsidence of sluggish nonspecific inflammation. Suppression of oxidative stress and normalization of immunological reactivity of hypertensive patients after interval hypoxytherapy led to the subsidence of sluggish nonspecific inflammation, reduction of endothelial dysfunction and restoration of the structure and tone of the vascular wall with a decrease in blood pressure and improvement of the clinical course of hypertension.

Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

Capsaicin: Emerging Pharmacological and Therapeutic Insights.

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.

Green synthesis of nanohydroxyapatite with Elaeagnus angustifolia L. extract as a metronidazole nanocarrier for in vitro pulpitis model treatment

The aim of this study is to introduce a dental capping agent for the treatment of pulp inflammation (pulpitis). Nanohydroxyapatite with Elaeagnus angustifolia L. extract (nHAEA) loaded with metronidazole (nHAEA@MTZ) was synthesized and evaluated using a lipopolysaccharide (LPS) in vitro model of pulpitis. nHAEA was synthesized through sol–gel method and analyzed using Scanning Electron Microscopy, Transmission Electron Microscopy, and Brunauer Emmett Teller. Inflammation in human dental pulp stem cells (HDPSCs) induced by LPS. A scratch test assessed cell migration, RT PCR measured cytokines levels, and Alizarin red staining quantified odontogenesis. The nHAEA nanorods were 17–23 nm wide and 93–146 nm length, with an average pore diameter of 27/312 nm, and a surface area of 210.89 m2/g. MTZ loading content with controlled release, suggesting suitability for therapeutic applications. nHAEA@MTZ did not affect the odontogenic abilities of HDPSCs more than nHAEA. However, it was observed that nHAEA@MTZ demonstrated a more pronounced anti-inflammatory effect. HDPSCs treated with nanoparticles exhibited improved migration compared to other groups. These findings demonstrated that nHAEA@MTZ could be an effective material for pulp capping and may be more effective than nHAEA in reducing inflammation and activating HDPSCs to enhance pulp repair after pulp damage.

Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy owing to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and invivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from patients with AD. Functionally, invitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and ROS production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

ASSESSMENT OF PHARMACOLOGICAL ACTIVITY OF THE FLAVONOID FRACTION OF THE HERBS SERPUHA CORONANA

Introduction. It is urgent to search for plants that can become sources of biologically active substances for the creation of new highly effective and safe medicines. One of these plants is the crowned sickle (Serratula coronata L.). The value of crowned serpuha is determined by its high content of phytoecdysteroids and flavonoids. The purpose of the work is to study the acute toxicity, anti-inflammatory activity and capillary-strengthening effect of the flavonoid fraction of the herb Serpucha crown. Material and methods. In the Department of Experimental Pharmacology of the Federal State Budgetary Institution VILAR, a study of the pharmaco-logical activity of the flavonoid fraction of the herb Serpucha crowned was carried out. Acute toxicity parameters were assessed using the Kerber method. The toxicity class of the test substance was determined according to GOST 12.1.007-76 "Harmful substances. Classification and general safe-ty requirements." The anti-inflammatory effect of the flavonoid fraction of the herb Serpucha crown was studied in models of formaldehyde edema and interstitial edema. The effectiveness of the anti-inflammatory effect of the flavonoid fraction of the herb crowned serpentine in vitro experiments was assessed by the rate of the enzymatic reaction catalyzed by inducible NO synthase. The activity of the iNOS enzyme in experiments was assessed by the rate of the reaction catalyzed by iNOS in vitro at 37 C. The study of the capillary-strengthening effect of the flavonoid fraction of the herb Serpucha crowned was carried out according to the "Method for determining the reactivity of skin capillaries to inflammatory stimuli" on a model of local in-flammatory reaction (xylene inflammation) in rats. Results. When studying the acute toxicity of the flavonoid fraction of the herb Serpucha crown, LD50 values were not established, since doses of the studied extract administered into the stomach of mice did not cause death of the animals. In accordance with the classification of toxicity of chemical substances according to GOST 12.1.007-76 "Harmful substances. Classification and general safety requirements", the flavonoid fraction of the herb crowned Serpucha is a low-hazard substance. As a result of the analysis of the data obtained, it was established that the flavonoid fraction of the herb serpukha crowned in doses of 100 and 200 mg/kg has an anti-inflammatory effect, significantly reducing formaldehyde edema in animals by 18 and 20%, respectively, compared with the control group of animals. It was established that the flavonoid fraction of the herb Serpucha crowned at a dose of 200 mg/kg has a pronounced anti-exudative effect, significantly reducing interstitial edema in animals by 22% compared to the control group of an-imals. In vitro experiments, the flavonoid fraction of the herb Serpucha crown inhibits the rate of the iNOS reaction by 1.5 times compared to the con-trol, which indicates the presence of pronounced anti-inflammatory activity of this sample. The studied fraction has a pronounced capillary-strengthening effect under the conditions of an experimental model of xylene inflammation, reducing the permeability of the vascular wall. Conclusions. The results of the studies indicate that the flavonoid fraction of the herb Serpucha crown, in terms of acute toxicity, belongs to the cat-egory of low-hazard substances and has a pronounced anti-inflammatory and capillary-strengthening effect.

Problems of late radiation injuries of the skin and possibilities of their treatment

Currently there is a problem of insufficient effectiveness of treatment of late radiation skin lesions. Possibilities of application of combined schemes of treatment of malignant neoplasms, including radiation therapy, show both good immediate and distant results, life expectancy of patients has increased. However, the issue of such remote local radiation lesions as radiation ulcers also remains relevant. Such lesions in the practice of clinical oncologists usually occur from 1-1,5 months and more after the end of the course of close-focus X-ray therapy for skin cancer. The peculiarity of radiation ulcers is that they heal extremely poorly even by secondary tension. In the pathogenesis of late radiation ulcers, along with disruption of microcirculation, the main role is played by the direct damaging effect of radiation on stem cells and, consequently, suppression of reparative processes. For this reason, such ulcerous defects are characterized by torpidity to drug and surgical treatment. The analysis of modern scientific and practical literature does not fully reveal the peculiarities of the pathogenesis of post-radiation skin lesions leading to the development of radiation ulcers. Researchers have set a goal to search for new modern methods of effective treatment of this pathology. The main purpose of the literature review was to theoretically substantiate the possibilities of including enzyme antioxidants and epidermal growth factor preparations into the complex of pathogenetic treatment of radiation skin ulcers. Superoxide dismutase (SOD) is an active enzyme-antioxidant, it neutralizes excessive free oxygen radicals, and also has a pronounced anti-inflammatory effect by means of oxidative post-radiation stress of skin tissues. Epidermal growth factor promotes cell growth and differentiation of stem cells (SC) involved in ulcer defect regeneration. Pathogenetically justified stepwise application of these drugs will improve the effectiveness of treatment of post-radiation skin ulcers. This paper presents the current information about the pathogenesis of late radiation skin ulcers, the mechanism of action of SOD, epidermal growth factor preparations, as well as the importance of the microenvironment and the homing effect in controlling the links of the pathogenesis of radiation ulcers and the possibility of their reparative regeneration.

Nephroprotective Effect of Hibiscus Sabdariffa Leaf Flavonoid Extracts via KIM-1 and TGF-1β Signaling Pathways in Streptozotocin-Induced Rats.

Diabetes-induced kidney damage represents a substantial health hazard, emphasizing the imperative to explore potential therapeutic interventions. This study investigates the nephroprotective activity of flavonoid-rich extracts from Hibiscus sabdariffa leaves in streptozotocin-induced diabetic rats. The flavonoid-rich extracts of H. sabdariffa leaves was obtained using a standard procedure. The animals were induced with streptozotocin and thereafter treated with both low (LDHSFL) and high doses (HDHSFL) of flavonoid-rich extracts from H. sabdariffa leaves and metformin (MET), and other groups are diabetic control (DC) and normal control (NC). The study assesses diverse renal parameters, encompassing kidney redox stress biomarkers, serum electrolyte levels, kidney inflammatory biomarkers, serum concentrations of creatinine, urea, and uric acid, kidney phosphatase activities, renal histopathology, and relative gene expressions of kidney injury molecule-1 (KIM-1) and transforming growth factor beta-1 (TGF-1β), comparing these measurements with normal and diabetic control groups (NC and DC). The findings indicate that the use of extracts from H. sabdariffa leaves markedly (p < 0.05) enhanced renal well-being by mitigating nephropathy, as demonstrated through the adjustment of various biochemical and gene expression biomarkers, indicating a pronounced antioxidative and anti-inflammatory effect, improved kidney morphology, and mitigation of renal dysfunction. These findings suggest that H. sabdariffa leaf flavonoid extracts exhibit nephroprotective properties, presenting a potential natural therapeutic approach for the treatment of diabetic nephropathy.

Anti-inflammatory effect of lignans from flaxseed after fermentation by lactiplantibacillus plantarum SCB0151 in vitro.

Lignan, a beneficial constituent of Flaxseed (Linum usitatissimum L.) showed great interest in researchers because of its multiple functional properties. Nonetheless, a challenge arises due to the glycosidic structure of lignans, which the gut epithelium cannot readily absorb. Therefore, we screened 18 strains of Lactiplantibacillus plantarum, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Pediococcus pentosaceus, Pediococcus acidilactici, and Enterococcus durans to remove glycosides from flaxseed lignan extract enzymatically. Among our findings, Lactiplantibacillus plantarum SCB0151 showed the highest activity of β-glucosidase (8.91 ± 0.04 U/mL) and higher transformed efficiency of Secoisolariciresinol (SECO) (8.21 ± 0.13%). The conversion rate of Secoisolariciresinol diglucoside (SDG) and the generation rate of SECO was 58.30 ± 3.78% and 32.13 ± 2.78%, respectively, under the optimized conditions. According to the LC-HRMSMS analysis, SECO (68.55 ± 6.57 µM), Ferulic acid (FA) (32.12 ± 2.50 µM), and Coumaric acid (CA) (79.60 ± 6.21 µM) were identified in the biotransformation products (TP) of flaxseed lignan extract. Results revealed that the TP exhibited a more pronounced anti-inflammatory effect than the flaxseed lignan extract. SECO, FA, and CA demonstrated a more inhibitory effect on NO than that of SDG. The expression of iNOS and COX-2 was significantly suppressed by TP treatment in LPS-induced Raw264.7 cells. The secretion of IL-6, IL-2, and IL-1β decreased by 87.09 ± 0.99%, 45.40 ± 0.87%, and 53.18 ± 0.83%, respectively, at 60µg/mL of TP treatment. Given these data, the bioavailability of flaxseed lignan extract and its anti-inflammatory effect were significantly enhanced by Lactiplantibacillus plantarum SCB0151, which provided a novel approach to commercializing flaxseed lignan extract for functional food.

The Immunomodulatory Potential of Short-Chain Fatty Acids in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative central nervous system (CNS) disorder, characterized by focal inflammation, demyelination, irreversible axonal loss and neurodegeneration. The proposed mechanism involves auto-reactive T lymphocytes crossing the blood-brain barrier (BBB), contributing to inflammation and demyelination. Pro-inflammatory Th1 and Th17 lymphocytes are pivotal in MS pathogenesis, highlighting an imbalanced interaction with regulatory T cells. Dysbiosis in the gut microbiota, characterized by microbial imbalance is implicated in systemic inflammation, yet its exact role in MS remains elusive. Short-chain fatty acids (SCFAs), including valerate, butyrate, propionate, and acetate, produced through dietary fiber fermentation by the gut microbiota, modulate inflammation and immune responses. Particularly, butyrate and propionate exhibit pronounced anti-inflammatory effects in both the gut and CNS. These SCFAs influence regulatory T lymphocyte expression and BBB permeability. This review discusses the potential therapeutic implications of SCFA in MS, highlighting their ability to modulate the gut-brain axis and restore immune balance.

Ацеклофенак (Аэртал) – баланс эффективности и безопасности в лечении боли и воспаления

The authors review the mechanism of action of the nonsteroidal anti-inflammatory drug (NSAID) aceclofenac and the results of its clinical trials in patients with pain and inflammatory syndromes. The studies suggest that aceclofenac has a pronounced analgesic and anti-inflammatory effects and promotes restoration of cartilage tissue, inhibiting catabolic processes associated with inflammation. In back pain, the drug can be used in monotherapy or in combination with a myorelaxant. A significant advantage of aceclofenac over other NSAIDs is a favourable safety profile and minimal risk of gastric and cardiac toxicity, which contributes to improved adherence to treatment. Aceclofenac is a NSAID with a favourable benefit/risk ratio.

Thermosensitive hydrogel with emodin-loaded triple-targeted nanoparticles for a rectal drug delivery system in the treatment of chronic non-bacterial prostatitis

BackgroundThe complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs.MethodsBy exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and β-glycerophosphate disodium salt (β-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel).ResultsCellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity.ConclusionThis triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP.Graphical

Experience in the use of cryotherapy in patients after total replacement

BACKGROUND: All over the world, total joint replacement is one of the most popular surgical technologies due to the widespread prevalence of joint diseases, as well as injuries. There is no doubt that rehabilitation is a necessary component of the complex treatment of the patient and plays an important role in the postoperative period. Physiotherapeutic methods of treatment occupy a special place in rehabilitation programs. Cryotherapy has been used for many years in the pathology of the musculoskeletal system and has proven its clinical effectiveness due to analgesic, anti-inflammatory and decongestant effects, which gives grounds for its use after surgical interventions.&#x0D; AIM: Based on the above, the purpose of this study was to study the effectiveness and rationale for the use of cryotherapy in combination with therapeutic gymnastics procedures in patients after total knee replacement for the third the rehabilitation stage.&#x0D; MATERIALS AND METHODS: The study included 60 patients after total knee replacement at the age of 57 to 79 years. All patients were admitted for outpatient treatment 3 months after surgery and were divided into 2 groups. The first group consisted of 30 patients who had therapeutic gymnastics classes with a physical therapy instructor (physical therapy), for a course of 10 daily procedures. The second group consisted of 30 patients who underwent a comprehensive rehabilitation program, including therapeutic gymnastics and air cryotherapy, for a course of 10 daily procedures.&#x0D; RESULTS: In all patients, before the start of the rehabilitation course, the intensity of the pain syndrome according to VAS averaged 4.5±0.6 points; according to the 10-meter walking test, a decrease in the level of mobility was detected, in most patients, the sum of the points on the two parts of the KSS scale averaged 62.8±4.5; according to the results of laser Doppler flowmetry, 44% of the subjects revealed spastic, and in 56% ― spastic-stagnant type of microcirculation. After a course of complex rehabilitation treatment, a significantly more significant reduction in pain syndrome (according to VAS) and microcirculatory disorders (according to laser Doppler flowmetry), improvement in the function of the operated joint (according to the KSS scale) was revealed, compared with the use of physical therapy as a monomethod, which contributed to an increase in the level of mobility of patients.&#x0D; CONCLUSION: The combined use of air cryotherapy and therapeutic gymnastics in patients after total knee replacement contributes to the formation of pronounced analgesic, anti-inflammatory and vasocorrecting effects, which allowed to increase the effectiveness of treatment at the 3rd stage of rehabilitation treatment.

Curcumin-incorporated EGCG-based nano-antioxidants alleviate colon and kidney inflammation via antioxidant and anti-inflammatory therapy.

Natural remedies are gaining attention as promising approaches to alleviating inflammation, yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects. To overcome these limitations, we have developed a novel nano-antioxidant (EK) based on epigallocatechin gallate (EGCG) aimed at enhancing the oral and systemic bioavailability, as well as the anti-inflammatory efficacy, of curcumin (Cur) in conditions such as acute colon and kidney inflammation. EK is synthesized using a straightforward Mannich reaction between EGCG and L-lysine (K), resulting in the formation of EGCG oligomers. These oligomers spontaneously self-assemble into nanoparticles with a spherical morphology and an average diameter of approximately 160 nm. In vitro studies reveal that EK nanoparticles exhibit remarkable radical-scavenging capabilities and effectively regulate redox processes within macrophages, a key component in the body's inflammatory response. By efficiently encapsulating curcumin within these EK nanoparticles, we create Cur@EK, a formulation that demonstrates a synergistic anti-inflammatory effect. Specifically, Cur@EK significantly reduces the levels of pro-inflammatory cytokines TNF-α and IL-6 while increasing the anti-inflammatory cytokine IL-10 in lipopolysaccharide-stimulated macrophages, highlighting its potent anti-inflammatory properties. When administered either orally or intravenously, Cur@EK shows superior bioavailability compared to free curcumin and exhibits pronounced anti-inflammatory effects in mouse models of ulcerative colitis and acute kidney injury. These findings suggest that the EK nano-antioxidant platform not only enhances the bioavailability of curcumin but also amplifies its therapeutic impact, offering a promising new avenue for the treatment and management of inflammation in both oral and systemic contexts.