Anti-inflammatory Ones Research Articles

INFLAMMATION AS A FUNDAMENTAL PATHOLOGICAL PROCESS: LECTURE 1 (ALTERATION, VASCULAR REACTIONS)

Inflammation is the most widespread pathological process in medical practice. Inflammation is the basis of the vast majority of diseases. In this connection, the topic is actual for any medical student, as well as a doctor of any specialty. Local signs of inflammation (redness, swelling, heat, pain, dysfunction) were described more than two thousand years ago. Like any typical pathological process, inflammation includes protective and damaging reactions. Their knowledge is very important for understanding the pathogenesis of inflammatory diseases. The first part of the lecture describes the causes and mechanisms leading to the development of inflammation, as well as the consequences of tissue damage (acidosis, hyperonkia, hyperosmia, synthesis and release of inflammatory mediators). Inflammatory mediators are biologically active substances those regulate all reactions in the focus of inflammation. Various cells (neutrophils, macrophages, lymphocytes, endothelial cells, hepatocytes, etc.) can be sources of mediators. By origin, mediators are divided into cell-derived (biogenic amines, derivatives of arachidonic acid, lysosomal enzymes and reactive oxygen species, cytokines) and plasma-derived (components of the complement system, kinins and the hemostasis system). There are pro-inflammatory mediators (they increase inflammatory response) and anti-inflammatory ones. Under the influence of inflammatory mediators, changes in microcirculatory blood flow begin (vasospasm, arterial hyperemia, venous congestion, stasis) and exudation develops. Exudation is caused by an increase in the permeability of microvessels, its mechanisms are different. The composition of the exudate is determined by the cause of the inflammation and degree of tissue damage, the spectrum and amount of chemoattractants influence the type of exudate as well. The main types of exudates are serous, purulent, fibrinous, hemorrhagic, ichorous, catarrhal.

Phlebotonics for conservative treatment of haemorrhoids: when, to whom, how?

Hemorrhoidal disease (HD) is a pathological enlargement of the external and/or internal hemorrhoidal piles, which may be accompanied by the bleeding and prolapse of haemorrhoids outside the anal canal. The incidence of HD among the population of the Russian Federation is 130–145 patients per 1000 people, occurring mainly in patients 45–65 years old. Among all coloproctological diseases in Russia, haemorrhoids became the reason for visiting a coloproctologist in 35–41.9% of cases. In outpatient department, the disease occurs with a frequency of 694 per 100,000 population. The treatment of hemorrhoids often begins at the coloproctologist’s office during outpatient visits. Typical clinical presentations of hemorrhoids include a complex of symptoms: periodic rectal bleeding during defecation, prolapsed hemorrhoids requiring manual reduction. Pain and itching are much less common symptoms. The treatment of hemorrhoidal disease consists of a complex of conservative measures, minimally invasive and surgical treatments, or a combination of above methods. Systemic phlebotropic drugs that affect various pathogenesis links of hemorrhoidal disease hold one of the first rightful places at the very core of modern conservative therapy regimens. Phlebotropic drugs are a large group of biologically active substances that are products of chemical synthesis or plant processing. The venotonic drugs containing flavonoids diosmin and hesperidin are the most studied ones. Various effects of diosmin and hesperidin from anti-ulcerogenic and antitumor to antioxidant and anti-inflammatory ones have been studied in clinical and experimental studies. Its venotonic and angioprotective effects are the most important actions for the treatment of hemorrhoidal disease. This review of literature is aimed determining the place of phlebotonics in outpatient practice for the treatment of haemorrhoidal disease.

A Comprehensive Review on Pharmacological Activities of Pachypodol: A Bioactive Compound of an Aromatic Medicinal Plant Pogostemon Cablin Benth.

As is well known, plant products have been increasingly utilized in the pharmaceutical industry in recent years. By combining conventional techniques and modern methodology, the future of phytomedicines appears promising. Pogostemon Cablin (patchouli) is an important herb used frequently in the fragrance industries and has various therapeutic benefits. Traditional medicine has long used the essential oil of patchouli (P. cablin) as a flavoring agent recognized by the FDA. This is a gold mine for battling pathogens in China and India. In recent years, this plant has seen a significant surge in use, and approximately 90% of the world's patchouli oil is produced by Indonesia. In traditional therapies, it is used for the treatment of colds, fever, vomiting, headaches, and stomachaches. Patchouli oil is used in curing many diseases and in aromatherapy to treat depression and stress, soothe nerves, regulate appetite, and enhance sexual attraction. More than 140 substances, including alcohols, terpenoids, flavonoids, organic acids, phytosterols, lignins, aldehydes, alkaloids, and glycosides, have been identified in P. cablin. Pachypodol (C18H16O7) is an important bioactive compound found in P. cablin. Pachypodol (C18H16O7) and many other biologically essential chemicals have been separated from the leaves of P. cablin and many other medicinally significant plants using repeated column chromatography on silica gel. Pachypodol's bioactive potential has been shown by a variety of assays and methodologies. It has been found to have a number of biological activities, including anti-inflammatory, antioxidant, anti-mutagenic, antimicrobial, antidepressant, anticancer, antiemetic, antiviral, and cytotoxic ones. The current study, which is based on the currently available scientific literature, intends to close the knowledge gap regarding the pharmacological effects of patchouli essential oil and pachypodol, a key bioactive molecule found in this plant.

Baicalin-Current Trends in Detection Methods and Health-Promoting Properties.

Baicalin (7-D-glucuronic acid-5,6-dihydroxyflavone) belongs to natural flavonoids extracted from the roots of Scutellaria baicalensis, the plant used in traditional Chinese medicine. It has been proven that baicalin has various pharmacological activities, such as antioxidant, anti-inflammatory, anticancer, antibacterial, and anti-apoptotic ones. However, it is essential not only to determine the medical usefulness of baicalin, but also to find and develop the most effective methods for its extraction and detection. Therefore, the aim of this review was to summarize the current methods of detection and identification of baicalin and to present the medical applications of baicalin and the underlying mechanisms of its action. Based on the review of the latest literature, it can be concluded that liquid chromatography alone or together with mass spectrometry is the most commonly used method for the determination of baicalin. Recently, also new electrochemical methods have been established, e.g., biosensors with fluorescence, which have better detection limits, sensitivity, and selectivity.

Impact of polystyrene microplastic exposure on gilthead seabream (Sparus aurata Linnaeus, 1758): Differential inflammatory and immune response between anterior and posterior intestine

Plastics are the most widely discharged waste into the aquatic ecosystems, where they break down into microplastics (MPs) and nanoplastics (NPs). MPs are ingested by several marine organisms, including benthic and pelagic fish species, contributing to organ damage and bioaccumulation.This study aimed to assess the effects of MPs ingestion on gut innate immunity and barrier integrity in gilthead seabreams (Sparus aurataLinnaeus, 1758) fed for 21 days with a diet enriched with polystyrene (PS-MPs; 1–20 μm; 0, 25 or 250 mg /kg b.w./die).Physiological fish growth and health status were not impacted by PS-MPs treatments at the end of experimental period. Inflammation and immune alterations were revealed by molecular analyses in both anterior (AI) and posterior intestine (PI) and were confirmed by histological evaluation. PS-MPs triggered TLR-Myd88 signaling pathway with following impairment of cytokines release. Specifically, PS-MPs increased pro-inflammatory cytokines gene expression (i.e., IL-1β, IL-6 and COX-2) and decreased anti-inflammatory ones (i.e., IL-10). Moreover, PS-MPs also induced an increase in other immune-associated genes, such as Lys, CSF1R and ALP. TLR-Myd88 signaling pathway may also lead to the mitogen-activated protein kinases (MAPK) signaling pathway activation. Here, MAPK (i.e., p38 and ERK) were activated by PS-MPs in PI, following the disruption of intestinal epithelial integrity, as evidenced by reduced gene expression of tight junctions (i.e. ZO-1, Cldn15, Occludin, and Tricellulin), integrins (i.e., Itgb6) and mucins (i.e., Muc2-like and Muc13-like). Thus, all the obtained results suggest that the subchronic oral exposure to PS-MPs induces inflammatory and immune alterations as well as an impact on intestinal functional integrity in gilthead seabream, with a more evident effect in PI.

Low-intensity pulsed ultrasound increases neurotrophic factors secretion and suppresses inflammation in in vitro models of peripheral neuropathies

Objective. In this study, we aimed to verify the beneficial effects of low-intensity pulsed ultrasound (LIPUS) stimulation on two cell types: H2O2-treated RSC96 Schwann cells and THP-1 macrophages, used to model neuropathic inflammation. Approach. Using a set-up guaranteeing a fine control of the ultrasound dose at the target, different frequencies (38 kHz, 1 MHz, 5 MHz) and different intensities (20, 100, 500 mW cm−2) were screened to find the most effective experimental conditions for triggering beneficial effects on metabolic activity and release of neurotrophic cytokines (β-nerve growth factor, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor) of RSC96 cells. The combination of parameters resulting the optimal one was applied to evaluate anti-inflammatory effects in terms of reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α) production, also investigating a possible anti-oxidant activity and mechanotransduction pathway for the anti-inflammatory process. The same optimal combination of parameters was then applied to THP-1 cells, differentiated into M1 and M2 phenotypes, to assess the effect on the expression and release of pro-inflammatory markers (TNF-α, interleukin (IL)-1β, IL-6, IL-8) and anti-inflammatory ones (IL-10 and CD206). Main results. 5 MHz and 500 mW cm−2 were found as the optimal stimulation parameters on RSC96 cells. Such parameters were also found to suppress ROS and TNF-α in the same cell line, thus highlighting a possible anti-inflammatory effect, involving the NF-kB pathway. An anti-oxidant effect induced by LIPUS was also observed. Finally, the same LIPUS parameters did not induce any differentiation towards the M1 phenotype of THP-1 cells, whereas they decreased TNF-α and IL-8 gene expression, reduced IL-8 cytokine release and increased IL-10 cytokine release in M1-polarized THP-1 cells. Significance. This study represents the first step towards the use of precisely controlled LIPUS for the treatment of peripheral neuropathies.

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process.

Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (Tnf-α, Cox-2, Il-8, Irak-2, Nf-kB, and Il-1) while increasing the expression of Il-10, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling.

Clinical and biochemical short-term effects of hyperbaric oxygen therapy on SARS-Cov-2+ hospitalized patients with hypoxemic respiratory failure

BackgroundHyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known. Method50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT). Blood was obtained at t = 0 and t = 5 days. Oxygen saturation (O2 Sat) was followed up. White blood cell (WC) count, lymphocytes (L) and platelets(P) and serum analysis (glucose, urea, creatinine, sodium, potassium, ferritin, D dimer, LDH and CRP) were carried out. Plasma levels of sVCAM, sICAM, sPselectin, SAA and MPO, and of cytokines (IL-1β, IL-1RA, IL-6, TNFα, IFNα, IFNγ, IL-15, VEGF, MIP1α, IL-12p70, IL-2 and IP-10) were measured by multiplex assays. Angiotensin Converting Enzyme 2 (ACE-2) levels were determined by ELISA. ResultsThe average basal O2 Sat was 85 ± 3%. The days needed to reach O2 Sat >90% were: H: 3 ± 1 and C: 5 ± 1 (P < 0,01). At term, H increased WC, L and P counts (all, H vs C: P < 0,01). Also, H diminished D dimer levels (H vs C, P < 0,001) and LDH concentration (H vs C, P < 0.01]. At term, H showed lower levels of sVCAM, sPselectin and SAA than C with respect to basal values (H vs C: ΔsVCAM: P < 0,01; ΔsPselectin: P < 0,05; ΔSAA: P < 0,01). Similarly, H showed diminished levels of TNFα (ΔTNFα: P < 0,05) and increased levels of IL-1RA and VEGF than C respect to basal values (H vs C: ΔIL-1RA and ΔVEGF: P < 0,05). ConclusionPatients underwent HBOT improved O2 Sat with lower levels of severity markers (WC and platelets count, D dimer, LDH, SAA). Moreover, HBOT reduced proinflammatory agents (sVCAM, sPselectin, TNFα) and increased anti-inflammatory and pro-angiogenic ones (IL-1RA and VEGF).

Potential of moringa (Moringa oleifera) leaf powder for functional food ingredients: A review

One of the efforts to produce functional foods is using ingredients containing health-beneficial bioactive compounds. Another way to produce functional foods is fermentation generating bioactive compounds or fortification with the bioactive compound extract. An ingredient historically believed to have benefits on health is moringa (Moringa oleifera) leaf powder. Moringa leaf powder is a valuable source of functional ingredients, including protein, vitamins, minerals, and phytonutrients such as carotenoids, tocopherols, polyphenols, flavonoids, alkaloids, and tannins. However, moringa is a plant that is distributed in various tropical countries in the world. Its quality depends on geographical differences, cultivars, environmental conditions, seasons, genotypes, and varieties. This article reviews the bioactive compounds of moringa leaf powder and the characteristics of moringa leaf powder extract. The effect of moringa leaf powder fortification on food product characteristics is also discussed. Moringa leaf powder possesses many pharmacological properties, such as anticancer, anti-inflammatory, hepatoprotective, cardioprotective, and antioxidant ones. The bioactivity of leaf extract is extracting solvent dependent. Therefore, fortification results in nutritional improvement and increasing health benefits of food products. However, the adverse effect is found in sensory. Thus properties, thus the moringa leaf powder fortification level usually is less than 10%. Changes in the functional properties of foods due to moringa leaf powder fortification have been studied to a limited extent. A low level of fortification might not affect the properties of food products. Therefore, moringa leaf powder is potentially used as a functional food ingredient. Some studies reported the toxicological effects of moringa leaf powder and the use of this ingredient, should be below the harmful doses.

Playing with Biophysics: How a Symphony of Different Electromagnetic Fields Acts to Reduce the Inflammation in Diabetic Derived Cells.

Several factors, such as ischemia, infection and skin injury impair the wound healing process. One common pathway in all these processes is related to the reactive oxygen species (ROS), whose production plays a vital role in wound healing. In this view, several strategies have been developed to stimulate the activation of the antioxidative system, thereby reducing the damage related to oxidative stress and improving wound healing. For this purpose, complex magnetic fields (CMFs) are used in this work on fibroblast and monocyte cultures derived from diabetic patients in order to evaluate their influence on the ROS production and related wound healing properties. Biocompatibility, cytotoxicity, mitochondrial ROS production and gene expression have been evaluated. The results confirm the complete biocompatibility of the treatment and the lack of side effects on cell physiology following the ISO standard indication. Moreover, the results confirm that the CMF treatment induced a reduction in the ROS production, an increase in the macrophage M2 anti-inflammatory phenotype through the activation of miRNA 5591, a reduction in inflammatory cytokines, such as interleukin-1 (IL-1) and IL-6, an increase in anti-inflammatory ones, such as IL-10 and IL-12 and an increase in the markers related to improved wound healing such as collagen type I and integrins. In conclusion, our findings encourage the use of CMFs for the treatment of diabetic foot.

Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid

In 2010, the Mediterranean diet was recognized by UNESCO as an Intangible Cultural Heritage of Humanity. Olive oil is the most characteristic food of this diet due to its high nutraceutical value. The positive effects of olive oil have often been attributed to its minor components; however, its oleic acid (OA) content (70-80%) is responsible for its many health properties. OA is an effective biomolecule, although the mechanism by which OA mediates beneficial physiological effects is not fully understood. OA influences cell membrane fluidity, receptors, intracellular signaling pathways, and gene expression. OA may directly regulate both the synthesis and activities of antioxidant enzymes. The anti-inflammatory effect may be related to the inhibition of proinflammatory cytokines and the activation of anti-inflammatory ones. The best-characterized mechanism highlights OA as a natural activator of sirtuin 1 (SIRT1). Oleoylethanolamide (OEA), derived from OA, is an endogenous ligand of the peroxisome proliferator-activated receptor alpha (PPARα) nuclear receptor. OEA regulates dietary fat intake and energy homeostasis and has therefore been suggested to be a potential therapeutic agent for the treatment of obesity. OEA has anti-inflammatory and antioxidant effects. The beneficial effects of olive oil may be related to the actions of OEA. New evidence suggests that oleic acid may influence epigenetic mechanisms, opening a new avenue in the exploration of therapies based on these mechanisms. OA can exert beneficial anti-inflammatory effects by regulating microRNA expression. In this review, we examine the cellular reactions and intracellular processes triggered by OA in T cells, macrophages, and neutrophils in order to better understand the immune modulation exerted by OA.

УРОВЕНЬ ЭКСПРЕССИИ ГЕНОВ ПРО- И ПРОТИВОВОСПАЛИТЕЛЬНЫХ ЦИТОКИНОВ В КРОВИ КОРОВ ПРИ ГИПОФУНКЦИИ ЯИЧНИКОВ И ПРИМЕНЕНИИ ПРЕПАРАТА НА ОСНОВЕ ГМ-КСФ

The article presents the material for studying the expression level of pro- and anti-inflammatory cytokine genes in the blood of cows with ovarian hypofunction and the use of the drug based on gm-csf (granulocyte-macrophage colony-stimulating factor). It has been established that disorders in the functional activity of the genital gonads in cows occur against the background of an increase in the relative expression level of genes of pro-inflammatory cytokines (IL-1β - by 1.56 and 2.11 times, IL-2 - by 1.41 and 2.29 times, TNFα - by 19.5 and 48.8%), while reducing anti-inflammatory ones (IL-4 - by 27.6 and 37.9%, IL-10 - by 8.3 and 36.1%). An imbalance between the expression level of pro- and anti-inflammatory cytokines in the blood of cows is one of the etiological factors leading to hormonal imbalance and the development of hypofunctional ovarian disorders. The administration of a drug based on gm-csf to cows during insemination once at a dose of 5.0 ml to normalize the functional activity of the ovaries in case of their hypofunctional state with anovulation phenomena contributed to a decrease in the expression level of IL-1β by 27.3%, IL-2 – by 16.7%, TNFα – by 8.2%, with an increase in the expression of IL-4 by 4.8%, IL-10 – by 6.1%, which ensured a clinical efficacy of 86.7%. The use of a drug based on gm-csf in the cows with ovarian hypofunction, manifested by anaphrodisia, twice with an interval of 7 days at a dose of 10.0 ml provided a decrease in the expression level of IL-1β - by 1.9 times, IL-2 – by 38.5%, TNFα – by 14.8%, with an increase in IL-4 - by 11.1%, IL-10 – by 39.1% and a clinical efficacy of 90.0%.

Can gene expression delay aging and increase longevity?

The reality of interacting genes and proteins is vastly complex and intricate with many unknowns which currently prevent us from solving the anti-ageing equation in terms of gene expression. Molecular studies involving genome modification should take into consideration the importance of apparently opposing genes and proteins which when seen as a whole, can orchestrate an optimal systemic balance. Gene expression is often a double-edged sword with positive effects turning negative when a particular gene is overexpressed. For this reason, the US National Academy of Sciences and the National Academy of Medicine have placed stringent restrictions on the promising genome editing methods to be used only for the specific DNA sequence associated with a transmissible genetic disease. Rejuvenation as a result of gene expression is still an open area of research with studies that have either been limited to in vitro research or clinical studies claiming success based on a limited perspective that selectively emphasises the benefits of certain genes while leaving the negative outcomes in the shadows of their silence. For example, some investigators relate the presence of ZMPSTE24, IGF1R, NGF4, EEF2, EIF4FBP1 CCL18, and other genes with “rejuvenation,” selectively focusing on potential benefits while ignoring the involvement of some of these genes in malignancies and inflammation. Well-controlled gene expression molecular experimental studies with mechanotherapy and effortless exercise have limited themselves to the observation of increased slow skeletal genes associated with muscle growth that do not present any adverse side effects. Overall, exercise and nutrition are still the safest and most ethical methods of gene expression at least until genome editing can be extended to delaying ageing, in the near or distant future. As observed in the research analysing gene expression as the result of different types of exercise, inflammatory events are counterbalanced by antagonizing anti-inflammatory ones. This signifies optimal biological homeostasis because health depends on the harmonious interaction of opposite processes levelling and stabilizing each other. Exercise modalities and lifestyle are still representing the cornerstone of delaying ageing and the most riskless method of increasing longevity by triggering processes that balance each other.

Nephrotoxicity induced by different diameters of sphere gold nanoparticles with special emphasis on the nephroprotective role of quercetin.

Although, gold nanoparticles (GNPs) are attracting more and more attention due to their ease of synthesis, modification, and great potential value in biomedical applications, exhibited harmful effects on human health and other living species. Quercetin (Qur) clarifies diverse pharmacological effects, especially anti-inflammatory, antiapoptotic, and antioxidant ones. This study aimed to evaluate the probable nephrotoxicity induced by different diameters of sphere GNPs, as well as the nephroprotective role of Qur. A total of 54 healthy mature male albino rats were grouped and treated with or without sphere GNPs; 10, 20, and 50 nm and Qur (200 mg/kg b.wt.). The effects of GNPs and Qur were estimated through the collection of blood and kidney samples from euthanized rats and performed biochemical, histopathological, and immunohistochemical investigations. In comparison between different diameters of GNPs, the 10 nm GNPs revealed more significant elevations in all renal function parameters: creatinine, urea, blood urea nitrogen, and uric acid followed by 20 nm then 50 nm. Pre-cotreatment with Qur decreased all renal functional values. Histopathologically, 10 nm revealed the most potent renal pathological changes represented in the renal cortex with cloudy swelling of renal tubules, hypercellularity of some glomeruli, severe congestion of renal blood vessels, focal inter tubular edema, and vascular endotheliosis (degeneration of endothelium). In addition, the renal medulla revealed perivascular inflammatory cellular infiltration, perivascular fibrosis, intra tubular glycogen deposition, and casts deposition of mainly cellular casts. On the other hand, the Qur treatment ameliorated most of these pathological changes. The size of GNPs is pivotal in their pathological effect on renal tissues where the small-sized GNPs; 10 nm have more potent cytotoxic, inflammatory, and apoptotic effects rather than the larger ones. Otherwise, Qur clarified a significant mitigating role against the nephrotoxicity of the GNPs.

The Role of Nanomaterials and Macrophage Polarization in Inflammation and Cancer Treatment

Macrophages (MΦs) are functionally plastic and can rapidly adopt different phenotypes based on the stimuli they received from their surroundings. For instance, (MΦs) can differentiate into pro-inflammatory M1-type secreting various pro-inflammatory cytokines, e.g., IL-6, IL-12 and TNF-α. This is an essential defensive mechanism against invading pathogens, but also contributes to tissue destruction. On the other hand, M2-type MΦs have immunosuppressive activity, produces high level of anti-inflammatory cytokine IL-10 and mediates tissue repair. Their unique plasticity and the balance in between different phenotypes maintain the immune homeostasis in the lung under healthy conditions. The role of these two forms of MΦs are also evident in cancer biology. While tissue resident MΦs those who are of M1 type are exerting the immune challenge to the tumor cells, the M2 type from the tumor microenvironment (TME) are supporting the growth and progression of cancer cells. Nanodevices are thought to be an ideal agent targeting macrophages owing to their intrinsic nanoscale property suitable for phagocytosis. The induction of MΦs polarization has been employed in various studies, where administration of IL-4 could reprogram the endogenous inflammatory macrophages (M1-type) to anti-inflammatory ones (M2-type), and accelerate resolution of inflammation and lung repair in a STAT6-dependent manner in both LPS and Pseudomonas aeruginosa bacterial pathogen-induced ALI (Acute Lung Injury) mouse models.

Antibacterial, Antidiabetic, and Toxicity Effects of Two Brown Algae: Sargassum buxifolium and Padina gymnospora

Seaweed has a variety or biological activities, including antibacterial, antioxidant, antidiabetic, and anti-inflammatory ones. Mexico has great macroalgae diversity, with nearly 1700 species; therefore, in this research two seaweeds from Mexico, Sargassum buxifolium and Padina gymnospora, were investigated for their antibacterial, antidiabetic, and toxic potential; and to understand their phytochemical components both were subjected to various extractions. Only the hexanic fraction was active, and the presence of fatty acids was detected. The two algal extracts showed interesting antimicrobial properties, which mostly inhibited the growth of Gram-positive bacteria (E. faecalis, S. aureus, and S. epidermidis). The α-glucosidase activity was estimated for checking the antidiabetic capacity; S. buxifolium had best α-glucosidase inhibition compared with P. gymnospora. For toxicity, the hexanic extracts administered orally as nontoxic in the treated mice. These results suggest that the two algae have potential as resources for the development of antimicrobial agents.

Curcumin Attenuates Lipopolysaccharide-Induced Neuroinflammation and Memory Deficiency by Inhibiting Microglia Activation in Mice Hippocampus

Background. Curcumin has a variety of properties, including antioxidant and anti-inflammatory ones, and has demonstrated some protective prospects on neurological conditions.&#x0D; Aim: This study explored the neuroprotective ability of curcumin in lipopolysaccharide-induced neuroinflammation in an animal model.&#x0D; Methods. A total of thirty-two adult male mice were randomly assigned to four groups (A, B, C, and D, n=8): Group A (Control) received distilled water; Group B was administered lipopolysaccharide (LPS) only to induce neuroinflammation for seven days; Group C was treated with both LPS and curcumin simultaneously for fourteen days; Group D received only curcumin for fourteen days. After appropriate exposure to the mice, their cognitive abilities were assessed using the Y-maze and novel object recognition tests. At the termination of the administration period, the mice were sacrificed, and the hippocampi were dissected for histology and immunostaining using GFAP and Iba1. Statistical analysis for the data generated was done with GraphPad prism. Tests of significance were with one-way ANOVA and Tukey tests for post-hoc.&#x0D; Results. Curcumin significantly (p &lt; 0.05) increased object recognition, mean alternation, and markedly restored neuronal distortion caused by LPS toxicity in the CA3 region and the dentate gyrus of the hippocampus of Group C animals as compared to Group B. In addition, curcumin significantly down-regulated Iba1 expression and GFAP cell activities of both the CA3 region and the dentate gyrus.&#x0D; Conclusions. Curcumin showed a promising role in attenuating LPS-induced neuroinflammation in the brain by inhibiting microglial activation and improving memory of neurotoxic mice.

A New in Vitro Model of Cortical Cerebral Organotypic Slices to Study Central Nervous System Microenvironment Modification By Leukemia Cells

Introduction: Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy, accounting for 25% of all childhood cancers. Although great strides have been made in the treatment of childhood leukemia, close to 20% of patients will have resistant disease eventually leading to death. In approximately 40% of relapses, the central nervous system (CNS) is involved, alone or in combination with other sites, thus representing a major clinical concern. We recently demonstrated that ActivinA, a pleiotropic cytokine that belongs to the TGF-β superfamily, plays a crucial role within the leukemic niche. In addition, we showed by using a xenograft mouse model of human B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL), the ability of ActivinA to enhance both bone marrow (BM) engraftment and metastatic potential into extra-medullary sites of leukemic cells. Interestingly, an increased leukemic burden was observed in the CNS of mice receiving ActivinA-treated cells (Portale et al., 2019). In this study, we attempted to elucidate how leukemic NALM-6 cell line pre-treated or not with ActivinA modifies the CNS microenvironment by using an in vitro model of organotypic cortical brain slices. Methods:200-µm-thick brain slices from C57BL/6J or CX3CR1+/GFP (that express GFP in microglial cells) postnatal (P1-3) mice were obtained using a vibratome and placed onto a cell culture insert. After 7 days of recovery from cut, slices were microinjected with NALM-6 cells expressing iRFP670 pre-treated or not with ActivinA (50ng/mL for 24h). Proliferation of NALM-6 was quantified as the area of iRFP670 fluorescent signal in the brain slices up to 72h after injection. Brain slice cell death was measured by propidium iodide incorporation assay. Microglia activation was evaluated in CX3CR1+/GFP slices by longitudinally quantifying GFP signal up to 7 days post injection. In addition, microglia morphology was evaluated by shape descriptor parameters at 3 and 7days post-injection. Lastly, qRT-PCR assay to evaluate the modulation of microglial pro-and anti-inflammatory genes, was conducted. Results: We observed an exponential increase of iRFP670+ NALM-6 cells in the brain tissue up to 72h post-injection. Of note, pre-treatment with ActivinA significantly increase NALM-6 proliferation at 48 hours (p<0,05; n=7) and 72 hours (p<0,05; n=7) compared to not treated cells. ActivinA pre-treatment of NALM-6 cells was also associated with an higher mortality of brain slices compared to not stimulated NALM-6 cells at 24 hours (p<0,001; n=6 independent experiments) and 72 hours (p<0,05; n=6 independent experiments) after microinjection. By using CX3CR1+/GFP slices, we observed an increased microglia activation in ActivinA-pretreated NALM-6 microinjected slices compared to not treated at 5 (p<0,05; n=7) and 7 days (p<0.01; n=7) post-injection. Microglia morphological analysis showed that at 3 days post-injection, ActivinA pre-treated NALM-6 cells induced a slight increase of round-shaped microglia compared to CTRL (p<0,05; n=3) and to untreated NALM-6 injected slices (p<0,05; n=3), indicative of microglia reactivity to leukemic cells. However, at 7 days post-injection microglia from ActivinA pre-treated NALM-6 injected slices, showed an increase of cell area and perimeters (p<0,05; n=3), a reduced circularity and solidity (p<0,01; n=3) and a slight increase of aspect ratio (p<0,05; n=3) compared to CTRL slices, indicative of a reduced phagocytic activity of microglial cells. These modifications were associated with significant changes in gene expression, characterized by a down-regulation of microglial pro-inflammatory genes (iNOS, PAI-1; p<0.001; n=7) and an up-regulation of the anti-inflammatory ones (Arginase-1, CD206; p<0.01; n=7). Conclusions: We established an in vitro model to study leukemia cell interactions with brain tissue. Our data indicate that ActivinA pre-treatment promote higher NALM-6 proliferation in organotypic cortical brain slices compared to unstimulated leukemic cells. ActivinA pre-treated NALM-6 induce microglial modifications, characterized by a decrease reactivity and an induction of anti-inflammatory phenotype, favoring leukemic cell survival and proliferation. Our model can aid in answering important questions about brain changes after leukemic cell infiltration and could speed up the process of drug screening for leukemic patients.

Dominance of Pro-Inflammatory Cytokines Over Anti-Inflammatory Ones in Placental Bed of Creta Cases.

The objective of the study is to investigate changes occurring in key inflammatory cytokines at molecular level (including genetic and protein) in placental bed of placenta creta compared to that of normal placenta and their correlation to interstitial extravillous trophoblasts (EVT) number. Case-control study including placentas of patients with invasive placentation (creta placentas, n = 19) compared with those of normal placentation (n = 19). Besides routine histology and immunocytochemistry detection (cytokeratin-7 [CK-7]), addition to biochemical evaluation of expression of various cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL6, IL-1RA, IL-8, IL-10, and IL-13 was carried out. Routine histological examination of placentas of creta cases revealed CK-7+ extravillous trophoblasts (EVT) penetrating deeply the myometrium with various histopathological arrangements and trophoblastic vascular invasion of the deep myometrial blood vessels. A significant increase (P < 0.05) in the mRNA expression of TNF-α, IL-1 β, and IL6 with an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 was observed in creta cases compared to the control ones. A corresponding significant increase was detected in the protein levels of TNF-α, IL-1 β, and IL-6 as well as an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 in creta cases compared to the normal ones. Moreover, we displayed a significant positive correlation (P < 0.05) between interstitial EVT number and mRNA expression of almost all pro-inflammatory cytokines with negative but insignificant correlation with anti-inflammatory cytokines in creta cases. The upregulated pro-inflammatory cytokines and the correlation of their expression with the increased interstitial EVT provide a supporting evidence of their potentially more relevant role in the development of placenta creta than the anti-inflammatory ones.

Anti-inflammatory potential of SGLT2 inhibitors: a systematic review and meta-analysis of preclinical studies in rodents

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibition is at the forefront of scientific research due to their astonishing effect in ameliorating the prognosis of cardiorenal diseases. Several mechanisms have been proposed for these pleiotropic effects, including anti-inflammatory ones. Purpose Our systematic review and meta-analysis aimed to assess the effect of SGLT2 inhibitors on inflammatory markers in experimental rodent models. Methods We conducted a literature search to detect studies examining the effect of SGLT2 inhibitors on inflammatory markers [interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP1)] in rodent animal models. Consequently, a meta-analysis of the included studies was performed, assessing the differences in the levels of the inflammatory markers between the treatment and the control group as its primary outcome. Studies not reporting in vivo experiments on mice/rats or not measuring inflammatory markers in the plasma or serum were excluded. Moreover, studies not administering SGLT2 inhibitors as treatment or simultaneously utilizing SGLT2 inhibitors with other treatment were further excluded. Effect sizes were pooled via random-effect model and results are expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). Correction for small-sample bias was also applied with the use of Hedge's g. I2 was chosen as the measure of between-studies heterogeneity. Results The systematic literature review yielded 30 studies whose meta-analysis suggested that treatment with an SGLT2 inhibitor resulted in decreases of IL-6 [standardized mean difference (SMD): −1.49, 95% CI −2.00 to −0.99, I2: 71%), CRP (SMD: −2.17, 95% CI −2.80 to −1.53, I2: 64%), TNF-α (SMD: −1.68, 95% CI −2.05 to −1.31, I2: 38%), and MCP1 (SMD: −2.04, 95% CI −2.91 to −1.17, I2: 66%) (Figure 1). The effect was of lesser magnitude in cases of empagliflozin use (p for interaction=0.03 to 0.05). Possible publication bias was noted in the case of IL-6 and CRP. The findings remained largely unaffected after the sensitivity analyses and the exclusion of outlying studies. Conclusion The present meta-analysis suggests that SGLT2 inhibition results in reduction of inflammatory markers in rodents, suggesting an anti-inflammatory mechanism of action Funding Acknowledgement Type of funding sources: None.