Leukocyte Infiltration Research Articles

Acetyl 11-Keto Beta-Boswellic Acid Improves Neurological Functions in a Mouse Model of Multiple Sclerosis.

Acetyl-11-keto-β-boswellic acid is one of the main active components of Boswellia sp. resin with the most potent anti-inflammatory activity. In recent years, herbal therapy has received considerable attention for the treatments of inflammatory and demyelinating diseases such as Multiple sclerosis (MS). Studies have shown that herbal compounds could enhance myelin repair and suppress inflammation. This study was designed to investigate the therapeutic effects of intraperitoneal administration of AKBA in Experimental Autoimmune Encephalomyelitis (EAE), as an animal model of MS. Following EAE induction in female C57BL/6J mice, animals were treated with AKBA and the levels of different serum inflammatory mediators, as well as motor functions, myelination, and inflammatory cell infiltration were assessed. Our results revealed that the application of AKBA alleviated EAE clinical severity, and suppressed inflammation, demyelination, leukocyte infiltration, and gliosis in EAE mice. Our findings suggest that the therapeutic effects of AKBA are likely a consequence of its neuroprotective and anti-inflammatory properties. The beneficial effects of AKBA may therefore provide new insights in various neuroinflammatory diseases such as MS and thereby could serve as a potential treatment candidate.

Expression of CCL2 signaling pathway genes in patients with periodontitis and atherosclerosis.

Periodontitis and atherosclerosis are chronic inflammatory diseases characterized by leukocyte infiltration. We investigated the expression of CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 as well as the possible mechanism involved in the regulation of CCL2 in human periodontitis tissues and atherosclerotic aorta based on previous research on the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathway leading to CCL2 expression in collagen-induced arthritis (CIA) rat. Sixty-five volunteers were recruited and the condition of their gingiva and coronary arteries were assessed. The subjects were divided into four groups: healthy control, chronic periodontitis (CP), coronary artery diseases (CAD), and noncoronary artery diseases (non-CAD). Total RNA was isolated from gingiva in periodontitis patients and control populations and from the aorta in patients with and without CAD. PCR was used to examine CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 levels. The production of CCL2 in the gingiva and aorta was analyzed by immunostaining. PCR revealed that CCL4, CCR5, and CCL2 mRNA levels were increased in CP patients' gingivae and aortas from coronary artery bypass grafting (CABG) patients. Marked c-Jun, c-Fos, and NF-κB gene productions were detected in CP patients' gingivae but did not show statistical differences between the CAD and non-CAD groups. Stronger immunoreactivity against CCL2 was observed in periodontitis gingiva and aorta from CABG patients. Our findings suggest that the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathways may be involved in CCL2 expression in periodontitis. CCL4, CCR5, and CCL2 might act as possible nodes to link the presence of periodontitis and atherosclerosis.

Barks of Dacryodes Kukachkana presents antiinflammatory effect in rat cutaneous wounds

Background: Dacryodes kukachkana (Burseraceae) is found in the Amazon rainforest of Brazil, being the genera widely used in folk medicine for several inflammatory conditions. Objective: In this study, it was investigated the anti-inflammatory effect of the Hydroethanolic Extract of D. kukachkana (HEDk) barks in the rat model of excisional skin wounds. Methods: The wounds were induced on the dorsal region of Wistar rats and treated daily by topical application of HEDk (500 mg/100 μL), compared to the control Saline (0.9% NaCl). Clinical parameters (edema, hyperemia, exudate, hypernociception), histopathological (leukocyte infiltrate, fibroblasts, blood vessels) and oxidative stress markers were evaluated from the 2nd to the 6th day post-ulceration. Results: HEDk reduced the following parameters at the 2nd day: inflammatory exudate (0 [0-0] vs. saline: 2 [1 – 3]); wound area (36%), healing index (48.56% ± 1.886 vs. saline: 27.99% ± 2.460) and malondialdehyde (27%). HEDk also reduced leukocyte infiltrate (49 – 34%) from the 4th to the 6th days post-ulceration. HEDk increased the parameters: nociceptive threshold (31 – 73%) from the 2nd to the 4th days; blood vessels (1.9x) and reduced glutathione (32%) at the 4th day; and the number of fibroblasts (91 – 44%) at the 2nd and 6th days. Conclusion: HEDk accelerates the healing process in the rat model of excisional cutaneous wounds via attenuation of inflammatory parameters and stimulation of fibroplasia and angiogenesis.

Neuroprotective effect of chelidonic acid through oxidative stress reduction in paclitaxel-induced peripheral neuropathy in rats.

The present study evaluated the effect of chelidonic acid on paclitaxel-induced neuropathy in male Wistar rats. Neuropathy was induced by administering paclitaxel (2mg/kg, i.p.) on 0, 2, 4, and 6days of the protocol. Chelidonic acid treatment (at doses of 10, 20, and 40mg/kg orally, for 21days) was initiated simultaneously with paclitaxel administration. After completion of the protocol, mechanical allodynia, hyperalgesia, and thermal hyperalgesia were measured. Additionally, nerve conduction velocity was assessed. The study investigated inflammatory cytokines, oxidative stress, and histological changes in the sciatic nerve. Furthermore, the Nrf2 was measured, and the protein expression of pAMPK and HIF-1α was assessed using western blotting. The results showed that chelidonic acid significantly normalized mechanical allodynia, hyperalgesia, and thermal hyperalgesia. It also led to a significant improvement in motor and sensory nerve conduction velocity and reduced oxidative stress compared with paclitaxel alone. Inflammatory markers such as TNF-alpha, IL-6, and IL-1β concentrations, as well as nitric oxide and C-reactive protein, were significantly decreased in the chelidonic acid-treated group. Histopathological examination revealed reduced neuronal damage, demyelination, and leukocyte infiltration with chelidonic acid treatment. Chelidonic acid treatment also resulted in a considerable rise in Nrf2 levels (p < 0.001) and increased protein expression of pAMPK in the sciatic nerve. Conversely, HIF-1α expression was significantly declined in the chelidonic acid treatment. Overall, the findings suggest that chelidonic acid treatment attenuates paclitaxel-induced neuropathic pain.

Conditional over-expression of heme-oxygenase 1 in myelomonocytic cells reduces AngII-induced hypertension and vascular inflammation in mice

Abstract Background Systemic arterial Hypertension is one of the most important risk factor responsible for morbidity and mortality world-wide. Angiotensin II (Ang II), a potent vasoconstrictor and key player in the renin-angiotensin-aldosterone system (RAAS) is responsible for vascular dysfunction, inflammation, and tissue damage. Heme oxygenase-1 (HO-1) overexpression may confer antioxidant and anti-inflammatory properties in Ang II-induced hypertension through its action on heme catabolism, generating carbon monoxide (CO), ferritin and biliverdin/bilirubin by the action of biliverdin reductase A (BLVRA). Methods and results Male 9–12-weeks-old HO-1indxLySMCre/wt and LySMCre/wt mice were infused with AngII (1mgAngII/Day/Kg) for 7 days to induce hypertension and compared to sham treatment. Blood pressure monitoring by tail-cuff method, and endothelium-dependent vasodilator studies via organ chamber system using acetylcholine (ACh) in isolated aortic segments (~4 mm), revealed that overexpression of HO-1 in myeloid cells resulted in decreased systolic blood pressure and improved endothelial function in AngII-infused HO-1indxLySMCre/wt mice compared to controls. Concurrently, increased BLVRA expression in liver tissue and elevated plasma bilirubin levels were detected by transcriptome analysis and high-performance liquid chromatography, respectively. These results were supported by a reduction in the expression of inducible cytokines and cell adhesion molecules (CAMs) in the aorta, assessed using qPCR. Bone marrow transplant experiments demonstrated that bone marrow from LysMcre mice in HO-1indxLySMCre/wt mice abrogated the protective effect of HO-1, resulting in endothelial damage and increased blood pressure, potentially due to decreased liver BLVRA expression and the accumulation of bone marrow-derived cells in the vessel wall in response to AngII. Additionally, adeno-associated viral vector (AAV) transfection targeting specifically BLVRA activity in liver lead to an increase in blood pressure values and worse endothelium relaxation, in parallel with higher oxidative stress and the blood neutrophils concentration, as assessed in whole blood by using oxidative burst method and blood count system respectively. Conclusion The overexpression of HO-1 in myeloid cells confers anti-inflammatory protection in AngII-induced arterial hypertension in mice. Myeloid cells bone marrow-derived overexpressing HO-1 regulate the differentiation and infiltration of pro-inflammatory immune cells in the vasculature. BLVRA expression and bilirubin levels downstream of HO-1 play a critical role in protecting against vascular damage by reducing leukocyte infiltration.

Acute Lymphoblastic Leukemia Presenting With Skin Rash And Forehead Swelling In A 31-Year-Old Male

Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis of patients with leukemia, resulting in clinically identifiable cutaneous lesions. It is especially rare as the presenting symptom of leukemia and is associated with a poor prognosis. We present a case of acute lymphoblastic leukemia, whose initial complaints were skin lesions and forehead swelling, which we believe to be features of leukemia cutis. J Dhaka Med Coll. 2023; 32(1) : 96-98

Leukocyte infiltration and cross-talk with cardiomyocytes exploit intracellular stress pathways in dilated cardiomyopathy of idiopathic origin.

Dilated cardiomyopathy (DCM) is a prevalent form of heart failure results in dilation and disruption of heart. Most strikingly a majority of the DCM cases do not have any identified etiology, hence known as idiopathic DCM (IDCM). Our study aimed to investigate the cross-talk between leukocytes and cardiomyocytes in terms of cardiac inflammation and stress response in IDCM. 60 IDCM patients and 60 age and sex matched healthy volunteers were recruited in this study based on the New York Heart Association (NYHA) guidelines. Their echocardiographic and biochemical markers were assessed and PBMCs were analyzed for leukocyte migration and inflammation. Also C2C12 myocyte cells were cultured with LPS-activated RAW264.7 monocytes to investigate the cross-talk between them. Left ventricular (LV) dysfunction was evident in the IDCM patients which were correlated with their physical discomfort level according to NYHA classification. Their serum levels of IL-1β and TNF-α (≈ 20 pg/ml) were found to be very high along with hs-CRP and IL-2. Elevated levels of ROCK, SMA and ICAM-1 proteins indicated activation and migration of the leukocytes. During monocyte-myocyte co-culture, robust diapedesis was observed in the cultured macrophage cells towards myocytes through the transwell pores (8 µM) in presence of IL-1β and TNF-α causing ER stress and cell death in the myocytes. Inhibition of this migration or by alleviating ER stress inhibits leukocyte recruitment and ensures protection to the myocytes. The present study showed that alleviating cellular stress and managing leukocyte migration promotes protection to the heart.

Low-Energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration and modulating the inflammation induced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: An experimental animal study.

Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical and immunofluorescence staining. The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions (run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan (BBB) score) and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1β, IL6 and macrophages (CD68) while increasing leucocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair and regeneration in SCI. This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.

NaHS protects brain, heart, and lungs as remote organs from renal ischemia/reperfusion-induced oxidative stress in male and female rats

Acute Kidney Injury (AKI) is frequently observed in hospitalized patients in intensive care units, often caused by renal ischemia-reperfusion injury (IRI). IRI disrupts the function of various ‘remote organs’ such as the lungs, pancreas, intestine, liver, heart, and brain through inflammation, oxidative stress, apoptosis, leukocyte infiltration, and increased urea and creatinine levels. Gender differences in renal IRI-induced injury are noted. H2S, an endogenous gaseous modulator, shows potential in vasodilation, bronchodilation, and hypotension and can regulate apoptosis, inflammation, angiogenesis, metabolism, and oxidative stress. This study aims to investigate the protective effects of NaHS on brain, heart, and lung injuries following renal IR and to assess the oxidative system status as a potential mechanism in male and female rats.Forty-eight Wistar rats were randomly divided into eight groups (n = 6): Control/Saline, Sham/Saline, IR/Saline, and IR/NaHS in both sexes. Forty-five minutes of bilateral renal ischemia followed by 24-hour reperfusion was induced in the IR groups. NaHS (100µM/Kg, IP) was administered 10 min before clamp release in treated groups. BUN, SCr, BUN/SCr, albuminuria, histopathology, and oxidative stress biomarkers of the brain, heart, and lung were assessed as remote organs. IR increased serum markers of renal function, albuminuria, malondialdehyde levels, and tissue injury scores while reducing nitrite levels and superoxide dismutase and glutathione peroxidase activities. NaHS treatment reversed the adverse effects of IR in remote organs in both sexes, although it showed limited improvement in renal function. Our findings demonstrate that NaHS has a beneficial effect on remote organ injury following renal IR by mitigating oxidative stress, with noted tissue-specific and gender-specific differences in response. These findings suggest NaHS as a potential therapeutic agent for mitigating multi-organ injury after renal IR, with effects varying by tissue and gender.

Sex differences in mortality among patients with lupus nephritis

ObjectiveTo evaluate the prognostic importance of sex in lupus nephritis (LN).MethodsA retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models.ResultsAmong the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients.ConclusionIn our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care.Graphical

Preventive impact of probiotic supplements on heart injury and inflammatory indices in a rat model of myocardial infarction: histopathological and gene expression evaluation.

Although there is a bulk of evidence on the favorable effect of probiotics on the cardiac system, their role in the management of myocardial infarction is not clear. Three viable probiotic bacterial strains, namely Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium lactis, were gavaged to the rats daily for 28 days prior to the induction of myocardial injury. Myocardial injury was induced by the use of isoproterenol (ISO) in the probiotics, control and sham groups. The heart tissues were catheterized to evaluate the histopathological parameters and measure the expression of genes related to inflammation. Treatment with ISO caused subendocardial necrosis and rupture of cardiac myofibrils. Pretreatment with probiotics reduced the size of myocardial infarction caused by ISO. Also, in the probiotic group, a relative decrease in the amount of tissue fibrosis and rupture of cardiomyocytes fibers was seen. Pretreatment with probiotics partially ameliorated myocardial necrosis, edema and leukocyte infiltration. Also, a remarkable decrease was detected in the expression of tissue proinflammatory genes in the pretreated group with probiotics. Thus, viable probiotic supplementation may ameliorate or prevent cardiac injury. Additional preclinical and clinical studies are required to clarify the impact of probiotics in the prevention and management of cardiovascular disease.

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity.

Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma. We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model. Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues. These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

Histomorphological scoring of murine colitis models: A practical guide for the evaluation of colitis and colitis-associated cancer

Background and aimsHistomorphology is a powerful and cost-efficient tool for evaluating inflammatory and neoplastic conditions. Inflammatory bowel disease (IBD) is a widespread condition with globally rising incidences, and a lot of research is done to better understand the pathogenesis of IBD and to identify potential therapeutic approaches. However, standardized and reproducible scores for the histomorphological evaluation of murine IBD models are lacking. Therefore, we aimed to develop an easy-to-use and reproducible score for standardized assessment of colitis and associated cancer models. MethodsIn this study, samples from three different colitis models with and without associated cancer formation were analyzed to develop a universal, robust, and reproducible score for the grading of murine colitis models using the following three parameters: 1. Extent of leucocyte infiltration, 2. Tissue damage, 3. Architectural disruption of the mucosa. ResultsA scoring system was established for different kinds of colitis models (genetically induced enterocolitis, genetically induced metabolic injury, and chemically induced colitis-associated cancer) and all stages of the disease, from mild inflammatory changes to severe inflammation with neoplastic changes as the extreme extent of IBD. The scoring scheme is easy to use, can easily be learned, and proves to have a high interrater reliability. ConclusionsWe propose a robust histological scoring system for the assessment of murine colitis and colitis-associated cancer models, giving more researchers access to conclusive and reliable histological assessment.

Identification of an active fraction of Kangfuxin in the treatment of periodontitis in a rat model.

Periodontitis is a serious gum infection that disrupts the soft tissue around teeth. This study aimed to identify the most effective fraction of the Chinese medicine Kangfuxin for periodontitis treatment in a rat model. Kangfuxin solution was subjected to sequential extraction using chloroform, ethyl acetate, n-butanol, and water. The extracts were evaporated, dissolved in DMSO, diluted in water, and administered to rats via gavage (0.5 mL/day) for 2 weeks. The n-butanol extract was further fractionated using macroporous resin chromatography with 10%, 30%, 50%, 70%, and 90% ethanol elution. Levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in periodontitis samples were examined by ELISA. Leukocyte infiltration in the cementum was analysed by haematoxylin and eosin (H&E) staining. The n-butanol extract showed the best anti-inflammatory effect, reducing IL-6, IL-1β, and TNF-α levels in periodontitis samples and alleviating tissue damage and leukocyte infiltration in the cementum. Further fractionation revealed that the 50% ethanol fraction of the n-butanol extract had the most potent action in attenuating inflammation. This fraction suppressed the activation of the PI3K-AKT-mTOR signalling pathway in periodontitis samples. Application of a PI3K activator counteracted the anti-inflammatory effect of the 50% ethanol fraction. We identified a potent anti-inflammatory fraction (50% ethanol fraction of the n-butanol extract) of Kangfuxin for periodontitis treatment. This fraction suppressed the activity of the PI3K-AKT-mTOR signalling pathway in periodontitis samples. Further research is needed to isolate and characterise the specific bioactive compounds within this fraction.

ENDOCARDITE E MIOCARDITE SECUNDÁRIA A COXSACKIEVIRUS: UM RELATO DE CASO

Myocarditis is marked by the infiltration of leukocytes in myocytes (heart muscles), while endocarditis is an infection of the inner lining and/or heart valves, usually of bacterial cause, which may or may not induce the formation of thrombi. Among the causes, infectious is prevalent, with Coxsackievirus B being one of the most common in the pediatric age group. The objective of this work is to report a case of myocarditis and endocarditis secondary to Coxsackievirus in order to train health professionals in the diagnosis and treatment of children with this pathology. A descriptive observational study was carried out by analyzing the medical records of a patient treated in the emergency room of a secondary hospital in the Federal District. To describe the case and discussion, a literature analysis was carried out in the UptoDate and American Heart Association databases, selecting the most relevant articles. The case reported is a male patient, 6 years old, previously healthy, who developed fever and asthenia seeking emergency care. In complementary exams, condensation of the middle lobe and cardiomegaly were visualized. With pneumonia and myocarditis suspected, the child was hospitalized and antibiotics were started. In subsequent investigations, thrombus/vegetation was identified on echocardiogram, increased D-dimer and serology with positive IgM antibodies to Coxsackie virus. He underwent treatment with Cefepime and Enoxaparin, showed clinical improvement and 4 months after diagnosis, the echocardiogram and serology for the virus in question were normal.

Chronic hyperglycemia alters retinal astrocyte microstructure and uptake of cholera toxin B in a murine model of diabetes.

Astrocytes are the principle glial cells of the central nervous system and play an active role in maintaining proper metabolism in surrounding neurons. Because of their involvement in metabolic control, it is likely that their physiology changes in response to metabolic diseases such as diabetes and associated diabetic retinopathy. Here, we investigated whether microstructural changes in astrocyte morphology occur during the early stages of chronic hyperglycemia that may be indicative of early pathogenic programs. We used MORF3 mice in conjunction with streptozotocin-induced hyperglycemia to investigate the morphology of single retinal astrocytes at an early timepoint in diabetic disease. We report that astrocytes initiate a morphological remodeling program, which depends on both the glycemic background and the presence of intravitreal injury, to alter the amount of the neuronal-associated pad and bristle microstructural motifs. Additionally, hyperglycemia increases astrocyte uptake of cholera toxin B, possibly reflecting changes in glycolipid and glycoprotein biosynthesis. Chronic hyperglycemia coupled with intravitreal injection of cholera toxin B also causes extensive leukocyte infiltration into the retina. Our results have important clinical relevance as current therapies for diabetic retinopathy involve intravitreal injection of pharmaceuticals in individuals with often poorly controlled blood glucose levels.

25-hydroxycholesterol promotes brain cytokine production and leukocyte infiltration in a mouse model of lipopolysaccharide-induced neuroinflammation

Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and, in response to different inflammatory stimuli, overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimer’s disease as well as various mouse models of neuroinflammation. Ch25h encodes cholesterol 25-hydroxylase, an enzyme upregulated in activated microglia under conditions of neuroinflammation, that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC can be further metabolized to 7α,25-dihydroxycholesterol, which is a potent chemoattractant of leukocytes. We have previously shown that 25HC increases the production and secretion of the proinflammatory cytokine, IL-1β, by primary mouse microglia treated with lipopolysaccharide (LPS). In the present study, wildtype (WT) and Ch25h-knockout (KO) mice were peripherally administered LPS to induce an inflammatory state in the brain. In LPS-treated WT mice, Ch25h expression and 25HC levels increased in the brain relative to vehicle-treated WT mice. Among LPS-treated WT mice, females produced significantly higher levels of 25HC and showed transcriptomic changes reflecting higher levels of cytokine production and leukocyte migration than WT male mice. However, females were similar to males among LPS-treated KO mice. Ch25h-deficiency coincided with decreased microglial activation in response to systemic LPS. Proinflammatory cytokine production and intra-parenchymal infiltration of leukocytes were significantly lower in KO compared to WT mice. Amounts of IL-1β and IL-6 in the brain strongly correlated with 25HC levels. Our results suggest a proinflammatory role for 25HC in the brain following peripheral administration of LPS.

Use of porous adhesive cement for fixation of fragments in fractures of the lower jaw

BACKGROUND:The preferred method of treating mandibular fractures is surgical, but it also has problems due to a number of complications associated with the presence of a metal structure in the surgical wound. AIM:To improve the efficiency of surgical treatment for mandibular fractures by developing and experimentally testing amethod for fixing mandibular fragments using porous adhesive cement. MATERIAL AND METHODS:The experiments were performed on 30male Agouti guinea pigs, which were divided into two groups: the main group— 20animals, the comparison group— 10guinea pigs. A mandible fracture was modeled in all animals. In the main group, the fragments were fixed with porous glue-cement “Rekost”, in the comparison group— with abone wire suture. All animals received prophylactic antibacterial therapy. All manipulations were performed under combined anesthesia. The statistical significance of the differences in the compared groups was assessed using Fisher's criterion. For all comparisons, the selected level of statistical significance was 5% (p≤0.05). RESULTS:The use of the method developed by us for fixation of bone fragments in mandible fractures allowed us to achieve a positive result in all 20laboratory animals included in the study. This was confirmed by the results of histological studies in the dynamics of observation: a reliable difference was established between the main group and the comparison group in the severity of inflammation signs on the 14th day, as well as the severity of regeneration signs. It was found that the use of porous glue-cement for fixation of mandible fragments, in contrast to bone wire suture, allows for reliable consolidation of bone fragments for the entire period of treatment (according to X-ray diagnostic data) and to stop by the 14th day (according to histological studies) signs of inflammation in the bone wound (no leukocyte infiltration and vascular congestion). In this case, the glue allows filling the fusion area with developing bone tissue by the 90th day of observation (according to histological studies) and excluding repeated surgical intervention to remove the fixing structure, since the porous adhesive cement, according to histological studies, was absorbed by the 90th day of observation, which indicates its biodegradable properties. CONCLUSION:The use of porous adhesive cement for fixation of mandibular fragments demonstrated better properties compared to bone wire suture.

Extracellular vesicles bearing serum amyloid A1 exacerbate neuroinflammation after intracerebral haemorrhage

IntroductionIntracerebral haemorrhage (ICH) elicits a robust inflammatory response, which significantly contributes to secondary brain damage. Extracellular vesicles (EVs) play a pivotal role in intercellular communication by transporting immune-regulatory proteins. However,...

Mesenchymal stem cells suppress inflammation by downregulating interleukin-6 expression in intestinal perforation animal model

Introduction: Intestinal perforation has significant fatality due to sepsis contamination and prolonged inflammation. Studies showed that mesenchymal stem cells (MSCs) secreted cytokines and growth factors to reduce inflammation. This study aims to reveal the role of MSCs in controlling inflammation in intestinal perforation wound healing by measuring interleukin-6 (IL-6) and leukocytes in injured tissue. Materials and methods: A total of 48 rat models with a 10-mm longitudinal incision at the small intestine were divided into four groups: sham, control, Treatment group 1 (T1) injected with MSC doses of 1.5×106 cells and Treatment group 2 (T2) with 3×106 cells. IL-6 expressions were determined using western blot analysis, whereas the leukocyte infiltrations were assessed using the histopathological examination. All variables were evaluated on day 3 and 7. Results: Leukocyte infiltration is significantly lower in T1 and T2 compared to control group in day 3 and 7 (P&lt;0.05), while there were no differences between the two treatment groups. The expression of IL-6 was found to be significantly lower in the T1 and T2 groups compared to the control group on days 3 and 7 (P&lt;0.05), with no significant differences observed between the two treatment groups. Conclusion: MSCs administration in rats with intestinal perforation reduced inflammation by controlling leukocyte infiltration and IL-6 expression.