The Role of Obesity in the Development of Preeclampsia.

PURPOSE OF REVIEW: This comprehensive review provides an in-depth exploration of the complex relationship between obesity and preeclampsia (PE) and emphasizes the clinical implications of this association. It highlights the crucial role of screening tools in assessing individual risk and determining the need for additional antenatal care among women with obesity. The review investigates various markers for identifying the risk of developing PE, while emphasizing the significance of interventions such as exercise, weight management, and a balanced diet in reducing the incidence of preeclampsia and improving outcomes for both mother and fetus. RECENT FINDINGS: Actually, there is a global pandemic of obesity, particularly among women of childbearing age and pregnant women. PE, which is characterized by maternal hypertension, proteinuria, and complications, affects 2-4% of pregnancies worldwide, posing significant risks to maternal and perinatal health. Women with obesity face an elevated risk of developing PE due to the systemic inflammation resulting from excess adiposity, which can adversely affect placental development. Adipose tissue, rich in proinflammatory cytokines and complement proteins, contributes to the pathogenesis of PE by promoting the expression of antiangiogenic factors in the mother. This review emphasizes the need for appropriate screening, interventions, and a holistic approach to reduce the incidence of preeclampsia and enhance maternal-fetal well-being, thus providing valuable insights into the multifaceted association between obesity and PE.

A narrative review of the therapeutic and remedial prospects of cannabidiol with emphasis on neurological and neuropsychiatric disorders.

BACKGROUND: The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed. MAIN BODY: This narrative review deliberates on the therapeutic and remedial prospects of CBD with an emphasis on neurological and neuropsychiatric disorders. An extensive literature search followed several scoping searches on available online databases such as PubMed, Web of Science, and Scopus with the main keywords: CBD, pro-inflammatory cytokines, and cannabinoids. After a purposive screening of the retrieved papers, 170 (41%) of the articles (published in English) aligned with the objective of this study and retained for inclusion. CONCLUSION: CBD is an antagonist against pro-inflammatory cytokines and the cytokine storm associated with neurological infections/disorders. CBD regulates adenosine/oxidative stress and aids the downregulation of TNF-α, restoration of BDNF mRNA expression, and recovery of serotonin levels. Thus, CBD is involved in immune suppression and anti-inflammation. Understanding the metabolites associated with response to CBD is imperative to understand the phenotype. We propose that metabolomics will be the next scientific frontier that will reveal novel information on CBD's therapeutic tendencies in neurological/neuropsychiatric disorders.

Piper retrofractum ameliorates imiquimod-induced skin inflammation via modulation of TLR4 axis and suppression of NF-κB activity.

Chronic inflammation is a significant concern due to its association with various pathological conditions. As a result, extensive research has been conducted to identify new natural products that can effectively treat acute inflammation, which has the potential to inhibit the chronic inflammation. In our study, we aimed to identify Indonesian medicinal plants with the ability to inhibit proinflammatory agents, specifically targeting NF-κB, a crucial regulator of gene transcription involved in the production of proinflammatory proteins/cytokines. Through a series of identification processes, we found that Piper retrofractum (Javanese chili) extract demonstrated promising inhibitory effects on NF-κB and proinflammatory molecules. Further investigation was conducted using a variety of assays, including reporter assay, viability test, ELISA, and Western blotting. The results revealed that the extract significantly reduced LPS, NO, COX-2, IL-6, IL-1, and NF-κB through the TLR4 axis. Notably, Piper retrofractum extract was found to enhance the survival of human keratinocytes by protecting them from cell death induced by TRAIL, a member of the TNF superfamily. Moreover, immunohistochemistry analysis in an Imiquimod-induced skin inflammation mice model showed downregulation of COX-2 and IL-1ß expression upon treatment with the extract. In conclusion, our findings suggest that Piper retrofractum extract possesses anti-inflammatory properties by reducing proinflammatory cytokine production through inhibition of NF-κB signaling pathway. These promising results highlight the potential of Piper retrofractum extract as a candidate for future drug development in the clinical treatment of inflammation-related conditions, offering hope for the advancement of therapeutic interventions.

Mitigating neuroinflammation in Parkinson's disease: Exploring the role of proinflammatory cytokines and the potential of phytochemicals as natural therapeutics.

Parkinson's disease (PD) is one of the most prevalent neuroinflammatory illnesses, characterized by the progressive loss of neurons in the brain. Proinflammatory cytokines play a key role in initiating and perpetuating neuroinflammation, which can lead to the activation of glial cells and the deregulation of inflammatory pathways, ultimately leading to permanent brain damage. Currently, available drugs for PD mostly alleviate symptoms but do not target underlying inflammatory processes. There is a growing interest in exploring the potential of phytochemicals to mitigate neuroinflammation. Phytochemicals such as resveratrol, apigenin, catechin, anthocyanins, amentoflavone, quercetin, berberine, and genistein have been studied for their ability to scavenge free radicals and reduce proinflammatory cytokine levels in the brain. These plant-derived compounds offer a natural and potentially safe alternative to conventional drugs for managing neuroinflammation in PD and other neurodegenerative diseases. However, further research is necessary to elucidate their underlying mechanisms of action and clinical effectiveness. So, this review delves into the pathophysiology of PD and its intricate relationship with proinflammatory cytokines, and explores how their insidious contributions fuel the disease's initiation and progression via cytokine-dependent signaling pathways. Additionally, we tried to give an account of PD management using existing drugs along with their limitations. Furthermore, our aim is to provide a thorough overview of the diverse groups of phytochemicals, their plentiful sources, and the current understanding of their anti-neuroinflammatory properties. Through this exploration, we posit the innovative idea that consuming nutrient-rich phytochemicals could be an effective approach to preventing and treating PD.

Study of dietary­induced progression of psoriasis­like mice based on gut macrophage polarization.

The aim of the present study was to investigate the influence of stimulating food (SF), a Traditional Chinese Medicine term for a high protein, high fat diet, on psoriasis exacerbation. It was hypothesized that SF disposed psoriasis-like aggravation might be related to inflammatory pathways induction via gut dysbiosis. In the present study, mice were fed either an SF or normal diet for 4 weeks. In the last week, their back hair was removed to establish psoriasis-like dermatitis by imiquimod. After sacrifice, blood samples, alimentary tissues and skin lesions were collected and tested by enzyme-linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Compared with normal diet groups, body weight and blood glucose of SF diet mice were not increased, but they exhibited higher modified Psoriasis Area and Severity Index scores and corresponding epithelial hyperproliferation. Unexpectedly, skin lesions showed abnormal lower protein expressions of Notch and TLR-2/NF-κB p65 signaling pathway, which was attributable to severe skin damage. No difference was observed in the structure and inflammatory cell infiltration of the gut between groups. Instead, macrophage polarization (M1/M2) in the gut of the SF diet group marked by high expression of CD11b (a marker of macrophage, M1) and mild low expression of MRC1 (a marker of macrophage, M2), which resulted in increased TNF-α, decreased IL-10, IL-35, and unchanged IL-17 in serum. Furthermore, serum derived from SF diet mice promoted translocation of NF-κB p65 in HaCaT cells, which indirectly suggested a systemic inflammation. These results suggested that mice fed a continuous SF diet for a time could change gut macrophage polarization, which secretes proinflammatory cytokines into blood circulation. Once transported to skin lesions, these cytokines activate psoriasis tissue resident immune cells and present as psoriasis exacerbation.

Enalapril attenuated CFA provoked arthritic manifestation by modulating proinflammatory and anti-inflammatory cytokine network.

Enalapril with documented anti-inflammatory potential was evaluated in current investigation to explore its anti-arthritic efficacy. For anti-arthritic evaluation of enalapril, CFA-instigated arthritic model was employed after which various parameters comprising paw volume, body weight, arthritic index, hematological and biochemical parameters, radiographic analysis and level of various cytokines were estimated. Enalapril demonstrated significant (p˂0.001) anti-arthritic activity by suppressing paw volume, arthritic index while preserved CFA instigated weight loss. Likewise, enalapril also normalized the hematological and biochemical alterations, suppressed the level of proinflammatory cytokines with elevation of anti-inflammatory cytokines. Radiographic and histopathological analysis also further validates the anti-arthritic attribute of enalapril where enalapril preserved the normal architecture of arthritis induced joints. Outcomes of the study pointed out a notable anti-arthritic activity of enalapril. However detailed mechanistic studies are still required to point out the exact mechanism of action.

Anti-inflammatory and analgesic effect of Forsythiaside B on complete Freund's adjuvant-induced inflammatory pain in mice.

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

The impact of Hyssop (Hyssopus officinalis) extract on activation of endosomal toll like receptors and their downstream signaling pathways.

OBJECTIVES: From the ancient, medicinal benefits of Hyssop (Hyssopus officinalis L.) have been implicated for respiratory and digestive diseases despite the effects of Hyssop on viral infections have not been mechanistically investigated. In this study, we examined whether the Hyssop extract activated anti-viral innate immunity, as a sentinel for immune system, through activation of endosomal TLRs recognizing nucleic acids and their downstream signaling. The Hyssop herb extracts was prepared and co-cultured with healthy individual's peripheral blood mononuclear cells (PBMCs). After viability assay, gene expression levels of TLR3,7,8,9, as well as MyD88 and NF-κB, were evaluated in treated PBMCs using Real-time PCR. Next, the secretion level of immune related cytokines was quantified via ELISA. RESULTS: Post 24 h, 40 µg/ml of the extract significantly inhibited the viability of less than 50% of cells compared to the control and had a maximum effect on cellular function. The Hyssop-treated PBMCs demonstrated an elevated expression of endosomal TLRs genes, as well as MyD88 and NF-κB. Moreover, the release of INF-α and ß notably enhanced in cell culture supernatant, while the content of inflammatory cytokines remarkably diminished (P < 0.05). The Hyssop extract was capable of inducing antiviral innate immune responses so can be promising in antiviral drug strategies.

Protective Effects of Topical Administration of Laminarin in Oxazolone-Induced Atopic Dermatitis-like Skin Lesions.

Laminarin is a polysaccharide isolated from brown marine algae and has a wide range of bioactivities, including immunoregulatory and anti-inflammatory properties. However, the effects of laminarin on atopic dermatitis have not been demonstrated. This study investigated the potential effects of topical administration of laminarin using a Balb/c mouse model of oxazolone-induced atopic dermatitis-like skin lesions. Our results showed that topical administration of laminarin to the ear of the mice improved the severity of the dermatitis, including swelling. Histological analysis revealed that topical laminarin significantly decreased the thickening of the epidermis and dermis and the infiltration of mast cells in the skin lesion. Serum immunoglobulin E levels were also significantly decreased by topical laminarin. Additionally, topical laminarin significantly suppressed protein levels of oxazolone-induced proinflammatory cytokines, such as interleukin-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α in the skin lesion. These results indicate that topical administration of laminarin can alleviate oxazolone-induced atopic dermatitis by inhibiting hyperproduction of IgE, mast cell infiltration, and expressions of proinflammatory cytokines. Based on these findings, we propose that laminarin can be a useful candidate for the treatment of atopic dermatitis.

Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and ameliorates inflammation in the lung of streptozotocin-induced diabetic rats.

CONTEXT: Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [Panax ginseng C.A. Meyer (Araliaceae)]. OBJECTIVE: This study determined the underlying mechanisms of Rb1 treatment that acted on diabetes-injured lungs in diabetic rats. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (n = 10): control, Rb1 (20 mg/kg), insulin (15 U/kg to attain the euglycaemic state) and diabetic (untreated). After treatment for six weeks, oxidative stress assay; histological and ultrastructure analyses; TNF-α, TGF-ß, IL-1 and IL-6 protein expression analyses; and the detection of apoptosis were performed. RESULTS: There was decreased activity of SOD (3.53-fold), CAT (2.55-fold) and GSH (1.63-fold) and increased levels of NO (4.47-fold) and MDA (3.86-fold) in the diabetic group from control. Rb1 treatment increased SOD (2.4-fold), CAT (1.9-fold) and GSH (1.29-fold) and decreased the levels of NO (1.76-fold) and MDA (1.51-fold) as compared with diabetic rats. The expression of IL-6 (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) and TGF-ß (2.39-fold) was increased in diabetic rats from control. IL-6 (2.43-fold), IL-1α (2.27-fold), TNF-α (1.68-fold) and TGF-ß (2.3-fold) were decreased in the Rb1 treatment group. Diabetes increased the apoptosis rate (2.23-fold vs. control), and Rb1 treatment decreased the apoptosis rate (1.73-fold vs. the diabetic rats). Rb1 and insulin ameliorated lung tissue injury. DISCUSSION AND CONCLUSIONS: These findings indicate that Rb1 could be useful for mitigating oxidative damage and inflammatory infiltration in the diabetic lung.

Influence of vitamin D supplementation on immune function of healthy aging people: A pilot randomized controlled trial.

Objectives: This study aims to investigate the influence of vitamin D supplementation on immune function of healthy older adults. Materials and methods: Designed as a randomized controlled trial, 21 participants (55-85 years) completed the study during May-November 2018 in Coventry, England. The participants were randomized into vitamin D or the control group, stratified by age, gender and body mass index. The vitamin D group (n = 12) took vitamin D3 tablets of 1,000 IU/day for 12 weeks plus vitamin D education leaflet, while the control group (n = 9) were only provided with the leaflet. At baseline, 6 and 12 weeks, plasma 25(OH)D levels and immunological and metabolic parameters including phagocytic activity of granulocytes and monocytes, tumor necrosis factor, interleukin 6, lymphocyte subsets and fasting blood glucose and lipid were measured. Dietary vitamin D intake was analyzed at baseline and week 12. Data were presented as mean ± SD. Two-way repeated measures ANOVA and independent t-test were used to analyze the data. Results: At baseline, 42.9% of the participants were vitamin D deficiency (25(OH)D < 25 nmol/L), only 10% achieved a level of 25(OH)D > 50 nmol/L. Overweight/obese participants (n = 9) had significantly lower mean plasma 25(OH)D concentration (22.3 ± 8.7 nmol/L) than normal weight participants (48.1 ± 34.3 nmol/L) (P = 0.043). There was a significant increase in plasma 25(OH)D concentration in vitamin D group compared with that in control group (P = 0.002) during the intervention period. The plasma 25(OH)D concentration in vitamin D group was increased at 6 weeks (from 38.4 ± 37.0 nmol/L at baseline to 51.0 ± 38.2 nmol/L) with little change observed between 6 and 12 weeks (51.8 ± 36.4 nmol/L). The plasma creatinine concentration in vitamin D group was significantly decreased compared with the control group (P = 0.036) (79.8 ± 7.0 µmol/L at baseline vs 75.1 ± 5.4 µmol/L at week 12). No significant effect of vitamin D supplementation was determined on immunological parameters. Conclusion: Vitamin D deficiency is common among the aging population in the UK even during the summertime. Vitamin D supplementation at 1,000 IU/day for 12 weeks significantly increased plasma 25(OH)D concentration but showed no effect on metabolic and immunological parameters except decreased plasma creatinine.

A Single Vitamin D3 Bolus Supplementation Improves Vitamin D Status and Reduces Proinflammatory Cytokines in Healthy Females.

Vitamin D deficiency is a global health problem that not only leads to metabolic bone disease but also to many other illnesses, most of which are associated with chronic inflammation. Thus, our aim was to investigate the safety and effectiveness of a single high dose of vitamin D3 (80,000 IU) on vitamin D status and proinflammatory cytokines such as interleukin (IL)6, IL8 and tumor necrosis factor (TNF) in healthy Saudi females. Fifty healthy females were recruited and orally supplemented with a single vitamin D3 bolus (80,000 IU). All participants donated fasting blood samples at baseline, one day and thirty days after supplementation. Serum 25-hydroxyvitamin D3 (25(OH)D3), IL6, IL8, TNF, calcium, phosphate, parathyroid hormone (PTH) and blood lipid levels were determined. Serum 25(OH)D3 significantly increased one and thirty days after supplementation when compared with baseline without causing elevation in calcium or phosphate or a decrease in PTH to abnormal levels. In contrast, the concentrations of the three representative proinflammatory cytokines decreased gradually until the end of the study period. In conclusion, a single high dose (80,000 IU) is effective in improving serum vitamin D status and reducing the concentration of the proinflammatory cytokines in a rapid and safe way in healthy females.

Pithecellobium dulce inhibits pulmonary metastasis induced by B16F10 melanoma cells in C57BL/6 via regulating EGFR/STAT/ NFκB /AKT signaling axis.

In this present study we analyzed anti-metastatic efficacy of fruit extract of Pithecellobium dulce (FPD) against B16F10 induced pulmonary metastatic model. FPD administration significantly (p < .01) reduced lung fibrosis, as evidenced by histochemical collagen analysis by Masson's trichome staining, total collagen, hexosamine, and uronic acid. Results showed that FPD treatment significantly attenuated the expression of EGFR mediated P38 and STAT1/3 expression, thus reduced NFκB mediated signaling cascade. Further, the expression of PIP3CA mediated activation of the AKT survival signaling pathway has been analyzed. Interestingly, in FPD treated group, the expression of AKT pathway has also downregulated. Further, we analyzed the downstream regulators of NFκB and AKT signaling pathways, which include, inflammatory genes (iNOS, COX2, NFκB, TGFß1, IL5, IL1ß, IFNγ, IL6, IL10, MCP1, GMCSF), anti-apoptotic genes (BCL2 and BCLXL), cell cycle regulators (cyclin D1 and Ki67), fibrosis activator (CT1α1), angiogenesis promoter (VEGF), metastatic promoter (MMP2/9, N CADH), mucin (MUC5AC), pro-apoptotic genes (Bax, CAS3 and CAS9) and metastasis inhibitors (TIMP1/2, E CADH, p53, PTEN). The expression of inflammatory, anti-apoptotic, cell cycle regulators, fibrosis activator, angiogenesis and metastasis promoter, and mucins were markedly reduced by FPD administration. Interestingly, the level of expression of anti-metastatic genes were markedly elevated in FPD administrated group. Lung histopathology further confirmed the anti-metastatic efficacy of FPD. PRACTICAL APPLICATIONS: Different parts of P. dulce has long been used as a folklore medicine against different diseases. This study demonstrated that bioactive constituents present in the fruit extract of P. dulce (FPD) significantly attenuated proliferation via regulating EGFR/STAT/NFκB/AKT signaling axis.

Modulation of Intestinal Corticotropin-Releasing Hormone Signaling by the Herbal Preparation STW 5-II: Possible Mechanisms for Irritable Bowel Syndrome Management.

Corticotropin-releasing factor (CRF) mediates stress responses and alters the gut-brain axis, contributing to the pathogenesis of irritable bowel syndrome (IBS), which is recognized by abdominal pain accompanied by bowel habit disturbance. STW 5-II, a mixture of six herbal extracts, is clinically effective in functional dyspepsia and IBS. Here we aimed to establish an organoid-based stress-induced IBS-like model to investigate the mechanisms of action of STW 5-II. STW 5-II (10, 20, and 30 g/mL) was applied to intestinal organoids for 24 h before being treated with CRF (100 nM) for 48 h. The effects of STW 5-II on CRF signaling were investigated using several in vitro and in silico approaches. STW 5-II activities were further explored by in silico PyRx screening followed by molecular docking of the main 52 identified compounds in STW 5-II with both CRF receptors CRFR1 and CRFR2. CRF exposure stimulated inflammation and increased proinflammatory mediators, while STW 5-II dose-dependently counteracted these effects. STW 5-II inhibited CRF-induced claudin-2 overexpression and serotonin release. Docking of the STW 5-II constituents oleanolic acid and licorice saponin G2 to CRFR1 and CRFR2, respectively, showed a good affinity. These multi-target activities support and elucidate the clinically proven efficacy of STW 5-II in disorders of gut-brain interaction.

Carrageenophyte Kappaphycus malesianus Inhibits Microglia-Mediated Neuroinflammation via Suppression of AKT/NF-κB and ERK Signaling Pathways.

Neuroinflammation is an inflammatory response in any part of the central nervous system triggered by the activation of microglia and astrocytes to produce proinflammatory cytokines in the brain. However, overproduction of proinflammatory cytokines further contributes to the development of neurodegenerative disorders. Red seaweed, Kappaphycus malesianus, is a predominant carrageenophyte commercially cultivated in Semporna, Sabah, Malaysia. It is an important source of raw material for kappa-carrageenan productions in the food, pharmaceutical and cosmetics industries. However, no studies have been conducted focusing on the antineuroinflammatory effects of K. malesianus. The aim of the present study was to investigate the effect of the antineuroinflammatory activity of K. malesianus extracts (ethyl acetate, ethanol and methanol) on lipopolysaccharide-stimulated BV2 microglia and the underlying mechanisms involved in the regulation of neuroinflammatory pathways. Extract with the most promising antineuroinflammatory activity was analyzed using liquid chromatography-mass spectrometry (LC-MS). Our results show that methanol extract has a convincing antineuroinflammatory effect by suppressing both AKT/NF-κB and ERK signaling pathways to inhibit the expression of all proinflammatory cytokines without causing a cytotoxicity effect. LC-MS analysis of methanol extract revealed two compounds: prosopinine and eplerenone. Our findings indicated that metabolites of K. malesianus are potent antineuroinflammatory agents with respect to prevention of neurological disorders.

Profiling vitamin D, its mediators and proinflammatory cytokines in rheumatoid arthritis: A case-control study.

INTRODUCTION: The active form of vitamin D has immunomodulatory and anti-inflammatory effect. Vitamin D is implicated in pathogenesis of rheumatoid arthritis (RA) and its deficiency leads to increased inflammation. Moreover, its production is dependent on concentration of calcium, phosphorus, and parathyroid hormone (PTH). Cytokines mediates inflammation in RA synovium. This study evaluated vitamin D, its mediators and proinflammatory cytokines among RA patients. METHODS: In a case-control study, 78 RA patients from Komfo Anokye Teaching Hospital rheumatology clinic and 60 healthy blood donors were recruited. Chemistry analyzer and enzyme-linked immunosorbent assay kits were used to measure biochemical parameters and cytokines. RESULTS: We found significantly higher levels of interleukin (IL)-1ß, interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α) in RA patients compared with controls (p < .05). There was a significant positive correlation between intact parathyroid hormone (iPTH) and IL-10 (r = .30, p < .05) and a negative correlation between IL-6 (r = -0.28, p > .05), IL-1ß (r = -0.25, p > .05), TNF-α (r = -0.26, p > .05), IFN-γ (r = -0.24, p > .05), and iPTH. There was a significant negative correlation between IL-1ß (r = -0.33, p < .05), IFN- γ (r = -0.29, p < .05), and calcium. CONCLUSION: Reduced PTH, calcium, and phosphorus is associated with higher levels of proinflammatory cytokines which may worsen RA disease condition. Vitamin D is therefore not an independent regulator of proinflammatory cytokines in RA.

Oral Cholecalciferol Supplementation in Sahara Black People with Chronic Kidney Disease Modulates Cytokine Storm, Oxidative Stress Damage and Athero-Thromboembolic Risk.

The 25-hydroxyvitamin D3 (25OHD3) deficiency in chronic kidney disease (CKD) is associated with immune system dysfunction (pro-inflammatory cytokines storm) through macrophages renal infiltration, oxidative stress (OxS) damage and athero-thromboembolic risk. Conversely, cholecalciferol supplementation (25OHD-S) prevents kidney fibrosis by inhibition of vascular calcification and nephrotic apoptosis (nephrons reduction). The objective of this study was to investigate the pleiotropic effects of 25OHD-S on immunomodulation, antioxidant status and in protecting against thromboembolic events in deficiency CKD Black and White individuals living in the Southern Sahara (SS). The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/day/24 weeks in Black (n = 156) and White (n = 150). Total serum vitamin D was determined by liquid chromatography-tandem mass spectrometry. All biomarkers of pro-inflammatory cytokines (PIC) were assessed by ELISA tests. OxS markers were assessed by Randox kits. Homocysteine and lipoproteine (a) were evaluated by biochemical methods as biomarkers of atherothromboembolic risk. All statistical analyses were performed with Student's t-test and one-way ANOVA. The Pearson test was used to calculate the correlation coefficient. The means will be significantly different at a level of p value < 0.05. Multiple logistic regressions were performed using Epi-info and Statview software. Vitamin D deficiency alters the PIC profile, OxS damage and atherothrombogenic biomarkers in both SS groups in the same manner; however, these disorders are more acute in Black compared to White SS individuals. The results showed that the serum 25OHD3 concentrations became normal (>75 nmol/L or >30 ng/mL) in the two groups. We have shown that the dose and duration of 25OHD-S treatment are not similar in Black SS residents compared to White SS subjects, whilst the same inhabit the south Sahara environment. It appears that a high dose intermittent over a long period (D60: 36 weeks) was more efficient in Black people; while a lower dose for a short time is sufficient (D2: 24 weeks) in their White counterparts. The oral 25OHD-S attenuates PIC overproduction and OxS damage, but does not reduce athero-thromboembolic risk, particularly in Black SS residents.

Effect of colostrum on the acute-phase response in neonatal dairy calves.

The core part of the mammal innate immune system is the acute-phase response (APR), during which acute-phase proteins (APP) are synthesized. Colostrum contains immunomodulating factors such as proinflammatory cytokines and APP in large quantities. We looked at proinflammatory cytokines [IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α)] and APP [serum amyloid A (SAA) and haptoglobin (Hp)] in colostrum and in calves' serum. The aim of this study was to evaluate the effects of colostrum on the calves' systemic APR and the associations of the calves' serum APR with short- and long-term weight gain (at the age of 1, 3, and 9 mo). A total of 143 female dairy calves were studied during their first 3 wk of life. The calves were separated from their mothers immediately after birth and bottle-fed 3 L of quality-controlled colostrum once within 2 h after birth. Serum samples were collected once a week during the first 3 wk of life (a total of 1-3 samples per calf). Mean sampling age (±standard deviation) was 4.3 (±2.0) d in the first week, 11.0 (±2.0) d in the second week, and 18.0 (±2.0) d in the third week. Linear regression models were used to study associations of colostrum APP and cytokine concentration with serum APR markers and for studying associations of colostrum and serum APR markers with calves' average daily weight gain (ADWG). Mixed linear regression models were used to compare serum concentrations of APR markers by study weeks. The colostrum IL-6 concentrations were positively associated with serum IL-6 in the first 3 wk of life. Colostrum IL-1ß was positively associated with calves' serum IL-1ß during the first week of life, and colostrum TNF-α was positively associated with calves' serum TNF-α during the first 2 wk of life. Serum IL-1ß concentrations differed over the 3 wk, being the highest during the first week and the lowest during the second week. For IL-6, the concentration during the first week was the highest, and for TNF-α, a steady decline in the concentration was observed. Serum SAA concentrations were elevated during the first 2 wk of life and subsequently declined during the third week. Albumin concentrations were lowest in the first week, whereas Hp concentrations were highest during the second week. Serum concentrations of SAA, Hp, IL-6, and TNF-α during the second week were negatively associated with ADWG at 9 mo of age. The SAA concentrations during the third week of age had a negative association with 9-mo ADWG. Serum Hp concentrations in the third week were negatively associated with 3-mo ADWG. The results of our study suggest that colostrum cytokines influence calf serum cytokine concentrations. Thus, they influence the newborn calves' adaptation to the environment and the development of their immune system. Factors that activate an APR during the second and third week of life have a long-term influence on calves' development.

Lonicerae Japonicae Flos Extract Promotes Sleep in Sleep-Deprived and Lipopolysaccharide-Challenged Mice.

Lonicerae Japonicae Flos (LJF) is commonly used in Chinese herbal medicines and exhibits anti-viral, anti-oxidative, and anti-inflammatory properties. The reciprocal relationship between sleep, the immune system and the central nervous system is well-established in the animal models. In this study, we used the mouse model to analyze the beneficial effects of the LJF on the dysregulated sleep-wakefulness cycle in response to acute sleep deprivation and lipopolysaccharide (LPS)-induced inflammation and the potential underlying mechanisms. Polysomnography data showed that LJF increased the time spent in non-rapid eye movement (NREM) sleep during the day under basal conditions. Furthermore, latency to sleep was reduced and the time spent in rapid eye movement (REM) sleep was increased during recovery from acute sleep deprivation. Furthermore, LJF-treated mice showed increased REM sleep and altered electroencephalogram (EEG) power spectrum in response to intra-peritoneal injection of LPS. LJF significantly reduced the levels of proinflammatory cytokines such as IL-6, TNF-α, and IL-1ß in the blood serum as well as hippocampus, and medial prefrontal cortex (mPFC) tissues in the LPS-challenged mice by inhibiting microglial activation. Moreover, LJF increased the time spent in REM sleep in the LPS-challenged mice compared to the control mice. These results suggested that LJF stimulated the sleep drive in response to acute sleep deprivation and LPS-induced inflammation, thereby increasing REM sleep for recovery and neuroprotection. In conclusion, our findings demonstrate that the clinical potential of LJF in treating sleep disorders related to sleep deprivation and neuro-inflammation.

Suppression of Oxidative Stress and Proinflammatory Cytokines Is a Potential Therapeutic Action of Ficus lepicarpa B. (Moraceae) against Carbon Tetrachloride (CCl4)-Induced Hepatotoxicity in Rats.

Local tribes use the leaves of Ficus lepicarpa B. (Moraceae), a traditional Malaysian medicine, as a vegetable dish, a tonic, and to treat ailments including fever, jaundice and ringworm. The purpose of this study was to look into the possible therapeutic effects of F. lepicarpa leaf extract against carbon tetrachloride (CCl4)-induced liver damage in rats. The DPPH test was used to measure the antioxidant activity of plants. Gas chromatography-mass spectrometry was used for the phytochemical analysis (GCMS). Six groups of male Sprague-Dawley rats were subjected to the following treatment regimens: control group, CCl4 alone, F. lepicarpa 400 mg/kg alone, CCl4 + F. lepicarpa 100 mg/kg, CCl4 + F. lepicarpa 200 mg/kg and CCl4 + F. lepicarpa 400 mg/kg. The rats were euthanized after two weeks, and biomarkers of liver function and antioxidant enzyme status were assessed. To assess the extent of liver damage and fibrosis, histopathological and immunohistochemical examinations of liver tissue were undertaken. The total phenolic content and the total flavonoid content in methanol extract of F. lepicarpa leaves were 58.86 ± 0.04 mg GAE/g and 44.31 ± 0.10 mg CAE/g, respectively. F. lepicarpa's inhibitory concentration (IC50) for free radical scavenging activity was reported to be 3.73 mg/mL. In a dose-related manner, F. lepicarpa was effective in preventing an increase in serum ALT, serum AST and liver MDA. Histopathological alterations revealed that F. lepicarpa protects against the oxidative stress caused by CCl4. The immunohistochemistry results showed that proinflammatory cytokines (tumour necrosis factor-α, interleukin-6, prostaglandin E2) were suppressed. The antioxidative, anti-inflammatory, and free-radical scavenging activities of F. lepicarpa can be related to its hepatoprotective benefits.