The combination of red palm oil and rooibos show anti-inflammatory effects in rats

BACKGROUND: Red palm oil (RPO) and rooibos have been shown to exhibit cardioprotective properties. RPO is rich in essential fatty acids and fat soluble antioxidants while rooibos contains polyphenolic compounds with a unique composition of flavonoids. They exert their biological effects in different cellular compartments. Therefore the combination of these two natural food compounds has the potential to enhance the spectrum of available dietary antioxidants in different cellular compartments, which could result in an enhanced protection against certain pathological conditions such as inflammation. METHODS: Male Wistar rats weighing 150-200 g were supplemented with RPO, rooibos or their combination for 28 days. The Langendorff system and the lipoposaccharide (LPS)-induced inflammatory model were used to establish if RPO and rooibos, when supplemented alone or in combination, will reverse the negative effects of LPS on cardiac function at baseline. The effect of dietary intervention was also investigated on modulation of pro-inflammatory and anti-inflammatory cytokines in plasma and myocardial tissue. RESULTS AND DISCUSSION: The LPS resulted in induction of systemic inflammation as evidenced by increased levels of IL-1beta in plasma of LPS-treated rats compared to their non-treated control counterparts. Dietary supplementation and LPS treatment did not have an effect on baseline cardiac functional parameters. However, the elevation of IL-1beta levels in plasma of LPS-induced rats consuming either RPO or rooibos alone were paralleled with increased levels of the anti-inflammatory cytokine, IL-10. The combination of rooibos and RPO was associated with enhanced endogenous production of myocardial IL-10 in LPS-induced rats. CONCLUSION: The results of this study indicate that RPO and rooibos when supplemented individually showed anti-inflammatory effect at systemic level while their combination exhibited an enhanced anti-inflammatory effect in the myocardial tissue. Therefore, the findings in the current study argue that the combination of these two natural food substances could be beneficial in clinically relevant conditions where inflammation plays a role

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease.

OBJECTIVE: We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB. METHODS: Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. RESULTS: 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. CONCLUSIONS: A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance

Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet

Abstract: AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg)..

Vindoline effectively ameliorated diabetes-induced hepatotoxicity by docking oxidative stress, inflammation and hypertriglyceridemia in type 2 diabetes-induced male Wistar rats

CITATION: Gobozaa, M., et al. 2019. Vindoline effectively ameliorated diabetes-induced hepatotoxicity by docking oxidative stress, inflammation and hypertriglyceridemia in type 2 diabetes-induced male Wistar rats. Biomedicine and Pharmacotherapy, 112:108638, doi:10.1016/j.biopha.2019.108638.The original publication is available at https://www.sciencedirect.comENGLISH ABSTRACT: Vindoline, an indole alkaloid present in the leaves of Catharanthus roseus plant, has been recently reported to have insulotropic effects. This present study evaluated the possible hepatoprotective effects of vindoline in a type 2 diabetes mellitus rat model. Diabetes mellitus was induced by exposing rats to 10% fructose water for two weeks followed by a single intraperitoneal injection of 40 mg/kg body weight of streptozotocin (STZ). Rats were randomly divided into six groups (n = 8) and treated daily for 6 weeks with the vehicle via oral gavage, vindoline (20 mg/kg) or glibenclamide (5 mg/kg). Weekly fasting blood glucose (FBG) levels and body weight were measured and recorded. Administration of vindoline significantly (p < 0.05) reduced FBG by 15% when compared to the diabetic controls. Vindoline significantly (p < 0.05) decreased diabetes-induced hepatic injury shown by decreased levels of serum alanine transferase (ALT) (-42%), aspartate aminotransferase (AST) (-42%) and alkaline phosphatase (-62%) compared to the diabetic controls. The oxygen radical absorbance capacity and the activities of superoxide dismutase (SOD) and catalase (CAT) were also improved following treatment with vindoline. The results also showed decreased levels of pro-inflammatory cytokines such as TNF-ɑ by (-41%) and IL-6 (-28%) which may have also contributed to the reduction of serum triglycerides (-65%) in the diabetic group treated with vindoline. Histopathological findings showed improvement of both the hepatic and pancreatic tissues following vindoline treatment. Overall, these findings suggest that vindoline may protect the diabetic hepatic tissue from injury via antioxidant, anti-inflammatory and anti-hypertriglyceredemia mechanisms thereby retarding the development of diabetic complications.https://www.sciencedirect.com/science/article/pii/S0753332218374663?via%3DihubPublisher's versio

Tuberculous Meningitis: Pathogenesis, Immune Responses, Diagnostic Challenges, and the Potential of Biomarker-Based Approaches

CITATION: Manyelo CM, Solomons RS, Walzl G, Chegou NN. 2021. Tuberculous meningitis: pathogenesis, immune responses, diagnostic challenges, and the potential of biomarker-based approaches. J Clin Microbiol 59:e01771-20. doi.10.1128/JCM.01771-20.The original publication is available at: asm.orgTuberculous meningitis (TBM) is the most devastating form of tuberculosis (TB), causing high mortality or disability. Clinical management of the disease is challenging due to limitations of the existing diagnostic approaches. Our knowledge on the immunology and pathogenesis of the disease is currently limited. More research is urgently needed to enhance our understanding of the immunopathogenesis of the disease and guide us toward the identification of targets that may be useful for vaccines or host-directed therapeutics. In this review, we summarize the current knowledge about the immunology and pathogenesis of TBM and summarize the literature on existing and new, especially biomarker-based, approaches that may be useful in the management of TBM. We identify research gaps and provide directions for research which may lead to the development of new tools for the control of the disease in the near future.Publisher’s versio

Potential of Host Markers Produced by Infection Phase-Dependent Antigen-Stimulated Cells for the Diagnosis of Tuberculosis in a Highly Endemic Area

CITATION: Chegou, N. N. et al. 2012. Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS ONE, 7(6): e38501, doi:10.1371/journal.pone.0038501.The original publication is available at http://journals.plos.org/plosoneBackground: Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays. © 2012 Chegou et al.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038501Publisher's versio

Host urinary biomarkers in HIV positive and HIV negative patients with tubercular uveitis and other uveitic diseases

The original publication is available at: https://www.sciencedirect.comPurpose To determine if host urinary biomarker profiles could distinguish between tubercular uveitis (TBU) and other uveitic diseases (OUD) in patients with and without HIV infection. Methods Concentrations of 29 different host biomarkers were measured in urine samples using the Luminex platform. Data were analyzed to describe differences between patients diagnosed with and without TBU and with and without HIV co-infection. Results One-hundred-and-eighteen urine samples were collected and 39% participants were diagnosed as TBU+. Mean age TBU+ was 39.3±13.6 years with 45.7% males. Anterior and panuveitis and unilateral involvement were most common. 32.6% were TBU+HIV+ (median CD4+=215) while 40.2% were OUD+HIV+ (median CD4+=234). Only sVEGF3 was decreased in TBU+ versus OUD+ (p=0.03), regardless of HIV status. Some biomarkers were significantly raised in HIV+ TBU+ compared to HIV- TBU+: sIL-6Rα, CD30, sRAGE , sTNFR I&-II, IP-10, MIP-1β, sEGFR and Ferritin. HIV+ OUD+ had increased sVEGFR3, CD30, sIL-6Rα, IP-10, sTNFR I&-II, Ferritin and Haptoglobin compared to HIV- OUD+. VEGF-A (p = 0.04) was decreased in HIV+ OUD+ versus HIV- OUD+. Conclusion Decreased urinary concentrations of VEGFR3 were observed in TBU+ compared to TBU-. HIV+ individuals demonstrated increased concentrations of multiple urinary analytes when compared to HIV- patients with uveitis.https://www.sciencedirect.com/science/article/pii/S1472979224000738Publisher’s versio

Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature