Idiopathic pulmonary fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists for effective therapeutics. The bioactive eicosanoid, prostaglandin F _2α , and its cognate receptor FPr ( Ptgfr ) are implicated as a TGF-β1–independent signaling hub for IPF. To assess this, we leveraged our published murine PF model (I ^ER - Sftpc ^I73T ) expressing a disease-associated missense mutation in the surfactant protein C ( Sftpc ) gene. Tamoxifen-treated I ^ER - Sftpc ^I73T mice developed an early multiphasic alveolitis and transition to spontaneous fibrotic remodeling by 28 days. I ^ER - Sftpc ^I73T mice crossed to a Ptgfr- null (FPr ^–/– ) line showed attenuated weight loss and gene dosage–dependent rescue of mortality compared with FPr ^+/+ cohorts. I ^ER -Sftpc ^I73T /FPr ^–/– mice also showed reductions in multiple fibrotic endpoints for which administration of nintedanib was not additive. Single-cell RNA-Seq, pseudotime analysis, and in vitro assays demonstrated Ptgfr expression predominantly within adventitial fibroblasts, which were reprogrammed to an “inflammatory/transitional” cell state in a PGF _2α /FPr-dependent manner. Collectively, the findings provide evidence for a role for PGF _2α signaling in IPF, mechanistically identify a susceptible fibroblast subpopulation, and establish a benchmark effect size for disruption of this pathway in mitigating fibrotic lung remodeling.

Cerebral malaria (CM) is a life-threatening disease, caused mainly by Plasmodium falciparum in humans. In adults only 1–2 % of P. falciparum-infected hosts transit to the cerebral form of the disease while most exhibit non-cerebral malaria (NCM). The perturbed metabolic pathways of CM and NCM have been reported. Early marker(s) of CM is(are) not known and by the time a patient exhibits the pathological symptoms of CM, the disease has progressed. Murine CM, like the human disease, is difficult to assign to specific animals at early stage and hence the challenge to treat CM at pre-clinical stage of the disease. This is the first report of prediction of CM in mice using a novel strategy based on 1H nuclear magnetic resonance (NMR)-based metabolomics. Mice were infected with malarial parasites, and serum was collected from all the animals (CM/NCM) before CM symptoms were apparent. The assignment of mice as NCM/CM at an early time point is based on their symptoms at days 8–9 post-infection (pi). The serum samples were subjected to 1H NMR-based metabolomics. 1H NMR spectra of the serum samples, collected at various time points (pi) in multiple sets of experiments, were subjected to multivariate analyses. The results from orthogonal partial least square discriminant analyses (OPLS-DA) suggest that the animals with CM start to diverge out in metabolic profile and were distinct on day 4 pi, although by physical observation they were indistinguishable from the NCM. The metabolites that appeared to contribute to this distinction were serum lipids and lipoproteins, and 14–19 % enhancement was observed in mice afflicted with CM. A cut-off of 14 % change of total lipoproteins in serum predicts 54–71 % CM in different experiments at day 4 pi. This study clearly demonstrates the possibility of differentiating and identifying animals with CM at an early, pre-clinical stage. The strategy, based on metabolite profile of serum, tested with different batches of animals in both the sex and across different times of the year, is found to be robust. This is the first such study of pre-clinical prognosis of CM.

Summary: Aim: Linoleic acid (LA) is an essential fatty acid involved in the biosynthesis of arachidonic acid and prostaglandins. LA is known to induce obesity and insulin resistance. In this study, two concentrations of LA with or without added glucose (G) were fed to mice to investigate their effects on endocannabinoid (EC) biology.Materials and Methods: Four groups of C57BL/6 mice were provided with diets containing 1% or 8% LA with or without added G (LAG) for 8 weeks. Body weights, food intake, circulating glucose and insulin levels were measured throughout the study. Following euthanasia, plasma, bowel and hepatic ECs, monoacylglycerol lipase and fatty acid amide hydroxylase protein levels (enzymes responsible for EC degradation) and transcriptional activity of PPARα in liver were quantified. Liver was probed for evidence of insulin receptor activity perturbation.Results: Increasing dietary LA from 1% to 8% significantly increased circulating, small bowel and hepatic ECs. 1%LAG fed mice had lowest feed efficiency, and only liver levels of both ECs were reduced by addition of G. Addition of G to 1% LA diets resulted in elevated monoacylglycerol lipase and fatty acid amide hydroxylase protein levels (p < 0.001 and p < 0.001, respectively) in liver due to increased transcriptional activity of PPARα (p < 0.05). The reduced EC levels with addition of G also correlated with a measure of enhanced insulin action.Conclusion: In conclusion, body weight of mice is influenced by the source of calorie intake. Furthermore, tissue EC/g are dependent on tissue‐specific synthesis and degradation that are modulated by dietary LA and G which also influence food efficiency, and down‐stream insulin signalling pathways. The findings could potentially be useful information for weight management efforts in humans.

Introduction. Falciparum malaria still remains as a major cause of morbidity and mortality worldwide. Acute kidney injury is a known complication of malaria, and it is reported to occur in up to 40% of adult patients with severe falciparum malaria in endemic regions like sub-Saharan Africa.Objectives. To determine the prevalence and factors associated with acute kidney injury among falciparum malaria patients in a tertiary level private hospital in Dar es Salaam.Methodology. In a cross-sectional study design, 104 adults with falciparum malaria were enrolled consecutively over 6 months from April to September 2015. The diagnosis of acute kidney injury (AKI) in these patients was established using the KDIGO classification criteria. The prevalence of AKI was obtained at 48 hours from admission and at day 7. Different sociodemographic and clinical parameters which were associated with acute kidney injury at 48 hours and at day 7 were identified by hypothesis testing using chi squared tests followed by multivariate logistic regression analysis. Factors with a p value less than 0.05 were considered significant.Results. The participants were predominantly males 65.4% (68/104) and a third (36.5% (38/104)) were between 46 and 65 years. The prevalence of AKI among malaria patients at 48 hours was 26% (27/104). The prevalence of AKI among malaria patients at day 7 was 18.3% (19/104). On multivariate logistic regression, we found that factors that were significantly associated with AKI at 48 hours were male sex (OR 127, CI 3.4–4700, P = 0.008) and hemoglobin <7.5g/dl (OR 36.5, CI 1.7–797.7, P = 0.022), and factor associated with AKI at day 7 was baseline platelet count <25×10³per mm³(OR 77.8 CI 1.045–5798.6, P = 0.048). Only two patients needed hemodialysis (1.9%) and there were no deaths.Conclusion. Acute kidney injury is a common complication in patient with falciparum malaria. When managed well it has an excellent prognosis and necessitates dialysis in only a minority of patients. Male sex and hemoglobin is associated with AKI at 48 hours and baseline platelet count is associated with AKI at 7 days.

The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed.