Dietary ketone body-escalated histone acetylation in megakaryocytes alleviates chemotherapy-induced thrombocytopenia.

Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet-induced circulating ß-hydroxybutyrate (ß-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-ß-hydroxybutyrate dehydrogenase (BDH)-mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked ß-OHB-induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body-MCT1-BDH-histone acetylation-platelet biogenesis axis in megakaryocytes and propose a nontoxic, low-cost dietary intervention for combating CIT.

The clinical significance of sCD14-ST for blood biomarker in neonatal hematosepsis: A diagnostic accuracy study.

Hematosepsis is a systemic inflammatory response syndrome (SIRS) with suspected or confirmed infection, which is the most common infectious disease in clinical neonatal intensive care unit. As the rapid development of neonatal hematosepsis caused by various basic diseases, the mortality rate is high, and there are some sequelae.We report the lasted study to date with 96 cases from Fujian Longyan First Hospital between 2013 and 2015. The aim of our study is to explore the value of soluble cluster of differentiation 14 subtype (sCD14-ST) in whole blood for differential diagnosis of neonatal hematosepsis at an early stage, and used in evaluation of the severity about sepsis combined with acute physiology and chronic health evaluation II (APACHE-II) score, procalcitonin (PCT), C reactive protein (CRP), and leukocyte (WBC).In our cohort, all cases met the diagnostic criteria for hematosepsis specific for newborns. We selected 42 neonates with hematosepsis, 54 neonates with nonhematosepsis, 44 noninfectious SIRS neonates, and 53 healthy neonatal controls. Which were determined the sCD14-ST, PCT, CRP, and WBC of all samples before treatment. Then assign the APACHE-II score for the all samples before and after treatment.The study shows, sCD14-ST levels were significantly higher in hematosepsis than nonhematosepsis group (t = -2.112, P = .041). Meanwhile, sCD14-ST levels were significantly higher in neonatal hematosepsis than in noninfectious SIRS group and controls (χ = 57.812, 68.944, P < .01). However, sCD14-ST in hematosepsis group was positively correlated with APACHE-II score (R-value = 0.415, P < .01). During treatment, the sCD14-ST level was decreased obviously along with APACHE-II score, PCT, CRP, and WBC (χ = 35.019, 78.399, 52.363, 25.912, 7.252, all P values <.01). The area under the curve (AUC) of sCD14-ST was 0.942. The differences in ROC of sCD14-ST compared with PCT, CRP, and WBC were statistically significant (Z = -6.034, -4.474, -5.722, all P values <.01). The sensitivity and specificity of sCD14-ST were 95.2% and 84.9%, respectively.sCD14-ST could be a blood biomarker for early identification and disease valuation in newborns hematosepsis infection; and its diagnostic value is superior to other laboratory indexes.

Soluble CD14 subtype (sCD14-ST) is a biomarker for neonatal sepsis.

This prospective observational study evaluated soluble CD14 subtype (sCD14-ST) as an early diagnosis and monitoring biomarker for neonatal sepsis in controls, patients with sepsis, or systemic inflammatory response syndrome (SIRS). sCD14-ST, procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), and acute physiology and chronic health evaluation II (APACHE-II) score were evaluated before and after therapy. sCD14-ST levels were significantly higher in sepsis than in SIRS, and higher in SIRS than controls. Treatment significantly decreased sCD14-ST, APACHE-II, PCT, CRP, and WBC. sCD14-ST levels correlated with APACHE-II before and after therapy, and with PCT before therapy (r=0.201, P=0.05). The receiver operating characteristic area under the curve of sCD14-ST was 0.958. A 304.5 pg/mL cutoff value was associated with 95.8% sensitivity and 84.9% specificity. sCD14-ST had superior diagnostic power for neonatal sepsis than the other indicators. In conclusion, sCD14-ST is a potential biomarker for the early diagnosis and monitoring of neonatal sepsis.