Metabolomic Identification of Exosome-Derived Biomarkers for Schizophrenia: A Large Multicenter Study

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.     

Genetics of Naphthalene Catabolism in Pseudomonads

At present, the modern two-step fermentation process is one of the major approaches for the industrial production of vitamin C. The key step in this process is the conversion of L-sorbose to 2-keto-L-gulonic acid (2-KLG), the vitamin C precursor, which is accomplished by an artificial microbial ecosystem consisting of Ketogulonicigenium vulgare and Bacillus megaterium. This review describes current progress in understanding this ecosystem, not only the individual physiological characteristics of the two strains, but also the interactions between them. Special emphasis is placed on recent systems biology studies of the ecosystem. We also discuss the regulation and improvement of this ecosystem, including analysis of the fermentation medium components and genetic engineering and optimum fermentative strategies. Finally, perspectives on the knowledge and engineering of this important artificial microbial ecosystem are discussed.     

From high definition precision healthcare to precision public oral health: opportunities and challenges

In anticipation of a major transformation in healthcare, this review provides highlights that anticipate the near future for oral public health (and beyond). Personalized or precision healthcare reflects the expectation that advances in genomics, imaging, and other domains will extend our risk assessment, diagnostic, and prognostic capabilities, and enables more effective prevention and therapeutic options for all Americans. Meanwhile, the current healthcare system does not meet cost, access, or quality criteria for all Americans. It is now an imperative that the success of “smart,” quality, and cost-effective high definition precision healthcare requires a public health perspective for several reasons: a) to enhance generalizability, b) to assess methods of implementation, and c) to focus on both risk and prevention in large and small populations, thereby providing a balance between the generation of long-term knowledge and short-term health gains. Sensitivity and resolution, reasonable cost, access to all Americans, coordinated comprehensive care, and advances in whole genome sequencing (WGS) and big data analyses, coupled to other advances in biotechnology and digital/artificial intelligence/machine learning devices, and the behavioral, social, and environmental sciences, offer remarkable opportunities to improve the health and wellness of the American people [genotype + phenotype + environment + behavior = high definition healthcare]. The opportunity is to significantly improve the well-being and life expectancy of all people across the lifespan including the least-advantaged people in our society and potentially increase access, reduce the national costs, and improve health outcomes.     

The therapy of gefitinib towards breast cancer partially through reversing breast cancer biomarker arginine

Background

Breast cancer remains the leading reason of cancer death among women worldwide, and gefitinib is the efficient drug for breast cancer.

Aims

To use targeted metabolomics method to elucidate the therapeutic mechanism of gefitinib through profiling the amino acids.

Methods

Healthy women (n=56) and women with breast cancer (n=60) were enrolled in Affiliated Yuhuangding hospital, medical college of Qingdao University from 2012–2014. API 3200 triple quadrupole mass spectrometer was used to analyze the serum samples.

Results

The concentration of amino acids was compared between healthy women and women with breast cancers. Compared with the healthy women, the concentration of arginine in breast cancer women significantly decreased (p<0.0001). To show the representative capability of arginine towards the pathogenesis of breast cancers, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to be 0.96 ± 0.02, indicating the high predictive capability of arginine for breast cancer . The reversing ability of gefitinib towards the level of arginine was further determined, and 1 month treatment of gefitinib (500 mg/day) significantly reversed the arginine level of breast cancer patients (p<0.0001)

Conclusion

The therapy of gefitinib towards breast cancer through reversing breast cancer biomarker arginine was demonstrated.     

Estrogen Deprivation and Myocardial Infarction: Role of Aerobic Exercise Training,Inflammation and Metabolomics

In general, postmenopausal women present higher mortality, and worse prognosis after myocardial infarction (MI) compared to men, due to estrogen deficiency. After MI, cardiovascular alterations occur such as the autonomic imbalance and the pro-inflammatory cytokines increase. In this sense, therapies that aim to minimize deleterious effects caused by myocardial ischemia are important. Aerobic training has been proposed as a promising intervention in the prevention of cardiovascular diseases. On the other hand, some studies have attempted to identify potential biomarkers for cardiovascular diseases or specifically for MI. For this purpose, metabolomics has been used as a tool in the discovery of cardiovascular biomarkers. Therefore, the objective of this work is to discuss the changes involved in ovariectomy, myocardial infarction, and aerobic training, with emphasis on inflammation and metabolism.     

Identification of new urinary gamma‐hydroxybutyric acid markers applying untargeted metabolomics analysis following placebo‐controlled administration to humans

Gamma‐hydroxybutyrate (GHB) is a short‐chain fatty acid that occurs naturally in the mammalian brain and is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock‐out drug in cases of drug‐facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 hours in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use. In the framework of a randomized, placebo‐controlled, crossover study in 20 healthy male volunteers, urine samples obtained 4.5 hours post‐administration were submitted to untargeted mass spectrometry [MS, quadrupole time of flight (QTOF)] analysis to identify possible new markers of GHB intake. MS data from four different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization) were filtered for significantly changed features applying univariate and multivariate statistics. From the resulting 42 compounds of interest, 8 were finally identified including conjugates of GHB with carnitine, glutamate, and glycine as well as the endogenous compounds glycolate and succinylcarnitine. While GHB conjugates were only detectable in the GHB, but not in the placebo group, glycolate and succinylcarnitine were present in both groups albeit significantly increased through GHB intake. Untargeted metabolomics proved as a suitable tool for the non‐hypothesis driven identification of new GHB markers. However, more studies on actual concentrations, detection windows, and stability will be necessary to assess the suitability of these markers for routine application.     

Conversion of the chill susceptible fruit fly larva (Drosophila melanogaster) to a freeze tolerant organism

Among vertebrates, only a few species of amphibians and reptiles tolerate the formation of ice crystals in their body fluids. Freeze tolerance is much more widespread in invertebrates, especially in overwintering insects. Evolutionary adaptations for freeze tolerance are considered to be highly complex. Here we show that surprisingly simple laboratory manipulations can change the chill susceptible insect to the freeze tolerant one. Larvae of Drosophila melanogaster, a fruit fly of tropical origin with a weak innate capacity to tolerate mild chilling, can survive when approximately 50% of their body water freezes. To achieve this goal, synergy of two fundamental prerequisites is required: (i) shutdown of larval development by exposing larvae to low temperatures (dormancy) and (ii) incorporating the free amino acid proline in tissues by feeding larvae a proline-augmented diet (cryopreservation).