Background: Circulating tumor cells (CTCs) are a burgeoning topic in cancer biomarker discovery research with minimal invasive blood draws. CTCs can be used as potential biomarkers for disease prognosis, early cancer diagnosis and pharmacodynamics. However, the extremely low abundance of CTCs limits their clinical utility because of technical challenges such as the isolation and subsequent detailed molecular and functional characterization of rare CTCs from patient blood samples.Methods: In this study, we present a novel density gradient centrifugation method employing biodegradable gelatin nanoparticles coated on silicon beads for the isolation, release, and downstream analysis of CTCs from colorectal and breast cancer patients.Results: Using clinical patient/spiked samples, we demonstrate that this method has significant CTC-capture efficiency (>80%) and purity (>85%), high CTC release efficiency (94%) and viability (92.5%). We also demonstrate the unparalleled robustness of our method in downstream CTC analyses such as the detection of PIK3CA mutations.Conclusion: The efficiency and versatility of the multifunctional density microbeads approach provides new opportunities for personalized cancer diagnostics and treatments.

We and others have shown that inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) or activating ERK1/2 confer neuroprotection. As bisperoxovanadium compounds are well-established inhibitors of PTEN, we designed bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and determined whether and how bpV(pis) exerts a neuroprotective effect in cerebral ischaemia-reperfusion injury. EXPERIMENTAL APPROACHMalachite green-based phosphatase assay was used to measure PTEN activity. A western blot assay was used to measure the phosphorylation level of Akt and ERK1/2 (p-Akt and p-ERK1/2). Oxygen-glucose deprivation (OGD) was used to injure cultured cortical neurons. Cell death and viability were assessed by LDH and MTT assays. To verify the effects of bpV(pis) in vivo, Sprague-Dawley rats were subjected to middle cerebral artery occlusion, and brain infarct volume was measured and neurological function tests performed. KEY RESULTSbpV(pis) inhibited PTEN activity and increased p-Akt in SH-SY5Y cells but not in PTEN-deleted U251 cells. bpV(pis) also elevated p-ERK1/2 in both SH-SY5Y and U251 cells. These data indicate that bpV(pis) enhances Akt activation through PTEN inhibition but increases ERK1/2 activation independently of PTEN signalling. bpV(pis) prevented OGD-induced neuronal death in vitro and reduced brain infarct volume and promoted functional recovery in stroke animals. This neuroprotective effect of bpV(pis) was blocked by inhibiting Akt and/or ERK1/2. CONCLUSIONS AND IMPLICATIONSbpV(pis) confers neuroprotection in OGD-induced injury in vitro and in cerebral ischaemia in vivo by suppressing PTEN and activating ERK1/2. Thus, bpV(pis) is a bi-target neuroprotectant that may be developed as a drug candidate for stroke treatment.Abbreviations bpV(pis), bisperoxovandium (pyridin-2-squaramide); MCAO, middle cerebral artery occlusion; OGD, oxygen-glucose deprivation; PTEN, phosphatase and tensin homolog deleted on chromosome 10

Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome–based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.

This study aimed to investigate the clinical courses and outcomes of diabetes mellitus patients with coronavirus disease 2019 (COVID-19) in Wuhan. Methods: This study enrolled 1,880 consecutive patients with confirmed COVID-19 in Leishenshan Hospital. We collected and analyzed their data, including demographic data, history of comorbidity, clinical symptoms, laboratory tests, chest computed tomography (CT) images, treatment options, and survival. Results: The percentages of patients with diabetes among the severe and critical COVID-19 cases were higher than those among the mild or general cases (89.2%, 10.8 vs. 0%, p = 0.001). However, patients with and without diabetes showed no difference in the follow-up period (p = 0.993). The mortality rate in patients with or without diabetes was 2.9% (n = 4) and 1.1% (n = 9), respectively (p = 0.114). Univariate and multivariate Cox regression analyses and the Kaplan-Meier curves did not show any statistically significant differences between patients with and without diabetes (all p > 0.05). Conclusions: Our study results suggested that diabetes had no effect on the prognosis of COVID-19 patients but had a negative association with their clinical courses. These results may be useful for clinicians in the management of diabetic patients with COVID-19.

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