Precision Clinical Medicine最新文献

Background: Ion channels are a large family of transmembrane proteins, accessible by soluble membrane-impermeable molecules, and thus are targets for development of therapeutic drugs. Ion channels are the second most common target for existing drugs, after G protein-coupled receptors, and are expected to make a big impact on precision medicine in many different diseases including wound repair and regeneration. Research has shown that endogenous bioelectric signaling mediated by ion channels is critical in non-mammalian limb regeneration. However, the role of ion channels in regeneration of limbs in mammalian systems is not yet defined.

Methods: To explore the role of potassium channels in limb wound repair and regeneration, the hindlimbs of mouse embryos were amputated at E12.5 when the wound is expected to regenerate and E15.5 when the wound is not expected to regenerate, and gene expression of potassium channels was studied.

Results: Most of the potassium channels were downregulated, except for the potassium channel kcnj8 (Kir6.1) which was upregulated in E12.5 embryos after amputation.

Conclusion: This study provides a new mouse limb regeneration model and demonstrates that potassium channels are potential drug targets for limb wound healing and regeneration.

Systemic lupus erythematosus (SLE) is an autoimmune disease that is a challenge to diagnose and treat. There is an urgent need for biomarkers to help define organ involvement, and more effective therapies. A unique population of T cells, the CD3⁺CD4^-CD8^- (DNeg) cells, is significantly increased in lupus patients. Twenty-seven cases (53%) of pediatric SLE patients had elevated DNeg cells in their peripheral blood, which correlated with kidney function (R²  = 0.54). Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by immunofluorescence. For the first time, this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus mice. In lupus mice, the increase in DNeg cells tracked with worsening disease and correlated with kidney function (R²  = 0.85). Our results show that DNeg cells per se can cause kidney dysfunction, increase in number with increase in disease pathology, and could serve as a potential biomarker.

In December 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On 7 January 2020, the causal organism was identified as a new coronavirus, later named as the 2019 novel coronavirus (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of severe acute respiratory syndrome-associated coronavirus. As of 29 January 2020, the virus had been diagnosed in more than 7000 patients in China and 77 patients in other countries. It is reported that both symptomatic and asymptomatic patients with 2019-nCoV can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible-or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed and on our experience with coronaviruses at West China Hospital in Chengdu, China.

It is been shown that spaceflight-induced molecular, cellular, and physiologic changes cause alterations across many modalities of the human body, including cardiovascular, musculoskeletal, hematological, immunological, ocular, and neurological systems. The Twin Study, a multi-year, multi-omic study of human response to spaceflight, provided detailed and comprehensive molecular and cellular maps of the human response to radiation, microgravity, isolation, and stress. These rich data identified epigenetic, gene expression, inflammatory, and metabolic responses to spaceflight, facilitating a better biomedical roadmap of features that should be monitored and safe-guarded in upcoming missions. Further, by exploring new developments in pre-clinical models and clinical trials, we can begin to design potential cellular interventions for exploration-class missions to Mars and potentially farther. This paper will discuss the overall risks astronauts face during spaceflight, what is currently known about human response to these risks, what pharmaceutical interventions exist for use in space, and which tools of precision medicine and cellular engineering could be applied to aerospace and astronaut medicine.

Background: Essential tremor (ET) is a neurological syndrome of unknown origin with poorly understood etiology and pathogenesis. It is suggested that the cerebellum and its tracts may be involved in the pathophysiology of ET. DNA methylome interrogation of cerebellar tissue may help shine some light on the understanding of the mechanism of the development of ET. Our study used postmortem human cerebellum tissue samples collected from 12 ET patients and 11 matched non-ET controls for DNA methylome study to identify differentially methylated genes in ET.

Results: Using Nugen's Ovation reduced representation bisulfite sequencing (RRBS), we identified 753 genes encompassing 938 CpG sites with significant differences in DNA methylation between the ET and the control group. Identified genes were further analyzed with Ingenuity Pathway Analysis (IPA) by which we identified certain significant pathways, upstream regulators, diseases and functions, and networks associated with ET.

Conclusions: Our study provides evidence that there are significant differences in DNA methylation patterns between the ET and control samples, suggesting that the methylation alteration of certain genes in the cerebellum may be associated with ET pathogenesis. The identified genes allude to the GABAergic hypothesis which supports the notation that ET is a neurodegenerative disease, particularly involving the cerebellum.