Precision Clinical Medicine最新文献

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder worldwide, and the most common reason for referral to gastroenterology clinics. However, the pathophysiology is still not fully understood and consequently current management guidelines are very symptom-specific, leading to mixed results. Here we present a study of 88 individuals with IBS who had baseline sequencing of their gut microbiome (stool samples), received targeted interventions that included dietary, supplement, prebiotic/probiotic, and lifestyle recommendations for a 30-day period, and a follow-up sequencing of their gut microbiome. The study's objectives were to demonstrate unique metagenomic signatures across the IBS phenotypes and to validate whether metagenomic-guided interventions could lead to improvement of symptom scores in individuals with IBS. Enrolled subjects also completed a baseline and post-intervention questionnaire that assessed their symptom scores. The average symptom score of an individual with IBS at baseline was 160 and at the endpoint of the study the average symptom score of the cohort was 100.9. The mixed IBS subtype showed the most significant reduction in symptom scores across the different subtypes (average decrease by 102 points, P = 0.005). The metagenomics analysis reveals shifts in the microbiome post-intervention that have been cross-validated with the literature as being associated with improvement of IBS symptoms. Given the complex nature of IBS, further studies with larger sample sizes, more targeted analyses, and a broader population cohort are needed to explore these results further.

Extracellular vesicles (EVs) are small membranous particles that can mediate cell-to-cell communication and which are divided into at least three categories according to their subcellular origin and size: exosomes, microvesicles, and apoptotic bodies. Exosomes are the smallest (30-150 nm) of these EVs, and play an important role in EV-mediated cell-to-cell interactions, by transferring proteins, nucleic acids and, lipids from their parental cells to adjacent or distant cells to alter their phenotypes. Most exosome studies in the past two decades have focused on their nucleic acid composition and their transfer of mRNAs and microRNAs to neighboring cells. However, exosomes also carry specific membrane proteins that can identify the physiological and pathological states of their parental cells or indicate their preferential target cells or tissues. Exosome membrane protein expression can also be directly employed or modified to allow exosomes to serve as drug delivery systems and therapeutic platforms, including in targeted therapy approaches. This review will briefly summarize information on exosome membrane proteins components and their role in exosome-cell interactions, including proteins associated with specific cell-interactions and diseases, and the potential for using exosome membrane proteins in therapeutic targeting approaches.

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.