Proliferating hepatic stellate cells (HSCs) respond to liver damage by secreting collagens that form fibrous scar tissue, which can lead to cirrhosis if in appropriately regulated. Advancement of microRNA (miRNA) hepatic therapies has been hampered by difficulties in delivering miRNA to damaged tissue. However, exosomes secreted by adipose‐derived mesenchymal stem cells (ADSCs) can be exploited to deliver miRNAs to HSCs. ADSCs were engineered to overexpress miRNA‐181‐5p (miR‐181‐5p‐ADSCs) to selectively home exosomes to mouse hepatic stellate (HST‐T6) cells or a CCl4‐induced liver fibrosis murine model and compared with non‐targeting control Caenorhabditis elegans miR‐67 (cel‐miR‐67)‐ADSCs. In vitro analysis confirmed that the transfer of miR‐181‐5p from miR‐181‐5p‐ADSCs occurred via secreted exosomal uptake. Exosomes were visualized in HST‐T6 cells using cyc3‐labelled pre‐miRNA‐transfected ADSCs with/without the exosomal inhibitor, GW4869. The effects of miRNA‐181‐5p overexpression on the fibrosis associated STAT3/Bcl‐2/Beclin 1 pathway and components of the extracellular matrix were assessed. Exosomes from miR181‐5p‐ADSCs down‐regulated Stat3 and Bcl‐2 and activated autophagy in the HST‐T6 cells. Furthermore, the up‐regulated expression of fibrotic genes in HST‐T6 cells induced by TGF‐β1 was repressed following the addition of isolated miR181‐5p‐ADSC exosomes compared with miR‐67‐ADSCexosomes. Exosome therapy attenuated liver injury and significantly down‐regulated collagen I, vimentin, α‐SMA and fibronectin in liver, compared with controls. Taken together, the effective anti‐fibrotic function of engineered ADSCs is able to selectively transfer miR‐181‐5p to damaged liver cells and will pave the way for the use of exosome‐ADSCs for therapeutic delivery of miRNA targeting liver disease.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

Fourteen volatile organic compound (VOC) biomarkers in the breath have been identified to distinguish early gastric cancer (EGC) and advanced gastric cancer (AGC) patients from healthy persons by gas chromatography-mass spectrometry coupled with solid phase microextraction (SPME). Then, a breath analysis approach based on a surface-enhanced Raman scattering (SERS) sensor was developed to detect these biomarkers. Utilizing hydrazine vapor adsorbed in graphene oxide (GO) film, the clean SERS sensor is facilely prepared by in situ formation of gold nanoparticles (AuNPs) on reduced graphene oxide (RGO) without any organic stabilizer. In the SERS sensor, RGO can selectively adsorb and enrich the identified biomarkers from breath as an SPME fiber, and AuNPs well dispersed on RGO endow the SERS sensor with an effective detection of adsorbed biomarkers. Fourteen Raman bands associated with the biomarkers are selected as the fingerprints of biomarker patterns to distinguish persons in different states. The approach has successfully analyzed and distinguished different simulated breath samples and 200 breath samples of clinical patients with a sensitivity of higher than 83% and a specificity of more than 92%. In conclusion, the VOC biomarkers and breath analysis approach in this study can not only diagnose gastric cancer but also distinguish EGC and AGC. This work has great potential for clinical translation in primary screening diagnosis and stage determination of stomach cancer in the near future.