Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients.

Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.

MicroRNA-103 represses hepatic de novo lipogenesis and alleviates NAFLD via targeting FASN and SCD1.

MicroRNAs are well acknowledged as key mediators in the development of chronic metabolic diseases, including NAFLD. However, their roles in hepatic lipid metabolism and fatty liver still remain well elucidated. Here, we found that miR-103 represses de novo lipogenesis (DNL) and dampens the development of obesity/diet-induced fatty liver through targeting at Fasn and Scd1 in mouse liver. miR-103, robustly amplified in obese livers, inhibits the expression of Fasn and Scd1 via directly interacting with their mRNA 3' untranslated regions. Upregulated miR-103 sufficiently reduces the expression of Fasn and Scd1 and blocks the lipid accumulation in oleate-incubated hepatocytes. Furthermore, specifically overexpressing miR-103 in mouse liver by adenovirus significantly inhibits hepatic DNL to repress HCD-promoted hepatic lipid contents as well as NAFLD development. Meanwhile, enforced expression of hepatic miR-103 also alleviates obesity-associated fatty liver via reducing Fasn and Scd1 in db/db mice. Together, our study reveals a critical role of miR-103 in lipid homeostasis of liver and pathogenesis of NAFLD.

Identification of an essential regulator controlling the production of raw-starch-digesting glucoamylase in Penicillium oxalicum.

BACKGROUND: Raw-starch-digesting glucoamylases (RSDGs) from filamentous fungi have great commercial values in starch processing; however, the regulatory mechanisms associated with their production in filamentous fungi remain unknown. Penicillium oxalicum HP7-1 isolated by our laboratory secretes RSDG with suitable properties but at low production levels. Here, we screened and identified novel regulators of RSDG gene expression in P. oxalicum through transcriptional profiling and genetic analyses. RESULTS: Penicillium oxalicum HP7-1 transcriptomes in the presence of glucose and starch, respectively, used as the sole carbon source were comparatively analyzed, resulting in screening of 23 candidate genes regulating the expression of RSDG genes. Following deletion of 15 of the candidate genes in the parental P. oxalicum strain ∆PoxKu70, enzymatic assays revealed five mutants exhibiting significant reduction in the production of raw-starch-digesting enzymes (RSDEs). The deleted genes (POX01907, POX03446, POX06509, POX07078, and POX09752), were the first report to regulate RSDE production of P. oxalicum. Further analysis revealed that ∆POX01907 lost the most RSDE production (83.4%), and that POX01907 regulated the expression of major amylase genes, including the RSDG gene POX01356/PoxGA15A, a glucoamylase gene POX02412, and the α-amylase gene POX09352/Amy13A, during the late-stage growth of P. oxalicum. CONCLUSION: Our results revealed a novel essential regulatory gene POX01907 encoding a transcription factor in controlling the production of RSDE, regulating the expression of an important RSDG gene POX01356/PoxGA15A, in P. oxalicum. These results provide insight into the regulatory mechanism of fungal amylolytic enzyme production.

Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid ß-oxidation and ketogenesis via activating XBP1 signaling in liver.

Liver coordinates a series of metabolic adaptations to maintain systemic energy balance and provide adequate nutrients for critical organs, tissues and cells during starvation. However, the mediator(s) implicated in orchestrating these fasting-induced adaptive responses and the underlying molecular mechanisms are still obscure. Here we show that hepatic growth differentiation factor 15 (GDF15) is regulated by IRE1α-XBP1s branch and promotes hepatic fatty acids ß-oxidation and ketogenesis upon fasting. GDF15 expression was exacerbated in liver of mice subjected to long-term fasted or ketogenic diet feeding. Abrogation of hepatic Gdf15 dramatically attenuated hepatic ß-oxidation and ketogenesis in fasted mice or mice with STZ-initiated type I diabetes. Further study revealed that XBP1s activated Gdf15 transcription via binding to its promoter. Elevated GDF15 in liver reduced lipid accumulation and impaired NALFD development in obese mice through enhancing fatty acids oxidation in liver. Therefore, our results demonstrate a novel and critical role of hepatic GDF15 activated by IRE1α-XBP1s branch in regulating adaptive responses of liver upon starvation stress.

MicroRNA-27a regulates hepatic lipid metabolism and alleviates NAFLD via repressing FAS and SCD1.

MicroRNAs are implicated as crucial mediators in metabolic diseases including obesity, diabetes, and non-alcoholic fatty liver diseases (NAFLD). Here, we show miR-27a attenuated hepatic de novo lipogenesis and alleviated obesity-initiated NAFLD through inhibiting Fasn and Scd1 in liver. Hepatic levels of miR-27a were significantly augmented in HFD-fed and ob/ob mice. Further studies demonstrated that miR-27a directly interacted with 3' untranslated region (3'-UTR) of hepatic Fasn and Scd1 mRNAs and reduced their expression levels in mice. Adenovirus-mediated overexpression of miR-27a robustly blocked sodium oleate-induced triglyceride (TG) accumulation in mouse primary hepatocytes and reduced liver TG contents in mice via repressing hepatic lipogenesis. Furthermore, ectopic expression of hepatic miR-27a impaired lipid contents of livers and attenuated NAFLD development through suppressing lipogenesis in HCD-fed and ob/ob mice. Together, our results reveal a critical role of miR-27a in lipid homeostasis of liver and pathogenesis of NAFLD.