Potential Nexus of Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Insulin Resistance Between Hepatic and Peripheral Tissues.

The liver is the central metabolic organ and plays a pivotal role in regulating homeostasis of glucose and lipid metabolism. Aberrant liver metabolism promotes insulin resistance, which is reported to be a common characteristic of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). There is a complex and bidirectional relationship between NAFLD and T2DM. NAFLD patients with hepatic insulin resistance generally share a high risk of impaired fasting glucose associated with early diabetes; most patients with T2DM experience non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and other more severe liver complications such as cirrhosis and hepatocellular carcinoma (HCC). Additionally, hepatic insulin resistance, which is caused by diacylglycerol-mediated activation of protein kinase C epsilon (PKC𝜀), may be the critical pathological link between NAFLD and T2DM. Therefore, this review aims to illuminate current insights regarding the complex and strong association between NAFLD and T2DM and summarize novel and emerging targets for the treatment of hepatic insulin resistance based on established mechanistic knowledge.

NAMPT inhibition synergizes with NQO1-targeting agents in inducing apoptotic cell death in non-small cell lung cancer cells.

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD(+), essential for a number of enzymes and regulatory proteins involved in a variety of cellular processes, including deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53 and FOXO. Herein we report that NQO1 substrates Tanshione IIA (TSA) and ß-lapachone (ß-lap) induced a rapid depletion of NAD(+) pool but adaptively a significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose significantly enhanced NQO1-targeting agent-induced apoptotic cell death. Compared with TSA or ß-lap treatment alone, co-treatment with FK866 induced a more dramatic depletion of NAD(+), repression of SIRT1 activity, and thereby the increased accumulation of acetylated FOXO1 and the activation of apoptotic pathway. In conclusion, the results from the present study support that NAMPT inhibition can synergize with NQO1 activation to induce apoptotic cell death, thereby providing a new rationale for the development of combinative therapeutic drugs in combating non-small lung cancer.

The complete mitochondrial genomes of four cockroaches (Insecta: Blattodea) and phylogenetic analyses within cockroaches.

Three complete mitochondrial genomes of Blaberidae (Insecta: Blattodea) (Gromphadorhina portentosa, Panchlora nivea, Blaptica dubia) and one complete mt genome of Blattidae (Insecta: Blattodea) (Shelfordella lateralis) were sequenced to further understand the characteristics of cockroach mitogenomes and reconstruct the phylogenetic relationship of Blattodea. The gene order and orientation of these four cockroach genomes were similar to known cockroach mt genomes, and contained 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one control region. The mt genomes of Blattodea exhibited a characteristics of a high A+T composition (70.7%-74.3%) and dominant usage of the TAA stop codon. The AT content of the whole mt genome, PCGs and total tRNAs in G. portentosa was the lowest in known cockroaches. The presence of a 71-bp intergenic spacer region between trnQ and trnM was a unique feature in B. dubia, but absent in other cockroaches, which can be explained by the duplication/random loss model. Based on the nucleotide and amino acid datasets of the 13 PCGs genes, neighbor-joining (NJ), maximum parsimony (MP), maximum likelihood (ML) and bayesian inference (BI) analyses were used to rebuild the phylogenetic relationship of cockroaches. All phylogenetic analyses consistently placed Isoptera as the sister cluster to Cryptocercidae of Blattodea. Ectobiidae and Blaberidae (Blaberoidea) formed a sister clade to Blattidae. Corydiidae is a sister clade of all the remaining cockroach species with a high value in NJ and MP analyses of nucleotide and amino acid datasets, and ML and BI analyses of the amino acid dataset.

Pharmacodynamics and potential synergistic effects of Mai-Luo-Ning injection on cardiovascular protection, based on molecular docking.

As a computer-assisted approach, molecular docking has been universally applied in drug research and development and plays an important role in the investigation and evaluation of herbal medicines. Herein, the method was used to estimate the pharmacodynamics of Mai-Luo-Ning injection, a traditional Chinese compound herbal prescription. Through investigating the interactions between several important proteins in cardiovascular system and characteristic components of the formula, its effect on cardiovascular protection was evaluated. Results showed the differences in the interactions between each component and the selected target proteins and revealed the possible mechanisms for synergistic effects of various characteristic components on cardiovascular protection. The study provided scientific evidence supporting the mechanistic study of the interactions among multi-components and targets, offering a general approach to investigating the pharmacodynamics of complicated materials in compound herbal prescriptions.