Microorganisms evolve resistance to antibiotics as a function of evolution. Antibiotics have accelerated bacterial resistance through mutations and acquired resistance through a combination of factors.

Introduction: Drug monotherapy was inadequate in controlling blood glucose levels and other comorbidities. An agent that selectively tunes multiple targets was regarded as a new therapeutic strategy for type 2 diabetes. Acanthopanax trifoliatus (L.) Merr polysaccharide (ATMP) is a bio-macromolecule isolated from Acanthopanax trifoliatus (L.) Merr and has therapeutic potential for diabetes management due to its anti-hyperglycemia activity.Methods: Type 2 diabetes mellitus was induced in mice using streptozotocin, and 40 and 80 mg/kg ATMP was administered daily via the intragastric route for 8 weeks. Food intake, water intake, and body weight were recorded. The fasting blood glucose (FBG), fasting insulin (FINS) and an oral glucose tolerance test (OGTT) were performed. Histological changes in the liver and pancreas were analyzed by H&E staining. The mRNA and the protein levels of key factors involved in glycogen synthesis, glycogenolysis, and gluconeogenesis were measured by quantitative real time PCR and Western blotting.Results: In this study, we found that ATMP could effectively improve glucose tolerance and alleviate insulin resistance by promoting insulin secretion and inhibiting glucagon secretion. In addition, ATMP decreases glycogen synthesis by inhibiting PI3K/Akt/GSK3β signaling, reduces glycogenolysis via suppressing cAMP/PKA signaling, and suppresses liver gluconeogenesis by activating AMPK signaling.Conclusion: Together, ATMP has the potential to be developed as a new multitargets therapeutics for type 2 diabetes.

Background: The development of drug resistance remains to be a major cause of therapeutic failure in breast cancer patients. How drug-sensitive cells first evade drug inhibition to proliferate remains to be fully investigated. Methods: Here we characterized the early transcriptional evolution in response to TGF-β in the human triple-negative breast cells through bioinformatical analysis using a published RNA-seq dataset, for which MCF10A cells were treated with 5 ng/ml TGF-β1 for 0 h, 24 h, 48 h and 72 h, and the RNA-seq were performed in biological duplicates. The protein-protein interaction networks of the differentially expressed genes were constructed. KEGG enrichment analysis, cis-regulatory sequence analysis and Kaplan-Meier analysis were also performed to analyze the cellular reprograming induced by TGF-β and its contribution to the survival probability decline of breast cancer patients. Result: Transcriptomic analysis revealed that cell growth was severely suppressed by TGF-β in the first 24 h but this anti-proliferate impact attenuated between 48 h and 72 h. The oncogenic actions of TGF-β happened within the same time frame with its anti-proliferative effects. In addition, sustained high expression of several drug resistance markers was observed after TGF-β treatment. We also identified 17 TGF-β induced genes that were highly correlated with the survival probability decline of breast cancer patients. Conclusion: Together, TGF-β plays an important role in tumorigenesis and the development of drug resistance, which implies potential therapeutic strategies targeting the early-stage TGF-β signaling activities.

Cell cycle is an important and complex biological system. A lot of efforts have been put in understanding cell cycle arrest for its vital role in clinical therapies. The cell-cycle-arrest outcomes upon stimulation are complicated. The response could be stringent or relaxed, and graded or quantized. A model fully addressing various cell-cycle-arrest outcomes is to be developed. Here, we developed a mathematical model of cell cycle control incorporating distinct characteristics of various cell-cycle-arrest outcomes. The model can simulate two typical properties of cell cycle arrest, quantized and graded. We also characterized the inheritable quiescence and refractory state, which were crucial in long-term response of the population. Then, we monitored cells respond to multiple stimulations, and the results indicated that cells responded to stimulations with small interval did not induce significantly sustained cell cycle arrest as the existence of refractory state. Our work will benefit fundamental research and make efforts to predicting outcomes of clinical therapeutics.