Coevolutionary methods enable robust design of modular repressors by reestablishing intra-protein interactions.

Genetic sensors with unique combinations of DNA recognition and allosteric response can be created by hybridizing DNA-binding modules (DBMs) and ligand-binding modules (LBMs) from distinct transcriptional repressors. This module swapping approach is limited by incompatibility between DBMs and LBMs from different proteins, due to the loss of critical module-module interactions after hybridization. We determine a design strategy for restoring key interactions between DBMs and LBMs by using a computational model informed by coevolutionary traits in the LacI family.

Engineering DNA recognition and allosteric response properties of TetR family proteins by using a module-swapping strategy.

The development of synthetic biological systems requires modular biomolecular components to flexibly alter response pathways. In previous studies, we have established a module-swapping design principle to engineer allosteric response and DNA recognition properties among regulators in the LacI family, in which the engineered regulators served as effective components for implementing new cellular behavior. Here we introduced this protein engineering strategy to two regulators in the TetR family: TetR (UniProt Accession ID: P04483) and MphR (Q9EVJ6).

Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset.

Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs.

Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus.

The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others.

High infiltration of CD68-tumor associated macrophages, predict poor prognosis in Kazakh esophageal cancer patients.

Tumor-associated macrophages (TAMs), the most important immune cells in tumor microenvironment, were reported to play a key role in cancer progression, but the correlation of TAMs and Kazakh esophageal squamous cell carcinoma (ESCC) was still not clear, so we sought to identify the function of TAMs in Kazakh ESCC clinicopathological and prognostic evaluation. CD68 as the TAMs marker, and immunohistochemistry (IHC) was used to quantify IHC staining was also used to evaluate the expression of MMP-9 in Kazakh ESCCs. The density of CD68-TAMs in ESCCs tumor nest and stromal, were significantly higher than those of CANs (P<0.

Revealing protein networks and gene-drug connectivity in cancer from direct information.

The connection between genetic variation and drug response has long been explored to facilitate the optimization and personalization of cancer therapy. Crucial to the identification of drug response related genetic features is the ability to separate indirect correlations from direct correlations across abundant datasets with large number of variables. Here we analyzed proteomic and pharmacogenomic data in cancer tissues and cell lines using a global statistical model connecting protein pairs, genes and anti-cancer drugs.

CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma.

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma.

The increased number of tumor-associated macrophage is associated with overexpression of VEGF-C, plays an important role in Kazakh ESCC invasion and metastasis.

Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC.

Induced apoptosis of osteoblasts proliferating on polyhydroxyalkanoates.

The mechanism study on behaviors of cells influenced by biomaterial surface properties can provide profound guidances for functional tissue engineering scaffolds design. In this study, regulation of integrin-mediated cell-substrate interactions using rat osteoblasts incubated on PHA films was investigated. Compared with tissue culture plate (TCP), poly-3-hydroxybutyrate (PHB), copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV) and copolymer of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx), osteoblasts inoculated on a terpolymer of 3-hydroxybutyrate, 3-hydroxyvalerate and 3-hydroxyhexanoate (PHBVHHx) were found to have higher apoptosis rates.

The differential effects of aligned electrospun PHBHHx fibers on adipogenic and osteogenic potential of MSCs through the regulation of PPARγ signaling.

Cell-substrate interaction was functionally essential for phenotypic maintenance and multipotency remodeling of stem cells. For bone tissue engineering, electrospinning techniques are useful to create fibrous scaffolds mimicking natural mineralized collagen fibrous structure in bone. In this study, influence of electrospun fiber alignment on MSCs differentiation potential was investigated on PHBHHx electrospun meshes.

MicroRNAs in the regulation of interfacial behaviors of MSCs cultured on microgrooved surface pattern.

Cell-substrate interaction is one of the most important aspects of tissue engineering. Changes of MSCs interfacial behaviors were found to be triggered by 10 μm wide grooved pattern on poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx). Global marker genes expression and miRNAs profiling analysis provided insights into the regulation network of the topography induced MSCs' cell responses including adhesion, proliferation, differentiation and apoptosis.