Effects of NGF pretreatment on cerebral injury in gerbils

Objective： To investigate the effects and underlying mechanisms of different doses of nerve growth factor（NGF） pretreatment on neuron apoptosis and the expressions of the apoptosis-related protein, Bcl-2 and Bax, in the gerbil cerebral prefrontal cortex following global cerebral ischemia-reperfusion（I/R） injury. Methods： Fifty-four gerbils were randomly divided into five groups, group C： sham operation（n = 6）; group I/R（n = 12）, group L（n = 12）： low-dose NGF＋I/R, group M（n = 12）： medium-dose NGF＋I/ R and group H （n = 12）： high-dose NGF＋I/R. Groups I/R, L, M and H were further divided into 2 subgroups according to the duration of reperfusion（24 h and 72 h）. The global cerebral I/R injury model was induced by bilateral carotid artery occlusion for 20 min, followed by removal of the clamps to permit reperfusion. In groups L, M and H, NGF was injected into the lateral ventricle 24 h prior to ischemia. Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling（TUNEL） and immunohistochemical staining were performed to detect neuron apoptosis and the expressions of Bcl-2 and Bax protein in the cerebral cortex, respectively. Results： In the I/R group and NGF pretreatment groups（L, M and H groups）, reperfusion for 72 h caused higher percentages of both neurons exhibiting apoptosis and Bax positive cells（P 〈 0.01）, but lower percentages of Bcl-2 positive cells compared with the corresponding 24 h reperfusion groups（P 〈 0.05）. All NGF pretreatment groups exhibited lower percentages of neurons exhibiting apoptosis and Bax positive cells but a higher percentage of Bcl-2 positive-cells relative to the I/R group（P 〈 0.01）. Moreover, the high-dose NGF pretreatment group had a greater decreased neuronal apoptosis and Bax protein expression and increased Bcl-2 protein expression than either the low-or medium-dose groups. Conclusion： Neuron apoptosis participates in the progression of cerebral ischemia-reperfusion injury. The protective effect of NGF pretreatment against ischemia-reperfusion-induced neuron apoptosis seems to be both time- and dose-dependent. This anti-apoptosis mechanism may be associated with upregulation of Bcl- 2 protein expression and downregulation of Bax protein expression.

Multiscale engineering of microbial cell factories: A step forward towards sustainable natural products industry

Microbial cell factories(bacteria and fungi)are the leading producers of beneficial natural products such as lycopene,carotene,herbal medicine,and biodiesel etc.These microorganisms are considered efficient due to their effective bioprocessing strategy(monoculture-and consortial-based approach)under distinct processing conditions.Meanwhile,the advancement in genetic and process optimization techniques leads to enhanced biosynthesis of natural products that are known functional ingredients with numerous applications in the food,cosmetic and medical industries.Natural consortia and monoculture thrive in nature in a small proportion,such as wastewater,food products,and soils.In similitude to natural consortia,it is possible to engineer artificial microbial consortia and program their behaviours via synthetic biology tools.Therefore,this review summarizes the optimization of genetic and physicochemical parameters of the microbial system for improved production of natural products.Also,this review presents a brief history of natural consortium and describes the functional properties of monocultures.This review focuses on synthetic biology tools that enable new approaches to design synthetic consortia;and highlights the syntropic interactions that determine the performance and stability of synthetic consortia.In particular,the effect of processing conditions and advanced genetic techniques to improve the productibility of both monoculture and consortial based systems have been greatly emphasized.In this context,possible strategies are also discussed to give an insight into microbial engineering for improved pro-duction of natural products in the future.In summary,it is concluded that the coupling of genomic modifications with optimum physicochemical factors would be promising for producing a robust microbial cell factory that shall contribute to the increased production of natural products.