Estimation of cancer cell migration in biomimetic random/oriented collagen fiber microenvironments

Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.

Band structures analysis of one-dimensional photonic crystals using plane wave expansion

A theoretical analysis is made, using plane wave expansion, on how the width of the first three band gaps is influenced by filling ratio, dielectric constant ratio, and periodic width in one-dimensional photonic crystals （PhCs）. From simulation and analysis, there are one, two, and three peak points on the first, second and third band gaps respectively with the changes of filling ratio un- der fixed dielectric constant ratio. When filling ratio is fixed, the bandwidth of the first band gap consistently increases with dielectric constant ratio. However, no similar trend is observed in the second and the third band gaps. Because of scaling properties, varying periodic width does not alter the relative bandwidth.

Biophysical model for high-throughput tumor and epithelial cell co-culture in complex biochemical microenvironments

The in vivo tumor microenvironment is a complex niche that includes heterogeneous physical structures,unique biochemical gradients and multiple cell interactions.Its high-fidelity in vitro reconstruction is of fundamental importance to improve current understandings of cell behavior,efficacy predictions and drug safety.In this study,we have developed a high-throughput biochip with hundreds of composite extracellular matrix(ECM)microchambers to co-culture invasive breast cancer cells(MDA-MB-231-RFP)and normal breast epithelial cells(MCF-10 A-GFP).The composite ECM is composed of type I collagen and Matrigel which provides a heterogeneous microenvironment that is similar to that of in vivo cell growth.Additionally,the growth factors and drug gradients that involve human epidermal growth factor(EGF),discoidin domain receptor 1(DDR1)inhibitor 7 rh and matrix metalloproteinase inhibitor batimastat allow for the mimicking of the complex in vivo biochemical microenvironment to investigate their effect on the spatial-temporal dynamics of cell growth.Our results demonstrate that the MDA-MB-231-RFP cells and MCF-10 A-GFP cells exhibit different spatial proliferation behaviors under the combination of growth factors and drugs.Basing on the experimental data,we have also developed a cellular automata(CA)model that incorporated drug diffusion to describe the experimental phenomenon,as well as employed Shannon entropy(SE)to explore the effect of the drug diffusion coefficient on the spatial-temporal dynamics of cell growth.The results indicate that the uniform cell growth is related to the drug diffusion coefficient,which reveals that the pore size of the ECM plays a key role in the formation of complex biochemical gradients.Therefore,our integrated,biomimetic and high-throughput co-culture platforms,as well as the computational model can be used as an effective tool for investigating cancer pathogenesis and drug development.

Association between Mycoplasma pneumoniae infection and acute coronary syndrome

Objective: To investigate the association between Mycoplasma pneumoniae (MP) infection and the occurrence of acute coronary syndromes (ACS), and its associated mechanism in ACS development. Methods: A total of 134 patients with confirmed ACS were selected as the ACS group, and another 102 healthy subjects were enrolled as the control group. Serum triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were detected using immuno-transmission turbidimetry in the ACS and control groups. An enzyme-linked immunosorbent assay was used to detect MP-specific IgG antibodies in the serum. Results:The MP infection rate in the ACS group was significantly higher than that in of the healthy control group. Although there were significant differences in the expression of TC, HDL, LDL, and ApoB between the ACS and control groups, there were no significant differences between the MP IgG-positive and negative groups for any the six serum lipid indexes in the ACS patients. The level of high-sensitivity C-reactive protein (hs-CRP) expression in ACS patients was significantly higher in the MP IgG-positive group compared with the negative group. Conclusions: MP infection is associated with ACS and may be a risk factor for ACS. MP infection may not affect blood lipid levels but rather induce the development of ACS by affecting the long-term inflammatory environment.

Clinical Efficacy and Transcriptomic Analysis of Congrong Shujing Granules (苁蓉舒痉颗粒) in Patients with Parkinson's Disease of Shen (Kidney) Essence Deficiency Syndrome

Objective:To evaluate the clinical efficacy and safety of Congrong Shujing Granules(苁蓉舒痉颗粒,CSGs)in treating patients with Parkinson's disease(PD)and Chinese medicine(CM)syndrome of Shen(Kidney)essence deficiency,and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach.Methods:Eligible PD patients with syndrome of Shen essence deficiency were randomly assigned to a treatment group or a control group by a random number table,and were treated with CSGs combined with Western medicine(WM),or placebo combined with WM,respectively.Both courses of treatment lasted for 12 weeks.The Unified Parkinson's Disease Rating Scale(UPDRS)score,the PD Question-39(PDQ-39)score,CM Syndrome Scale score,and drug usage of all patients were evaluated before and after treatment.Safety was evaluated by clinical laboratory tests and electrocardiographs.Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.Differentially expressed genes were validated using reverse transcription-polymerase chain reaction.Results:A total of 86 PD patients were selected from the Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017.Finally,72 patients completed the trial,including 35 in the treatment group and 37 in the control group.When compared with the control group after treatment,patients in the treatment group showed significant decreases in UPDRS sub-Ⅱscore,PDQ-39 score,CM syndrome score,and Levodopa equivalent dose(P<0.05).During the treatment course,no significant changes were observed in safety indicators between the two groups(P>0.05).A possible mechanism of clinical efficacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways.Treatment with CSGs had shown to affect relevant gene loci for PD,including AIDA,ANKRD36BP2,BCL2A1,BCL2L11,FTH1P2,GCH1,HPRT1,NFE2L2,RMRP,RPS7,TGFBR1,WIPF2,and COX7B.Conclusions:CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence deficiency with a good safety.The possible mechanism of action and relevant gene loci were proposed.

A mutated CRYGD associated with congenital coralliform cataracts in two Chinese pedigrees

AIM:To investigate the causal gene mutation and clinical characteristics for two Chinese families with autosomal dominant congenital coralliform cataract.METHODS:Two Chinese pedigrees with congenital cataract were investigated.Routine ophthalmic examinations were performed on all patients and non-affected family members.Peripheral blood samples were collected,and the genomic DNAs were extracted.The coding regions of proband’s DNAs were analyzed with cataract gene panel.The identified mutation was amplified by polymerase chain reaction,and automated sequencing was performed in other members of two families to verify whether the mutated gene was co-segregated with the disease.RESULTS:Congenital coralliform cataract was inherited in an autosomal dominant mode in both pedigrees.For each family,more than half of the family members were affected.All patients presented with severe visual impairment after birth as a result of bilateral symmetric coralliform lens opacification.An exact the same defect in the same gene,a heterozygous mutation of c.70 C>A(p.P24 T)in exon 2 of γ Dcrystallin gene,was detected in both probands from each family.Sanger sequencing analysis demonstrated that the mutated CRYGD was co-segregated in these two families.CONCLUSION:A c.70 C>A(p.P24 T)variant in CRYGD gene was reconfirmed to be the causal gene in two Chinese pedigrees.It is known that mutated CRYGD caused most of the congenital coralliform cataracts,suggesting that the CRYGD gene is associated with coralliform congenital cataract.

A Method for Increasing X-ray Protection Capability Based on Photonic Crystal Technology

In this paper, we propose a method to improve anti-radiation capability by coating heavy metal X-ray protection glass with compound photonic crystal layers, based on the unique property of photonic crystal that light cannot be propagated within the range of band gaps. Using the plane wave expansion method,we made a theoretical study of parameters affecting the band gap structures of one-dimensional photonic crystals. Based on the findings, we chose appropriate materials and compound structure of photonic crystal so as to get high X-ray reflection coating photonic crystal layers. By this method, the reflection rate within X-ray wavelength can reach the maximum value of 100%, and the average value of over 90%. Even low-cost heavy metal X-ray protection glass of absorption coefficient value can achieve the desired effect. Thus, this method greatly decreases the anti-radiation requirements of heavy X-ray protection glass.