Principle of relative positioning of structures in the human body

The arrangement of various biological structures should generally ensure the safety of crucial structures and increase their working efficiency; however, other principles governing the relative positions of structures in humans have not been reported. The present study therefore investigated other principles using nerves and their companion vessels in the human body as an example. Nerves and blood vessels usually travel together and in the most direct way towards their targets. Human embryology, histology, and gross anatomy suggest that there are many possible positions for these structures during development. However, for mechanical reasons, tougher or stronger structures should take priority. Nerves are tougher than most other structures, followed by arteries, veins, and lymphatic vessels. Nerves should therefore follow the most direct route, and be followed by the arteries, veins, and lymphatic vessels. This general principle should be applicable to all living things.

Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation

AIM:To investigate large tumor suppressor 1 (LATS1 ) expression, promoter hypermethylation, and microsatellite instability in colorectal cancer (CRC).METHODS:RNA was isolated from tumor tissue of 142 CRC patients and 40 colon mucosal biopsies of healthy controls. After reverse transcription, quantitative polymerase chain reaction (PCR) was performed, and LATS1 expression was normalized to expression of the ACTB and RPL32 housekeeping genes. To analyze hypermethylation, genomic DNA was isolated from 44 tumor CRC biopsies, and methylation-specific PCR was performed. Microsatellite instability (MSI) status was checked with PCR using BAT26, BAT25, and BAT40 markers in the genomic DNA of 84 CRC patients, followed by denaturing gel electrophoresis. RESULTS:Decreased LATS1 expression was found in 127/142 (89.4%) CRC cases with the average ratio of the LATS1 level 10.33 ± 32.64 in CRC patients vs 32.85 ± 33.56 in healthy controls. The lowest expression was found in Dukes' B stage tumors and G1 (welldifferentiated) cells. Hypermethylation of the LATS1 promoter was present in 25/44 (57%) CRC cases analyzed. LATS1 promoter hypermethylation was strongly associated with decreased gene expression; methylated cases showed 162× lower expression of LATS1 than unmethylated cases. Although high-grade MSI (mutation in all three markers) was found in 14/84 (17%) cases and low-grade MSI (mutation in 1-2 markers) was found in 30/84 (36%) cases, we found no association with LATS1 expression. CONCLUSION:Decreased expression of LATS1 in CRC was associated with promoter hypermethylation, but not MSI status. Such reduced expression may promote progression of CRC.

BTN2A2 protein ameliorates collagen-induced arthritis in mice

Rheumatoid arthritis(RA)is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs,resulting in the destruction of joints.Collagen type II(CII)-induced arthritis(CIA)is the most used animal model for human RA.Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro,its effect on autoimmune arthritis has not been reported.In this study,we investigate the ability of a recombinant BTN2A2-IgG2a Fc(BTN2A2-Ig)fusion protein to treat CIA.We show here that administration of BTN2A2-Ig attenuates established CIA,as compared with control Ig protein treatment.

ERMAP is a B7 family-related molecule that negatively regulates T cell and macrophage responses

T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune responses.In this study,we identified erythroid membrane-associated protein(ERMAP)as a novel T cell inhibitory molecule.ERMAP shares significant sequence and structural homology with existing B7 family members in its extracellular domain.The ERMAP protein is expressed on the cell surface of resting and activated antigen-presenting cells(APCs)and in some tumor tissues.The putative ERMAP receptor is expressed on activated CD4 and CD8 T cells and macrophages.Both mouse and human ERMAP-IgG2a Fc(ERMAP-Ig)fusion proteins inhibit T cell functions in vitro.Administration of ERMAP-Ig protein ameliorates autoimmune diseases,including experimental autoimmune encephalomyelitis and type 1 diabetes,in mice.Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro.Furthermore,administration of an anti-ERMAP antibody inhibits tumor growth in mice likely by blocking the inhibitory effects of ERMAP on T cells and macrophages.Our results suggest that therapeutic interaction with the ERMAP inhibitory pathway may represent a novel strategy for treating patients with autoimmune disease or cancer.

Three-dimensional (3D) hydrogel serves as a platform to identify potential markers of chondrocyte dedifferentiation by combining RNA sequencing

Dedifferentiation of chondrocyte greatly restricts its function and application,however,it is poorly understood except a small number of canonical markers.The non-cell-adhesive property endows polysaccharide hydrogel with the ability to maintain chondrocyte phenotype,which can serve as a platform to identify new molecular markers and therapeutic targets of chondrocyte dedifferentiation.In this study,the high-throughput RNA sequencing(RNA-seq)was first performed on articular chondrocytes at primary(P0)and passage 1(P1)stages to explore the global alteration of gene expression along with chondrocyte dedifferentiation.Significantly,several potential marker genes,such as PFKFB3,KDM6B,had been identified via comparatively analyzing their expression in P0 and P1 chondrocytes as well as in 3D constructs(i.e.chondrocyte-laden alginate hydrogel and HA-MA hydrogel)at both mRNA and protein level.Besides,the changes in cellular morphology and enriched pathway of differentially expressed genes during chondrocyte dedifferentiation was studied in detail.This study developed the use of hydrogel as a platform to investigate chondrocyte dedifferentiation;the results provided new molecular markers and potential therapeutic targets of chondrocyte dedifferentiation.