Pyroptosis in bone loss.

Pyroptosis could be responsible for the bone loss from bone metabolic diseases, leading to the negative impact on people's health and life. It has been shown that osteoclasts, osteoblasts, macrophages, chondrocytes, periodontal and gingival cells may be involved in bone loss linked with pyroptosis. So far, the involved mechanisms have not been fully elucidated. In this review, we introduced the related cells involved in the pyroptosis associated with bone loss and summarized the role of these cells in the bone metabolism during the process of pyroptosis. We also discuss the clinical potential of targeting mechanisms in the osteoclasts, osteoblasts, macrophages, chondrocytes, periodontal and gingival cells touched upon pyroptosis to treat bone loss from bone metabolic diseases as well as the challenges of avoiding potential side effects and producing efficient treatment methods.

Association between an insertion/deletion polymorphism in the interleukin-1α gene and the risk of colorectal cancer in a Chinese population.

BACKGROUND: Previous studies have reported that polymorphisms in the interleukin-1 gene may be involved in tumorigenesis and tumor progression. AIM: The purpose of the present study was to evaluate whether an insertion/deletion polymorphism, rs3783553, located in the miR-122 target gene interleukin-1α, was associated with the risk of colorectal cancer. METHODS: Genomic DNA was extracted from peripheral venous blood of 382 patients with colorectal cancer and 433 controls, and the polymorphism was genotyped using a polymerase chain reaction assay. RESULTS: Significantly decreased colorectal cancer risk was observed to be associated with the interleukin-1α rs3783553 insertion/insertion genotype ( P=0.0001; OR=0.41; 95% CI 0.26, 0.65) and the insertion allele ( P<0.001; OR=0.68; 95% CI 0.55, 0.83). Stratification analysis based on clinical and pathological features also revealed that the "TTCA" insertion allele of rs3783553 contributes to slow the progression of colorectal cancer. CONCLUSION: These results suggest that the rs3783553 polymorphism could be a useful genetic marker to predict the size/extent of colorectal cancer.

Pressure-loaded MSCs during early osteodifferentiation promote osteoclastogenesis by increase of RANKL/OPG ratio.

Mechanical stress plays an important role in bone remodeling. However, it is still unclear whether mechanical stress regulates osteoclastogenesis mediated by mesenchymal stem cells (MSCs) during initial osteodifferentiation. We investigated the effects of static and dynamic pressures on osteoclast-inducing potential of MSCs during early osteodifferentiation. The osteoclastogenesis was examined using TRAP staining. The mRNA levels of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) genes were analyzed using real-time RT-PCR. It was shown that MSCs exposed to either pressure during initial osteodifferentiation promoted osteoclastogenesis with the up-regulation of RANKL/OPG ratio. MSCs displayed diverse responses to pressures at different points of initial osteodifferentiation. The RANKL/OPG ratio was significantly increased after osteoinduction in the primary MSCs without pressures exposure, which contradicted the previous report. These results suggest novel mechanisms of the initial biological responses of bone remodeling upon mechanical stimuli.

[Exploitation of a new noninvasive animal's blood pressure measuring apparatus and its function characterization].

AIM: To produce a new, noninvasive, animal's blood pressure measuring apparatus. METHODS: By applying the principle similar with the measurement of human blood pressure, we developed a software which knowledge property owned by this research group and solved the problems of exactly demarcating the measuring spot of diastolic pressure. The blood pressure of rabbits was measured by the novel noninvasive animal's blood pressure measuring apparatus and the classic surgical catheterizing method simultaneously. RESULTS: The novel noninvasive animal's blood pressure measuring apparatus was successfully set up. The measured blood pressures by this apparatus are very similar (r > 0.9) with the values obtained from the classic, surgical catheterizing method, no matter the blood pressures are normal, high or low. CONCLUSION: Our new apparatus can be a reliable method for noninvasive measurement of the blood pressure of rabbits and rats.

Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E. coli.

AIM: To investigate the therapeutic effects of recombinant human growth hormone (rhGH) on rat septic shock with intraabdominal infection by E. coli and its possible mechanism. METHODS: 76 SD rats were divided into 3 groups randomly: control group (group C, n=16) without any special treatment, septic shock group (group S, n=30) received bolus injection of E.coli (1X10(10) cfu x L(-1), 15 ml x kg(-1), ip), treated group (group T, n=30) received bolus injection of E.coli, and then followed by rhGH injection (2.25 U x k g(-1) x d(-1), im). Group S and group T were further divided into 1d and 3d subgroups, respectively (n=15 each). Mean arterial pressure (MAP), levels of plasma TNFalpha and endotoxin and leukocyte count were determined on 1st day and 3rd day after E.coli injection. Another 39 SD rats were divided into groups C, S and T (n=13 each) just for observing survival rate within 1 week. RESULTS: (1) On 1st and 3rd day, MAP in group S decreased markedly, and MAP on 1st day lowered more than that of 3rd day (P<0.01), while MAP in group T just decreased slightly. The survival rate within 1 week was much higher in group T (84.6 %) than in group S (46.2 %) (P<0.01). (2)On 1st day, plasma TNFalpha and endotoxin elevated significantly in group S and group T (P<0.05), and endotoxin in group S had more increase (P<0.01). On 3rd day, TNFagr in group S returned to the level of group C (P>0.05),while TNFagr in group T went down below the level of group C(P<0.01). On 3rd day, endotoxin in group S declined, but was still higher than that of group C (P<0.01), endotoxin in group T returned to the level of group C (P>0.05). (3) On 1st day, neutrophil ratio in total leukocyte count in both group S and group T increased significantly (P<0.05 vs group C). CONCLUSION: rhGH showed beneficial effects on rat septic shock. The possible mechanisms may involve the attenuation of bacteria/endotoxin translocation and decreased systemic endotoxin level; inhibition of the production and release of TNFalpha; improved circulatory function; improved systemic host defenses and maintenance of intestinal mucosa barrier.