Inhibition of BAP31 expression inhibits cervical cancer progression by suppressing metastasis and inducing intrinsic and extrinsic apoptosis

Cervical cancer is reported as one of the most lethal types of cancer among female. However, extensive studies of the molecular mechanisms that regulate the progression of cervical cancer are still required. B-cell associated protein (BAP)-31 is a 28-kDa integral membrane protein in the endoplasmic reticulum (ER), playing essential role in modulating various physiological processes. The present study indicated that BAP31 was a novel gene associated with cervical cancer development. Here, we demonstrated that BAP31 was significantly increased in human cervical cancer specimens, which was positively correlated to histological grade of the cancer. BAP31 knockdown suppressed cell proliferation, clonogenic ability and metastasis-associated traits in vitro, as well as carcinogenesis and pulmonary metastasis in vivo. Further studies indicated that the expression levels of transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-2, MMP-9, Rho-associated protein kinase 1 (ROCK1), α-smooth muscle actin (α-SMA), Vimentin and N-cadherin were markedly reduced by BAP31 knockdown in cervical cancer cells. In addition, intrinsic and extrinsic apoptosis was significantly induced in BAP31 knockdown cells, as evidenced by the increased expression of cleaved Caspase-8/-9/-3 and poly (ADP-ribose) polymerases (PARP). Notably, suppressing the activities of Caspase-8/-9 and ?3 obviously diminished BAP31 silence-triggered apoptosis. Together, these findings highlighted an essential role for BAP31 in the modulation of tumorigenesis and metastatic potential of cervical cancer, and demonstrated a promising application of BAP31 in cancer prevention.     

Selected furanochalcones as inhibitors of monoamine oxidase

The validity of the chalcone scaffold for the design of inhibitors of monoamine oxidase has previously been illustrated. In a systematic attempt to investigate the effect of heterocyclic substitution on the monoamine oxidase inhibitory properties of this versatile scaffold, a series of furanochalcones were synthesized. The results demonstrate that these furan substituted phenylpropenones exhibited moderate to good inhibitory activities towards MAO-B, but showed weak or no inhibition of the MAO-A enzyme. The most active compound, 2E-3-(5-chlorofuran-2-yl)-1-(3-chlorophenyl)prop-2-en-1-one, exhibited an IC₅₀ value of 0.174 μM for the inhibition of MAO-B and 28.6 μM for the inhibition of MAO-A. Interestingly, contrary to data previously reported for chalcones, these furan substituted derivatives acted as reversible inhibitors, while kinetic analysis revealed a competitive mode of binding.     

猫嗅球外丛层和僧帽细胞层年龄相关形态学变化

分别用Nissl法及免疫组织化学ABC法标记青、老年猫嗅球中嗅觉二级神经元和外丛层胶质细胞,显微镜下观察其分布并计数,对嗅觉二级神经元胞体直径和外丛层厚度进行测量,比较其年龄相关性变化,研究神经元与胶质细胞之间的关系,探讨老年性嗅觉功能衰退的相关神经机理。结果显示,老年猫嗅觉二级神经元胞体直径和分布密度均有不同程度的显著性下降(P<0.05);外丛层厚度变化不明显(P>0.05);外丛层胶质细胞特别是星形胶质细胞显著性增生(P<0.05)。表明在衰老过程中嗅觉二级神经元有丢失,并呈现功能下降,可能是老年性嗅觉功能衰退的原因之一。同时外丛层胶质细胞增生以进一步保护神经元,延缓其衰老。     

Cell proliferation is promoted by compressive stress during early stage of chondrogenic differentiation of rat BMSCs

The presence of an appropriate number of viable cells is prerequisite for successive differentiation during chondrogenesis. Chondrogenic differentiation has been reported to be influenced by mechanical stimuli. This research aimed to study the effects of cyclic compressive stress on cell viability of rat bone marrow‐derived MSCs (BMSCs) during chondrogenesis as well as its underlying mechanisms. The results showed that dynamic compression increased cell quantity and viability remarkably in the early stage of chondrogenesis, during which the expression of Ihh, Cyclin D1, CDK4, and Col2α1 were enhanced significantly. Possible signal pathways implicated in the process were explored in our study. MEK/ERK and p38 MAPK were not found to function in this process while BMP signaling seemed to play an important role in the mechanotransduction during chondrogenic proliferation. In conclusion, dynamic compressive stress could enhance cell viability during chondrogenesis, which might be achieved by activating BMP signaling. J. Cell. Physiol. 228: 1935–1942, 2013. © 2013 Wiley Periodicals, Inc.     

Development of polymorphic microsatellite markers for the Trichoglossus haematodus and cross-species amplification in Trichoglossus moluccanus

Molecular Biology Reports - Trichoglossus haematodus is the most popular parrots globally and one of the most bred species in Korea's zoos. However, despite its popularity, there are limited...     

Inhibition of Sucrose Enhancer Effect of the Potato Proteinase Inhibitor II Promoter by Salicylic Acid

Effect of salicylic acid (SA) on the expression of the potato proteinase inhibitor (PI) II promoter was studied with transgenic tobacco plants (Nicotiana tabacum) carrying a gene fusion between the PI-II promoter and the chloramphenicol acetyltransferase (cat) reporter. As previously observed, the PI-II promoter was inducible by wounding and the promoter activity was further enhanced by sucrose. Addition of SA did not influence the wound induction of the PI-II promoter but significantly inhibited the sucrose response. The 5′-deletion mutant −573 was unable to respond to wounding but did respond to sucrose and SA. The 3′-deletion analysis indicated the presence of a sucrose-responsive element between −574 and −520. A study of the insertion mutants revealed the function of another sucrose-responsive element between −522 and −500. Enhancer effects of these sucrose-responsive elements were inhibited by SA. These studies suggest that SA inhibits PI-II promoter activity by decreasing the sucrose response. Analysis of SA-related chemicals revealed that only acetyl-SA showed a similar inhibitory effect, and other hydroxybenzoic acids had little or no effect on the sucrose enhancer activity. Therefore, it seems that the interaction between SA and the receptor molecule is specific.     

Avicularin alleviates acute liver failure by regulation of the TLR4/MyD88/NF-κB and Nrf2/HO-1/GPX4 pathways to reduce inflammation and ferroptosis

Acute liver failure (ALF) is an inflammation-mediated hepatocyte death process associated with ferroptosis. Avicularin (AL), a Chinese herbal medicine, exerts anti-inflammatory and antioxidative effects. However, the protective effect of AL and the mechanism on ALF have not been reported. Our in vivo results suggest that AL significantly alleviated lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced hepatic pathological injury, liver enzymes, inflammatory cytokines, reactive oxygen species and iron levels and increased the antioxidant enzyme activities (malondialdehyde and glutathione). Our further in vitro experiments demonstrated that AL suppressed inflammatory response in LPS-stimulated RAW 264.7 cells via blocking the toll-like receptor 4 (TLR4)/myeloid differentiation protein-88 (MyD88)/nuclear factor kappa B (NF-κB) pathway. Moreover, AL attenuated ferroptosis in D-GalN-induced HepG2 cells by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway. Therefore, AL can alleviate inflammatory response and ferroptosis in LPS/D-GalN-induced ALF, and its protective effects are associated with blocking TLR4/MyD88/NF-κB pathway and activating Nrf2/HO-1/GPX4 pathway. Moreover, AL is a promising therapeutic option for ALF and should be clinically explored.     

Contribution of the Two Genes Encoding Histone Variant H3.3 to Viability and Fertility in Mice

Histones package DNA and regulate epigenetic states. For the latter, probably the most important histone is H3. Mammals have three near-identical H3 isoforms: canonical H3.1 and H3.2, and the replication-independent variant H3.3. This variant can accumulate in slowly dividing somatic cells, replacing canonical H3. Some replication-independent histones, through their ability to incorporate outside S-phase, are functionally important in the very slowly dividing mammalian germ line. Much remains to be learned of H3.3 functions in germ cell development.Histone H3.3 presents a unique genetic paradigm in that two conventional intron-containing genes encode the identical protein. Here, we present a comprehensive analysis of the developmental effects of null mutations in each of these genes. H3f3a mutants were viable to adulthood. Females were fertile, while males were subfertile with dysmorphic spermatozoa. H3f3b mutants were growth-deficient, dying at birth. H3f3b heterozygotes were also growth-deficient, with males being sterile because of arrest of round spermatids. This sterility was not accompanied by abnormalities in sex chromosome inactivation in meiosis I. Conditional ablation of H3f3b at the beginning of folliculogenesis resulted in zygote cleavage failure, establishing H3f3b as a maternal-effect gene, and revealing a requirement for H3.3 in the first mitosis. Simultaneous ablation of H3f3a and H3f3b in folliculogenesis resulted in early primary oocyte death, demonstrating a crucial role for H3.3 in oogenesis.These findings reveal a heavy reliance on H3.3 for growth, gametogenesis, and fertilization, identifying developmental processes that are particularly susceptible to H3.3 deficiency. They also reveal partial redundancy in function of H3f3a and H3f3b, with the latter gene being generally the most important.     

Subcellular Distribution and Chemical Forms of Cadmium in the Medicine Food Homology Plant <i>Platycodon grandiflorum</i> (Jacq.) A.DC.

Although Platycodon grandiflorum (Jacq.) A.DC. is a renowned medicine food homology plant, reports of excessive cadmium (Cd) levels are common, which affects its safety for clinical use and food consumption. To enable its Cd levels to be regulated or reduced, it is necessary to first elucidate the mechanism of Cd uptake and accumulation in the plant, in addition to its detoxification mechanisms. This present study used inductively couple plasma-mass-spectrometry to analyze the subcellular distribution and chemical forms of Cd in different tissues of P. grandiflorum. The experimental results showed that Cd was mainly accumulated in the roots [predominantly in the cell wall (50.96%–61.42%)], and it was found primarily in hypomobile and hypotoxic forms. The proportion of Cd in the soluble fraction increased after Cd exposure, and the proportion of insoluble phosphate Cd and oxalate Cd increased in roots and leaves, with a higher increase in oxalate Cd. Therefore, it is likely that root retention mechanisms, cell wall deposition, vacuole sequestration, and the formation of low mobility and low toxicity forms are tolerance strategies for Cd detoxification used by P. grandiflorum. The results of this study provide a theoretical grounding for the study of Cd accumulation and detoxification mechanisms in P. grandiflorum, and they can be used as a reference for developing Cd limits and standards for other medicine food homology plants.