Cytokinesis regulators as potential diagnostic and therapeutic biomarkers for human hepatocellular carcinoma

Cytokinesis, the final step of mitosis, is critical for maintaining the ploidy level of cells. Cytokinesis is a complex, highly regulated process and its failure can lead to genetic instability and apoptosis, contributing to the development of cancer. Human hepatocellular carcinoma is often accompanied by a high frequency of aneuploidy and the DNA ploidy pattern observed in human hepatocellular carcinoma results mostly from impairments in cytokinesis. Many key regulators of cytokinesis are abnormally expressed in human hepatocellular carcinoma, and their expression levels are often correlated with patient prognosis. Moreover, preclinical studies have demonstrated that the inhibition of key cytokinesis regulators can suppress the growth of human hepatocellular carcinoma. Here, we provide an overview of the current understanding of the signaling networks regulating cytokinesis, the key cytokinesis regulators involved in the initiation and development of human hepatocellular carcinoma, and their applications as potential diagnostic and therapeutic biomarkers.     

Screening of chemopreventive effect of naringenin-loaded nanoparticles in DMBA-induced hamster buccal pouch carcinogenesis by FT-IR spectroscopy

The aim of the present study is to investigate the chemopreventive effects of the prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) in modifying the functional, structural, and compositional changes at the molecular level during 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that a significant increase in the amount of proteins and nucleic acid contents and a decrease in the amount of lipids and glycogen contents are observed in DMBA-induced tumor tissues. In addition, in tumor tissues a decrease in lipid order and a significant increase in membrane dynamics were noticed. Further, the composition and secondary structure of proteins were found to be altered, which indicates some important structural alterations in the existing proteins and/or the expression of new types of proteins occurring under the tumor transformation. Furthermore, oral administration of free NAR and NARNPs significantly increased lipids and their order as well as increased the glycogen contents and decreased the levels of proteins and nucleic acid contents. On a comparative basis, NARNPs were found to have a more potent antitumor effect than free NAR in completely preventing the formation of squamous cell carcinoma and in improving the biochemical constituents to a normal range in DMBA-induced HBP carcinogenesis. The present study further shows a great potential of FT-IR spectroscopy as a complimentary tool for the screening of various anticancer drugs and follow-up, which may allow faster response to critical problems arising during treatment.     

Chemometric Studies of Multielemental Composition of Few Seagrasses from Gulf of Mannar,India

This paper discusses the determination of minerals content (cadmium, cobalt, chromium, copper, nickel, lead, manganese, magnesium, iron, zinc, sodium, potassium and calcium) of six seagrass samples, Enhalus acoroides, Thalassia hemprichii, Halodule pinifolia, Syringodium isoetifolium, Cymodocea serrulata and Cymodocea rotundata using inductively coupled plasma optical emission spectrophotometry and flame photometer. Principal component analysis (PCA) and hierarchical cluster analysis revealed different mineral compositions of the seagrass samples. Among the 13 elements investigated, Ni 1.513, Na 690.167 and Ca 220.333; Cr 3.957; Mn 23.427, Zn 17.593 and Fe 156.567; Cd 0.357, Co 0.431, Pb 2.040, Mg 912.733 and K 300.9; Cu 7.8 mg/kg dry weight, respectively, were found at high concentrations in E. acoroides; T. hemprichii; H. pinifolia; S. isoetifolium and C. rotundata. PCA analysis confirmed the presence of three components with 91.28% of the total variance. The toxic elements Pb, Cr and Cd were also found in all six seagrasses, although the concentrations were below the permissible limits proposed by the World Health Organization.     

Interactions of tight junctions with membrane channels and transporters

Tight junctions are unique organelles in epithelial cells. They are localized to the apico-lateral region and essential for the epithelial cell transport functions. The paracellular transport process that occurs via tight junctions is extensively studied and is intricately regulated by various extracellular and intracellular signals. Fine regulation of this transport pathway is crucial for normal epithelial cell functions. Among factors that control tight junction permeability are ions and their transporters. However, this area of research is still in its infancy and much more needs to be learned about how these molecules regulate tight junction structure and functions. In this review we have attempted to compile literature on ion transporters and channels involved in the regulation of tight junctions.     

The relation of DNA synthesis and mitosis in tobacco pith tissue cultured in vitro

Summary DNA synthesis and mitosis were initiated in cultured tobacco pith tissue by means of IAA and kinetin. DNA classes were determined by microspectrophotometric measurements (Feulgen); autoradiographs (tritiated thymidine) served to ascertain whether or not nuclei had undergone DNA synthesis during culture.All mitoses in new cells (resulting from divisions in culture) were diploid and had been preceded by DNA synthesis in culture.Whereas many of the old cells (which had not previously divided in culture) found in diploid or polyploid mitosis had undergone DNA synthesis during culture, others had not. Such non-radioactive mitoses still occurred after 16 days.In view of this, a 4 C nucleus in differentiated tissue should be considered as potentially both diploid and tetraploid, for it appears impossible to predict whether it would, upon restoration of conditions conducive to DNA synthesis and mitosis, enter a diploid mitosis or, after undergoing DNA synthesis, a tetraploid one.A high nuclear DNA content seems to have a much more inhibiting effect on the onset of DNA doubling than on that of mitosis.Somatic polyploidization is understood as the result of two DNA doublings between which mitosis was omitted, or aborted, or in effect undone by a failure of cytokinesis leading to fusion during a later mitosis.This work has been supported by research grants to K. Patau from the U.S. Public Health Service (grant No. C-3313) and the American Cancer Society.     

MyD88-dependent signals are essential for the host immune response in experimental brain abscess

Brain abscesses form in response to a parenchymal infection by pyogenic bacteria, with Staphylococcus aureus representing a common etiologic agent of human disease. Numerous receptors that participate in immune responses to bacteria, including the majority of TLRs, the IL-1R, and the IL-18R, use a common adaptor molecule, MyD88, for transducing activation signals leading to proinflammatory mediator expression and immune effector functions. To delineate the importance of MyD88-dependent signals in brain abscesses, we compared disease pathogenesis using MyD88 knockout (KO) and wild-type (WT) mice. Mortality rates were significantly higher in MyD88 KO mice, which correlated with a significant reduction in the expression of several proinflammatory mediators, including but not limited to IL-1beta, TNF-alpha, and MIP-2/CXCL2. These changes were associated with a significant reduction in neutrophil and macrophage recruitment into brain abscesses of MyD88 KO animals. In addition, microglia, macrophages, and neutrophils isolated from the brain abscesses of MyD88 KO mice produced significantly less TNF-alpha, IL-6, MIP-1alpha/CCL3, and IFN-gamma-induced protein 10/CXCL10 compared with WT cells. The lack of MyD88-dependent signals had a dramatic effect on the extent of tissue injury, with significantly larger brain abscesses typified by exaggerated edema and necrosis in MyD88 KO animals. Interestingly, despite these striking changes in MyD88 KO mice, bacterial burdens did not significantly differ between the two strains at the early time points examined. Collectively, these findings indicate that MyD88 plays an essential role in establishing a protective CNS host response during the early stages of brain abscess development, whereas MyD88-independent pathway(s) are responsible for pathogen containment.     

KINETIN-INDUCED PSEUDONODULES ON TOBACCO ROOTS

Arora , Nirmal , F. Skoog , and O. N. Allen . (U. Wisconsin, Madison.) Kinetin-induced pseudonodules on tobacco roots. Amer. Jour. Bot. 46(8): 610–613. Illus. 1959.—Tobacco stem segments were cultured on modified White's medium containing 0.02–0.1 mg./l. of kinetin, 2 mg./l. of IAA and 2 g./l. of casein hydrolysate. Roots grew profusely from these stem pieces. In the presence of kinetin, especially when a second supply (0.2 mg./l.) was introduced after the roots had developed, large numbers of pseudonodules were formed along the root surfaces. The protuberances were spherical in shape and were invariably associated with the axial area of lateral rootlets derived as root primordia from parent root pericycle. Development of the pseudonodules started with the division and enlargement of cortical cells. The center of each pseudonodule contained either a simple provascular strand constituting a modified rootlet with a poorly defined apex and layers of tracheids at the base, or a normal lateral root primordium capable of continued growth and eventual emergence as a rootlet. In later stages, the swellings became lobed and the mature cells showed a high starch content. Although these kinetin-induced pseudonodules arose from cortical tissue, their anatomical structure remained undifferentiated and unspecialized and bore no resemblance to that of typical nodules caused by rhizobia.     

Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron

Humans have two nearly identical copies of the Survival Motor Neuron (SMN) gene, SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to exclusion of exon 7. Here we describe a novel inhibitory element located immediately downstream of the 5' splice site in intron 7. We call this element intronic splicing silencer N1 (ISS-N1). Deletion of ISS-N1 promoted exon 7 inclusion in mRNAs derived from the SMN2 minigene. Underlining the dominant role of ISS-N1 in exon 7 skipping, abrogation of a number of positive cis elements was tolerated when ISS-N1 was deleted. Confirming the silencer function of ISS-N1, an antisense oligonucleotide against ISS-N1 restored exon 7 inclusion in mRNAs derived from the SMN2 minigene or from endogenous SMN2. Consistently, this oligonucleotide increased the levels of SMN protein in SMA patient-derived cells that carry only the SMN2 gene. Our findings underscore for the first time the profound impact of an evolutionarily nonconserved intronic element on SMN2 exon 7 splicing. Considering that oligonucleotides annealing to intronic sequences do not interfere with exon-junction complex formation or mRNA transport and translation, ISS-N1 provides a very specific and efficient therapeutic target for antisense oligonucleotide-mediated correction of SMN2 splicing in SMA.     

Metal–Organic Framework: A Novel Material for Triboelectric Nanogenerator–Based Self‐Powered Sensors and Systems

The triboelectric nanogenerator (TENG) offers a simple and cost‐effective method to harness waste energy and works on the principle of contact electrification and electrostatic induction. The performance and application of TENG depend to a great extent on the material used for fabrication. The most widely used materials include polymers and a few metals, well‐arranged in the triboelectric series so as to promote electrification upon contact. New triboelectric materials are important for extending the applications and specificity of the TENG. A TENG based on a metal–organic framework (MOF) of the zeolitic imidazole family is reported here. The zeolitic imidazole framework‐8 (ZIF‐8) and Kapton are used as the active materials for MOF–TENG fabrication. Surface potential, structural, morphological and electrical measurements reveals detailed characteristics of ZIF‐8, confirming the MOF as a potential candidate for TENG applications. The MOF–TENG generates a sustainable output of 164 V and 7 µA in vertical contact–separation mode. Finally, a self‐powered UV counterfeit system and a tetracycline sensor are successfully developed and demonstrated with the MOF–TENG. The sensor is highly selective and reusable simply by washing.