Tafazzin Protein Expression Is Associated with Tumorigenesis and Radiation Response in Rectal Cancer: A Study of Swedish Clinical Trial on Preoperative Radiotherapy

Background

Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT.

Methods

140 rectal cancer patients were included in this study, of which 65 received RT before surgery and the rest underwent surgery alone. TAZ expression was determined by immunohistochemistry in primary cancer, distant, adjacent normal mucosa and lymph node metastasis. In-silico protein-protein interaction analysis was performed to study the predictive functional interaction of TAZ with other oncoproteins.

Results

TAZ showed stronger expression in primary cancer and lymph node metastasis compared to distant or adjacent normal mucosa in both non-RT and RT patients. Strong TAZ expression was significantly higher in stages I-III and non-mucinious cancer of non-RT patients. In RT patients, strong TAZ expression in biopsy was related to distant recurrence, independent of gender, age, stages and grade (p = 0.043, HR, 6.160, 95% CI, 1.063–35.704). In silico protein-protein interaction study demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30 and FXYD-3.

Conclusions

Strong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT.     

Adipokines and Obesity Are Associated with Colorectal Polyps in Adult Males: A Cross-Sectional Study

Background

Obesity increases the risk of colon cancer. It is also known that most colorectal cancers develop from adenomatous polyps. However, the effects of obesity and adipokines on colonic polyp formation are unknown.

Methods

To determine if BMI, waist circumference or adipokines are associated with colon polyps in males, 126 asymptomatic men (48–65 yr) were recruited at time of colonoscopy, and anthropometric measures as well as blood were collected. Odds ratios were determined using polytomous logistic regression for polyp number (0 or ≥3) and polyp type (no polyp, hyperplastic polyp, tubular adenoma).

Results

41% of the men in our study were obese (BMI ≥30). The odds of an obese individual having ≥3 polyps was 6.5 (CI: 1.3–33.0) times greater than those of a lean (BMI<25) individual. Additionally, relative to lean individuals, obese individuals were 7.8 (CI: 2.0–30.8) times more likely to have a tubular adenoma than no polyp. As BMI category increased, participants were 2.9 (CI: 1.5–5.4) times more likely to have a tubular adenoma than no polyps. Serum leptin, IP-10 and TNF-α were significantly associated with tubular adenoma presence. Serum leptin and IP-10 were significantly associated with increased likelihood of ≥3 polyps, and TNF-α showed a trend (p = 0.09).

Conclusions

Obese men are more likely to have at least three polyps and adenomas. This cross-sectional study provides evidence that colonoscopy should be recommended for obese, white males.     

Harmful effects of 41 and 202 MHz radiations on some body parts and tissues

Many types of invisible electromagnetic waves are produced in our atmosphere. When these radiations penetrate our body, electric fields are induced inside the body, resulting in the absorption of power, which is different for different body parts and also depends on the frequency of radiations. Higher power absorption may result into health problems. In this communication, effects of electromagnetic waves (EMW) of 41 and 202 MHz frequencies transmitted by the TV tower have been studied on skin, muscles, bone and fat of human. Using international standards for safe exposure limits of specific absorption rate (SAR), we have found the safe distance from TV transmission towers for two frequencies. It is suggested that transmission towers should be located away from the thickly populated areas and people should keep away from the transmission towers, as they radiate electromagnetic radiations that are harmful to some parts/tissues of body.     

Enhancement of ethyl propionate synthesis by poly (AAc-co-HPMA-cl-MBAm)-immobilized Pseudomonas aeruginosa MTCC-4713, exposed to Hg2+ and NH4+ ions

A purified alkaline thermo-tolerant bacterial lipase from Pseudomonas aeruginosa MTCC-4713 was immobilized on a poly (AAc-co-HPMA-cl-MBAm) hydrogel. The hydrogel-bound lipase achieved 93.6% esterification of ethanol and propionic acid (300 mM: 100 mM) into ethyl propionate at temperature 65 degrees C in 3 h in the presence of a molecular sieve (3 angstroms). In contrast, hydrogel-immobilized lipase pre-exposed to 5 mM of HgCl2 orNH4Cl resulted in approximately 97% conversion of reactants in 3 h into ethyl propionate under identical conditions. The salt-exposed hydrogel was relatively more efficient in repetitive esterification than the hydrogel-bound lipase not exposed to any of the cations. Moreover, bound lipase exposed Hg2+ or NH4+ ions showed altered specificity towards p-nitrophenyl esters and was more hydrolytic towards higher C-chain p-nitrophenyl esters (p-nitrophenyl laurate and p-nitrophenyl palmitate with C 12 and C 16 chain) than the immobilized lipase not exposed to any of the salts. The later showed greater specificity towards p-nitrophenyl caprylate (C 8).     

Analysis of p53 and NF-κB signaling in modulating the cardiomyocyte fate during hypertrophy

Cardiac hypertrophy leading to eventual heart failure is the most common cause of mortality throughout the world. The triggering mechanisms for cardiac hypertrophy are not clear but both apoptosis and cell proliferation have been reported in sections of failing hearts. In this study, we utilized both angiotensin II (AngII) treatment of cardiomyocytes and aortic ligation in rats (Rattus norvegicus, Wistar strain) for induction of hypertrophy to understand the cellular factors responsible for activation of apoptotic or anti-apoptotic pathway. Hypertrophy markers (ANF, β-MHC), apoptotic proteins (Bax, Bad, Fas, p53, caspase-3, PARP), and anti-apoptotic or cell proliferation marker proteins (Bcl2, NF-κB, Ki-67) were induced significantly during hypertrophy, both in vitro as well as in vivo. Co-localization of both active caspase-3 and Ki-67 was observed in hypertrophied myocytes. p53 and NF-κBp65 binding to co-activator p300 was also increased in AngII treated myocytes. Inhibition of p53 resulted in downregulation of apoptosis, NF-κB activation, and NF-κB-p300 binding; however, NF-κB inhibition did not inhibit apoptosis or p53-p300 binding. Blocking of either p53 or NF-κB by specific inhibitors resulted in decrease in cell proliferation and hypertrophy markers, suggesting that p53 initially binds to p300 and then this complex recruits NF-κB. Thus, these results indicate the crucial role of p53 in regulating both apoptotic and cell proliferation during hypertrophy.     

The effect of estrogen on the tubal epithelium of immature ovariectomized rhesus monkey (Macaca mulatta).

The effect of 3 doses of estradiol dipropionate (EDP) on tubal epithelium of immature ovariectomized rhesus monkey (Macaca mulatta) was studied under both light and electron microscopy. EDP at a dose of 5 microgram/kg/day for 6 consecutive days changed differentiation of the epithelial cells into clear and dark cell-types; ciliogenesis, formation of some ciliary buds and even a few cilia were also induced in some clear cells throughout the tubal epithelium. Development of ciliated cells with fully formed ciliary apparatus was accelerated at 10 microgram/kg dosage. The secretory granules (SG) appeared at this dose in some nonciliated cells of the infundibular and ampullary but not the isthmic segments of the tube; some of the infundibular secretory cells, so formed, exhibited even a tendency to secrete. Nearly complete maturation of the tubal epithelium occurred at 20 microgram/kg dose; further signs of secretory activity appeared in all tubal segments. The results indicated that--(i) Nearly complete transformation of tubal epithelium of the immature animal into one of the adult type could be achieved by EDP at a dose not less than 20 microgram/kg under the present conditions. (ii) The response of undifferentiated cells to EDP differed depending upon the location of the epithelial cell within the tube and nature of the cell-type to be formed. (iii) The mode of tubal secretion in this infra-human species was probably apocrine.     

Relation between corpus allatum and haemolymph proteins in Sphaerodema rusticum Fabr.

The active and inactive stages of the corpora allata have been described on the basis of size and nucleo-cytoplasmic ratio. The polyacrylamide gel disc electrophoresis of the haemolymph has been done in the males and different stages of reproducing females. A protein fraction with a value 14 less than or equal to Rm less than 16 has been observed only in females. Out of 8 protein fractions, 5 showed oscillations in their concentration at the time of vitellogenesis. Finally active stages in the corpora allata are correlated with the fluctuations in haemolymph protein concentration.     

Recent trends in non-viral vector-mediated gene delivery

Nucleic acids-based next generation biopharmaceuticals (i.e., pDNA, oligonucleotides, short interfering RNA) are potential pioneering materials to cope with various incurable diseases. However, several biological barriers present a challenge for efficient gene delivery. On the other hand, developments in nanotechnology now offer numerous non-viral vectors that have been fabricated and found capable of transmitting the biopharmaceuticals into the cell and even into specific subcellular compartments like mitochondria. This overview illustrates cellular barriers and current status of non-viral gene vectors, i.e., lipoplexes, liposomes, polyplexes, and nanoparticles, to relocate therapeutic DNA-based nanomedicine into the target cell. Despite the awesome impact of physical methods (i.e., ultrasound, electroporation), chemical methods have been shown to accomplish high-level and safe transgene expression. Further comprehension of barriers and the mechanism of cellular uptake will facilitate development of nucleic acids-based nanotherapy for alleviation of various disorders.