Distribution and characterization of cyclo(His-Pro)-like immunoreactivity in the rat gastrointestinal tract

The distribution of cyclo(His-Pro), thyrotropin-releasing hormone (TRH) and $\text{pyroglutamate aminopeptidase}$ activity was examined in the rat gastrointestinal (GI) tract. Cyclo(His-Pro)-like immunoreactivity was present in the following order of distribution (fmoles/mg protein): caecum > colon = jejunum = ileum > stomach = duodenum = rectum, and was immunologically and chromatographically identical with the authentic cyclo(His-Pro). Cyclo(His-Pro) concentrations showed significantly positive correlations with TRH concentrations, but not with $\text{pyroglutamate aminopeptidase}$ activities, in most tissues of the GI tract, suggesting a precursor role of TRH for gut cyclo(His-Pro). These data suggest that cyclo(His-Pro) may be involved in regulating rat GI functions.     

Oxygen-derived free radicals and hemolysis during open heart surgery

Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH·). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH·.     

Passage number of cancer cell lines: Importance,intricacies, and way-forward

Cancer cell lines play a crucial role as invaluable models in cancer research, facilitating the examination of cancer progression as well as the advancement of diagnostics and treatments. While they may not perfectly replicate the original tumor, they generally exhibit similar characteristics. Low-passage cancer cell lines are generally preferred due to their closer resemblance to the original tumor, as long-term culturing can alter the genetic and molecular profiles of a cell line thereby highlighting the importance of monitoring the passage number (PN). Variations in proliferation, migration, gene expression, and drug sensitivity can be linked to PN differences. PN can also influence DNA methylation levels, metabolic profiles, and the expression of genes/or proteins in cancer cell lines. When conducting research on cancer cell lines, it is crucial for researchers to carefully select the appropriate PN to maintain consistency and reliability of results. Moreover, to ensure dependability and replicability, scientists ought to actively track the growth, migration, and gene/or protein profiles of cancer cell lines at specific PNs. This approach enables the identification of the most suitable range of PNs for experiments, guaranteeing consistent and precise results. Additionally, such efforts serve to minimize disparities and uphold the integrity of research. In this review, we have laid out recommendations for laboratories to overcome these PN discrepancies when working with cancer cell lines.     

Population status and habitat occupancy of endangered river dolphins in the Karnali River system of Nepal during low water season

Ganges river dolphin abundance has undergone a predominant decline across its range since monitoring began. In Nepal, disappearance from some of the rivers it once used has already occurred. Today this species can only be found in three river systems in Nepal, the Karnali, Sapta Koshi, and Narayani, but numbers are low in these locations. To determine the abundance of dolphins remaining in the Karnali system (which includes the Karnali, Geruwa, and Mohana), and factors affecting dolphin habitat use, we conducted surveys where we recorded dolphin presence. Dolphins within this river system were sighted only in the Karnali and an abundance estimate of 5.04 ± 0.753 SE was calculated. This pattern of ranging differed from that previously reported (from previous sightings only in the Geruwa to current sightings only in the Karnali). River depth likely contributed to the presence or absence of dolphins. Shifts in available habitat between the Geruwa and Karnali have resulted from changes in the course of the main stream Karnali following construction of the Chisapani irrigation intake. Because of the low numbers of dolphins reported, there is great concern that loss of this species in Nepal is likely in the near future.     

Vibrio cholerae Porin OmpU Induces Caspase-independent Programmed Cell Death upon Translocation to the Host Cell Mitochondria

Porins, a major class of outer membrane proteins in Gram-negative bacteria, primarily act as transport channels. OmpU is one of the major porins of human pathogen, Vibrio cholerae. In the present study, we show that V. cholerae OmpU has the ability to induce target cell death. Although OmpU-mediated cell death shows some characteristics of apoptosis, such as flipping of phosphatidylserine in the membrane as well as cell size shrinkage and increased cell granularity, it does not show the caspase-3 activation and DNA laddering pattern typical of apoptotic cells. Increased release of lactate dehydrogenase in OmpU-treated cells indicates that the OmpU-mediated cell death also has characteristics of necrosis. Further, we show that the mechanism of OmpU-mediated cell death involves major mitochondrial changes in the target cells. We observe that OmpU treatment leads to the disruption of mitochondrial membrane potential, resulting in the release of cytochrome c and apoptosis-inducing factor (AIF). AIF translocates to the host cell nucleus, implying that it has a crucial role in OmpU-mediated cell death. Finally, we observe that OmpU translocates to the target cell mitochondria, where it directly initiates mitochondrial changes leading to mitochondrial membrane permeability transition and AIF release. Partial blocking of AIF release by cyclosporine A in OmpU-treated cells further suggests that OmpU may be inducing the opening of the mitochondrial permeability transition pore. All of these results lead us to the conclusion that OmpU induces cell death in target cells in a programmed manner in which mitochondria play a central role.     

Cord Blood Levels of Toxic and Essential Trace Elements and Their Determinants in the Terai Region of Nepal: A Birth Cohort Study

The purpose of this study is to evaluate the cord blood level of toxic and trace elements and to identify their determinants in Terai, Nepal. One hundred pregnant women were recruited from one hospital in Chitwan, Nepal in 2008. The cord blood levels of toxic [lead (Pb), arsenic (As), and cadmium (Cd)], essential trace elements [zinc (Zn), selenium (Se), and copper (Cu)], demographic, socioeconomic, and behavioral variables were measured. The mean values of Pb, As, Cd, Zn, Se, and Cu in cord blood level were found as 31.7, 1.46, 0.39, 2,286, 175, and 667 μg/L, respectively. In the multivariate regression model, cord blood As levels from less educated mothers were higher than those from educated mothers (coefficient = -0.01, 95% confidence interval [CI] = -0.02-0.00). The maternal age was positively associated with the cord blood Cd level (coefficient = 0.02, 95% CI = 0.01-0.03), while it was negatively associated with the cord blood As level (coefficient = -0.01, 95% CI = -0.03--0.01). Cord blood levels of Pb, Zn, Se, and Cu were not associated with maternal age, socioeconomic status, living environment, and smoking status. As and Cd levels were relatively lower than those reported in previous studies in Asia, while the levels of Pb and the trace elements were similar. Less educated mothers are more likely to become a higher in utero As source to their fetus, and fetuses of older mothers were more likely to have higher in utero Cd exposure in Terai, Nepal.