Conodont biostratigraphy of the Upper Devonian-Lower Carboniferous Shahmirzad section, central Alborz, Iran

The conodont fauna from the Devonian-Carboniferous Shahmirzad section, located in the Central Alborz Mountains (North Iran), have been studied mainly for biostratigraphic purposes. Some levels were barren of conodonts, whereas others yielded a not very abundant, but quite differentiated fauna. No conodonts have been found from the mainly terrigenous and shaly Geirud Formation, whereas representative of genera Bispathodus, Clydagnathus, Gnathodus, Hindeodus, Mehlina, Polygnathus, Protognathodus, Pseudopolygnathus and Siphonodella have been collected from the mainly calcareous overlaying Mobarak Formation. The fauna allowed to discriminate five biointervals, from the sulcata Zone to a “Lower typicus - anchoralis-latus interval” in the central part of the section, while the lower and upper parts cannot be zoned on the basis of conodonts. This paper is the first report on lowermost Carboniferous conodonts from the Mobarak Formation in central Alborz.     

Effects of Buprenorphine on Balance of Oxidant/Antioxidant System in the Different Ages of Male Rat Liver

Our knowledge about a link between buprenorphine and hepatotoxicity is controversial. This study evaluated the effects of buprenorphine on the liver of young, adult, and aged rats. For this reason, young, adult, and aged rats received intraperitoneally 0.25, 0.5, and 1 mg/kg buprenorphine for 30 days. The present results revealed that the normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in the liver lipid peroxidation, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities in the aged rats. This study also demonstrated that buprenorphine led to a significant increase in the serum activities of ALT, AST, and LDH as well as liver lipid peroxidation content with a decrease in the antioxidant enzymes in the liver of buprenorphine‐treated aged rat versus the aged matched control animals. In conclusion, the present results demonstrate that buprenorphine deteriorated oxidative damage in the aged livers.     

Study of the mechanisms of crocetin-induced differentiation and apoptosis in human acute promyelocytic leukemia cells

Crocetin, the major carotenoid in saffron, exhibits potent anticancer effects. However, the antileukemic effects of crocetin are still unclear, especially in primary acute promyelocytic leukemia (APL) cells. In the current study, the potential antipromyelocytic leukemia activity of crocetin and the underlying molecular mechanisms were investigated. Crocetin (100 µM), like standard anti-APL drugs, all-trans retinoic acid (ATRA, 10 µM) and As₂O ₃ (arsenic trioxide, 50 µM), significantly inhibited proliferation and induced apoptosis in primary APL cells, as well as NB4 and HL60 cells. The effect was associated with the decreased expressions of prosurvival genes Akt and BCL2, the multidrug resistance (MDR) proteins, ABCB1 and ABCC1 and the inhibition of tyrosyl-DNA phosphodiesterase 1 (TDP1), while the expressions of proapoptotic genes CASP3, CASP9, and BAX/BCL2 ratio were significantly increased. In contrast, crocetin at relatively low concentration (10 µM), like ATRA (1 µM) and As ₂O ₃ (0.5 µM), induced differentiation of leukemic cells toward granulocytic pattern, and increased the number of differentiated cells expressing CD11b and CD14, while the number of the immature cells expressing CD34 or CD33 was decreased. Furthermore, crocetin suppressed the expression of clinical marker promyelocytic leukemia/retinoic acid receptor-α ( PML/RARα) in NB4 and primary APL cells, and reduced the expression of histone deacetylase 1 ( HDAC1) in all leukemic cells. The results suggested that crocetin can be considered as a candidate for future preclinical and clinical trials of complementary APL treatment.     

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells

Mechanical ventilation with hyperoxia is necessary to treat critically ill patients. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), which can cause acute inflammatory lung injury. One of the major effects of hyperoxia is the injury and death of pulmonary epithelium, which is accompanied by increased levels of pulmonary proinflammatory cytokines and excessive leukocyte infiltration. A thorough understanding of the signaling pathways leading to pulmonary epithelial cell injury/death may provide some insights into the pathogenesis of hyperoxia-induced acute inflammatory lung injury. This review focuses on epithelial responses to hyperoxia and some of the major factors regulating pathways to epithelial cell injury/death, and proinflammatory responses on exposure to hyperoxia. We discuss in detail some of the most interesting players, such as NF-kappaB, that can modulate both proinflammatory responses and cell injury/death of lung epithelial cells. A better appreciation for the functions of these factors will no doubt help us to delineate the pathways to hyperoxic cell death and proinflammatory responses.     

Effects of aminophylline on hypoxemia-induced ventilatory depression in the cat

We designed experiments to evaluate changes in ventral medullary (VM) extracellular fluid (ECF) PCO2 and pH during hypoxemia-induced ventilatory depression (VD). Our aim was to investigate effects of aminophylline on VD and VM ECF acid-base variables. We used aminophylline because it inhibits adenosine, which is released within the brain during hypoxemia and could mediate VD. Experiments were performed in seven cats with acute bilateral denervation of carotid sinus nerves and vagi. Cats were anesthetized with chloralose-urethan and breathed spontaneously at a regulated and elevated arterial PCO2 (PaCO2). Measurements were made during normoxemia, hypoxemia, and recovery before (phase I) and after (phase II) aminophylline. By use of strict criteria for definition of VD, during phase II two kinds of responses were observed. Aminophylline prevented VD in five cats. In these cats in phase I, with mean arterial PO2 (PaO2) = 105 and PaCO2 = 42.2 Torr, VM ECF PCO2, [H+], and [HCO3-] were 59.5 +/- 8.6 Torr (mean +/- SD), 60.2 +/- 9.4 neq/l, and 23.1 +/- 3.7 meq/l, respectively. When mean PaO2 dropped to 49 Torr, ventilation decreased 21%, with only small changes in VM ECF acid-base variables. Studies were repeated 30 min after aminophylline (17 mg/kg iv). In phase II, during normoxemia (PaO2 = 110 Torr) VM ECF Pco2, [H+], and [HCO3-] were 55.4 +/- 8.1 Torr, 62.0 +/- 8.0 neq/l and 20.7 +/- 2.5 meq/l, respectively. During hypoxemia (PaO2 = 48 +/- 4 Torr) mean ventilation, VM ECF PCO2, [H+], and [HCO3-] did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the yeast-extract signaling pathway leading to silymarin biosynthesis in milk thistle hairy root culture

The biosynthesis of silymarin, a potent antihepatotoxic compound, from the dried fruits of Silybum marianum L. Gaertn in hairy root cultures can be stimulated by a yeast extract elicitor. These results correlated with culture time, and the biosynthesis reached a maximum of 0.47 mg g^?1 DW by 72 h after culture (2-fold higher than the control). Lipoxygenase activity and linoleic acid content were stimulated by this treatment, suggesting that the jasmonate pathway may mediate the elicitor-induced accumulation of silymarin. The H₂O₂ content increased 24 h after elicitation and did not have marked changes between 48 and 72 h. In addition, the tocopherol content (especially α- and δ-tocopherols) increased 72 h after elicitation in comparison with non-treated cultures. Ascorbate had trace changes during feeding time and was lower than the control. The antioxidant activity was assayed by the 1-1-diphenyl-2-picrylhydrazyl stable free radical method and results were calculated base on an IC₅₀ that increased upon treatment, especially 24 h after treatment, with changes related to H₂O₂ content. These observations suggested that reactive oxygen species may mediate elicitor signals to the jasmonate pathway that lead to the production of silymarin.     

miRNA-143 replacement therapy harnesses the proliferation and migration of colorectal cancer cells in vitro

miR-143 is a tumor suppressor miRNA which its downregulation is frequently reported in colorectal cancer (CRC). This miRNA is a negative regulator of K-RAS, c-MYC, BCL-2, and MMP-9 genes which are engaged in tumor growth and metastasis. In the present study, miR-143 restoration was performed by transfection of the pCMV-miR-143 vector into the SW-480 CRC cells. Subsequently, alterations in proliferative and migratory potential of the cells were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and wound-healing assays, respectively. Moreover, to detect apoptosis incidence in the transfected cells, 4',6-diamidino-2-phenylindole (DAPI) staining was used. Furthermore, mRNA levels of c-MYC, K-RAS, MMP-9, and BCL-2, as potential targets of miR-143, were assessed by quantitative Real-Time PCR (qRT-PCR). Also the expression levels of c-MYC, K-RAS, and MMP-9 proteins were investigated by the western blot analysis. Finally, the ratio of BAX to BCL-2 expression, as a potential marker of the response to apoptosis stimuli, was compared between the control and test groups. Furthermore, the trypan blue test was performed to determine the cell viability in cell suspension. According to the results, a decreased viability and migratory potential was observed for the miR-143 receiving cells. The DAPI staining also confirmed the occurrence of apoptosis. Moreover, BCL-2, K-RAS, MMP-9, and c-MYC mRNAs were significantly downregulated in the miR-143 grafted cells. The BAX/BCL-2 ratio also indicated a notable increase in the cells with miR-143 overexpression. In brief, miR-143 replacement could be considered as an effective strategy for the management of CRC and attenuating its invasive features.     

The role of arsenic in obesity and diabetes

As many individuals worlwide are exposed to arsenic, it is necessary to unravel the role of arsenic in the risk of obesity and diabetes. Therefore, the present study reviewed the effects of arsenic exposure on the risk and potential etiologic mechanisms of obesity and diabetes. It has been suggested that inflammation, oxidative stress, and apoptosis contribute to the pathogenesis of arsenic-induced diabetes and obesity. Though arsenic is known to cause diabetes through different mechanisms, the role of adipose tissue in diabetes is still unclear. This review exhibited the effects of arsenic on the metabolism and signaling pathways within adipose tissue (such as sirtuin 3 [SIRT3]- forkhead box O3 [FOXO3a], mitogen-activated protein kinase [MAPK], phosphoinositide-dependant kinase-1 [PDK-1], unfolded protein response, and C/EBP homologous protein [CHOP10]). Different types of adipokines involved in arsenic-induced diabetes are yet to be elucidated. Arsenic exerts negative effects on the white adipose tissue by decreasing adipogenesis and enhancing lipolysis. Some epidemiological studies have shown that arsenic can promote obesity. Nevertheless, few studies have indicated that arsenic may induce lipodystrophy. Arsenic multifactorial effects include accelerating birth and postnatal weight gains, elevated body fat content, glucose intolerance, insulin resistance, and increased serum lipid profile. Arsenic also elevated cord blood and placental, as well as postnatal serum leptin levels. The data from human studies indicate an association between inorganic arsenic exposure and the risk of diabetes and obesity. However, the currently available evidence is insufficient to conclude that low-moderate dose arsenic is associated with diabetes or obesity development. Therefore, more investigations are needed to determine biological mechanisms linking arsenic exposure to obesity and diabetes.