tRNA-derived fragments: Key determinants of cancer metastasis with emerging therapeutic and diagnostic potentials.

Metastasis is a significant clinical challenge responsible for cancer mortality and non-response to treatment. However, the molecular mechanisms driving metastasis remain unclear, limiting the development of efficient diagnostic and therapeutic approaches. Recent breakthroughs in cancer biology have discovered a group of small non-coding RNAs called tRNA-derived fragments (tRFs), which play a critical role in the metastatic behavior of various tumors. tRFs are produced from cleavage modifications of tRNAs and have different functional classes based on the pattern of these modifications. They perform post-transcriptional regulation through microRNA-like functions, displacing RNA-binding proteins, and play a role in translational regulation by inducing ribosome synthesis, translation initiation, and epigenetic regulation. Tumor cells manipulate tRFs to develop and survive the tumor mass, primarily by inducing metastasis. Multiple studies have demonstrated the potential of tRFs as therapeutic, diagnostic, and prognostic targets for tumor metastasis. This review discusses the production and function of tRFs in cells, their aberrant molecular contributions to the metastatic environment, and their potential as promising targets for anti-metastasis treatment strategies.

Comparing The Effect Of Electroacupuncture And Glibenclamide On Blood Glucose Level And Histological Markers Of Pancreas In Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Diabetes lowers the quality of life and leads to several complications. Glibenclamide is a commonly used step-two treatment in diabetes but it causes weight gain, hypoglycemia and cardiovascular problems. Electroacupuncture (EA) can enhance insulin sensitivity and reduce blood glucose levels. OBJECTIVES: To compare the effects of EA plus glibenclamide (G) with single therapy by G or EA on blood glucose, pancreas volume, islet volume, ratio of islet volume to pancreas volume, apoptotic and beta cells numbers and body weight in diabetic rats. METHODS: Sixty adult male Wistar rats were randomly divided to 10 groups: 2 non-diabetic control groups and 8 diabetic groups (1 control and 7 experimental groups; D/G 2.5, D/G 5, D/G 10 mg/kg, EA, D/EA/G 2.5, D/EA/G 5, and D/EA/G 10). Diabetes was induced by intraperitoneal injection of 35 mg/kg streptozotocin with high-fat diet. At the end of the course, blood samples were obtained and pancreases were dissected. RESULTS: EA was as effective as D/G 5 and D/G 10 in all outcomes. Combination therapy of EA and glibenclamide 5 and 10 mg/kg resulted in a better glucose-lowering effect, greater islet volume and ratio of islet volume to pancreas volume than single therapies (P < .05). EA increased the pancreas volume as much as the combination therapies (P > .05). CONCLUSION: Combination of EA and glibenclamide 5 showed the best effects on blood glucose, islet volume and ratio of islet to pancreas volume. Combination of EA and glibenclamide 2.5 illustrated the best effects on apoptotic and beta cell number of diabetic rats.

The effect of methamphetamine exposure during pregnancy and lactation on hippocampal doublecortin expression, learning and memory of rat offspring.

The aim of this study was to evaluate the effect of methamphetamine (MA) exposure during pregnancy and lactation on doublecortin (DCX) expression in the hippocampus of rat offspring and also on learning/memory. Thirty-five pregnant Wistar rats were randomly divided into seven groups of 5 rats each: three experimental groups, each receiving 5 mg/kg body weight (BW) intraperitoneal (i.p.) injections of MA during pregnancy or/and lactation; three sham groups, each receiving saline injections; one control group, receiving no injection. After the interventions, two male pups (1 and 22 days old) were randomly selected from each mother, sacrificed and their brains subjected to DCX immunohistochemistry. One additional male pup from each mother was randomly selected and maintained for 60 days for testing in the Morris water maze and passive avoidance tests. MA administration during pregnancy was found to have significantly decreased the number of DCX-positive cells in the CA1, CA3 and DG regions of the hippocampus in the 1-day pups (P ≤ 0.05) and to have significantly decreased the number of DCX-positive cells in only two regions of the hippocampus, the CA1 and DG regions, in 22-day old pups. In comparison, exposure to MA during lactation was only associated with a significant decrease in the number of DCX-positive cells in the DG. Exposure to MA during pregnancy had significant impact on the intensity of DCX expression in the hippocampus of 1- and 22-day pups (P ≤ 0.05). There was no significant difference in memory/learning among the study groups. Our results indicate the administration of MA during pregnancy had a greater effect that during the lactation period on DCX expression in the hippocampus of rat offspring.

Effect of methamphetamine exposure during pregnancy and lactation on polysialic acid-neural cell adhesion molecule expression in rat's offspring hippocampus.

Pregnant women constitute about half the users of methamphetamine (MA), in whom the consumption may continue during breastfeeding. This study aimed to evaluate the effects of MA use during pregnancy and lactation on the hippocampus of pups. 35 pregnant Wistar rats were divided into seven groups, including three experimental groups daily administered with 5 mg/kg of MA (i.p.) during the prenatal and/or postnatal period (PND1-22). In addition, three sham control groups received normal saline at the same dose, and one normal control group received no interventions since early pregnancy until the end of lactation. After the interventions, two pups (aged one and 22 days) were randomly selected from each mother and their brain tissue sections were prepared to determine the expression of PSA-NCAM molecules and sialic acids using immunohistochemical and lectinhistochemical techniques, respectively. In one-day infant rats with MA exposure during pregnancy, a significant decrease was observed in the number of PSA-NCAM positive cells in the CA1 (P = 0.047), CA3 (P = 0.05) and DG (P = 0.006) hippocampus regions compared to control and expression intensity of these molecules in all the three regions (P ≤ 0.05). Moreover, in 22-day pups with MA exposure during pregnancy and lactation, number of PSA-NCAM positive cells and expression intensity of these molecules significantly reduced in all the three regions of the hippocampus (P ≤ 0.05). Findings regarding the intensity of sialic acid expression were aligned with PSA-NCAM expression. According to our results, MA administration during pregnancy and lactation may effect on polysialic acid-neural cell adhesion molecule expression in rat's offspring hippocampus.

Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis.

INTRODUCTION: The usage of Titanium dioxide nanoparticles (TiO2-NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO2-NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO2-NPs on rat offspring hippocampus during developmental period. MATERIAL AND METHODS: Pregnant and lactating Wistar rats received intragastric TiO2-NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage. At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring's brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n=6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level. RESULTS: Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO2-NPs during pregnancy and lactation periods increased apoptotic cells significantly (P<0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO2-NPs reduced neurogenesis in the hippocampus of the offspring (P<0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO2-NPs group significantly increased and decreased, respectively (P<0.01). CONCLUSION: These findings provide strong evidence that maternal exposure to TiO2-NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and their offspring across the world is potentially devastating.

The prevention and treatment effects of egg yolk high density lipoprotein on the formation of atherosclerosis plaque in rabbits.

OBJECTIVES: Atherosclerosis is the main leading cause of cardiovascular diseases. The purpose of this study was to assess the potential preventive effect of egg yolk HDL on the atherosclerosis plaque formation. MATERIALS AND METHODS: Thirty rabbits were divided into five groups: A; normal diet, B; hyper-cholesterolemic diet, C; hypercholesterolemic + 400 mg/kg egg yolk HDL D; hypercholesterolemic +100 mg/kg egg yolk HDL and E; 200 mg/kg egg yolk HDL. At the end of the experiment, the lipid profiles were measured by spectrophotometric method. The histological sections of thoracic aorta also were taken and analyzed under light microscope. RESULTS: At the end of the 2(nd) and the 4(th) weeks, there was a significant increase of cholesterol level in groups B, C, and D compared to group A (P<0.05). Following HDL treatment, triglyceride (TG) levels increased significantly versus group A and also the TG level decreased significantly in group C, D, and E versus group B (P<0.01). Egg yolk HDL significantly increased HDL-C in groups C, D, and E (P<0.01) compared to groups A and B (P<0.05). The surface area of the atherosclerotic plaque was increased significantly in group B versus group A (P<0.001). Egg yolk HDL consumption reduced the plaque size significantly (P<0.001). CONCLUSION: Our findings indicated that treatment with egg yolk HDL increased serum HDL-C and decreased atherosclerotic plaque size in rabbits. Thus, egg yolk HDL may be considered as an anti-atherosclerotic treatment for cardiovascular diseases.

The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats.

BACKGROUND: Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring. METHODS: Forty timed-pregnant Wistar rats were divided into four groups: A) Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy) rats that received repeated intraperitoneal (i.p.) pentylenetetrazol, PTZ injections on gestational days (GD) 14-19; B) Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C) Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D) Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates' hippocampi were analyzed by Western blots and immunohistochemistry. RESULTS: Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001) and Kind-/Seiz+ (p = 0.001) groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007) and Kind-/Seiz+ (p = 0.007) group's newborns on both PD1 and 14. CONCLUSION: Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring's hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.