NUTR455: Advanced Nutrition and Human Metabolism- A Peer Review of Teaching Project Benchmark Portfolio

NUTR455, Advanced Nutrition and Human Metabolism is a capstone, ACE 10 course for undergraduate seniors in nutrition and health sciences that I teach in spring semesters since 2017. Among the 3 classes that I taught, spring 2019 class did awesome job in their overall performance, in-class participation, and in-class exams and in their final poster assignment. We analyzed three questions to as part of this teaching benchmark portfolio. 1) The role of in-class iClicker questions in improving student students understanding the key concepts and test whether it motivates the students to study course materials; 2) Tested whether review session impacted/improve student learning experience and 3) we also examined whether draft poster peer review of poster helped them improve final poster project. We found solid evidence from student response for in-class clicker questions motivates students to prepare and aids in understanding course materials. Further, review session prior to each exam facilitated and improved student preparation to obtain higher grades. Also students who attended review session significantly improved and obtained higher grades compared to students compared to students who did not attend the review session. We also found evidence that draft poster peer review significantly impacted and helped improved final poster assignment and helped improved final poster grades. In conclusion, in-class clicker questions, review session and draft peer review of poster profoundly impacts student learning experience and improved their overall grades in the exams and final poster assignments

Zika Virus Induces Apoptosis in Retinal Pigmented Epithelial Cells

Zika virus is a single-stranded positive sense RNA virus that attracted international attention in 2015 when an epidemic broke out in Brazil. This vector borne virus is transmitted by mosquitos and is especially concerning for pregnant women because the virus can affect the development of the fetus. One known complication is the destruction of infected retinal epithelial cells. The transduction of light is interrupted due to cell death and results in blind spots. Previous research has demonstrated that palmitoleate can reduce the observed levels of apoptosis in ZIKAV infected JEG-3 cells. We have also seen the protection of retinal pigmented epithelial cells when treated with 200 uL and 100 uL of palmitoleate. In addition, 12-hour pre-treatment of palmitoleate has been shown to significantly reduce observed apoptosis. Treating for 72-96 hours post-infection has shown to protect from observed apoptosis more effectively than pre-treatments. Therefore, palmitoleate should be investigated as a possible nutritional supplement to protect the fetus of mothers in affected or high-risk areas

Trophoblast Changes in Maternal Obesity

Maternal obesity has become a common metabolic dysfunction among reproductive age women affecting at least 1 in 5 women. Pregnancy complicated with maternal obesity is associated with adverse outcomes to both mother and the fetus. Maternal obesity increases the risk of adverse pregnancy outcome including pre‑eclampsia, fetal growth restriction and overgrowth and stillbirth. Recent studies show that children born to obese mother have increased adiposity and are vulnerable to develop metabolic syndromes later in their life. Placenta, which plays an important part during pregnancy and fetal development has become a major research focus of scientists around the world for its impact on fetal health. Increased evidence suggest that a maternal obesogenic environment influences placental normal function and in turn programs the developing fetus towards adverse health outcomes in adult life. Here, we briefly discuss how maternal obesogenic environment impacts placental functions and influence child health later in life

3-Hydroxy Fatty Acid Induce Trophoblast and Hepatocyte Lipoapoptosis

Acute Fatty Liver of Pregnancy (AFLP) is a very rare and fatal condition for both the mother and the unborn offspring accompanied by severe maternal liver dysfunction. AFLP usually develops during the third trimester of pregnancy with symptoms of liver disease. AFLP is associated with a mutation in the enzyme, long-chain 3-hydroxy acyl CoA dehydrogenase (LCHAD) which is involved in the mitochondrial beta-oxidation of fatty acids. Defective beta-oxidation of fatty acids results in the individual unable to metabolize fatty acids which then causes fatty infiltration in their organs, such as the liver. This interferes with normal function of the liver and since fatty acids are an essential nutrient for mothers in the third trimester of pregnancy, an individual with this disease will not be able to survive long after child birth without the proper treatment. AFLP is an in-born error of metabolism and occurs in an autosomal recessive pattern, meaning it will take effect if an individual has both recessive alleles. This occurs when both the mother and father are heterozygous for the mutation in LCHAD and pass on their recessive alleles to the offspring. The placenta acts as a lung, liver and kidney for the fetus and it also has the genetic make-up of the fetus. In AFLP, a fetus with homozygous mutation for LCHAD will have his/her placenta defective to metabolize the long chain fatty acids resulting in the accumulation of 3-hydroxyl fatty acids. Accumulated 3-hydroxyl fatty acids and other fatty acids enter the mother’s circulation and affects the maternal liver resulting in the complication of maternal liver disease observed in AFLP. The only form of treatment is for the mother to deliver the offspring, this will allow her to recover from maternal liver disease. As the liver accumulates with toxic 3-hydroxy fatty acids, it is not able to properly function. The hepatocytes, liver cells, are not able to maintain a proper balance between cell death and cells being produced. Cell death occurs at a higher rate than cells being replaced and results in liver dysfunction. Here our hypothesis is that the 3-hydroxy fatty acids that are released from the placenta induces hepatocyte lipoapoptosis, a metabolic programed cell death caused by the increased exposure of fatty acids. This study will help clarify the mechanism of maternal liver damage that happens during AFLP. Our hypothesis will help identify the role of placental exosomes exacerbates hepatocyte lipoapoptosis due to the exposure of 3-hydroxy fatty acids

Zika Virus Induces Apoptosis in Retinal Pigmented Epithelial Cells

Zika virus is a single-stranded positive sense RNA virus that attracted international attention in 2015 when an epidemic broke out in Brazil. This vector borne virus is transmitted by mosquitos and is especially concerning for pregnant women because the virus can affect the development of the fetus. One known complication is the destruction of infected retinal epithelial cells. The transduction of light is interrupted due to cell death and results in blind spots. Previous research has demonstrated that palmitoleate can reduce the observed levels of apoptosis in ZIKAV infected JEG-3 cells. We have also seen the protection of retinal pigmented epithelial cells when treated with 200 uL and 100 uL of palmitoleate. In addition, 12-hour pre-treatment of palmitoleate has been shown to significantly reduce observed apoptosis. Treating for 72-96 hours post-infection has shown to protect from observed apoptosis more effectively than pre-treatments. Therefore, palmitoleate should be investigated as a possible nutritional supplement to protect the fetus of mothers in affected or high-risk areas

Role of microRNAs in Alcohol-Induced Multi-Organ Injury

Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption

Role of microRNAs in Alcohol-Induced Multi-Organ Injury

Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption

Role of microRNAs in Alcohol-Induced Multi-Organ Injury.

Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption

Evidence for Pipecolate Oxidase in Mediating Protection Against Hydrogen Peroxide Stress

Pipecolate, an intermediate of the lysine catabolic pathway, is oxidized to Δ1-piperideine-6-carboxylate (P6C) by the flavoenzyme lpipecolate oxidase (PIPOX). P6C spontaneously hydrolyzes to generate α-aminoadipate semialdehyde, which is then converted into α-aminoadipate acid by α-aminoadipatesemialdehyde dehydrogenase. l-pipecolate was previously reported to protect mammalian cells against oxidative stress. Here, we examined whether PIPOX is involved in the mechanism of pipecolate stress protection. Knockdown of PIPOX by small interference RNA abolished pipecolate protection against hydrogen peroxide-induced cell death in HEK293 cells suggesting a critical role for PIPOX. Subcellular fractionation analysis showed that PIPOX is localized in the mitochondria of HEK293 cells consistent with its role in lysine catabolism. Signaling pathways potentially involved in pipecolate protection were explored by treating cells with small molecule inhibitors. Inhibition of both mTORC1 and mTORC2 kinase complexes or inhibition of Akt kinase alone blocked pipecolate protection suggesting the involvement of these signaling pathways. Phosphorylation of the Akt downstream target, forkhead transcription factor O3 (FoxO3), was also significantly increased in cells treated with pipecolate, further implicating Akt in the protective mechanism and revealing FoxO3 inhibition as a potentially key step. The results presented here demonstrate that pipecolate metabolism can influence cell signaling during oxidative stress to promote cell survival and suggest that the mechanism of pipecolate protection parallels that of proline, which is also metabolized in the mitochondria

XIAP antagonist embelin inhibited proliferation of cholangiocarcinoma cells.

Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentration-dependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL). However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis