Ovarian Cancer and Parkinson's Disease: A Bidirectional Mendelian Randomization Study.

(1) Background: Ovarian cancer (OC) and Parkinson's disease (PD) represent a huge public health burden. The relationship of these two diseases is suggested in the literature while not fully understood. To better understand this relationship, we conducted a bidirectional Mendelian ran-domization analysis using genetic markers as a proxy. (2) Methods: Utilizing single nucleotide polymorphisms associated with PD risk, we assessed the association between genetically predicted PD and OC risk, overall and by histotypes, using summary statistics from previously conducted genome-wide association studies of OC within the Ovarian Cancer Association Consortium. Similarly, we assessed the association between genetically predicted OC and PD risk. The inverse variance weighted method was used as the main method to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations of interest. (3) Results: There was no significant association between genetically predicted PD and OC risk: OR = 0.95 (95% CI: 0.88-1.03), or between genetically predicted OC and PD risk: OR = 0.80 (95% CI: 0.61-1.06). On the other hand, when examined by histotypes, a suggestive inverse association was observed between genetically predicted high grade serous OC and PD risk: OR = 0.91 (95% CI: 0.84-0.99). (4) Conclusions: Overall, our study did not observe a strong genetic association between PD and OC, but the observed potential association between high grade serous OC and reduced PD risk warrants further investigation.

Review of Mendelian Randomization Studies on Endometrial Cancer.

Endometrial cancer (EC) is a common gynecological cancer. In some parts of the world, the incidence and mortality of EC are on the rise. Understanding the risk factors of EC is necessary to prevent the occurrence of this disease. Observational studies have revealed the association between certain modifiable environmental risk factors and EC risk. However, due to unmeasured confounding, measurement errors, and reverse causality, observational studies sometimes have limited ability to judge robust causal inferences. In recent years, Mendelian randomization (MR) analysis has received extensive attention, providing valuable insights for cancer-related research, and is expected to identify potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly assigned during meiosis and are usually independent of environmental or lifestyle factors) is used instead of modifiable exposure to study the relationship between risk factors and disease. Therefore, MR analysis can make causal inference about exposure and disease risk. This review briefly describes the key principles and assumptions of MR analysis; summarizes published MR studies on EC; focuses on the correlation between different risk factors and EC risks; and discusses the application of MR methods in EC research. The results of MR studies on EC showed that type 2 diabetes, uterine fibroids, higher body mass index, higher plasminogen activator inhibitor-1 (PAI-1), higher fasting insulin, early insulin secretion, longer telomere length, higher testosterone and higher plasma cortisol levels are associated with increased risk of EC. In contrast, later age of menarche, higher circulatory tumor necrosis factor, higher low-density lipoprotein cholesterol, and higher sex hormone-binding globulin levels are associated with reduced risk of EC. In general, despite some limitations, MR analysis still provides an effective way to explore the causal relationship between different risk factors and EC.

Review of Mendelian Randomization Studies on Ovarian Cancer.

Ovarian cancer (OC) is one of the deadliest gynecological cancers worldwide. Previous observational epidemiological studies have revealed associations between modifiable environmental risk factors and OC risk. However, these studies are prone to confounding, measurement error, and reverse causation, undermining robust causal inference. Mendelian randomization (MR) analysis has been established as a reliable method to investigate the causal relationship between risk factors and diseases using genetic variants to proxy modifiable exposures. Over recent years, MR analysis in OC research has received extensive attention, providing valuable insights into the etiology of OC as well as holding promise for identifying potential therapeutic interventions. This review provides a comprehensive overview of the key principles and assumptions of MR analysis. Published MR studies focusing on the causality between different risk factors and OC risk are summarized, along with comprehensive analysis of the method and its future applications. The results of MR studies on OC showed that higher BMI and height, earlier age at menarche, endometriosis, schizophrenia, and higher circulating ß-carotene and circulating zinc levels are associated with an increased risk of OC. In contrast, polycystic ovary syndrome; vitiligo; higher circulating vitamin D, magnesium, and testosterone levels; and HMG-CoA reductase inhibition are associated with a reduced risk of OC. MR analysis presents a2 valuable approach to understanding the causality between different risk factors and OC after full consideration of its inherent assumptions and limitations.

Mushroom bodies modulate salience-based selective fixation behavior in Drosophila.

Mushroom bodies (MBs), one of the central brain structures in Drosophila melanogaster, are involved in several cognitive behaviors, such as olfactory learning and memory, visual context generalization, choice behavior facing conflicting cues. Attention is a cognitive behavior, and it facilitates a focus on the attended event while filtering out irrelevant events, thereby allowing more rapid and accurate reactions at a lower threshold in primates. Using the visual orientation paradigm in a flight simulator, we observed that MBs modulate salience-based selective fixation behavior, which resembles attention in primates to a certain degree. We found that the fixation ability of MB-deficient flies was significantly reduced when the contrast levels were lowered as well as when a certain amount of background noise was applied. Moreover, MB-deficient flies exhibited poor object fixation ability in the presence of an olfactory 'distracter'. Furthermore, during visual selection among multiple objects of different contrast, flies with MBs were able to 'pop-out' of the most salient object in a three-object selection paradigm. Finally, we determined that flies exhibited cross-modal synergistic integration between olfactory and visual signals during object-fixation behavior, which was independent of MBs. Taken together, our findings suggest that MBs do not contribute to cross-modal synergetic integration between olfactory and visual signals; instead, they confer sensory gain control and inhibitory gating in flies, this property allows entry of the salient signal as well as filters out background noise and irrelevant signals.

The homeostasis of iron and suppression of HO-1 involved in the protective effects of nimodipine on neurodegeneration induced by aluminum overloading in mice.

Aluminum intoxication can cause damage to the cognitive function and neurodegenerative diseases. In the present study, we investigated the role of iron homeostasis and heme oxygenase-1 (HO-1) expression in the protective effects of nimodipine on the neurodegeneration induced by aluminum overloading in mice. 2 microl of 0.25% aluminum chloride solution was intracerebroventricularly injected once a day for five days to induce the neurodegeneration of mice. Nimodipine was administered by intragastric gavage (80 mg/kg per day) for 30 days. We observed that nimodipine could improve the performance of behavior test related to the learning and memory function and ameliorate pathological changes of hippocampi caused by aluminum. Results of western blot, immunohistochemistry study, biochemical test and inductively coupled plasma-atomic emission spectrometry showed that nimodipine could suppress the increased expression of HO-1 protein, and decrease the elevation of both HO activity and iron level in hippocampi, induced by aluminum overloading. These results indicate that nimodipine can suppress the neurodegenerative development induced by aluminum overloading and the mechanism of its action is at least partly related to keeping the homeostasis of iron through blunting the expression of HO-1 in hippocampus.

Crossmodal interactions between olfactory and visual learning in Drosophila.

Different modalities of sensation interact in a synergistic or antagonistic manner during sensory perception, but whether there is also interaction during memory acquisition is largely unknown. In Drosophila reinforcement learning, we found that conditioning with concurrent visual and olfactory cues reduced the threshold for unimodal memory retrieval. Furthermore, bimodal preconditioning followed by unimodal conditioning with either a visual or olfactory cue led to crossmodal memory transfer. Crossmodal memory acquisition in Drosophila may contribute significantly to learning in a natural environment.

[The research into functions of heme oxygenase system in brain].

Heme oxygenase(HO) is a microsomal enzyme involved in the degradation of heme, resulting in the generation of biliverdin, iron, and carbon monoxide. Two HO isoenzymes, HO-1 and HO-2, have been found to distribute widely in brain with different mechanism of regulation. Both of them may play important roles in modulating intracellular NO, balancing antioxidative/oxidative stress, and accelerating neurodegeneration.