Article
Biochemistry & Molecular Biology
Ting Gong, Ann C. Hashimoto, Alexandru R. Sasuclark, Vedbar S. Khadka, Alexandra Gurary, Matthew W. Pitts
Summary: SELENOM is a positive regulator of leptin signaling and thioredoxin antioxidant activity in the hypothalamus. Deficiency of SELENOM impairs downstream STAT3 phosphorylation and cytosolic calcium responses evoked by leptin treatment.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Neurosciences
Hao-Hua Wei, Xiang-Shan Yuan, Ze-Ka Chen, Pei-Pei Chen, Zhe Xiang, Wei-Min Qu, Rui-Xi Li, Guo-Min Zhou, Zhi-Li Huang
Summary: The AVP neurons in SON and PVN receive similar input patterns from multiple brain regions, with PVNAVP neurons having broader and denser inputs compared to SONAVP neurons. Additionally, differentiated input sources were found, with SONAVP neurons receiving more projections from thermoregulatory nuclei and PVNAVP neurons receiving more afferent inputs from circadian rhythm-regulating nuclei. The study provides insights into the distinct afferent framework of AVP neurons in SON and PVN, laying the foundation for further research on their diverse roles.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biology
Chang-Rui Chen, Yu-Heng Zhong, Shan Jiang, Wei Xu, Lei Xiao, Zan Wang, Wei-Min Qu, Zhi-Li Huang
Summary: Hypersomnolence disorder is characterized by excessive sleep following stroke, infection, or tumorigenesis, and is traditionally associated with lesions of wake-promoting nuclei. The paraventricular nucleus of the hypothalamus (PVH) with glutamatergic neurons was found to be critical for arousal promotion and maintenance, as activating PVHvglut2 neurons induced wakefulness and driving transitions from sleep to wakefulness.
Article
Multidisciplinary Sciences
D. S. Engelke, X. O. Zhang, J. J. O'Malley, J. A. Fernandez-Leon, S. Li, G. J. Kirouac, M. Beierlein, F. H. Do-Monte
Summary: The study reveals that specific CRF-positive neurons in the paraventricular thalamus of rats are crucial in mediating defensive behaviors during conflicts between seeking rewards and avoiding threats. These neurons project to the nucleus accumbens, impacting food seeking and avoidance behaviors. Furthermore, the interaction between the ventromedial hypothalamus and aPVT neurons plays a key role in the modulation of defensive responses during conflicts.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
Xiao-Jing Liu, Xiao-Jing Yu, Yu-Kun Su, Jin-An Qiao, Yao-Jun Sun, Xiao-Jie Bai, Nana Zhang, Hui-Yu Yang, Li-Xi Yin, Yu-Ming Kang, Zhi-Ming Yang
Summary: This study demonstrates that angiotensin II-induced hypertensive rats have more activated microglia in the PVN, which release proinflammatory cytokines and cause oxidative stress, leading to sympathetic overactivity and hypertensive response.
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Physiology
Caitlin R. Coker, Melissa White, Aneesh Singal, Sarah S. Bingaman, Anirban Paul, Amy C. Arnold, Yuval Silberman
Summary: Obesity is associated with metabolic dysregulation and inflammation in the brain. This study demonstrates that minocycline, an anti-inflammatory drug, can alleviate the adverse metabolic consequences of high-fat diet-induced obesity in mice by reducing hypothalamic microglia activity.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xin Wang, Joan B. Escobar, David Mendelowitz
Summary: This study explores the potential involvement of atypical activity in the locus coeruleus in autism spectrum disorder (ASD) and investigates the neurotransmission from hypothalamic paraventricular (PVN) oxytocin (OXT) neurons to LC NA neurons. The research demonstrates the release of oxytocin from PVN OXT fibers in the LC and shows that optogenetic excitation of PVN OXT fibers excites LC NA neurons through co-release of oxytocin and glutamate, with a greater effect observed in males. Additionally, chemogenetic activation of PVN OXT neurons increases attention to novel objects specifically in male animals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Xiao-Jing Yu, Tong Xiao, Xiao-Jing Liu, Ying Li, Jie Qi, Nianping Zhang, Li-Yan Fu, Kai-Li Liu, Yanjun Li, Yu-Ming Kang
Summary: Knocking down Nrf1 suppresses sympathoexcitation in hypertension by reducing PVN transcription of NMDAR subunits (GluN1, GluN2A, and GluN2B), rebalancing PVN excitatory and inhibitory neurotransmitters, inhibiting PVN neuronal activity and oxidative stress, and attenuating sympathetic activity.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Immunology
Garyfallia Gouna, Christian Klose, Mar Bosch-Queralt, Lu Liu, Ozgun Gokce, Martina Schifferer, Ludovico Cantuti-Castelvetri, Mikael Simons
Summary: Microglia play a key role in promoting myelin repair after demyelinating injury, with cholesterol esterification being essential for myelin debris clearance and lipid droplet generation. TREM2 is crucial for adapting to excess cholesterol exposure and regulating lipid droplet formation, ultimately impacting the innate immune response and remyelination.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Cell Biology
Ruiyuan Xu, Jianlu Song, Rexiati Ruze, Yuan Chen, Xinpeng Yin, Chengcheng Wang, Yupei Zhao
Summary: This study reveals squalene epoxidase (SQLE) as a novel oncogene that promotes pancreatic cancer (PC) growth by mitigating endoplasmic reticulum stress and activating lipid raft-regulated Src/PI3K/Akt signaling pathway. SQLE facilitates cell proliferation, induces cell cycle progression, and inhibits apoptosis in vitro, while promoting tumor growth in vivo. SQLE inhibitors effectively suppress PC cell proliferation and xenograft tumor growth, highlighting the potential of SQLE as a therapeutic target for PC.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Amelia M. Douglass, Jon M. Resch, Joseph C. Madara, Hakan Kucukdereli, Ofer Yizhar, Abhinav Grama, Masahito Yamagata, Zongfang Yang, Bradford B. Lowell
Summary: Fasting activates the HPA axis through the inhibition of GABAergic afferents by AgRP neurons in the PVH. This study reveals the neural basis for fasting-induced HPA axis activation and provides insights into the mechanisms underlying stress-induced HPA axis activation.
Article
Immunology
Xiao Fan Xu, Meng Meng Shi, Ming Ying Luo, Dan Dan Liu, Dong Ming Guo, Ling Chen, Xiao Lin Zhong, Yang Xu, Wen Yu Cao
Summary: Neuroinflammation plays a key role in the development of depression-like behaviors, and endoplasmic reticulum stress is suggested to collaborate with inflammation process to drive sustained neuroinflammation. This study found that targeting the PERK pathway can improve LPS-induced depression-like behaviors, indicating that targeting PERK pathway may be a promising antidepressant and anti-inflammatory drug.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Environmental Sciences
Xiaowei He, Dan Wu, Yanan Xu, Yaqin Zhang, Yue Sun, Xiaoai Chang, Yunxia Zhu, Wei Tang
Summary: This study found that PFOA leads to damage and apoptosis of pancreatic beta cells, resulting in reduced insulin secretion. The increased expression of ER stress-related genes, particularly Trib3, contributes to this process. Inhibiting Trib3 expression can protect beta cells from PFOA-induced damage and apoptosis by alleviating ER stress.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Peripheral Vascular Disease
Xiao-Jing Yu, Xiao-Jing Liu, Jing Guo, Yu-Kun Su, Nianping Zhang, Jie Qi, Ying Li, Li-Yan Fu, Kai-Li Liu, Yanjun Li, Yu-Ming Kang
Summary: This study demonstrates that high salt intake leads to microglial activation in the hypothalamic paraventricular nucleus, resulting in the release of proinflammatory cytokines and oxidative stress. These processes contribute to sympathetic overactivity and the development of hypertension. Inhibiting microglial activation can attenuate inflammation and oxidative stress, thereby reducing the development of high salt-induced hypertension.
AMERICAN JOURNAL OF HYPERTENSION
(2022)
Article
Biochemistry & Molecular Biology
Haven Griffin, Sarah C. Sullivan, Steven W. Barger, Kevin D. Phelan, Giulia Baldini
Summary: One feature of high-fat diet-induced neurodegeneration in the hypothalamus is increased palmitate level and associated endoplasmic reticulum (ER) stress, mitochondrial fragmentation, and decreased MC4R abundance. Liraglutide effectively counteracts altered ER proteostasis, morphology, and folding capacity, while metformin only normalizes SERCA2 expression. Both drugs do not protect against loss of CoxIV and mitochondrial membrane potential. ER recovery can occur in hypothalamic neurons without restored mitochondrial homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chaoyang Li, Jiangwen Sun, Qianglin Liu, Sanjeeva Dodlapati, Hao Ming, Leshan Wang, Yuxia Li, Rui Li, Zongliang Jiang, Joseph Francis, Xing Fu
Summary: After myocardial infarction, cardiac fibroblasts undergo different differentiation states with distinct gene expression profiles, and the mechanisms underlying gene expression changes during activation and differentiation events remain unclear. The study utilized RNA-seq and ATAC-seq to analyze gene expression and chromatin accessibility in mouse cardiac fibroblasts from uninjured and infarcted myocardium, identifying transcription factors that may contribute to differential gene expression between different fibroblast states.
Article
Biochemistry & Molecular Biology
D. Parker Kelley, Katy Venable, Aspasia Destouni, Gerald Billac, Philip Ebenezer, Krisztian Stadler, Charles Nichols, Steven Barker, Joseph Francis
Summary: This study compared differentially expressed genes (DEGs) in the brain between post-traumatic stress disorder (PTSD) and animal models of traumatic stress. The researchers found overlapping DEGs between these two groups and tested the effects of N,N-dimethyltryptamine (DMT) and harmaline on reducing reactive oxygen species (ROS) production and inflammatory gene expression in the animal model. Treatment with DMT and pharmahuasca reduced ROS production and normalized overlapping DEGs associated with ROS production, inflammation, growth factor signaling, neurotransmission, and neuroplasticity.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Ting Liu, Andrew G. Howarth, Yinyin Chen, Anand R. Nair, Hsin-Jung Yang, Daoyuan Ren, Richard Tang, Jane Sykes, Michael S. Kovacs, Damini Dey, Piotr Slomka, John C. Wood, Robert Finney, Mengsu Zeng, Frank S. Prato, Joseph Francis, Daniel S. Berman, Prediman K. Shah, Andreas Kumar, Rohan Dharmakumar
Summary: Reperfusion therapy for acute myocardial infarction can lead to myocardial hemorrhage, which increases the size of the infarction. Myocardial hemorrhage drives the expansion of myocardial infarction after reperfusion and compromises myocardial salvage. This has implications for acute care management, risk assessment, and future therapeutics.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)
Article
Nutrition & Dietetics
Paul J. Pistell, Tadanobu Utsuki, Joseph Francis, Philip J. Ebenezer, Jennifer Terrebonne, George S. Roth, Donald K. Ingram
Summary: This study found that consumption of a high-fat diet led to weight gain, increased body fat, elevated blood lipids and leptin levels, as well as reduced adiponectin levels, insulin sensitivity, VO2max, and motor capabilities in mice. However, the addition of an avocado extract enriched in MH to the high-fat diet completely protected the mice from these changes and attenuated oxidative stress. Furthermore, the MH-enriched avocado extract also mitigated the effects of the high-fat diet on the mechanistic target of rapamycin pathway.
Review
Physiology
Gabriel Dias Rodrigues, Jonas Lirio Gurgel, Antonio Claudio Lucas da Nobrega, Pedro Paulo da Silva Soares
Summary: The impaired hemodynamics and postural balance responses to orthostatic stress cannot be solely attributed to aging or sedentarism. Comparative studies and follow-up studies on aging should be conducted to investigate the isolated effects of aging and sedentarism. Furthermore, orthostatic intolerance cannot be solely attributed to aging, as physical inactivity plays an important role in this process.
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hiviny A. Raquel, Louisi A. Manica, Alexandre Ceroni, Lisete C. Michelini
Summary: Previous studies have shown that removing baroreceptors and chemoreceptors impairs central autonomic circuitry and worsens cardiovascular function in rats. Exercise training can improve autonomic control of circulation. In rats without baroreceptors, exercise training can improve cardiovascular control but does not reduce blood pressure levels.
Article
Multidisciplinary Sciences
Ivan Cokic, Shing Fai Chan, Xingmin Guan, Anand R. Nair, Hsin-Jung Yang, Ting Liu, Yinyin Chen, Diego Hernando, Jane Sykes, Richard Tang, John Butler, Alice Dohnalkova, Libor Kovarik, Robert Finney, Avinash Kali, Behzad Sharif, Louis S. Bouchard, Rajesh Gupta, Mayil Singaram Krishnam, Keyur Vora, Balaji Tamarappoo, Andrew G. Howarth, Andreas Kumar, Joseph Francis, Scott B. Reeder, John C. Wood, Frank S. Prato, Rohan Dharmakumar
Summary: After myocardial infarction, intramyocardial hemorrhage contributes to fatty degeneration and adverse remodeling of the heart, but timely reduction of iron within the hemorrhagic infarction zone can mitigate these effects.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
D. Parker Kelley, Ardalan Chaichi, Alexander Duplooy, Dhirendra Singh, Manas Ranjan Gartia, Joseph Francis
Summary: Stress and trauma alter oxidative and lipid homeostasis, and PTSD is associated with changes in lipid species in plasma. However, there is limited research on stress-induced lipidomic changes in the brain. In this study, Raman imaging was used to quantify lipid species in the hippocampus, revealing increased cholesterol, altered lipid concentrations, increased free radical production, and reduced oxidized polyunsaturated fatty acids (PUFAs) after traumatic stress.
NEUROBIOLOGY OF STRESS
(2022)
Article
Oncology
Rui Zhang, Samantha D. Clark, Beibei Guod, Tianyi Zhang, Duane Jeansonne, Samithamby J. Jeyaseelan, Joseph Francis, Weishan Huang
Summary: Immunotherapy combined with radiotherapy shows promise in breast cancer treatment, but more research is needed to optimize the synergy between the two treatments and personalize IRT for individual patients. The abscopal effect of radiotherapy on distant cancer metastases and the potential impact of biomarkers need further exploration. Designing effective pre-clinical and clinical trials is urgently needed to improve IRT for breast cancer patients.
EXPERT REVIEW OF ANTICANCER THERAPY
(2023)
Article
Behavioral Sciences
D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S. V. P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V. G. Katakam, Nicholas W. Gilpin, Joseph Francis
Summary: Stress is associated with contextual memory deficits, which may lead to avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may result from impaired pattern separation in the brain, which affects the ability to distinguish similar experiences. The production of reactive oxygen species in the hippocampus has been found to be related to pattern separation and may play a role in the effects of stress on memory.
GENES BRAIN AND BEHAVIOR
(2023)
Article
Virology
Cassandra M. Bonavita, Timothy M. White, Joseph Francis, Helen E. Farrell, Nicholas J. Davis-Poynter, Rhonda D. Cardin
Summary: Human cytomegalovirus (HCMV) is a widespread pathogen infecting a large portion of the population worldwide, causing lifelong latent infection and exacerbating cardiovascular diseases. Murine CMV (MCMV) has been shown to replicate cardiovascular dysfunction observed in HCMV-induced myocarditis. In this study, the role of viral G-protein-coupled receptor homologs (vGPCRs) US28 and M33 in promoting heart infection was examined. The results revealed that M33 plays a role in promoting cardiac dysfunction during acute infection, while US28 protein could complement the function of M33 in the heart. These findings suggest that vGPCRs may contribute to long-term cardiac damage and dysfunction.
Article
Cell Biology
Qianglin Liu, Chaoyang Li, Buhao Deng, Peidong Gao, Leshan Wang, Yuxia Li, Mohammad Shiri, Fozi Alkaifi, Junxin Zhao, Jacqueline M. Stephens, Constantine A. Simintiras, Joseph Francis, Jiangwen Sun, Xing Fu
Summary: This study reveals the existence of a population of Tcf21 lineage cells (Tcf21 LCs) exclusively in visceral adipose tissue (VAT), which play a role in the development and expansion of VAT. Multiomics analyses and single-cell RNA sequencing (scRNA-seq) uncover the heterogeneity of Tcf21 LCs. Mechanistic studies show that Tcf21 inhibits adipogenesis at least partially through accentuating Dlk1 expression.
Article
Physiology
Vanessa B. Candido, Sany M. Perego, Alexandre Ceroni, Martin Metzger, Alison Colquhoun, Lisete C. Michelini
Summary: Chronic hypertension is accompanied by blood-brain barrier (BBB) leakage and autonomic dysfunction. The mechanism determining increased BBB permeability within autonomic areas is unclear. Exercise training can restore BBB permeability and autonomic control of the circulation. This study aimed to clarify the mechanism(s) governing hypertension- and exercise-induced BBB permeability. The results showed that transcytosis, not the paracellular transport, is the primary mechanism underlying both hypertension- and exercise-induced BBB permeability changes within autonomic areas.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Drew Theobald, Anand R. Nair, Srinivas Sriramula, Joseph Francis
Summary: Toll-like receptor 4 (TLR4) plays a crucial role in the innate immune response and cardiovascular diseases. This study found that cardiomyocyte-specific deletion of TLR4 provides protection against hypertension, cardiac hypertrophy, and remodeling. The results showed that in mice with cardiomyocyte-specific TLR4 knockdown, angiotensin II-induced hypertension and cardiac hypertrophy were attenuated, myocardial fibrosis was reduced, and cardiac function was improved.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Hiviny de Ataides Raquel, Sany M. Perego, Gustavo S. Masson, Leonardo Jensen, Alison Colquhoun, Lisete C. Michelini