Review
Neurosciences
Arbi Nazarian, S. Stevens Negus, Thomas J. Martin
Summary: Pain is a complex experience influenced by biological, psychological, and social factors, which can increase susceptibility to opioid use disorder. Chronic pain and opioid use disorder often co-occur, driven by increased availability of opioid analgesics for non-medical use. Brain imaging studies suggest mechanisms related to opioid abuse in individuals with chronic pain who use opioids.
Review
Pharmacology & Pharmacy
Yue Zhao, Feng Qin, Shuang Han, Shu Li, Ying Zhao, Hongbo Wang, Jingwei Tian, Xiaobo Cen
Summary: Drug addiction is a chronic brain disorder characterized by compulsive drug seeking and continued drug use. Abnormal gene expression and aberrant neural adaptation play key roles in addiction, and recent studies have shown that miRNAs are strong modulators of gene expression in drug addiction. This suggests that miRNAs could be potential therapeutic targets for drug addiction.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Soichiro Ide, Noriaki Iwase, Kenichi Arai, Masahiro Kojima, Shigeru Ushiyama, Kaori Taniko, Kazutaka Ikeda
Summary: Despite the widespread use of opioids for pain management, opioid addiction and the overdose crisis are becoming increasingly serious. A new nonpeptide ligand, UD-030, has been found to be a selective mu-opioid receptor antagonist and shows promise as a treatment option for opioid use disorder, with different characteristics from traditional medications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pathology
Sarah Abdulmalek, Gary Hardiman
Summary: Opioid use disorder is a global problem with the challenge of relapse hindering long-term efficacy of treatments. Understanding the neurobiology of addiction and relapse can lead to more targeted and effective treatment, as well as diagnostic tools for identifying vulnerable individuals. The limitations of current screening tools for opioid use disorder are also discussed.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2023)
Article
Psychiatry
Javier Ballester, Anne K. Baker, Ilkka K. Martikainen, Vincent Koppelmans, Jon-Kar Zubieta, Tiffany M. Love
Summary: This study found that chronic pain patients at high risk for opioid misuse showed higher baseline MOR availability in the right amygdala, while patients at low risk for opioid misuse showed less pain-induced activation of MOR-mediated, endogenous opioid neurotransmission in the nucleus accumbens.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Chemistry, Medicinal
Ying-Ting Hsu, Shen-Ren Chen, Yung-Chiao Chang, Hsiao-Fu Chang, Teng-Kuang Yeh, Jian-Ying Chuang, Horace H. Loh, Hsing-Pang Hsieh, Shau-Hua Ueng, Shiu-Hwa Yeh
Summary: The demand for a non-addictive analgesic medication is increasing due to clinical misuse. Compound 14 is a dual agonist of the mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor, providing pain relief at very small doses and reducing unwanted side effects. Evaluating its effects in wild type and humanized mice can help develop a safer prescription analgesic drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Neurosciences
Sophia C. Levis, Stephen V. Mahler, Tallie Z. Baram
Summary: Opioid use disorder (OUD) is not typically a singular psychiatric condition, with comorbid symptoms likely tied to various risk factors. Early life adversity may disrupt reward circuit development, potentially contributing to OUD and other comorbid neuropsychiatric disorders.
FRONTIERS IN HUMAN NEUROSCIENCE
(2021)
Article
Cell Biology
Wei Wang, Xueyi Xie, Xiaowen Zhuang, Yufei Huang, Tao Tan, Himanshu Gangal, Zhenbo Huang, William Purvines, Xuehua Wang, Alexander Stefanov, Ruifeng Chen, Lucas Rodriggs, Anita Chaiprasert, Emily Yu, Valerie Vierkant, Michelle Hook, Yun Huang, Emmanuel Darcq, Jun Wang
Summary: Withdrawal from chronic opioid use leads to hypodopaminergic states and negative affect, promoting relapse. Activation of MORs in dMSNs in the striatal patch compartment suppresses striatopallidal transmission, and withdrawal potentiated this transmission. Fentanyl self-administration enhances striatonigral transmission and reduces dopaminergic activity, while activated striatal neurons mediate contextual memory retrieval. Inhibition of striatal MOR+ neurons rescues fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These findings suggest that chronic opioid use induces GABAergic striatopallidal and striatonigral plasticity, leading to hypodopaminergic states and relapse.
Article
Cell Biology
Gui-Ying Zan, Yu-Jun Wang, Xue-Ping Li, Jun-Fan Fang, Song-Yu Yao, Jun-Ying Du, Qian Wang, Xiang Sun, Rui Liu, Xiao-Mei Shao, Jian-Dong Long, Jing-Rui Chai, Ying-Zhi Deng, Ye-Qing Chen, Qing-Lin Li, Jian-Qiao Fang, Zhi-Qiang Liu, Jing-Gen Liu
Summary: The study reveals that morphine abstinence activates KORs by increasing endogenous KOR ligand dynorphin expression in the amygdala, leading to upregulation of GLT1 expression and subsequent modulation of glutamate inputs to the NAc, resulting in depressive-like behaviors associated with opiate abstinence.
Article
Cell Biology
Xinbei Tian, Ying Wang, Ying Lu, Weipeng Wang, Jun Du, Shanshan Chen, Huiping Zhou, Wei Cai, Yongtao Xiao
Summary: The study found that macrophages play a significant role in the progression of cholestatic liver fibrosis in biliary atresia (BA) patients. Selective depletion of macrophages can halt liver fibrosis progression and regulate cholangiocyte proliferation by modulating lncRNA-H19.
CELL DEATH & DISEASE
(2021)
Article
Neurosciences
Jessica L. Huebschman, Megan C. Davis, Catherina Tovar Pensa, Yuhong Guo, Laura N. Smith
Summary: The study revealed that mice lacking the FMRP protein exhibited deficits in learning and reward-related functions during cocaine self-administration experiments, particularly in failing to adjust response levels normally during dose-response testing, indicating the important role of FMRP in regulating drug self-administration behavior. Additionally, similar deficits were not observed when using palatable food as reinforcement, suggesting the specific impact of FMRP on drug self-administration behavior.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Primary Health Care
Mark D. Sullivan, Jane C. Ballantyne
Summary: The opioid epidemic in the US challenges us to reconsider the function of opioids and the nature of chronic pain, highlighting the interconnection between physical and social pain. Patients using opioids long term for chronic pain treatment may experience both physical and social pain, with these medications potentially leading to persistent negative effects on the brain. Recognizing the social aspects of chronic pain and opioid action can lead to improved treatment and usage of opioid medications.
ANNALS OF FAMILY MEDICINE
(2021)
Article
Psychiatry
Serenella Tolomeo, Alex Baldacchino, Nora D. Volkow, J. Douglas Steele
Summary: Opioid use disorder has a significant impact globally, with limited recovery observed during protracted abstinence. Neuroimaging findings from this study support the allostasis theory by demonstrating improved negative valence brain function and similar positive valence function during protracted abstinence among patients.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Huan Sheng, Chao Lei, Yu Yuan, Yali Fu, Dongyang Cui, Li Yang, Da Shao, Zixuan Cao, Hao Yang, Xinli Guo, Chenshan Chu, Yaxian Wen, Zhangyin Cai, Ming Chen, Bin Lai, Ping Zheng
Summary: The lateral hypothalamus (LH) is implicated in drug addiction, specifically in the context-induced expression of morphine withdrawal memory. This study demonstrates that LH glutamatergic neurons are activated by neural circuits from the nucleus accumbens core (NAcC) through dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs). The disinhibited LH glutamatergic neurons contribute to context-induced expression of morphine withdrawal memory.
NATURE COMMUNICATIONS
(2023)
Article
Sport Sciences
Yu Zhou, Graham Finlayson, Xudong Liu, Qichen Zhou, Tianze Liu, Chenglin Zhou
Summary: The study examined the effects of acute moderate-intensity dance and aerobic exercise on drug craving, appetite, prefrontal neural activation to food cues, and food reward in women with methamphetamine dependence. Results showed that both interventions reduced subjective craving for drugs and increased implicit wanting and relative preferences for high-calorie savory foods. The findings suggest that moderate-intensity exercise can be used as a therapeutic intervention to restore the balance between drug and nondrug rewards.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2021)
Article
Behavioral Sciences
G. I. Elmer, H. Palacorolla, C. L. Mayo, P. L. Brown, T. C. Jhou, D. Brady, P. D. Shepard
BEHAVIOURAL BRAIN RESEARCH
(2019)
Article
Clinical Neurology
P. Leon Brown, Panos Zanos, Leiming Wang, Greg Elmer, Todd D. Gould, Paul D. Shepard
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2018)
Article
Multidisciplinary Sciences
Manjistha Sengupta, Bi-Dar Wang, Norman H. Lee, Alexander Marx, Linda L. Kusner, Henry J. Kaminski
Article
Neurosciences
Ana Pocivavsek, Greg I. Elmer, Robert Schwarcz
Review
Oncology
Bi-Dar Wang, Norman H. Lee
Article
Biochemistry & Molecular Biology
Andrea L. Johnstone, Nadja S. Andrade, Estelle Barbier, Bohdan B. Khomtchouk, Christopher A. Rienas, Kenneth Lowe, Derek J. Van Booven, Esi Domi, Rustam Esanov, Samara Vilca, Jenica D. Tapocik, Keli Rodriguez, Danielle Maryanski, Michael Christopher Keogh, Marcus W. Meinhardt, Wolfgang H. Sommer, Markus Heilig, Zane Zeier, Claes Wahlestedt
Summary: This study identified 11 dysregulated epigenetic enzymes in the brain of alcohol-dependent rats during protracted abstinence, with KDM6B showing region-specific dysregulation in the prefrontal cortex and nucleus accumbens. The upregulation of KDM6B in alcohol-dependent rats was associated with decreased trimethylation levels at histone H3, lysine 27, and enrichment of alcohol-induced changes in H3K27me3 at genes in the IL-6 signaling pathway, implicating a novel KDM6B-mediated epigenetic signaling pathway integrated with inflammatory pathways in the development of alcohol addiction.
Article
Oncology
Jacqueline Olender, Bi-Dar Wang, Travers Ching, Lana X. Garmire, Kaitlin Garofano, Youngmi Ji, Tessa Knox, Patricia Latham, Kenneth Nguyen, Johng Rhim, Norman H. Lee
MOLECULAR CANCER RESEARCH
(2019)
Article
Surgery
Ivy N. Haskins, Bi-Dar Wang, James P. Bernot, Edmund Cauley, Anelia Horvath, John H. Marks, Norman H. Lee, Samir Agarwal
Summary: Differences in gene expression and genetic pathways between Black Americans and non-Hispanic White Americans with colon cancer were identified, particularly in inflammation and immune cell function-related pathways. Further multi-institutional studies are needed to validate these findings and understand their impact on the incidence and mortality rate of colon cancer in these populations.
Article
Biochemistry & Molecular Biology
Ali Calderon-Aparicio, Bi-Dar Wang
Summary: Prostate cancer is the most frequently diagnosed cancer in American men and often leads to treatment resistance, relapse, and decreased survival rates. Aberrant RNA splicing, which increases proteome diversity, has been linked to prostate cancer development and progression. Targeting aberrant splicing mechanisms through pharmacological and molecular approaches offers potential for improved clinical outcomes in prostate cancer patients.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Himali Gujrati, Siyoung Ha, Azah Mohamed, Bi-Dar Wang
Summary: This study suggests that differential miRNA-mRNA regulatory networks contribute to the disparities in prostate cancer (PCa) between African American (AA) and European American (EA) populations. The study identifies differential expression of miRNAs and mRNA pathways, particularly mTOR and VEGF signaling, in AA PCa compared to EA PCa. Further analysis reveals that certain miRNAs negatively regulate genes involved in PCa progression, providing potential targets for reducing PCa aggressiveness and chemoresistance in AA patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Himali Gujrati, Siyoung Ha, Mohammad Waseem, Bi-Dar Wang
Summary: This study validated the expression profiles of miR-99b-5p and mTOR in different types of cancer, revealing that mTOR is upregulated while miR-99b-5p is downregulated. The results suggest that miR-99b-5p inhibits mTOR and AR expression and their nuclear translocation, and targets the AR-mTOR axis to induce apoptosis and increase chemosensitivity. The miR-99b-5p/nuclear mTOR pairing may serve as a more precise diagnostic/prognostic biomarker for aggressive prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Mohammad Waseem, Bi-Dar Wang
Summary: Cancer is a major global health concern and cancer determent is a significant public health challenge. Mitochondrial dysfunction is highlighted as a hallmark of cancer cells and mitochondrial membrane permeabilization is considered a major feature in apoptosis-mediated cancer cell death. The mitochondrial permeability transition pore (mPTP) plays a critical role in regulating apoptosis-mediated cancer cell death and is linked with the enzyme hexokinase II for cellular defense and cytochrome c release reduction. The opening/activation of mPTP is influenced by factors such as mitochondrial calcium overload, oxidative stress, and mitochondrial depolarization. This review focuses on the structure and regulation of mPTP-mediated apoptosis mechanisms and discusses the development of novel mPTP-targeting drugs/molecules in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Siyoung Ha, Bi-Dar Wang
Summary: The study found that African American men have higher incidence and mortality rates of prostate cancer compared to European American men. It was discovered that an aberrant splice variant, PIK3CD-S, is overexpressed in aggressive African American prostate cancer and confers resistance to PI3K delta inhibitors. Targeting the alternative splicing mechanism can significantly enhance the sensitivity to PI3K delta inhibitors and overcome drug resistance in aggressive cancers.
Review
Oncology
Himali Gujrati, Siyoung Ha, Bi-Dar Wang
Summary: This article systematically reviews the roles of microRNAs in the development and progression of prostate cancer. It highlights the current understanding and knowledge gap related to the deregulation of microRNAs in prostate cancer diseases, as well as summarizes the progress on the development of microRNA-based diagnostic/prognostic biomarkers and therapies for prostate cancer.
Article
Endocrinology & Metabolism
Siyoung Ha, Himali Gujrati, Bi-Dar Wang
Summary: Our study has identified PI3Kδ-S as an oncogenic isoform that is resistant to drugs and independent of PTEN regulation, making it a potential prognostic biomarker and drug target in endocrine cancers.
FRONTIERS IN ENDOCRINOLOGY
(2023)