Article
Microbiology
Mariusz Madej, Zuzanna Nowakowska, Miroslaw Ksiazek, Anna M. Lasica, Danuta Mizgalska, Magdalena Nowak, Anna Jacula, Monika Bzowska, Carsten Scavenius, Jan J. Enghild, Joseph Aduse-Opoku, Michael A. Curtis, F. Xavier Gomis-Ruth, Jan Potempa
Summary: The T9SS component PorZ interacts with sortase and specifically binds A-LPS, mediated by a phosphorylated branched mannan repeat in A-LPS polysaccharide. ALPS-bound PorZ interacts with sortase with significantly higher affinity, facilitating modification of cargo proteins by the cell surface attachment complex of the T9SS.
Article
Neurosciences
Wanyi Huang, Fan Zeng, Yebo Gu, Muzhou Jiang, Xinwen Zhang, Xu Yan, Tomoko Kadowaki, Shinsuke Mizutani, Haruhiko Kashiwazaki, Junjun Ni, Zhou Wu
Summary: The study investigated the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. Results showed that systemic P. gingivalis infection led to reduced synaptophysin expression and increased IL-1 beta production in leptomeninges, indicating that P. gingivalis-induced synaptic damage may contribute to the onset and cognitive decline of Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Microbiology
Anna Gasiorek, Ewelina Dobosz, Barbara Potempa, Izabela Ciaston, Mateusz Wilamowski, Zuzanna Oruba, Richard J. Lamont, Jolanta Jura, Jan Potempa, Joanna Koziel
Summary: Periodontal disease is an inflammatory disease of the supporting tissues of the teeth caused by dysbiotic biofilm on the tooth surface. The negative regulator MCPIP-1 plays a key role in controlling inflammatory responses, but its stability can be influenced by periodontal pathogens like Porphyromonas gingivalis. The proteolytic activity of gingipains from these pathogens can lead to rapid degradation of MCPIP-1, exacerbating the inflammatory response. This provides insights into potential new treatment strategies for periodontitis.
Article
Medicine, Research & Experimental
Jing Li, Jing Deng, Shuxian Shang, Guirong Liu, Wenbin Song, Pei Sun, Wenjing Jiang, Keqing Pan
Summary: Periodontitis is an independent risk factor for coronary heart disease, and Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) is considered a major virulence factor. Co-culturing with HPDLCs enhances the calcification effect of Pg-LPS on HUASMCs and significantly increases the expression of specific osteogenic genes.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Dentistry, Oral Surgery & Medicine
Shuwei Qiao, Baosheng Li, Qing Cai, Zhen Li, Zhaoyi Yin, Jie He, Yuyang Li, Weiyan Meng
Summary: Ferroptosis is involved in the inflammatory processes in HGFs upon P. gingivalis-LPS stimulation. This study found that P. gingivalis-LPS induces ferroptosis in HGFs and that ferroptosis is positively correlated with inflammation levels. Ferroptosis was also observed in the gingival tissue of periodontitis rats.
Article
Immunology
Ranya Elsayed, Mahmoud Elashiry, Yutao Liu, Ahmed El-Awady, Mark Hamrick, Christopher W. Cutler
Summary: The study suggests that P. gingivalis induces early cell senescence in dendritic cells (DCs) by direct cellular invasion and greatly amplifies senescence in bystander DCs by secreting inflammatory exosomes.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Pablo Veloso, Alejandra Fernandez, Jessica Astorga, David Gonzalez-Quintanilla, Alfredo Castro, Alejandro Escobar, Anilei Hoare, Marcela Hernandez
Summary: The study found that Pg LPS can induce a macrophage M1 phenotype (pro-inflammatory) while Pe LPS does not elicit a significant response. Additionally, the expressions of TLR2 and TLR4 were not modified by Pg or Pe LPS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Ranya Elsayed, Mahmoud Elashiry, Yutao Liu, Ana C. Morandini, Ahmed El-Awady, Mohamed M. Elashiry, Mark Hamrick, Christopher W. Cutler
Summary: As the aging population grows, chronic age-related bone degenerative diseases become more prevalent and severe. One such disease, periodontitis (PD), rises to 70.1% prevalence in Americans 65 years and older. Recent in vitro studies indicate that murine dendritic cells (DCs) and T cells are vulnerable to immune senescence caused by invasion of dysbiotic pathogen Porphyromonas gingivalis (Pg) and activation of the senescence associated secretory phenotype (SASP). Pg-induced DC exosomes transmit senescence to normal bystander DC and T cells, ablating antigen presentation. This study examines the biological significance of these findings in vivo, showing that immune senescence, compounded by advanced age and accelerated by oral dysbiosis and its induced SASP exosomes, play a pivotal role in the pathophysiology of experimental periodontitis.
Review
Environmental Sciences
Devaraj Ezhilarasan
Summary: Periodontitis is a prevalent infectious disease linked to various forms of liver disease. Maintaining oral hygiene through scaling and root planning can significantly improve liver damage in patients with periodontitis.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2021)
Review
Microbiology
Mohamed M. Meghil, Mira Ghaly, Christopher W. Cutler
Summary: P. gingivalis is a pathogen implicated in severe periodontitis and plays a crucial role in invading dendritic cells and immune regulation.
Article
Pharmacology & Pharmacy
Cheng-Hsiang Kuo, Ban-Hua Zhang, Shang-En Huang, Jong-Hau Hsu, Yan-Hsiung Wang, Thi Tuyet Ngan Nguyen, Chao-Han Lai, Jwu-Lai Yeh
Summary: This study demonstrates the therapeutic potential of KMUP-1 in the treatment of periodontitis. KMUP-1 attenuates inflammation and osteoclast differentiation, thus reducing the symptoms of periodontitis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Jian-Yu Gu, Zi-Bo Fu, Jia-Lu Chen, Yu-Jie Liu, Xian-Zi Cao, Ying Sun
Summary: Endotoxin tolerance induced by P. gingivalis LPS resulted in a reduced inflammatory response and enhanced wound healing abilities in macrophages. The tolerant macrophages showed an intermediate state between M1/M2 polarization, functioning as M2-like cells. The PTP1B-MEK1/2-STAT6 signaling pathway may play a role in the polarization of tolerant macrophages.
MICROBIAL PATHOGENESIS
(2022)
Article
Biochemistry & Molecular Biology
Erika Inoue, Shiyo Minatozaki, Yui Katsuta, Saori Nonaka, Hiroshi Nakanishi
Summary: Recently, the potential therapeutic effects of antibacterial peptides in Alzheimer's disease have been suggested. This study investigated whether human beta-defensins (hBDs) can suppress Pg LPS-induced oxidative and inflammatory responses in microglia. The results showed that hBD3 significantly inhibited the production of nitric oxide and interleukin-6 (IL-6) in mouse and human microglial cells. Furthermore, hBD3 suppressed the translocation of p65 nuclear and inhibited the enzymatic activities of cathepsins B and L, which are necessary for NF-kappa B activation. This study suggests that hBD3 can suppress oxidative and inflammatory responses in microglia by inhibiting cathepsins B and L.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Xueshen Qian, Shuang Zhang, Lian Duan, Fengchun Yang, Kun Zhang, Fuhua Yan, Song Ge
Summary: The study found that periodontitis exacerbated learning and memory impairment in A beta PP/PS1 mice, leading to an increase in A beta and neuroinflammatory responses.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Cell Biology
Yu-Yang Li, Qing Cai, Bao-Sheng Li, Shu-Wei Qiao, Jia-Yang Jiang, Dan Wang, Xue-Chun Du, Wei-Yan Meng
Summary: The study found that P. gingivalis-LPS can induce pyroptosis in human gingival fibroblasts, exacerbating the inflammatory response of periodontitis, and similar results were observed in animal models.
Article
Cell Biology
Zhen Xie, Jie Meng, Wei Kong, Zhou Wu, Fei Lan, Narengaowa, Yoshinori Hayashi, Qinghu Yang, Zhantao Bai, Hiroshi Nakanishi, Hong Qing, Junjun Ni
Summary: The regulation of neuroinflammation and beta-amyloid production is important in the development of Alzheimer's disease. In this study, it was found that the elimination of CatE significantly reduced A beta accumulation, neuroinflammation, and cognitive impairments. The findings suggest that CatE may be a therapeutic target for Alzheimer's disease.
Article
Immunology
Yuki Kimura, Yoshinori Hayashi, Suzuro Hitomi, Daisuke Ikutame, Kentaro Urata, Ikuko Shibuta, Atsushi Sakai, Junjun Ni, Koichi Iwata, Morio Tonogi, Masamichi Shinoda
Summary: The study found that IL-33 plays a crucial role in mechanical allodynia in orofacial neuropathic pain patients, and neutralization of IL-33 can alleviate symptoms. IL-33 induces GluN2B phosphorylation through the Fyn kinase pathway to regulate synaptic transmission.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Immunology
Muzhou Jiang, Xinwen Zhang, Xu Yan, Shinsuke Mizutani, Haruhiko Kashiwazaki, Junjun Ni, Zhou Wu
Summary: Chronic systemic exposure to PgLPS derived from Pg induces neuroinflammation and tau hyperphosphorylation in an AD mouse model, leading to learning and memory deficits. This process is mediated by the activation of GSK3 beta and the increase of pro-inflammatory cytokines, suggesting a potential link between periodontitis and the progression of AD pathology.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Pinduo Liu, Anping Wu, Hui Li, Jun Zhang, Junjun Ni, Zhenzhen Quan, Hong Qing
Summary: This study revealed the degradation pathways of Rab21 protein through the ubiquitin-proteasome pathway and the autophagy-lysosome pathway, and demonstrated increased ubiquitination of Rab21 protein in the AD model. Moreover, the study suggested the involvement of the autophagy-lysosome pathway in maintaining the protein level of Rab21.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Yicong Liu, Hui Li, Jiangqi Hu, Zhou Wu, Jie Meng, Yoshinori Hayashi, Hiroshi Nakanishi, Hong Qing, Junjun Ni
Summary: The study found that PAR2 expression was abundant in neurons but barely in microglia after hypoxia-ischemia injury. Conversely, PAR2 expression was barely in neurons but significantly increased in activated microglia. PAR2 activation mediated cross-talk between microglia and neurons, leading to inflammatory responses, neuronal damage, chemokine regulation, and phagocytosis control. Interventions targeting PAR2 may provide insights into inflammatory-related diseases.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Heao Zhang, Lin Xiang, Liang Yang, Si Wu, Sisi Liu, Juan Zhao, Da Song, Congxuan Ma, Junjun Ni, Zhenzhen Quan, Jianhua Liang, Hong Qing
Summary: WS6 treatment shows promising neuroprotective and antidepressant-like effects against CUMS-induced depression, possibly through promoting neurogenesis in the hippocampus.
Review
Behavioral Sciences
Yan Yan, Ailikemu Aierken, Chunjian Wang, Da Song, Junjun Ni, Zhe Wang, Zhenzhen Quan, Hong Qing
Summary: Olfactory dysfunction may serve as a potential biomarker of preclinical AD, but the precise regulatory mechanism of its impact on AD neuropathogenesis remains unclear. Impairment of neural networks in the olfaction system is closely associated with AD, particularly in the olfactory bulb and piriform cortex. This review explores the mechanism of olfactory dysfunction in preclinical AD by studying aberrant oscillations and synaptic plasticity damages, providing insight into the underlying mechanism of olfactory neural network damages related to AD.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Review
Clinical Neurology
Yan Yan, Ailikemu Aierken, Chunjian Wang, Wei Jin, Zhenzhen Quan, Zhe Wang, Hong Qing, Junjun Ni, Juan Zhao
Summary: This review discusses the use of optogenetics and in vivo imaging techniques to study the neural circuits underlying the extinction and discrimination of fear memory. It also highlights the challenge of translating these findings into effective therapeutic treatments for PTSD.
Review
Clinical Neurology
Junjun Ni, Fei Lan, Yan Xu, Hiroshi Nakanishi, Xue Li
Summary: This review summarizes the physiological and pathological functions of CatB in the central nervous system and discusses its potential therapeutic applications.
Review
Clinical Neurology
Zhen Xie, Jie Meng, Zhou Wu, Hiroshi Nakanishi, Yoshinori Hayashi, Wei Kong, Fei Lan, Narengaowa, Qinghu Yang, Hong Qing, Junjun Ni
Summary: Microglia play a critical role in Alzheimer's disease, but whether they have a positive or negative effect remains controversial. Their interaction with neurons is key, as they can prune synapses causing excessive loss, but they can also promote synapse formation and enhance neural network plasticity. Additionally, microglia have dual opposing roles in the development of major pathological features in the disease.
Review
Pharmacology & Pharmacy
Gregory Hook, Thomas Reinheckel, Junjun Ni, Zhou Wu, Mark Kindy, Christoph Peters, Vivian Hook
Summary: This review evaluates the effects of deleting the CTSB gene on brain dysfunctions in neurological diseases and aging animal models. The findings suggest that CTSB gene knockout improves behavioral deficits, neuropathology, and biomarkers, supporting CTSB as a rational drug target for treating neurologic disorders.
PHARMACOLOGICAL REVIEWS
(2022)
Review
Pharmacology & Pharmacy
Yanfeng Wang, Juan Zhao, Yebo Gu, Haiping Wang, Muzhou Jiang, Shuxuan Zhao, Hong Qing, Junjun Ni
Summary: CatH is a lysosomal cysteine protease with a unique aminopeptidase activity that is extensively expressed in various organs. Its specific enzymatic activity has critical effects on cancer cells and brain diseases. This review summarizes the expression, maturation, and enzymatic properties of CatH, and discusses the potential of CatH inhibitors in disease therapy.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Shuxuan Zhao, Muzhou Jiang, Hong Qing, Junjun Ni
Summary: Coronavirus disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The COVID-19 pandemic, which started in March 2020, has had devastating effects on global health and economies. Currently, there is a lack of effective treatment for COVID-19, with only preventive measures and supportive care available. Studies have suggested that lysosomal cathepsins may play a role in the pathogenesis and outcome of COVID-19.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Neurosciences
Junjun Ni, Zhen Xie, Zhenzhen Quan, Jie Meng, Hong Qing
Summary: This review summarizes the current knowledge of the molecular mechanisms involved in microglial phagocytosis in Alzheimer's disease (AD) through a wide range of pre-clinical, post-mortem, ex vivo, and clinical studies. It also discusses the limitations regarding the detection of microglial phagocytosis in AD and the rationale of targeting microglial phagocytosis as a therapeutic strategy for preventing or slowing down the progression of AD.
Review
Neurosciences
Xinjian Li, Junjun Ni, Hong Qing, Zhenzhen Quan
Summary: Rab proteins are crucial for intracellular transportation and cargo delivery. Dysfunction of Rab proteins and their effectors is closely related to various human diseases. This review focuses on Rab21, discussing its structures, functions, and regulatory mechanisms in neurodegenerative diseases, cancer, and inflammation.
MOLECULAR NEUROBIOLOGY
(2023)