Review
Endocrinology & Metabolism
Yue Wu, Yunjiao Yang, Lan Wang, Yiding Chen, Xuke Han, Lisha Sun, Huizhen Chen, Qiu Chen
Summary: Osteoporosis is a bone disease characterized by low bone quality and density, causing bone fragility and vulnerability to fractures. Increased osteoclast differentiation and activity contribute to bone loss, a common manifestation of osteoporosis. The TNF-a/NF-κB inflammatory pathway plays a key role in regulating osteoclast formation, along with the classical RANKL/RANK/OPG pathway. Probiotics, particularly Bifidobacterium, have shown potential beneficial effects on bone health by modulating this pathway. This review discusses the molecular mechanisms of the TNF-a/NF-κB pathway in osteoclast formation and explores the secretions produced by Bifidobacterium, providing new directions for future research.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Clement Agoni, Ilias Stavropoulos, Anna Kirwan, Margharitha M. Mysior, Therese Holton, Tilen Kranjc, Jeremy C. Simpson, Helen M. Roche, Denis C. Shields
Summary: This study identified and synthesized peptides from milk protein Alpha-S1-casein that were predicted to be cell-penetrating. The peptides showed cell penetrating behavior without affecting cell homeostatic mechanisms. Further investigation is warranted to explore their potential bioactivities.
Article
Biochemistry & Molecular Biology
Patricia Garcia-Fernandez, Colette Reinhold, Nurcan Ueceyler, Claudia Sommer
Summary: Polyneuropathy (PNP) refers to diseases of the peripheral nervous system, with 50% of cases presenting with neuropathic pain. Certain types of PNP show pain restricted to the distal leg skin, indicating a local regulatory process leading to pain. This study suggests that a pro-inflammatory pathway mediated by NF-κB may contribute to pain development in patients with painful PNP. Our findings support the hypothesis of local inflammatory processes involved in pain in PNP, and suggest disrupted anti-inflammatory pathways in inflammatory PNP involving TRPV1 and SIRT1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Milton Roy, Rajesh Singh
Summary: TRIMs, as RING domain-containing E3 ligases, are involved in regulating the NF-kappa B pathway and may lead to unique outcomes in different pathophysiological conditions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Silvia Marino, Nicole Hannemann, Ryan T. Bishop, Feier Zeng, Giovana Carrasco, Sandrine Meurisse, Boya Li, Antonia Sophocleous, Anna Sparatore, Tobias Baeuerle, Slobodan Vukicevic, Marielle Auberval, Patrick Mollat, Aline Bozec, Aymen I. Idris
Summary: TRAF6 inhibitors may be beneficial in managing the inflammatory component of bone disorders, but they may not provide protection against local or systemic bone loss unless combined with anti-resorptive therapy.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Plant Sciences
Yixi Yang, Yujin Zhang, Xun Chen, Zhou Su, Yu Deng, Qi Zhao
Summary: This study explored the bioactivity of Khasianine and showed that it possessed highly anti-inflammatory bioactivity which rapidly alleviated psoriasis-like mice skin inflammation.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Food Science & Technology
Kanittha Chantarasakha, Thiti Asawapanumas, Rinrada Suntivich, Atikorn Panya, Natthaporn Phonsatta, Parameth Thiennimitr, Kobkul Laoteng, Surapun Tepaamorndech
Summary: This study demonstrated the anti-inflammatory potential and mechanism of Hatakabb herbal extract, with pyrogallol identified as a novel mediator inhibiting LPS-induced inflammation.
JOURNAL OF FUNCTIONAL FOODS
(2022)
Article
Cardiac & Cardiovascular Systems
Denuja Karunakaran, My-Anh Nguyen, Michele Geoffrion, Dianne Vreeken, Zachary Lister, Henry S. Cheng, Nicola Otte, Patricia Essebier, Hailey Wyatt, Joshua W. Kandiah, Richard Jung, Francis J. Alenghat, Ana Mompeon, Richard Lee, Calvin Pan, Emma Gordon, Adil Rasheed, Aldons J. Lusis, Peter Liu, Ljubica Perisic Matic, Ulf Hedin, Jason E. Fish, Liang Guo, Frank Kolodgie, Renu Virmani, Janine M. van Gils, Katey J. Rayner
Summary: The study indicates that RIPK1 plays a central role in driving inflammation in atherosclerosis by activating the NF-kappa B pathway and promoting the release of inflammatory cytokines. Knockdown of RIPK1 reduces inflammatory cell activation and protects against the progression of atherosclerosis. These findings suggest RIPK1 as a potential therapeutic target to reduce residual inflammation in patients at high risk of coronary artery disease.
Article
Biochemistry & Molecular Biology
Victor L. Bass, Victor C. Wong, M. Elise Bullock, Suzanne Gaudet, Kathryn Miller-Jensen
Summary: The study found that TNF primarily activates transcription by increasing burst size while maintaining burst frequency for gene promoters with relatively high basal AcH3. When AcH3 is lower or decreased, the contribution of burst frequency to TNF activation increases. TNF positive feedback amplifies gene expression noise resulting from burst size-mediated transcription.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Palanisamy Nallasamy, Zi Yae Kang, Xiaolun Sun, Pon Velayutham Anandh Babu, Dongmin Liu, Zhenquan Jia
Summary: Resveratrol at physiologically achievable concentrations displayed protective effects against TNF-alpha-induced vascular endothelial inflammation both in vitro and In Vivo, potentially through its role as a down-regulator of the NF-kappa B pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Zhenzhen Yan, Jingwei Dai, Jiayue Wang, Qianxi Feng, Yaguang Wang, Tongye Han, Chen Wu
Summary: In this study, the post-translational modification of Tollip by ubiquitination was identified. Tollip interacts with RNF167 and RNF167 functions as the E3 ligase to attach poly-ubiquitin chains to Tollip. The ubiquitination of Tollip plays a crucial role in TNF-alpha signaling.
Article
Biochemistry & Molecular Biology
Zhenzhen Yan, Jingwei Dai, Jiayue Wang, Qianxi Feng, Yaguang Wang, Tongye Han, Chen Wu
Summary: In this study, ubiquitination was identified as a post-translational modification on Tollip, and RNF167 was found to be the potential E3 ligase for Tollip. Tollip's ubiquitination plays a crucial role in TNF-a signaling.
Article
Medicine, Research & Experimental
Huanhuan Xu, Chunxia Gan, Zemin Xiang, Ting Xiang, Jin Li, Xueqin Huang, Xiangdong Qin, Titi Liu, Jun Sheng, Xuanjun Wang
Summary: The tumor necrosis factor alpha (TNF-a)-TNF-a receptor (TNFR) interaction is crucial in the development of autoimmune diseases like rheumatoid arthritis, making it an important target for drug discovery. This study found that (-)-Epigallocatechin-3-gallate (EGCG), a polyphenolic compound found in green tea, can bind to TNF-a, TNFR1, and TNFR2 and disrupt their interactions. This leads to inhibition of TNF-a-induced cell death and NF-kB signaling pathway, suggesting that regular consumption of EGCG in green tea could potentially be used as a therapeutic agent for TNF-a-associated diseases.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Weiwei Yuan, Jinxi Huang, Shanshan Hou, Huahua Li, Liangyu Bie, Beibei Chen, Gaofeng Li, Yang Zhou, Xiaobing Chen
Summary: The study found that pretreatment of gastric cancer cells with triptolide can enhance its anti-tumor effect. This effect is dependent on the disruption of the H19/miR-204-5p/NF-kappa B/FLIP axis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
German A. Arenas, Jose G. Valenzuela, Estefania Penaloza, Adolfo A. Paz, Rodrigo Iturriaga, Claudia G. Saez, Bernardo J. Krause
Summary: This study found that altered shear stress patterns affect the expression of PIEZO1 and mechanosensitive-related genes in endothelial cells, resulting in an inflammatory response. Activation of NF-kappa B via p65 signaling pathway regulates PIEZO1 expression, providing a new molecular link between prooxidant and inflammatory responses and mechanosensitive pathways in the endothelium.
Article
Pharmacology & Pharmacy
Tullio V. F. Esposito, Cristina Rodriguez-Rodriguez, Colin Blackadar, Evan F. Haney, Daniel Pletzer, Robert E. W. Hancock, Katayoun Saatchi, Urs O. Hafeli
Summary: This study investigated the pharmacokinetics of a well-characterized IDR molecule, IDR-1018. The distribution and clearance of the peptide were found to vary depending on the route of administration and dose. The study also revealed that local administration could avoid peptide toxicity associated with systemic administration.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Katharine Sedivy-Haley, Travis Blimkie, Reza Falsafi, Amy Huei-Yi Lee, Robert E. W. Hancock
Summary: Salmonella is an intracellular pathogen that causes significant morbidity and mortality. The ability of Salmonella to grow inside macrophages is important for its virulence. Different types of macrophages have different effects on the growth of Salmonella. Endotoxin-primed macrophages show similar levels of resistance to Salmonella as classically activated macrophages after 2 hours of infection, but become susceptible like alternatively activated macrophages at later time points. The JAK-STAT pathway plays an important role in the resistance of macrophages to Salmonella, and early activation of this pathway is crucial for M1 macrophage resistance.
Article
Microbiology
Melanie Dostert, Corrie R. Belanger, Lucas Pedraz, Morgan A. Alford, Travis M. Blimkie, Reza F. Falsafi, Manjeet Bains, Bhavjinder Kaur Dhillon, Cara H. Haney, Amy H. Lee, Robert E. W. Hancock
Summary: Biofilms are the most common cause of bacterial infections in humans. Finding effective antibiofilm therapies is challenging. A study identified 349 genes, including 47 regulators, involved in biofilm growth in Pseudomonas aeruginosa PA14 using a transposon insertion sequencing approach. The study also discovered several novel biofilm regulators, suggesting the involvement of multiple transcriptional regulators in biofilm growth. These findings contribute to the identification of potential new drug targets for biofilm infections.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Ecology
Christina L. Wiesmann, Yue Zhang, Morgan Alford, Corri D. Hamilton, Manisha Dosanjh, David Thoms, Melanie Dostert, Andrew Wilson, Daniel Pletzer, Robert E. W. Hancock, Cara H. Haney
Summary: Members of the bacterial genus Pseudomonas can form mutualistic, commensal, and pathogenic associations with diverse hosts. The study found that the regulatory gene ColR/S is functionally conserved between Pseudomonas aeruginosa and Pseudomonas fluorescens, but there are differences in the regulon. ColR/S allows Pseudomonas to sense and respond to a host, and the divergence of the ColR regulon may be related to different lifestyles.
Article
Multidisciplinary Sciences
Arjun Baghela, Andy An, Peter Zhang, Erica Acton, Jeff Gauthier, Elsa Brunet-Ratnasingham, Travis Blimkie, Gabriela Cohen Freue, Daniel Kaufmann, Amy H. Y. Lee, Roger C. Levesque, Robert E. W. Hancock
Summary: Severely-afflicted COVID-19 patients can exhibit sepsis-like disease manifestations, and the diagnostic tools used in managing sepsis may also be applicable to COVID-19 patients. This study analyzed the blood transcriptome of COVID-19 patients and identified gene expression signatures that are associated with severity and potential therapeutic opportunities. The expression of sepsis gene expression signatures in severely-afflicted COVID-19 patients indicates the importance of considering severe sepsis classification and using these signatures for mechanistic characterization, diagnosis, and guidance of treatment using repurposed drugs.
SCIENTIFIC REPORTS
(2023)
Article
Rheumatology
Kristen I. Gibson, Britt Drogemoller, Dirk M. Foell, Susanne Benseler, Jinko Graham, Robert E. W. A. Hancock, Raashid A. Luqmani, David L. Cabral, Kelly J. Brown, Colin Ross
Summary: This study conducted a genome-wide association study of pediatric ANCA-associated vasculitis (AAV) and found a significant genetic association between HLA-DPB1*04:01 allele and pediatric AAV. The study also suggested that childhood- and adult-onset vasculitis may share a common genetic predisposition. These findings contribute to improved classification tools and treatment strategies for AAV.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Shahid Chaudhary, Zahir Ali, Muhammad Tehseen, Evan F. Haney, Aaron Pantoja-Angles, Salwa Alshehri, Tiannyu Wang, Gerard J. Clancy, Maya Ayach, Charlotte Hauser, Pei-Ying Hong, Samir M. Hamdan, Robert E. W. Hancock, Magdy Mahfouz
Summary: This study demonstrates the efficient production of bioactive amidated AMPs through transient expression in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine alpha-amidating mono-oxygenase. The AMPs purified from plants exhibit robust killing activity against highly virulent and antibiotic-resistant pathogens, and can prevent their biofilm formation when used in combination with antibiotics. The techno-economic analysis also shows the potential economic advantages and scalability for industrial use of this platform.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Arjun S. Baghela, Jasmine Tam, Travis M. Blimkie, Bhavjinder K. Dhillon, Robert E. W. Hancock
Summary: In this study, a compendium of 103 gene sets related to sepsis was built by collecting data from transcriptomic studies. The gene sets comprise 20,899 unique genes, and the study describes the commonly involved molecular mechanisms. A database called SeptiSearch was created to provide bioinformatic tools for the sepsis community to explore and validate these gene sets.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Andy Y. An, Arjun Baghela, Peter Zhang, Reza Falsafi, Amy H. Lee, Uriel Trahtemberg, Andrew J. Baker, Claudia C. dos Santos, Robert E. W. Hancock
Summary: This study compared the gene expression trajectories between severe COVID-19 patients and contemporaneous non-COVID-19 severe sepsis patients during hospitalization. COVID-19 patients had 1,215 differentially expressed genes compared to non-COVID-19 sepsis patients at ICU admission, but the number dropped to 9 genes after one week. The findings highlight the importance of early antiviral treatment for COVID-19 and the potential for heme-related therapeutics.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Hashem Etayash, Fione Yip, Robert E. W. Hancock
Summary: In this study, the impacts of pegylation and glycosylation on the biocompatibility and biological properties of host defense peptides (HDPs) were investigated. It was found that both modifications significantly reduced aggregation, hemolysis, and cytotoxicity, and enhanced immunomodulatory and anti-inflammatory effects of the peptides. However, antimicrobial and antibiofilm activity was partially reduced.
Review
Pharmacology & Pharmacy
Cesar de la Fuente-Nunez, Angela Cesaro, Robert E. W. Hancock
Summary: Despite advances in antibiotic discovery, millions of people still die from infections every year. Antibiotic failure is not solely due to antibiotic resistance, but also related to biofilm formation, sepsis, and the microbiome. To address the crisis of antibiotic failure, it is necessary to explore treatment strategies beyond antibiotics and develop new anti-infectives or host-directed therapies.
DRUG RESISTANCE UPDATES
(2023)
Article
Dentistry, Oral Surgery & Medicine
Jinghao Hu, Jian Yu, He Liu, Zhejun Wang, Markus Haapasalo, Evan F. Haney, Robert E. W. Hancock, Shuli Deng, Ya Shen
Summary: This study evaluated the antimicrobial effects of commercially available mouthrinses and a D-enantiomeric peptide on oral multispecies biofilms. The results showed that DJK-5 demonstrated the highest percentage of dead bacteria and may be a potential candidate for future mouthrinses.
JOURNAL OF DENTISTRY
(2023)
Article
Immunology
Andy Y. An, Arjun Baghela, Peter Zhang, Reza Falsafi, Amy H. Lee, Uriel Trahtemberg, Andrew J. Baker, Claudia C. dos Santos, Robert E. W. Hancock
Summary: Transcriptional evidence showed persistent immune dysfunction in both severe COVID-19 and non-COVID-19 septic patients, associated with increased mortality. This highlights the potential for immunomodulatory therapies targeting common mechanisms of immune dysfunction in both diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dentistry, Oral Surgery & Medicine
Dan Wang, Jian Yu, He Liu, Tian Zhang, Evan F. Haney, Robert E. W. Hancock, Lin Peng, Ya Shen
Summary: This study aimed to investigate the effectiveness of DJK-5-D enantiomeric antibiofilm peptide on the corrosion resistance of titanium with different surface roughness. The results showed that DJK-5 effectively enhanced the corrosion resistance of titanium while killing S. mutans biofilms, with smooth surfaces more susceptible to peptide treatment.
JOURNAL OF DENTISTRY
(2023)
Article
Engineering, Environmental
Alberto Baldelli, Hashem Etayash, Hale Oguzlu, Ronit Mandal, Feng Jiang, Robert E. W. Hancock, Anubhav Pratap-Singh
Summary: Spray-dried nanoparticle-in-microsphere formulations composed of aluminum oxide nanoparticles, zinc oxide, zinc oxide nanoparticles, and cellulose nanocrystals are reported to have potent antimicrobial and antibiofilm activity against various bacteria. The study emphasizes the importance of matrix compositions in manipulating the antimicrobial properties and toxicity of metal oxide biomaterials. The formulations showed higher antimicrobial activity compared to individual raw materials, and a specific formulation with CNCs, aluminum oxide, and zinc oxide nanoparticles exhibited the highest antimicrobial and antibiofilm activity. Importantly, these formulations also had minimal toxicity when tested against blood cells. Thus, low-toxicity and high antimicrobial nanoparticle-in-microsphere formulations could be used for targeted drug delivery and reducing the use of antibiotics.
CHEMICAL ENGINEERING JOURNAL ADVANCES
(2022)