Article
Neurosciences
Ivan J. M. Bonet, Eugen Khomula, Dioneia Araldi, Paul G. Green, Jon D. Levine
Summary: High molecular weight hyaluronan (HMWH) exerts anti-hyperalgesic effects in preclinical models of inflammatory and neuropathic pain through its action on the CD44 receptor and downstream signaling molecule PI3K gamma. Intervention targeting PI3K gamma attenuates HMWH-induced anti-hyperalgesia, indicating a potential novel molecular target for diverse pain syndromes.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Nerry T. Cecilio, Guilherme R. Souza, Jose C. Alves-Filho, Fernando Q. Cunha, Thiago M. Cunha
Summary: The study investigated the mechanism of peripheral analgesic effect of DIP, revealing that DIP's action depends on the activation of the PI3Kγ/AKT signaling pathway, which promotes the production of nitric oxide in sensory neurons.
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2021)
Article
Integrative & Complementary Medicine
Barbara B. Garrido-Suarez, Gabino Garrido, Addis Bellma Menendez, Nelson Merino, Odalys Valdes, Nilia de la Paz, Aylema Romero, Livan Delgado, Miguel D. Fernandez, Octavio Pineros, Rene Delgado-Hernandez
Summary: The present study evaluated the antinociceptive activity of Calendula officinalis L. cream on inflammatory hypernociception. The results showed that 10% or 30% concentration of Calendula cream could reduce licking/biting behavior and edema in rats, and it worked through antioxidant stress and peripheral opioid mechanisms. These findings may have an impact on the clinical management of painful inflammatory diseases.
JOURNAL OF INTEGRATIVE MEDICINE-JIM
(2023)
Article
Physiology
Sergey V. Popov, Alexander V. Mukhomedzyanov, Sergey Y. Tsibulnikov, Igor Khaliulin, Peter R. Oeltgen, N. Rajendra Prasad, Leonid N. Maslov
Summary: This study demonstrated that the activation of opioid kappa(2) receptor does not affect cardiac tolerance to reperfusion, while peripheral opioid kappa(1) receptor stimulation can prevent reperfusion cardiac injury. Additionally, administration of ICI 199,441 at reperfusion showed a reduction in infarct size.
PHYSIOLOGICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Anushree N. Karkhanis, Alyssa M. West, Sara R. Jones
Summary: The nucleus accumbens (NAc) core plays a role in regulating stress and shaping reward seeking behaviours. The activation of kappa opioid receptor (KOR) inhibits dopamine release and transmission, and this impact is regionally specific in the NAc shell. The inhibition of dopamine release by KOR is greater in the caudal compared to the rostral subregion of NAc core, suggesting a differential regulation along the rostro-caudal axis.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Jayane Lais Dias Quintao, Amanda Cristina Reis Gonzaga, Giovane Galdino, Thiago Roberto Lima Romero, JosianeFernandes Silva, VirginiaSoares Lemos, Gabriel Henrique Campolina-Silva, Cleida Aparecida de Oliveira, GermanAnarturo Bohorquez Mahecha, IgorDimitri Gama Duarte
Summary: Tissue injury leads to the release of inflammatory mediators and nociceptive substances, contributing to hyperalgesia. The study investigated the involvement of inflammatory mediators in the modulation of inflammatory pain by the opioid system, finding that TNF-alpha, CXCL-1, and IL-beta cause hyperalgesia and the release of endogenous opioid peptides for pain control.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qiaohong Xu, Fang Cui, Xiaodong Li, Nan Wang, Yingrui Gao, Shiping Yin, Fangdi Hu
Summary: Dangshen, a medicinal and edible plant, has been found to have protective effects on gastric mucosa. It can improve chronic non-atrophic gastritis by enhancing antioxidant capacity, suppressing inflammatory responses, and reducing cell apoptosis. This study reveals the potential value of Dangshen in the treatment of gastric diseases.
Letter
Chemistry, Medicinal
Azzurra Stefanucci, Alice Della Valle, Giuseppe Scioli, Lorenza Marinaccio, Stefano Pieretti, Paola Minosi, Edina Szucs, Sandor Benyhe, Domiziana Masci, Parthasaradhireddy Tanguturi, Kerry Chou, Deborah Barlow, Karen Houseknecht, John M. Streicher, Adriano Mollica
Summary: Peripherally active tetrapeptides with selective KOR agonistic properties were synthesized via solid-phase peptide synthesis and structural modifications, showing high efficacy in antinociceptive activity.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Dermatology
Brian S. Kim, Saadet Inan, Sonja Staender, Thomas Sciascia, Jacek C. Szepietowski, Gil Yosipovitch
Summary: Modern genetic approaches have identified new neural pathways specific to itch, providing potential for drug development. Opioid receptors play a role in modulating itch, but the precise mechanisms are still being investigated. Nevertheless, several drugs have shown efficacy in clinical trials by targeting opioid receptor signaling.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Chemistry, Medicinal
Yuyan Bai, Jin Zhou, Han Zhu, Yanlin Tao, Lupeng Wang, Liu Yang, Hui Wu, Fei Huang, Hailian Shi, Xiaojun Wu
Summary: This study found that Isoliquiritigenin (ISL) can inhibit microglia-mediated neuroinflammation in Parkinson's disease (PD) by deactivating JNK/AKT/NFκB signaling pathways. These findings suggest the therapeutic potential of ISL for microglia-mediated neuroinflammation in PD.
PHYTOTHERAPY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Aina Porta, Laura Rodriguez, Xue Bai, Gerard Batalle, Gerad Roch, Enric Pouso-Vazquez, Gianfranco Balboni, Olga Pol
Summary: This study demonstrates that slow-releasing H2S donors can inhibit allodynia and hyperalgesia, potentiate the analgesic effects and expression of DOR, activate the antioxidant system, and reduce nociceptive and apoptotic pathways in inflammatory pain models. The data also suggest the involvement of potassium channels and the Nrf2 transcription factor signaling pathway in the pain-relieving activities of DADS and P-ITC. Systemic administration of DADS and P-ITC, along with local application of DOR agonists in combination with H2S donors, offer new strategies for the treatment of inflammatory pain.
Article
Immunology
Xavier Mas-Orea, Lilian Basso, Catherine Blanpied, Claire Gaveriaux-Ruff, Nicolas Cenac, Gilles Dietrich
Summary: This study identifies the important role of the delta opioid receptor (DOR) in relieving intestinal inflammatory pain and suggests the potential of developing peripherally restricted DOR analgesics for intestinal disorders, which could avoid the side effects associated with drugs targeting the mu opioid receptor (MOR).
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Anesthesiology
Larissa Staurengo-Ferrari, Paul G. Green, Dioneia Araldi, Luiz F. Ferrari, Christine Miaskowski, Jon D. Levine
Summary: This study found that stress has a significant impact on oxaliplatin-induced neuropathic pain, with clear gender differences in the role of the two major neuroendocrine stress axes. The findings demonstrate the importance of the neuroendocrine stress axes in CIPN and highlight the sexually dimorphic nature of the condition.
Article
Immunology
Hisatake Matsumoto, Brendon P. Scicluna, Kin Ki Jim, Fahimeh Falahi, Wanhai Qin, Berke Gurkan, Erik Malmstrom, Mariska T. Meijer, Joe M. Butler, Hina N. Khan, Tsuyoshi Takagi, Shunsuke Ishii, Marcus J. Schultz, Diederik van de Beek, Alex F. de Vos, Cornelis van 't Veer, Tom van der Poll
Summary: The study indicates that HIVEP1 acts as a negative regulator of NF-κB in monocytes, inhibiting the proinflammatory response induced by bacterial agonists. Dysregulation of HIVEP1 leads to significant changes in the monocyte transcriptome and modulation of NF-κB responsive genes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Anesthesiology
William M. McDonald, Michael M. Wilkinson, Ankush Jain, Steven P. Cohen
Summary: Chronic opioid therapy can lead to tolerance, hyperalgesia, and central sensitization, which complicates the management of chronic pain patients. In this case, a patient who was receiving high doses of opioids through an intrathecal pain pump had to be treated with a four-day ketamine infusion after an accidental pump cut during surgery. The ketamine infusion resulted in significant pain improvement and no withdrawal symptoms.
Editorial Material
Biochemistry & Molecular Biology
Sergio Marques Borghi, Rubia Casagrande, Waldiceu Aparecido Verri
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Vanessa de Fatima Borges, Leticia Selinger Galant, Alexandre Kanashiro, Fernanda Vargas e Silva Castanheira, Valter Vinicius Silva Monteiro, Diego angelo Duarte, Filipe Camargo Rodrigues, Camila Meirelles de Souza Silva, Ayda Henriques Schneider, Guilherme Cesar Martelossi Cebinelli, Mikhael Haruo Fernandes de Lima, Joao Paulo de Biaso Viola, Thiago Mattar Cunha, Claudio Miguel da Costa Neto, Jose Carlos Farias Alves-Filho, Andre Sampaio Pupo, Fernando de Queiroz Cunha
Summary: This study investigated the effects of FK506 on sepsis immunopathology and found that FK506 treatment resulted in failed neutrophil migration, leading to increased bacteremia and systemic inflammatory response, causing higher organ damage and mortality rates.
INFLAMMATION RESEARCH
(2023)
Article
Cell Biology
Marcelo Franchin, Thaise Mayumi Taira, Douglas da Silva Prado, Cesar Augusto Speck Hernandez, Fabio Bonifacio de Andrade, Henrique Ballassini Abdalla, Marcelo Henrique Napimoga, Thiago Mattar Cunha, Sandra Yasuyo Fukada, Pedro Luiz Rosalen
Summary: In this study, we investigated the modulatory effects of PI3K gamma on IL-17A expression and the progression of experimental periodontitis in vivo. Our results showed that PI3K gamma inhibitor can attenuate alveolar bone loss and downregulate IL-17A and Rankl gene expression.
INFLAMMATION RESEARCH
(2023)
Article
Infectious Diseases
Felipe Cerni, Isadora Oliveira, Francielle Cordeiro, Karla Bordon, Isabela Ferreira, Wuelton Monteiro, Eliane Arantes, Thiago Cunha, Manuela Pucca
Summary: This study evaluated the pain behavior induced by T. serrulatus venom and its isolated neurotoxins in mice, and found that different neurotoxins caused varying degrees of pain behavior. Additionally, the researchers developed a mice-derived polyclonal antibody targeting Ts5, which was able to neutralize the effect of this neurotoxin and significantly reduce the nociception produced by the whole venom. This study is the first to explore the effects of different classes of T. serrulatus neurotoxins on nociception, and demonstrates the important role of Ts5 in scorpion sting-induced pain.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Pharmacology & Pharmacy
Sergio M. Borghi, Tiago H. Zaninelli, Telma Saraiva-Santos, Mariana M. Bertozzi, Renato D. R. Cardoso, Thacyana T. Carvalho, Camila R. Ferraz, Doumit Camilios-Neto, Fernando Q. Cunha, Thiago M. Cunha, Felipe A. Pinho-Ribeiro, Rubia Casagrande, Waldiceu A. Verri
Summary: In this study, the researchers investigated the effect of pentoxifylline (Ptx) on delayed-onset muscle soreness (DOMS) in untrained mice exposed to intense acute swimming exercise. They found that Ptx treatment reduced mechanical hyperalgesia caused by intense acute swimming in a dose-dependent manner. Ptx also inhibited neutrophil recruitment, oxidative stress, and cytokine production in the muscle tissue and spinal cord, as well as reduced glial cell activation in the spinal cord. These findings suggest that Ptx can alleviate pain in DOMS by targeting peripheral and spinal cord mechanisms.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Sergio M. Borghi, Tiago H. Zaninelli, Jessica B. Carra, Olivia K. Heintz, Marcela M. Baracat, Sandra R. Georgetti, Fabiana T. M. C. Vicentini, Waldiceu A. Verri, Rubia Casagrande
Summary: Asthma is a chronic disease characterized by allergic inflammatory reactions. Current treatment options have limitations and can have adverse effects, leading to poor management of the disease. Flavonoids, with their antioxidant and anti-inflammatory properties, have shown potential benefits for asthma treatment.
Article
Physiology
Monica Z. Luque, Andreo F. Aguiar, Amanda K. da Silva-Araujo, Tiago H. Zaninelli, Olivia K. Heintz, Telma Saraiva-Santos, Mariana M. Bertozzi, Natalia A. Souza, Eros O. Junior, Waldiceu A. A. Verri, Sergio M. Borghi
Summary: This study evaluated the effects of hesperidin methyl chalcone on delayed-onset muscle soreness (DOMS). The results showed that taking hesperidin methyl chalcone can improve performance during exercise, reduce muscle soreness, and enhance muscle strength recovery and postural balance without causing adverse effects.
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Article
Cell Biology
N. B. Amaral, T. S. Rodrigues, M. C. Giannini, M. I. Lopes, L. P. Bonjorno, P. I. S. O. Menezes, S. M. Dib, S. L. G. Gigante, M. N. Benatti, U. C. Rezek, L. L. Emrich-Filho, B. A. Sousa, S. C. L. Almeida, R. Luppino-Assad, F. P. Veras, A. H. Schneider, L. O. S. Leiria, L. D. Cunha, J. C. Alves-Filho, T. M. Cunha, E. Arruda, C. H. Miranda, A. Pazin-Filho, M. Auxiliadora-Martins, M. C. Borges, B. A. L. Fonseca, V. R. Bollela, C. M. Del-Ben, F. Q. Cunha, R. C. Santana, F. C. Vilar, D. S. Zamboni, P. Louzada-Junior, R. D. R. Oliveira
Summary: This study evaluated whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. The results showed that colchicine reduced the need for supplemental oxygen and the length of hospitalization, and lowered the serum levels of Casp1p20 and IL-18 in the first two days of treatment.
INFLAMMATION RESEARCH
(2023)
Article
Immunology
Tamara S. Rodrigues, Camila C. S. Caetano, Keyla S. G. de Sa, Leticia Almeida, Amanda Becerra, Augusto Goncalves, Leticia de Sousa Lopes, Samuel Oliveira, Danielle P. A. Mascarenhas, Sabrina S. Batah, Bruna M. Silva, Giovanni F. Gomes, Ricardo Castro, Ronaldo B. Martins, Jonathan Avila, Fabiani G. Frantz, Thiago M. Cunha, Eurico Arruda, Fernando Q. Cunha, Helder Nakaya, Larissa D. Cunha, Alexandre T. Fabro, Paulo Louzada-Junior, Rene D. R. de Oliveira, Dario S. Zamboni
Summary: SARS-CoV-2 infection activates the NLRP3 inflammasome and leads to inflammation and severe COVID-19. Human caspase-4 (mouse caspase-11) is upregulated and activated by SARS-CoV-2, contributing to NLRP3 activation. In vivo studies using transgenic hACE2 humanized mice show that hACE2 Casp11(-/-) mice are protected from disease development, with reduced lung damage, clinical symptoms, and mortality. Analysis of human samples from fatal COVID-19 cases reveals the expression of CASP4 in patient lungs, which correlates with inflammasome components and inflammatory mediators. These findings suggest CASP4/11 as a potential target for therapeutic interventions in COVID-19.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Cristina P. B. Melo, Priscila Saito, Renata M. M. Martinez, Larissa Staurengo-Ferrari, Ingrid C. C. Pinto, Camilla C. A. Rodrigues, Stephanie Badaro-Garcia, Josiane A. A. Vignoli, Marcela M. M. Baracat, Allan J. C. Bussmann, Sandra R. R. Georgetti, Waldiceu A. A. Verri, Rubia Casagrande
Summary: This study investigates the protective effect of AT-RvD1 on UVB-induced inflammation and oxidative stress in hairless mice. The results show that AT-RvD1 can restrict various inflammatory and oxidative stress markers and restore the skin's natural antioxidant defense. AT-RvD1 achieves this by upregulating the Nrf2 pathway and promoting the expression of ARE genes.
Article
Biotechnology & Applied Microbiology
Marilia F. Manchope, Mariana M. Bertozzi, Sergio M. Borghi, Cintia L. Handa, Mariana A. Queiroz-Cancian, Camila R. Ferraz, Sandra S. Mizokami, Stephanie Badaro-Garcia, Ketlem C. Andrade, Tiago H. Zaninelli, Wilma A. Spinosa, Sandra R. Georgetti, Elza I. Ida, Waldiceu A. Verri, Rubia Casagrande
Summary: This study evaluates the biological activity of fermented and non-fermented defatted soybean flour (DSF) extracts in pain and inflammation. The results demonstrate that both fermented and non-fermented DSF extracts have analgesic and anti-inflammatory effects, with differences in the mechanism of action depending on the fungi used for fermentation.
FERMENTATION-BASEL
(2023)
Review
Pharmacology & Pharmacy
Tiago H. Zaninelli, Geovana Martelossi-Cebinelli, Telma Saraiva-Santos, Sergio M. Borghi, Victor Fattori, Rubia Casagrande, Waldiceu A. Verri Jr
Summary: Gout arthritis is an intermittent inflammatory disease that affects approximately 10% of the global population. Current therapies are not fully effective and have numerous side effects, highlighting the need for new drug targets and effector molecules in the development of novel treatments for gout arthritis.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Review
Biochemistry & Molecular Biology
Fernanda S. S. Rasquel-Oliveira, Matheus Deroco Veloso da Silva, Geovana Martelossi-Cebinelli, Victor Fattori, Rubia Casagrande, Waldiceu A. A. Verri Jr
Summary: During infection, inflammation can be harmful when it becomes excessive or chronic. Specialized pro-resolving lipid mediators (SPMs), derived from omega-3 and -6 polyunsaturated fatty acids, play a crucial role in resolving inflammation and promoting a coordinated immune response against pathogens. SPMs regulate leukocyte influx, reduce cytokine and chemokine levels, enhance bacterial clearance, inhibit viral replication, stimulate tissue healing, and decrease antibiotic requirements. Understanding the biosynthesis and effects of SPMs in different infections could have important implications for developing new therapeutic strategies.
Article
Agriculture, Dairy & Animal Science
Suellen Miguez Gonzalez, Marcela Bortoletto Cerezetti, Larissa Zamparone Bergamo, Camila Rodrigues Ferraz, Waldiceu Aparecido Verri Jr, Marcelo Marcondes Seneda
Summary: The aim of this study was to evaluate oxidative stress in ovaries and corpus luteum (CL) of Bos taurus indicus females and the oxidant effect of CL in ovarian tissues. The results showed that luteal tissues had higher antioxidant activity than ovarian tissues, and there was no difference in antioxidant activity and oxidative stress between ovarian fragments obtained from different regions (with or without CL). The presence of CL in the ovaries did not influence oxidative stress or antioxidant potential.
ANIMAL REPRODUCTION
(2023)
Article
Chemistry, Multidisciplinary
Lucas Braganca Carvalho, Isabela Silva Godoy, Ana Cristina Preisler, Patricia Luiza de Freitas Proenca, Telma Saraiva-Santos, Waldiceu Aparecido Verri Jr, Halley Caixeta Oliveira, Giliardi Dalazen, Leonardo Fernandes Fraceto
Summary: In this study, zein nanoparticles associated with the herbicide atrazine were developed and their efficacy in weed control was evaluated. The nanoformulation showed good stability and encapsulation efficiency. It exhibited greater effectiveness against the target plant, Brassica juncea, even at low doses, without causing toxicity to the crop species. The nanoparticles were captured and accumulated in roots but had limited transportation to the shoot. The atrazine nanoencapsulation did not increase the mobility of the herbicide in the soil.
ENVIRONMENTAL SCIENCE-NANO
(2023)