Article
Biochemistry & Molecular Biology
Simeon Eche, Ajit Kumar, Nelson Sonela, Michelle L. Gordon
Summary: The study found that HIV-1 PR variants with multidrug resistance mutations exhibited increased relative resistance to LPV and DRV, along with a progressive decrease in catalytic efficiency. The structural changes in the mutant HIV-1 PR were attributed to intrinsic alterations caused by multidrug resistance mutations affecting the binding landscape of LPV and DRV. Despite DRV showing superiority over LPV in inhibiting the HIV-1 PR variants, the structural changes resulting from mutations selected during LPV therapy could shape the outcome of DRV treatment after the therapy switch.
Article
Medicine, General & Internal
Zhongli Liu, Xiaola Guo, Aijiang Guo, Shengying Zhang, Yang Zou, Yugui Wang, Xiaolu Li, Wei He, Lixia Pu, Shaohua Zhang, Qiaoying Zeng, Xuepeng Cai, Shuai Wang
Summary: This study identifies nelfinavir as the most effective drug against echinococcosis and elucidates its mechanism of action on the parasite. Through comparison of drug efficacy, this research provides valuable insights into the development of single-drug therapy for co-infection between HIV and helminth diseases.
Review
Biochemistry & Molecular Biology
Paola Magro, Isabella Zanella, Marta Pescarolo, Francesco Castelli, Eugenia Quiros-Roldan
Summary: Despite the lack of clear benefits observed with Lopinavir/ritonavir (LPV/r) treatment for COVID-19, its efficacy against SARS-CoV-2 infection deserves further evaluation.
BIOMEDICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Sunday N. Okafor, Pavimol Angsantikul, Hashim Ahmed
Summary: This research utilized computational tools to screen a large compound library and identified potential HIV-1 protease inhibitors. Two optimized molecules showed promising activity and should be further investigated in vitro and in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Matthew Weichseldorfer, Marvin Reitz, Olga S. Latinovic
Summary: Combined antiretroviral therapy (cART) is widely recommended for controlling HIV-1 replication and improving the quality of life of infected individuals. However, latent infected cells remain a major barrier to treatment efficacy in the long term.
Article
Microbiology
Andre L. S. Santos, Lys A. Braga-Silva, Diego S. Goncalves, Livia S. Ramos, Simone S. C. Oliveira, Lucieri O. P. Souza, Vanessa S. Oliveira, Roberto D. Lins, Marcia R. Pinto, Julian E. Munoz, Carlos P. Taborda, Marta H. Branquinha
Summary: The study found that lopinavir exhibits antifungal effects by inhibiting the aspartic proteases (Saps) of Candida albicans, leading to growth inhibition and irreversible morphological changes in the fungus.
Article
Biochemical Research Methods
Susana Posada-Cespedes, Gert Van Zyl, Hesam Montazeri, Jack Kuipers, Soo-Yon Rhee, Roger Kouyos, Huldrych F. Guenthard, Niko Beerenwinkel
Summary: The distribution of HIV-1 subtypes shows variation globally, leading to potential differences in drug resistance development between different subtypes. The statistical framework proposed by the authors can effectively compare the mutation patterns of different HIV-1 subtypes, revealing significant differences in resistance development between subtype B and C. It highlights the importance of subtype-specific research in understanding drug resistance and evolutionary processes.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Boris Khalfin, Alexandra Lichtenstein, Amnon Albeck, Ilana Nathan
Summary: Cell death through necrosis is a significant clinical issue affecting millions worldwide, with its molecular mechanisms still poorly understood. However, identifying key proteolytic activities essential for necrosis has opened up new strategies for treatment and prevention. Inhibitors targeting these pathways have shown protective effects in animal models, offering promising potential for treating a wide range of diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Roberto Arrigoni, Luigi Santacroce, Andrea Ballini, Luigi Leonardo Palese
Summary: The availability of drugs capable of blocking microorganism replication is a major accomplishment in medicine, but the increasing number of resistant strains poses a significant challenge for infectious disease treatment. Therefore, the search for new potential ligands for pathogens' life cycle is a crucial research area today.
Article
Biochemistry & Molecular Biology
Sunday N. Okafor, Abigail Meyer, Jay Gadsden, Fadi Ahmed, Lilian Guzman, Hashim Ahmed, Jose A. Fernandez Romero, Pavimol Angsantikul
Summary: This study screened FDA-approved and investigational drugs for their potential as HIV-1 protease inhibitors. The findings revealed that CBR003PS and CBR013PS exhibited significant binding affinity to the HIV-1 protease with high stability, showing potential for repurposing as HIV-1 protease inhibitors.
Review
Pharmacology & Pharmacy
Violet Dismas Kajogoo, Mary Gorret Atim, Demeke Amare, Melka Geleta, Yilkal Muchie, Hanna Amanuel Tesfahunei, Willyhelmina Olomi, Joan Acam, Tsegahun Manyazewal
Summary: This study analyzed the impact of Protease Inhibitors (PIs) on insulin sensitivity and the onset of diabetes mellitus (DM) in HIV patients. The results showed that among PIs, atazanavir, fosamprenavir, and darunavir did not demonstrate significant changes in insulin sensitivity.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Urology & Nephrology
Zunaid Barday, Kathryn Manning, Robert Freercks, Laurie Bertels, Nicola Wearne, Elmi Muller
Summary: Managing the interaction between ART and CNI immunosuppression in HIV-positive kidney transplant recipients is challenging. This study retrospectively analyzed ART regimen switches in 53 patients and found that PI-based regimen may be associated with increased rejection rates.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Neurosciences
Pariya Khodabakhsh, Safura Pournajaf, Leila Mohaghegh Shalmani, Abolhassan Ahmadiani, Leila Dargahi
Summary: This study investigated the effect of insulin on directing epidermal neural crest stem cells (EPI-NCSCs) into the Schwann cell lineage, showing that insulin can promote differentiation towards the SC lineage, increase neurotrophins, and upregulate genes involved in myelination.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kathleen Chwen Ming Lie, Camila Ramalho Bonturi, Bruno Ramos Salu, Juliana Rodrigues de Oliveira, Marcia Bonini Galo, Patricia Maria Guedes Paiva, Maria Tereza dos Santos Correia, Maria Luiza Vilela Oliva
Summary: Melanoma is difficult to treat with chemotherapy, but protease inhibitors show promise in blocking melanoma cells. Researchers have developed a chimeric form of the Bauhinia bauhinioides kallikrein inhibitor, rBbKIm, which has negative effects on prostate tumor cells. Crataeva tapia bark lectin, CrataBL, has deleterious effects on prostate and glioblastoma tumor cells. However, neither rBbKIm nor its derived peptides affect melanoma cell viability, while CrataBL reduces viability by over 60%. Two peptides, Pep. 26 and Pep. 27, inhibit cell migration and reduce nitric oxide and the number of viable cells. Vemurafenib, a chemotherapy drug, decreases cytokine release and potentiates the effects of proteins and peptides in reducing cytokines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Ehab A. Salama, Hassan E. Eldesouky, Yehia Elgammal, Nader S. Abutaleb, Mohamed N. Seleem
Summary: This study found that the HIV protease inhibitors lopinavir and ritonavir, when used in combination with azole antifungals, can effectively treat Candida auris infections that have developed resistance to antifungal drugs. The study demonstrated the synergistic interactions between lopinavir, ritonavir, and azole antifungals, and the potential of ritonavir to interfere with fungal efflux pumps. In a mouse model, ritonavir enhanced the activity of lopinavir and significantly reduced the fungal burden in the kidneys.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Neurosciences
Roberta Celli, Pasquale Striano, Rita Citraro, Luisa Di Menna, Milena Cannella, Tiziana Imbriglio, Mahmoud Koko, Euro Epinomics-Cogie Euro Epinomics-Cogie Consortium, Giovambattista De Sarro, James A. Monn, Giuseppe Battaglia, Gilles van Luijtelaar, Ferdinando Nicoletti, Emilio Russo, Antonio Leo
Summary: Previous studies suggest that modulation of mGlu3 receptors may be a potential treatment for absence epilepsy. This study found that mGlu3 receptor expression and signaling were decreased in the somatosensory cortex and thalamus of epileptic rats, and selective activation of mGlu3 receptors reduced seizures and depressive-like behavior. However, no association was found between genetic variants of GRM3 and absence epilepsy.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Immunology
Qing Li, Jialuo He, Senlin Li, Cheng Tian, Jian Yang, Huimin Yuan, Yi Lu, Paolo Fagone, Ferdinando Nicoletti, Ming Xiang
Summary: Pancreatic cancer (PC) has a cold tumor immune microenvironment (TIME) with minimal dendritic cell (DC) and T cell infiltration, leading to inadequate immunotherapy and chemotherapy. Combining gemcitabine (GEM) with ginsenoside Rh2 (Rh2) can enhance tumor immunogenicity and induce lasting anti-tumor immunity in PC. The activation of DCs by Rh2 via the CARD9-BCL10-MALT1/NF-KB pathway may reverse the cold TIME and optimize GEM chemotherapy, providing a potentially feasible and safe treatment strategy for PC.
CLINICAL IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Philipp Stockmann, Lydia Kuhnert, Wencke Leinung, Cathleen Lakoma, Birte Scholz, Svetlana Paskas, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Walther Honscha, Evamarie Hey-Hawkins
Summary: The overexpression of ATP-binding cassette (ABC) transporter proteins, particularly ABCG2, in cancer cells is a major cause of multidrug resistance (MDR) and the failure of chemotherapeutic treatments. Inhibition of ABCG2 activity during chemotherapy has the potential to reverse MDR and improve the efficacy of anti-cancer agents. However, the development of selective and non-toxic inhibitors of ABCG2 has been challenging, with limited success in clinical applications. This study focuses on the synthesis and evaluation of carboranyl quinazoline-based inhibitors of ABCG2, identifying a promising compound, DMQCd, which exhibits strong inhibitory effects and the ability to reverse MDR mediated by BCRP.
Review
Clinical Neurology
Francesco Weiss, Valerio Caruso, Ugo De Rosa, Maria Francesca Beatino, Margherita Barbuti, Ferdinando Nicoletti, Giulio Perugi
Summary: This systematic review aims to investigate the role of NMDARs in bipolar disorder (BD) and its neurobiological and clinical implications. The results suggest that NMDARs may be linked to the severity and chronicity of BD.
Article
Chemistry, Medicinal
Sebastian Braun, Svetlana Paskas, Markus Laube, Sven George, Bettina Hofmann, Peter Loennecke, Dieter Steinhilber, Jens Pietzsch, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Evamarie Hey-Hawkins
Summary: The presence of inflammatory mediators in the tumor microenvironment indicates cancer-related inflammatory processes, and targeting these mediators and related signal pathways may provide a rational strategy for cancer treatment. This study focuses on incorporating carboranes into dual COX-2/5-LO inhibitors, key enzymes in eicosanoid biosynthesis. The results show that carborane-based tebufelone analogs exhibit no COX inhibition but 5-LO inhibitory activity, and structural modifications enhance their anticancer activity. Thus, this strategy is promising for designing potent 5-LO inhibitors with potential application as cytostatic agents.
Article
Cardiac & Cardiovascular Systems
Carla Letizia Busceti, Albino Carrizzo, Franca Bianchi, Massimiliano De Lucia, Antonio Damato, Chiara Cazzin, Eleonora Venturini, Paola Di Pietro, Roxana Paula Ginerete, Luisa Di Menna, Maria Cotugno, Rosita Stanzione, Simona Marchitti, Serena Migliarino, Michele Ciccarelli, Sebastiano Sciarretta, Valeria Bruno, Giuseppe Battaglia, Francesco Fornai, Massimo Volpe, Speranza Rubattu, Ferdinando Nicoletti, Carmine Vecchione
Summary: Dkk3 plays a crucial role in cardiovascular homeostasis, and its deficiency leads to hypertension and impaired vascular function, which can be rescued by restoring Dkk3 expression. This effect is achieved through promoting VEGF expression and activating the VEGF/Akt/eNOS hypotensive pathway.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Andrea Ferrigno, Marta Cagna, Oriana Bosco, Michelangelo Trucchi, Clarissa Berardo, Ferdinando Nicoletti, Mariapia Vairetti, Laura G. Di Pasqua
Summary: In this study, the effects of mGluR5 blockade were evaluated in a mouse model of steatosis. It was found that MPEP can reduce fat accumulation and oxidative stress. This study provides the first in vivo evidence of the beneficial effects of MPEP in a murine model of steatosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ralitza Alexova, Simona Alexandrova, Stela Dragomanova, Reni Kalfin, Ayten Solak, Sidharth Mehan, Maria Cristina Petralia, Paolo Fagone, Katia Mangano, Ferdinando Nicoletti, Lyubka Tancheva
Summary: Pomegranate is a rich source of polyphenols that have anti-inflammatory and antioxidant activity, and can support the immune system during viral infection and recovery. Studies have shown that pomegranate polyphenol extract and its components can control immune cell infiltration, regulate cytokine secretion, inhibit viruses like SARS-CoV-2, and modulate the NF-κB pathway. Further research is needed to understand the interactions between polyphenols, viruses, and the host immune response.
Review
Medicine, General & Internal
Gian Marco Leone, Katia Mangano, Maria Cristina Petralia, Ferdinando Nicoletti, Paolo Fagone
Summary: Due to the important role of TNF-alpha in immunoinflammatory diseases, TNF-alpha inhibitors have been successfully developed and used in the treatment of autoimmune disorders. Currently, there are five approved anti-TNF-alpha drugs and biosimilars available. This review discusses the historical development, current and potential future applications, as well as the search for biomarkers to predict responsiveness to these therapies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Medicine, General & Internal
Hazael Ramiro Ceja-Galvez, Francisco Israel Renteria-Flores, Ferdinando Nicoletti, Jorge Hernandez-Bello, Gabriela Macedo-Ojeda, Jose Francisco Munoz-Valle
Summary: By January of 2023, the COVID-19 pandemic had resulted in 6,700,883 deaths and 662,631,114 cases worldwide, with no effective therapies or standardized treatment schemes available. This review aims to analyze the most efficient and promising therapies and drugs for prevention and treatment of severe COVID-19, providing support for healthcare professionals in choosing the best pharmacological approach.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Immunology
Katia Mangano, Maria Cristina Petralia, Rita Bella, Manuela Pennisi, Jose Francisco Munoz-Valle, Jorge Hernandez-Bello, Ferdinando Nicoletti, Paolo Fagone
Summary: This study evaluated the expression levels of galectin-3 in different cell populations involved in the pathogenesis of multiple sclerosis (MS). Higher levels of galectin-3 were observed in encephalitogenic CD4+ T cells, microglial cells, astrocytes, and oligodendrocytes from MS models and human MS-related white matter lesions. Galectin-3 was found to be co-expressed with genes involved in the regulation of microglia, cytokine production, and chemotaxis. This study provides comprehensive evidence for the potential pathogenic role of galectin-3 in the development of MS.
IMMUNOLOGIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Simone D'Angiolini, Maria Sofia Basile, Emanuela Mazzon, Agnese Gugliandolo
Summary: This study analyzed the transcriptional profile of the cerebellum in Alzheimer's disease patients and non-AD subjects. The results showed an overrepresentation of active ion transmembrane transporter activity in the cerebellum. Some differentially expressed genes in the cerebellum may be associated with a protective phenotype and explain the initial resistance of the cerebellum to neurodegeneration in AD. The findings provide insights into the role of the cerebellum in Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Nikola Ralchev Ralchev, Silviya Lyubenova Bradyanova, Yana Valerieva Doneva, Nikolina Mihaylova, Elena Vikentieva Elefterova-Florova, Andrey Ivanov Tchorbanov, Jose Francisco Munoz-Valle, Maria Cristina Petralia, Paola Checconi, Ferdinando Nicoletti, Paolo Fagone
Summary: The COVID-19 pandemic poses a significant threat to global public health. The involvement of CD74 and D-DT in COVID-19 patients has been investigated, and further research is needed to fully understand the mechanisms and potential therapeutic value of targeting CD74 and IL-13 in COVID-19.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Paolo Fagone, Eliana Piombino, Katia Mangano, Rocco De Pasquale, Ferdinando Nicoletti, Rosario Caltabiano
Summary: This study found a negative correlation between HMOX1 levels and the inflammatory status, as well as the infiltration of M1 macrophages and activated mastocytes in DLE lesions. These findings suggest that HMOX1 plays a crucial role in the regulation of inflammation in DLE and could be a potential therapeutic target and biomarker for DLE.
Meeting Abstract
Gastroenterology & Hepatology
M. Ferhat, K. Mangano, F. Nicoletti, C. Landlinger, T. Michael
JOURNAL OF CROHNS & COLITIS
(2023)
