keyword
https://read.qxmd.com/read/38534112/accelerating-therapeutics-development-during-a-pandemic-population-pharmacokinetics-of-the-long-acting-antibody-combination-azd7442-tixagevimab-cilgavimab-in-the-prophylaxis-and-treatment-of-covid-19
#1
JOURNAL ARTICLE
Lindsay E Clegg, Oleg Stepanov, Henning Schmidt, Weifeng Tang, Huixia Zhang, Chris Webber, Taylor S Cohen, Mark T Esser, Mats Någård
AZD7442 is a combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies, tixagevimab and cilgavimab, developed for pre-exposure prophylaxis (PrEP) and treatment of coronavirus disease 2019 (COVID-19). Using data from eight clinical trials, we describe a population pharmacokinetic (popPK) model of AZD7442 and show how modeling of "interim" data accelerated decision-making during the COVID-19 pandemic. The final model was a two-compartmental distribution model with first-order absorption and elimination, including standard allometric exponents for the effect of body weight on clearance and volume...
March 27, 2024: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38532431/novel-synthesis-of-new-triazine-sulfonamides-with-antitumor-anti-microbial-and-anti-sars-cov-2-activities
#2
JOURNAL ARTICLE
Reham A Mohamed-Ezzat, Galal H Elgemeie
Novel approach for synthesizing triazine sulfonamide derivatives is accomplished via reacting the sulfaguanidine derivatives with N-cyanodithioiminocarbonate. Further reaction of the novel triazine sulfonamide analogues with various secondary amines and anilines generated various substituted triazine sulfonamide analogues of promising broad-spectrum activities including anti-microbial, anti-tumor, and anti-viral properties. The in vitro anti-proliferative activities of most of the novel compounds were evaluated on the NCI-60 cell line panel...
March 26, 2024: BMC chemistry
https://read.qxmd.com/read/38530862/rilpivirine-and-cabotegravir-trough-concentrations-in-people-with-hiv-on-long-term-treatment-with-long-acting-injectable-antiretrovirals
#3
JOURNAL ARTICLE
Maria Vittoria Cossu, Dario Cattaneo, Davide Moschese, Andrea Giacomelli, Sara Soloperto, Antonio D'Avolio, Spinello Antinori, Andrea Gori, Giuliano Rizzardini, Cristina Gervasoni
OBJECTIVE: Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. METHODS: Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered...
March 26, 2024: Journal of Antimicrobial Chemotherapy
https://read.qxmd.com/read/38529865/-factors-of-the-hemostasis-system-as-biomarkers-of-severe-course-of-acute-viral-infections
#4
JOURNAL ARTICLE
N V Skripchenko, L A Alekseeva, G F Zheleznikova, E Yu Skripchenko, T V Bessonova, A A Zhirkov
The authors give literature review of hemostasis and immune system factors intraction as main biomarkers of a severe cause of viral infectious diseases. Pro-inflamatory cytokines as the main markers of inflammation, can serve both as biomarkers of the clinical severity of the infectious process and reflect the state of the hemostatic and fibrinolytic systems, since components of these systems are present in various structures of the central nervous system and affect the development of neurons and synaptic plasticity...
2024: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://read.qxmd.com/read/38529189/sesquiterpene-lactones-as-emerging-biomolecules-to-cease-cancer-by-targeting-apoptosis
#5
REVIEW
Chou-Yi Hsu, Sadegh Rajabi, Maryam Hamzeloo-Moghadam, Abhinav Kumar, Marc Maresca, Pallavi Ghildiyal
Apoptosis is a programmed cell death comprising two signaling cascades including the intrinsic and extrinsic pathways. This process has been shown to be involved in the therapy response of different cancer types, making it an effective target for treating cancer. Cancer has been considered a challenging issue in global health. Cancer cells possess six biological characteristics during their developmental process known as cancer hallmarks. Hallmarks of cancer include continuous growth signals, unlimited proliferation, resistance to proliferation inhibitors, apoptosis escaping, active angiogenesis, and metastasis...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38526562/viruses-exploit-growth-factor-mechanisms-to-achieve-augmented-pathogenicity-and-promote-tumorigenesis
#6
REVIEW
Sarvenaz Sabourirad, Evdokia Dimitriadis, Theo Mantamadiotis
Cellular homeostasis is regulated by growth factors (GFs) which orchestrate various cellular processes including proliferation, survival, differentiation, motility, inflammation and angiogenesis. Dysregulation of GFs in microbial infections and malignancies have been reported previously. Viral pathogens exemplify the exploitation of host cell GFs and their signalling pathways contributing to viral entry, virulence, and evasion of anti-viral immune responses. Viruses can also perturb cellular metabolism and the cell cycle by manipulation of GF signaling...
March 25, 2024: Archives of Microbiology
https://read.qxmd.com/read/38526139/diammonium-glycyrrhizinate-inhibited-inflammatory-response-and-modulated-serum-metabolism-in-poly-i-c-induced-pneumonia-model-mice
#7
JOURNAL ARTICLE
Yan Meng, Xuanlin Cai, Shan Cong, Jiao Sun, Wenjing Du, Xiumin Ma, Huantian Cui, Li Luo, Li Wang
Currently, the coronavirus disease 2019 (COVID-19) is becoming a serious threat to human health worldwide. Therefore, there is a great need to develop effective drugs against viral pneumonia. Diammonium glycyrrhizinate (DG), derived from Glycyrrhiza glabra L., has been demonstrated with significant anti-inflammatory properties. However, the therapeutic effects and mechanisms of DG on pneumonia require further clarification. In this study, mice received intratracheal injection of polyinosinic-polycytidylic acid (poly(I:C)) to induce pneumonia and were treated with DG...
March 25, 2024: Shock
https://read.qxmd.com/read/38523906/case-report-neglected-subacute-thyroiditis-a-case-following-covid-19-vaccination
#8
Shuai Yang, Ting Guan, HuanYi Yang, YiRong Hu, Yan Zhao
We report a case of overlooked Subacute Thyroiditis (SAT) potentially induced by the administration of a COVID-19 vaccine. This case prompted a thorough review of the existing literature to elucidate possible mechanisms by which immune responses to the COVID-19 vaccine might precipitate thyroid damage. The primary objective is to enhance the clinical understanding and awareness of SAT among healthcare professionals. Subacute thyroiditis is a prevalent form of self-limiting thyroid disorder characterized by fever, neck pain or tenderness, and palpitations subsequent to viral infection...
2024: Frontiers in Medicine
https://read.qxmd.com/read/38520574/curcumol-a-review-of-its-pharmacology-pharmacokinetics-drug-delivery-systems-structure-activity-relationships-and-potential-applications
#9
REVIEW
Sicheng Zhai, Rui Wang, Jingyuan Wang, Xiangdong Xu, Le Niu, Min Guo, Yongling Zhang, Yajun Shi, Xuexue Tang
Curcumol (Cur), a guaiane-type sesquiterpenoid hemiketal, is an important and representative bioactive component extracted from the essential oil of the rhizomes of Curcumae rhizoma which is also known as "Ezhu" in traditional Chinese medicine. Recently, Cur has received considerable attention from the research community due to its favorable pharmacological activities, including anti-cancer, hepatoprotective, anti-inflammatory, anti-viral, anti-convulsant, and other activities, and has also exerted therapeutic effect on various cancers, liver diseases, inflammatory diseases, and infectious diseases...
March 23, 2024: Inflammopharmacology
https://read.qxmd.com/read/38518956/establishment-optimization-and-validation-of-a-fluorescence-polarization-based-high-throughput-screening-assay-targeting-cathepsin-l-inhibitors
#10
JOURNAL ARTICLE
Wenwen Zhou, Baoqing You, Xiaomeng Zhao, Shuyi Si, Yan Li, Jing Zhang
Cathepsin L (CTSL), a lysosomal cysteine proteinase, is primarily dedicated to the metabolic turnover of intracellular proteins. It is involved in various physiological processes and contributes to pathological conditions such as viral infection, tumor invasion and metastasis, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, and other ailments. The coronavirus disease 2019 (COVID-19), with its rapid global spread and significant mortality, has been a worldwide epidemic since the late 2019s...
March 20, 2024: SLAS Discovery
https://read.qxmd.com/read/38517251/targeting-human-inosine-5-monophosphate-dehydrogenase-type-2-for-anti-dengue-lead-identification-a-computational-approach
#11
JOURNAL ARTICLE
Lekshmi Radha Kesavan, Biju Charuvil Kamalan, Sreekumar Sivanandan
Dengue is a rapidly evolving arboviral disease that mainly affects tropical and subtropical regions of the world. The lack of therapeutic drugs and effective vaccines suggests that further resources need to be investigated. The effectiveness of the existing dengue vaccine is improbable as its efficacy depends on prior exposure to the dengue virus(DENV). Although the mechanism underlying the action of bioactive compounds to limit viral replication is less studied and still needs to be further explored, medicinal plants are excellent alternatives to combat DENV infection...
March 22, 2024: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/38513729/synthesis-and-characterisation-of-a-nucleotide-based-pro-drug-formulated-with-a-peptide-into-a-nano-chemotherapy-for-colorectal-cancer
#12
JOURNAL ARTICLE
Jordan J Wilson, Lindsey Bennie, Olga Eguaogie, Ahmed Elkashif, Patrick F Conlon, Lynn Jena, Emma McErlean, Niamh Buckley, Klaudia Englert, Nicholas J Dunne, James H R Tucker, Joseph S Vyle, Helen O McCarthy
Recent studies in colorectal cancer patients (CRC) have shown that increased resistance to thymidylate synthase (TS) inhibitors such as 5-fluorouracil (5-FU), reduce the efficacy of standard of care (SoC) treatment regimens. The nucleotide pool cleanser dUTPase is highly expressed in CRC and is an attractive target for potentiating anticancer activity of chemotherapy. The purpose of the current work was to investigate the activity of P1 , P4 -di(2',5'-dideoxy-5'-selenouridinyl)-tetraphosphate (P4 -SedU2 ), a selenium-modified symmetrically capped dinucleoside with prodrug capabilities that is specifically activated by dUTPase...
March 19, 2024: Journal of Controlled Release
https://read.qxmd.com/read/38511603/development-and-preclinical-evaluation-of-equine-derived-hyperimmune-serum-against-sars-cov-2-infection-in-k-18-hace2-transgenic-tg-mice
#13
JOURNAL ARTICLE
E A Onen, E K Demirci
This study aimed to develop an equine-derived hyperimmune serum against SARS-CoV-2 and evaluate its efficacy as a potential immunotherapy tool for the treatment of known and potential variants of COVID-19 in preclinical trials. The novelty of this study is the whole virus and ALUM gel adjuvant formula. The horses were immunized using a whole inactivated SARS-CoV-2 antigen, and the final purified hyperimmune serum showed high plaque reduction neutralization (PRNT 50) neutralizing titers. The efficacy of the hyperimmune serum was evaluated histopathologically and biochemically in the lungs, hearts, and serum of K18 hACE2 transgenic mice (n=45), which is an accepted model organism for SARS-CoV-2 studies and was challenged with live SARS-CoV-2...
March 20, 2024: Polish Journal of Veterinary Sciences
https://read.qxmd.com/read/38508326/a-review-of-the-ethnopharmacology-phytochemistry-pharmacology-pharmacokinetics-and-toxicology-of-abri-herba-ji-gu-cao
#14
REVIEW
Cheng-Jun Liu, Hong-Xin Li, Zi-Hao Chen, Jin-Jin Li, Wei Shi, Feng-Xiang Zhang
Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids...
March 18, 2024: Phytochemistry
https://read.qxmd.com/read/38504586/a-retrospective-cohort-study-on-early-antibiotic-use-in-vaccinated-and-unvaccinated-covid-19-patients
#15
JOURNAL ARTICLE
Carlo Brogna, Luigi Montano, Maria Elisabetta Zanolin, Domenico Rocco Bisaccia, Gianluca Ciammetti, Valentina Viduto, Mark Fabrowski, Abdul M Baig, Joachim Gerlach, Iapicca Gennaro, Elio Bignardi, Barbara Brogna, Aquilino Frongillo, Simone Cristoni, Marina Piscopo
The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs)...
March 2024: Journal of Medical Virology
https://read.qxmd.com/read/38503169/dt-13-attenuates-inflammation-by-inhibiting-nlrp3-inflammasome-related-genes-in-raw264-7-macrophages
#16
JOURNAL ARTICLE
Shikha Raina, Emely Hübner, Esther Samuel, Gregor Nagel, Hendrik Fuchs
Plant derived saponins or other glycosides are widely used for their anti-inflammatory, antioxidant, and anti-viral properties in therapeutic medicine. In this study, we focus on understanding the function of the less known steroidal saponin from the roots of Liriope muscari L. H. Bailey - saponin C (also known as DT-13) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in comparison to the well-known saponin ginsenoside Rk1 and anti-inflammatory drug dexamethasone. We proved that DT-13 reduces LPS-induced inflammation by inhibiting nitric oxide (NO) production, interleukin-6 (IL-6) release, cycloxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-α) gene expression, and nuclear factor kappa-B (NFκB) translocation into the nucleus...
March 13, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38500396/amg487-alleviates-influenza-a-h1n1-virus-induced-pulmonary-inflammation-through-decreasing-ifn-%C3%AE-producing-lymphocytes-and-ifn-%C3%AE-concentrations
#17
JOURNAL ARTICLE
Wenbin Ding, Runfeng Li, Tongtong Song, Zifeng Yang, Dongting Xu, Chuqin Huang, Shuirong Shen, Nanshan Zhong, Kefang Lai, Zheng Deng
BACKGROUND AND PURPOSE: Severe influenza virus-infected patients have high systemic levels of Th1 cytokines (including IFN-γ). Intrapulmonary IFN-γ increases pulmonary IFN-γ-producing T lymphocytes through the CXCR3 pathway. Virus-infected mice lacking IP-10/CXCR3 demonstrate lower pulmonary neutrophilic inflammation. AMG487, an IP-10/CXCR3 antagonist, ameliorates virus-induced lung injury in vivo through decreasing viral loads. This study examined whether AMG487 could treat H1N1 virus-induced mouse illness through reducing viral loads or decreasing the number of lymphocytes or neutrophils...
March 18, 2024: British Journal of Pharmacology
https://read.qxmd.com/read/38498805/revolutionizing-infection-control-harnessing-mxene-based-nanostructures-for-versatile-antimicrobial-strategies-and-healthcare-advancements
#18
JOURNAL ARTICLE
Israa Habeeb Naser, Youssef Ali Naeem, Eyhab Ali, Amina Yarab Hamed, Nafaa Farhan Muften, Fadhil Turky Maan, Israa Hussein Mohammed, Noor Alhuda Mohammad Ali Khalil, Irfan Ahmad, Mohammed Abed Jawad, Ahmed Elwadi
The escalating global health challenge posed by infections prompts the exploration of innovative solutions utilizing MXene-based nanostructures. Societally, the need for effective antimicrobial strategies is crucial for public health, while scientifically, MXenes present promising properties for therapeutic applications, necessitating scalable production and comprehensive characterization techniques. Here we review the versatile physicochemical properties of MXene materials for combatting microbial threats and their various synthesis methods, including etching and top-down or bottom-up techniques...
March 18, 2024: Chemistry & Biodiversity
https://read.qxmd.com/read/38498260/effect-of-polyphenols-against-complications-of-covid-19-current-evidence-and-potential-efficacy
#19
REVIEW
Mahdi Vajdi, Arash Karimi, Shirin Hassanizadeh, Mahdieh Abbasalizad Farhangi, Mohammad Bagherniya, Gholamreza Askari, Basil D Roufogalis, Neal M Davies, Amirhossein Sahebkar
The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic potential. Researchers have developed methods for separating and isolating polyphenols from complex matrices...
March 18, 2024: Pharmacological Reports: PR
https://read.qxmd.com/read/38496952/unveiling-the-antiviral-capabilities-of-targeting-human-dihydroorotate-dehydrogenase-against-sars-cov-2
#20
JOURNAL ARTICLE
Aline D Purificação, Sabrina Silva-Mendonça, Luiza V Cruz, Carolina Q Sacramento, Jairo R Temerozo, Natalia Fintelman-Rodrigues, Caroline Souza de Freitas, Bruna Fleck Godoi, Miguel Menezes Vaidergorn, Juliana Almeida Leite, Luis Carlos Salazar Alvarez, Murillo V Freitas, Meryck F B Silvac, Bianca A Martin, Renata F V Lopez, Bruno J Neves, Fabio T M Costa, Thiago M L Souza, Flavio da Silva Emery, Carolina Horta Andrade, M Cristina Nonato
The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase ( Hs DHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent Hs DHODH inhibition with IC50 ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC50 ranging from 1...
March 12, 2024: ACS Omega
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