Diagnosis of pyruvate kinase deficiency (PKD) remains challenging in clinical practice. The pyruvate kinase (PK) to hexokinase (HK) activity ratio (PK/HK) was proposed to reduce the confounding effect of reticulocytosis on PK activity measurement. Ho...
Antibiotic development traditionally involved large Phase 3 programs, preceded by Phase 2 studies. Recognizing the high unmet medical need for new antibiotics and, in some cases, challenges to conducting large clinical trials, regulators created a st...
The DNA dependent protein kinase (DNA-PK) is a trimeric nuclear complex consisting of a large protein kinase and the Ku heterodimer. The kinase activity of DNA-PK is required for efficient repair of DNA double-strand breaks (DSB) by non-homologous en...
To quantitatively characterize the pharmacokinetic and pharmacodynamic interactions between Hydroxysafflor Yellow A (HSYA) and Calycosin (CA) in cerebral ischemia–reperfusion injury (CIRI), a factorial experimental design was combined with a hi...
L-4-[(10B)]Boronophenylalanine (BPA) is an amino acid analogue with a boron-10 moiety. It is most widely used as a boron carrier in boron neutron capture therapy. In this study, a Bayesian predictive platform of blood boron concentration based on a B...
Cefoperazone/sulbactam (CPZ/SUL) is a β-lactam and β-lactamase inhibitor combination therapy for the treatment of respiratory tract infections. Using data from a prospective, multiple-center, open-label clinical trial in 54 patients with ho...
DNA-dependent protein kinase (DNA-PK) is a key effector of non-homologous end joining (NHEJ)-mediated double-strand break (DSB) repair. Since its identification, a substantial body of evidence has demonstrated that DNA-PK is frequently overexpressed...
Beauveria bassiana is a globally distributed entomopathogenic fungus that produces various secondary metabolites to support its pathogenesis in insects. Two polyketide synthase genes, pks14 and pks15, are highly conserved in entomopathogenic fungi an...
Cold stress limits plant growth and development; however, the precise mechanisms underpinning plant acclimation to cold stress remain largely unknown. In this study, the Ser/Thr protein kinase SOS2-LIKE PROTEIN KINASE5 (PKS5) was shown to play a posi...
Colibactin toxin-producing Escherichia coli (pks+ E. coli) strains are associated with the occurrence of colorectal cancer in humans. These strains induce DNA damage when in close contact with the cells of the intestinal epithelium. Therefore, mainta...
Here, we have presented the development of a systems pharmacokinetics-pharmacodynamics (PK-PD) model for antibody-drug conjugates (ADCs), which uses intracellular target occupancy to drive in-vivo efficacy. The model is built based on PK and efficacy...
The human DNA-dependent protein kinase (DNA-PK), composed of the heterodimeric protein Ku and catalytic subunit DNA-PKcs, is a sensor of double-strand DNA breaks in the non-homologous end-joining DNA repair pathway. The key role of DNA-PK in the post...
Glioblastoma is the most common primary brain tumor in adults. Our previous studies revealed a functional interplay of myelin transcription factor 1-like (MYT1L) with the DNA-dependent protein kinase (DNA-PK) in the regulation of p21 transcription. H...
Using degenerated primers (LC1–LC2c) and two novel primer pairs, namely (KSLB–LC6) for Aspergillus niger and (AFl1F–LC2) for Aspergillus tubingensis, created for the acyl transferase (AT) and the KS sequences of fungal PKSs genes, a...
Across the diverse family of flavoenzymes, the isoalloxazine cofactor was found to display extremely diverse redox properties, both with respect to the absolute value of the potential regime wherein it operates and to its redox cooperativity, that is...
Conventional in vitro drug evaluation relies largely on static concentration–response assays that fail to reproduce the dynamic pharmacokinetic (PK) profiles observed in vivo, contributing to the gap between preclinical findings and clinical ou...
Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority...
Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clon...
This study aims at analyzing the impact of the pharmacological inhibition of DNA damage response (DDR) targets (DNA-PK and ATR) on radiosensitization of bladder cancer cell lines of different molecular/histological subtypes. Applying DNA-PK (AZD7648)...
Background: Breast tumor inflammation is an immunological process that occurs mainly by mediation of Tumor-Associated Macrophages (TAM). Aiming for a specific measurement of tumor inflammation, the current study evaluated the potential of Positron Em...
Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-...
Streptococcus suis (S. suis) causes severe respiratory diseases in pigs and is also an important pathogen causing hidden dangers to public health and safety. Acetylkitasamycin is a new macrolide agent that has shown good activity to Gram-positive coc...
Background/Objectives: Covalent inhibitors often demonstrate prolonged pharmacological effects even after their disappearance from the site of action because target recovery depends on target turnover. This disconnect between pharmacokinetics (PK) an...
Torsemide is a diuretic drug used for several cardiovascular and chronic diseases. With regard to the clinical application of torsemide, studies on individualized pharmacotherapy and modeling that take variability in pharmacokinetics (PKs) within a p...
The containment of the phenomenon of resistance towards antimicrobials is a priority, especially in preserving molecules acting against Gram-negative pathogens, which represent the isolates more frequently found in the fragile population of patients...
Background: High-dose melphalan 140–200 mg/m2 (HDM) with autologous stem cell transplant (ASCT) is standard first-line treatment in multiple myeloma (MM), yet standard BSA-based dosing results in wide variation in systemic exposure (AUC). We de...
The mental health of prekindergarten (PK)-12th grade students is of extreme importance. Therapy dogs are a unique intervention to address mental health needs in educational frameworks. The purpose of this pilot study is to examine the components of a...
Uveal melanoma (UM) is the most common primary intraocular tumour in adults, with a mean survival of six months following metastasis. The survival rates have not improved in over 30 years. This study has shown that sister chromatid exchange (SCE) is...
The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (Morus alba L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. Morus alba fruit is a well-known edible...
P. aeruginosa is the most common microorganism involved in many ICU-acquired infections. A correct dosage regimen is pivotal to avoiding resistance development, worse outcomes and higher mortality rates. The aim of this study was to perform a pharmac...
Cisplatin, one of the most common antitumor agents, is widely applied to treat various cancerous diseases and is included in the World Health Organization Model List of Essential Medicines. Cisplatin therapy is used to treat 10–20% of all cance...
Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indi...
Pseudomonas aeruginosa remains one of the major causes of healthcare-associated infection in Europe; in 2019, 12.5% of invasive isolates of P. aeruginosa in Spain presented combined resistance to ≥3 antimicrobial groups. The Spanish nationwide survey...
Klebsiella pneumoniae (K. pneumoniae) colonizes the human gut and is a causative factor of pyogenic liver abscess (PLA). Retrospective studies conducted on K. pneumoniae PLA patients revealed subsequent CRC development in later years of their life wi...
Foot-and-mouth disease (FMD) is a highly contagious disease that results in enormous economic loses worldwide. Although the protection provided by vaccination is limited during early infection, it is recognized as the best method to prevent FMD outbr...
We reviewed X-ray flux and spectral variability properties studied to date by various X-ray satellites for Mrk 421 and PKS 2155-304, which are TeV emitting blazars. Mrk 421 and PKS 2155-304 are the most X-ray luminous blazars in the northern and sout...
Background: Pharmacokinetic/pharmacodynamic (PK/PD)-guided intravenous anesthesia and target-controlled infusion (TCI) have progressively transformed modern anesthetic practice from empirical drug administration toward individualized, model-informed...
The excessive use of antibiotics has triggered the appearance of new resistant strains, which is why great interest has been taken in the search for new bioactive compounds capable of overcoming this emergency in recent years. Massive sequencing tool...
Adiponectin is an adipokine that mediates cellular cholesterol efflux and plays important roles in neuroinflammatory processes. In this study, we undertook positron emission tomography (PET) with the translocator protein (TSPO) ligand [11C]PK11195 an...
Translocator protein (TSPO) regulates mitochondrial function, inflammation, and oxidative stress; however, its role in acute myocardial injury (MI) remains incompletely understood. While previous studies have examined TSPO ligands in cardiac injury,...
The integration of a DNA copy of an HIV-1 RNA genome into the host genome, carried out by the viral enzyme integrase, results in the formation of single-stranded gaps in cellular DNA that must be repaired. Here, we have analyzed the involvement of th...
Marine environments harbor a wide range of microorganisms from the three domains of life. These microorganisms have great potential to enable discovery of new enzymes and bioactive compounds for industrial use. However, only ~1% of microorganisms fro...
Korean pine (Pinus koraiensis) is a vital woody oil tree species native to Northeast Asia, with its pine nuts serving as the primary global source of edible pine nuts globally due to their rich nutritional content. Currently, seed yield from Korean p...
The mitochondrial translocator protein (TSPO) is a modulator of the apoptotic pathway involving reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) collapse, activation of caspases, and eventually initiation of...
Colletotrichum higginsianum is a major pathogen causing anthracnose in Chinese flowering cabbage (Brassica parachinensis), posing a significant threat to the Chinese flowering cabbage industry. The conidia of C. higginsianum germinate and form melani...
Monascus spp. are renowned for producing valuable Monascus azaphilone pigments (MonAzPs), yet their biosynthesis is intrinsically linked to the co-production of the mycotoxin citrinin, posing a significant safety challenge and limiting industrial app...
Objectives: Investigating how nanoparticle systems interact in whole blood (WB) is critical to evaluating the effectiveness of malaria therapy. Methods: We decided to establish a pharmacokinetic/pharmacodynamic (PK/PD) model of the quinine population...
The aim of this study was to apply molecular epidemiology, antimicrobial surveillance, and PK/PD analysis to guide the antimicrobial treatment of gonococci infections in a region of the north of Spain. Antibiotic susceptibility testing was performed...
Background: The pharmacokinetic/pharmacodynamic (PK/PD) index of carbapenems that best correlates with in vivo antimicrobial activity is percent time of dosing interval in which free drug concentration remains above MIC (%fT > MIC), while the magn...
Despite substantial advancements in understanding the pathomechanisms of head and neck squamous cell carcinoma (HNSCC), effective therapy remains challenging. The application of kinase inhibitors (KIs) in HNSCC, specifically mTOR and DNA-PK inhibitor...
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