Search Results (7)

Alzheimer’s disease (AD) is a worldwide problem due to the lack of effective therapy and accurate methods for timely diagnosis. The complexity of AD’s pathophysiology complicates the development of effective therapeutic agents, as most drugs act on only one therapeutic target, bypassing others. The design and development of multifunctional agents capable of altering metal ion-induced abnormalities, oxidative stress, and toxic beta amyloid (Aβ) aggregates is of interest. Herein, we report the first boron dipyrromethene (BODIPY) based bifunctional copper chelator with clioquinol, BDP-CLQ, capable of both optical detection of Aβ fibrils and copper chelation, with multiple anti-AD properties. Foremost, BDP-CLQ demonstrated a 3-fold and 5-fold fluorescence increase at 650 nm and 565 nm in the presence of Aβ and effective copper chelation (pK_d = 16.6 ± 0.3). In addition, BDP-CLQ demonstrated a potent inhibition of Aβ aggregation, reduction in Aβ-induced stiffness of neuronal cells, and antioxidant activity. BDP-CLQ is the first BODIPY-based fluorescent probe with multiple anti-AD activities, as well as the first clioquinol-based probe capable of Aβ optical visualization. This study demonstrates the prospects of the development of clioquinol-based theranostic probes since this allows combining several promising anti-AD actions in a single molecule and developing multi-targeted drugs. Full article

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients. Aim: This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis. Methods: This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score. Results: ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH. Conclusions: In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD. Full article

Pt(IV) prodrugs remain one of the most promising alternatives to conventional Pt(II) therapy due to their versatility in axial ligand choice and delayed mode of action. Selective activation from an external source is especially attractive due to the opportunity to control the activity of an antitumor drug in space and time and avoid damage to normal tissues. In this review, we discuss recent advances in photoabsorber-mediated photocontrollable activation of Pt(IV) prodrugs. Two main approaches developed are the focus of the review. The first one is the photocatalytic strategy based on the flavin derivatives that are not covalently bound to the Pt(IV) substrate. The second one is the conjugation of photoactive molecules with the Pt(II) drug via axial position, yielding dual-action Pt(IV) molecules capable of the controllable release of Pt(II) cytotoxic agents. Thus, Pt(IV) prodrugs with a light-controlled mode of activation are non-toxic in the absence of light, but show high antiproliferative activity when irradiated. The susceptibility of Pt(IV) prodrugs to photoreduction, photoactivation mechanisms, and biological activity is considered in this review. Full article

Background: The complex isolation and purification process of hepatocytes for transplantation is labor intensive and with great contamination risk. Here, as a pilot and feasibility study, we examined in vitro and in vivo hepatocyte isolation feasibility and cell function of Cell Saver^® Elite^®, an intraoperative blood-cell-recovery system. Methods: Rat and pig liver cells were collected using this system and then cultured in vitro, and their hepatocyte-specific enzymes were characterized. We then transplanted the hepatocytes in an established acute liver–injured (retrorsine+D-galactosamine-treated) rat model for engraftment. Recipient rats were sacrificed 1, 2, and 4 weeks after transplantation, followed by donor-cell identification and histological, serologic, and immunohistopathological examination. To demonstrate this Cell Saver^® strategy is workable in the first place, traditional (classical) strategy, in our study, behaved as certainty during the cell manufacturing process for monitoring quality assurance throughout the course, from the start of cell isolation to post-transplantation. Results: We noted that in situ collagenase perfusion was followed by filtration, centrifugation, and collection in the Cell Saver^® until the process ended. Most (>85%) isolated cells were hepatocytes (>80% viability) freshly demonstrating hepatocyte nuclear factor 4α and carbamoyl-phosphate synthase 1 (a key enzyme in the urea cycle), and proliferating through intercellular contact in culture, with expression of albumin and CYP3A4. After hepatocyte transplantation in dipeptidyl peptidase IV (−/−) rat liver, wild-type donor hepatocytes engrafted and repopulated progressively in 4 weeks with liver functional improvement. Proliferating donor hepatocyte–native biliary ductular cell interaction was identified. Post-transplantation global liver functional recovery after Cell Saver and traditional methods was comparable. Conclusions: Cell Saver^® requires reduced manual manipulation for isolating transplantable hepatocytes. Full article

A chemo-anti-inflammatory strategy is of interest for the treatment of aggressive cancers. The platinum (IV) prodrug with non-steroidal anti-inflammatory drugs (NSAIDs) as axial ligands is designed to efficiently enter tumor cells due to high lipophilicity and release the cytotoxic metabolite and NSAID intracellularly, thereby reducing side effects and increasing the therapeutic efficacy of platinum chemotherapy. Over the last 7 years, a number of publications have been devoted to the design of such Pt(IV) prodrugs in combination with anti-inflammatory chemotherapy, with high therapeutic efficacy in vitro and In vivo. In this review, we summarize the studies devoted to the development of Pt(IV) prodrugs with NSAIDs as axial ligands, the study of the mechanism of their cytotoxic action and anti-inflammatory activity, the structure–activity ratio, and therapeutic efficacy. Full article

One of the hallmarks of Alzheimer’s disease (AD) is the deposition of amyloid plaques in the brain parenchyma, which occurs 7–15 years before the onset of cognitive symptoms of the pathology. Timely diagnostics of amyloid formations allows identifying AD at an early stage and initiating inhibitor therapy, delaying the progression of the disease. However, clinically used radiopharmaceuticals based on ¹¹C and ¹⁸F are synchrotron-dependent and short-lived. The design of new metal-containing radiopharmaceuticals for AD visualization is of interest. The development of coordination compounds capable of effectively crossing the blood-brain barrier (BBB) requires careful selection of a ligand moiety, a metal chelating scaffold, and a metal cation, defining the method of supposed Aβ visualization. In this review, we have summarized metal-containing drugs for positron emission tomography (PET), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) imaging of Alzheimer’s disease. The obtained data allow assessing the structure-ability to cross the BBB ratio. Full article

Copper-containing coordination compounds attract wide attention due to the redox activity and biogenicity of copper ions, providing multiple pathways of biological activity. The pharmacological properties of metal complexes can be fine-tuned by varying the nature of the ligand and donor atoms. Copper-containing coordination compounds are effective antitumor agents, constituting a less expensive and safer alternative to classical platinum-containing chemotherapy, and are also effective as antimicrobial, antituberculosis, antimalarial, antifugal, and anti-inflammatory drugs. ⁶⁴Cu-labeled coordination compounds are promising PET imaging agents for diagnosing malignant pathologies, including head and neck cancer, as well as the hallmark of Alzheimer’s disease amyloid-β (Aβ). In this review article, we summarize different strategies for possible use of coordination compounds in the treatment and diagnosis of various diseases, and also various studies of the mechanisms of antitumor and antimicrobial action. Full article