<b>Background:</b> Metabolic dysfunction-associated steatosis liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD), has emerged as the most prevalent cause of chronic liver disease worldwide. For decades, the absence of approved pharmacological therapies has hindered effective clinical management, leaving lifestyle modification and sustained weight reduction as the only recommended interventions. Yet, achieving and maintaining clinically meaningful weight loss remains an enduring challenge for most patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally established as cornerstone therapies for type 2 diabetes (T2D) and obesity, have recently gained FDA approval for MASLD. Extensive mechanistic, preclinical, and clinical evidence demonstrates their ability to reduce hepatic steatosis, attenuate inflammatory pathways, and impede disease progression, establishing GLP-1RAs as the first pharmacological class with robust, multi-level efficacy in MASLD. <b>Scope of review:</b> This review synthesizes the evidence-based knowledge that led to the approval of GLP-1RAs for MASLD management. Integrating findings from (A) in vitro hepatocellular and multicellular models, (B) established animal models of steatosis-induced liver injury, and (C) clinical trials in patients with MASLD and its inflammatory subtype. We also discuss current limitations, unresolved questions, and future research priorities to optimize the therapeutic potential of GLP-1RAs in MASLD.
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) being the most prevalent subtype. NSCLC is marked by a complex genetic makeup, involving numerous driver mutations and epigenetic changes that drive tumor growth and resistance to treatment. While several approaches, including chemotherapy and targeted therapy, have been used for lung cancer treatment, their overall responses remain dismal, indicating the need to explore alternative targets implicated in cancer growth. Among various candidates, peroxisome proliferator-activated receptor-gamma (PPARγ), which plays critical roles in regulating cellular functions related to tumorigenesis, has been explored as a promising target for NSCLC intervention. To that end, thiazolidinediones, including pioglitazone, that target PPARγ have shown promise in multiple cellular and preclinical models of NSCLC. Mechanistically, pioglitazone inhibits cancer growth and induces apoptosis via downregulating key signaling pathways, including mitogen-activated protein kinase (MAPK), which play critical roles in regulating cellular activities such as epithelial-to-mesenchymal transition (EMT), cellular bioenergetics, and glucose metabolism. This review highlights the recent updates on the mechanistic insights and the efficacy of PPARγ agonist-based approaches, with an emphasis on pioglitazone, for the treatment of NSCLC. We logically discuss the experimental evidence from the in vitro and in vivo studies exploring pioglitazone’s effect on metabolic pathways, chemical-carcinogen-induced tumorigenesis, the targeting of cell signaling pathways, and then its combination with other therapeutic agents. We also present clinical studies that support pioglitazone’s potential in chemoprevention and underscore its further exploration in large cohorts of NSCLC patients.
In this study, healthy volunteers in Pakistan were asked to compare the single-dose pharmacokinetics of 16 mg of the angiotensin receptor blocker candesartan cilexetil following oral administration. Blood samples were taken over a 72-hour period while the medication was administered orally to 16 healthy individuals. Following a freeze-thaw cycle, the samples were subjected to reversed-phase HPLC analysis at a wavelength of 258 nm using an isocratic mobile phase consisting of potassium dihydrogen phosphate and methanol (25:75 v/v). Pharmacokinetic parameters such as Cmax, Tmax, t1/2, Ka, Vd, and AUC were computed.
Magdalena Podolak, Volodymyr Horishny, Rostyslav Dudchak
et al.
<b>Background/Objectives</b>: Cancer persists as a leading concern in the current medical field. As such, scientists are continuously researching new compounds with anticancer potential. In this study, we explored fifteen new 4-thiazolidinone derivatives as potential anticancer compounds. 4-Thiazolidinones are a well-established group of active structures, most commonly applied for the treatment of Parkinson’s disease and diabetic neuropathy. However, they are actively researched as potential anticancer agents. A number of derivatives have qualified for Phase II and III clinical trials as antitumor agents. <b>Methods</b>: MTT cytotoxicity assay was applied to identify the most active compounds. Three out of the fifteen tested structures displayed a significant inhibitory effect on the MCF-7 and MDA-MB-231 cell lines. To further investigate the influence of compounds on breast cancer cells, we analyzed their capability to induce apoptosis using flow cytometry assessment with Annexin V and propidium iodide dyes. Next, flow cytometry analysis of JC-1 dye was utilized to research their capability to affect mitochondrial membrane. Afterwards, concentrations of important proapoptotic proteins such as Bax and cytochrome C were assessed with a highly sensitive ELISA method. <b>Results</b>: Further analysis with a fluorescent microscope displayed that novel compounds significantly increase the generation of reactive oxygen species. <b>Conclusions</b>: The results represented in this article displayed that the most active compounds positively affected the activation of the intrinsic apoptotic pathway in the tested breast cancer cells.
<b>Background/Objectives</b>: Clozapine remains the gold standard for treatment-resistant schizophrenia. However, its narrow therapeutic window and risk of severe side effects require close monitoring of both clozapine and its primary metabolite, norclozapine. Existing therapeutic drug monitoring (TDM) methods are limited by delays, high costs, and operational complexity. This study introduces three rapid point-of-care (POC) assays utilizing a miniature mass spectrometer (Mini-MS) to quantify clozapine and norclozapine in plasma, whole blood, and dried blood spots (DBSs), facilitating applications across diverse clinical settings. <b>Methods</b>: The analytical performance of the assay was evaluated for sensitivity, specificity, reproducibility, and correlation with reference methods. Clinical samples from two hospitals were analysed and validated against conventional liquid chromatography tandem mass spectrometry (LC-MS/MS) reference standards at New South Wales Health Pathology (NSWHP) and Tsinghua University laboratories. <b>Results</b>: The Mini-MS assay accurately quantified both analytes within therapeutic ranges across all matrices. Inter-assay coefficients of variation ranged from 7.9 to 14.1% for clozapine and from 1.6 to 14.6% for norclozapine. Accuracy fell between 85 and 117% in plasma and blood extracts. Strong linearity was demonstrated (R<sup>2</sup> = 0.98–0.99) over the concentration range of 10–1000 ng/mL. Results from the Mini-MS analysis showed excellent correlations with LC-MS/MS results (r = 0.998). <b>Conclusions</b>: In this proof-of-concept study, the Mini-MS-based POC assays enable rapid, reliable quantification of clozapine and norclozapine, with performance comparable to conventional laboratory methods. This platform supports real-time TDM, facilitating timely dose adjustments, adherence monitoring, and ultimately improving patient outcomes.
Mohammed Ibrahim Mathar, Manish Chadha, AlMoataz Mohamed Amin Soliman
et al.
Objectives:
To evaluate the Vickers hardness and flexural strength of computer-aided design/computer-aided manufacture (CAD/CAM) milled, 3D-printed, and traditional heat-polymerized denture base resins used in computer-aided design and manufacture.
Materials and Methods:
A total of 60 samples were fabricated from CAD/CAM milled resin (PMMA dental material-Ruthinium disc, Badia Polesine (Rovigo) Italy), CAD/CAM 3D-printed resin (NextDent Denture 3D+, Soesterberg, The Netherlands) and conventional heat-polymerized (HP) denture base resin (DBR) (Triplex hot Ivoclar-Vivadent, Liechtenstein). Based on the three different denture base resin materials (n = 10/material) (30/flexural strength and 30/microhardness), the samples were split into six groups. The 3-point bending test was used to assess flexural strength, while Vickers microhardness test was used to assess surface hardness. The acquired data was statistically assessed.
Results:
CAD/CAM milled resins showed appreciably greater values for both the flexural strength and surface hardness, followed by conventional HP denture base resin and CAD/CAM 3D-printed resin. Pairwise comparison for Flexural Strength and Vickers microhardness revealed significant differences between groups.
Conclusion:
CAD/CAM milled resins had the highest surface hardness and flexural strength compared to Conventional HP denture base resin and CAD/CAM 3D-printed resin.
BackgroundDental imaging plays a crucial role in diagnosis and treatment planning, with cone-beam computed tomography (CBCT) and medical computed tomography (CT) being two common modalities. This study aims to compare the radiation doses associated with CBCT and medical CT imaging in dental applications to assess their relative safety and efficacy.
Materials and MethodsWe conducted a retrospective study using data from 100 patients who underwent both CBCT and medical CT scans for dental purposes. The radiation doses were measured in terms of dose-length product (DLP) for medical CT and dose-area product (DAP) for CBCT. The effective dose (ED) was calculated using appropriate conversion factors. Patient demographics, scan parameters, and radiation doses were recorded and analyzed.
ResultsThe results indicated that the mean DLP for medical CT scans was 220 mGycm, whereas the mean DAP for CBCT scans was 150 mGycm². The corresponding mean effective doses for medical CT and CBCT were 2.5 mSv and 1.8 mSv, respectively. The radiation dose from CBCT was found to be approximately 28% lower than that from medical CT.
ConclusionThis study demonstrates that CBCT imaging for dental applications results in significantly lower radiation doses compared to medical CT. While both modalities provide valuable diagnostic information, the choice of imaging technique should consider the balance between diagnostic quality and radiation exposure, especially for pediatric and high-risk patients. Dental practitioners should be aware of the potential dose reduction benefits associated with CBCT when appropriate for the clinical scenario.
Numerous drugs have emerged to treat various diseases, such as COVID-19, cancer, and protect human health. Approximately 40% of them are lipophilic and are used for treating diseases through various delivery routes, including skin absorption, oral administration, and injection. However, as lipophilic drugs have a low solubility in the human body, drug delivery systems (DDSs) are being actively developed to increase drug bioavailability. Liposomes, micro-sponges, and polymer-based nanoparticles have been proposed as DDS carriers for lipophilic drugs. However, their instability, cytotoxicity, and lack of targeting ability limit their commercialization. Lipid nanoparticles (LNPs) have fewer side effects, excellent biocompatibility, and high physical stability. LNPs are considered efficient vehicles of lipophilic drugs owing to their lipid-based internal structure. In addition, recent LNP studies suggest that the bioavailability of LNP can be increased through surface modifications, such as PEGylation, chitosan, and surfactant protein coating. Thus, their combinations have an abundant utilization potential in the fields of DDSs for carrying lipophilic drugs. In this review, the functions and efficiencies of various types of LNPs and surface modifications developed to optimize lipophilic drug delivery are discussed.
Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment.
Friederike Wolbert, Christian Luebbert, Gabriele Sadowski
Amorphous solid dispersions (ASDs) are a widely used formulation technology for poorly water-soluble active pharmaceutical ingredients (API). Depending on the API-polymer combination and API load in the ASD, the amorphous API might be thermodynamically metastable and crystallize over time. The crystallization onset is one critical factor that can define the shelf life of the ASD. Thus, for ASD formulations, long-term stability against crystallization of the API is of particular interest. This work presents a method for predicting the long-term physical stability of ASDs (crystallization onset time). The new approach combines the Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation with classical nucleation theory. The shelf life predicted using the new approach depends on supersaturation (determined with PC-SAFT), viscosity (determined with WLF equation or Arrhenius equation) and two specific model parameters k’ and B. The latter were fitted to a few fast crystallization-kinetics measurements above the glass transition of the ASD. An additional crystallization-kinetics measurement below the glass-transition temperature of the ASD was used to determine the Arrhenius parameters. Once all parameters are determined for a given API/polymer combination and manufacturing method, they are valid for any API load, temperature, and RH. The proposed approach allows predicting the shelf life (crystallization onset) of a potential ASD in early stage of development within a few days. It was successfully verified for ASDs stored at 25 °C and 10% RH or 60% RH.
Elżbieta Żmudzka, Klaudia Lustyk, Monika Głuch-Lutwin
et al.
Depression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is an urgent need to develop novel multimodal compounds that can be used to treat depression, anxiety, and schizophrenia, as well as memory deficits. Thus, this study aimed to evaluate the potential antidepressant-like, anxiolytic-like, antipsychotic-like effects, and anti-amnesic properties, of the novel arylpiperazine derivative of salicylamide, JJGW07, with an affinity towards serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub> and dopamine D<sub>2</sub> receptors. Firstly, we investigated the compound’s affinity for 5-HT<sub>6</sub> receptors and its functional activity by using in vitro assays. JJGW07 did not bind to 5-HT<sub>6</sub> receptors and showed antagonistic properties for 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>7</sub>, and D<sub>2</sub> receptors. Based on the receptor profile, we performed behavioral studies in mice to evaluate the antidepressant-like, anxiolytic-like, and antipsychotic-like activity of the tested compound using forced swim and tail suspension tests; four-plate, marble-burying, and elevated plus maze tests; and MK-801- and amphetamine-induced hyperlocomotion tests, respectively. JJGW07 revealed antidepressant-like properties in the tail suspension test, anxiolytic-like effects in the four-plate and marble-burying tests, and antipsychotic-like activity in the MK-801-induced hyperlocomotion test. Importantly, the tested compound did not induce catalepsy and motor impairments or influence locomotor activity in rodents. Finally, to assess the potential procognitive and anti-amnesic properties of JJGW07, we used passive avoidance and object recognition tests in mice. JJGW07 demonstrated positive effects on long-term emotional memory and also ameliorated MK-801-induced emotional memory impairments in mice, but showed no procognitive properties in the case of recognition memory. Our results encourage the search for new compounds among salicylamide derivatives, which could be model structures with multitarget mechanisms of action that could be used in psychiatric disorder therapy.
In a published article in <i>Pharmaceutics</i>, researchers developed a sialic acid (SA) stabilized Au nanoparticle system based on SA’s binding ability that exists on the surface of lungs epithelial cells. The authors reported that many respiratory viruses including influenza, Middle-East respiratory syndrome (MERS-CoV), and the current coronavirus (SARS-CoV-2) bind to SA as one of the main binding targets of the surface protein hemagglutinin (HA).
Hamed Aramjoo, Habibollah Ebrahim Zadeh, Mina Hemmati
Background: Chemotherapy drugs such as vinblastine cause oxidative stress in the bone marrow resulting changes in blood cell production and anemia. In this study, the antioxidant and therapeutic potential of quercetin was evaluated. Methods: Twenty-one male Wistar rats were divided into three groups; The Control group received a daily dose of normal saline, group 2 received a single dose of 2 mg/kg b.w. vinblastine intraperitoneally (i.p.) on the first day of study, and group 3 received a single dose of vinblastine (2mg/kg b.w. i.p.) along with quercetin (20 mg/kg b.w. i.p.) for 14 days. To evaluate oxidative stress in bone marrow; malondialdehyde (MDA), Total Antioxidant Capacity (TAC) and Pro-Oxidant/Antioxidant Balance (PAB) were also measured using specified methods. Results: The blood analysis showed that the mean level of RBC, Hemoglobin, and Hematocritwere significantly higher in the vinblastine group compared to the control group. Treatment with quercetin could elevate them into the normal range. Administration of vinblastine elevated the levels of bone marrow MDA and PAB significantly (p<0.05) compared to the control group but had no effect on total antioxidant capacity. The use of quercetin with vinblastine showed a decrease in the levels of bone marrow MDA and PAB compared to the vinblastine group alone. Conclusion: The findings of this study showed that quercetin at a dose of 20 mg/kg could improve the anemia induced by vinblastine chemotherapy, and it can also be useful in improving vinblastine-induced lipotoxicity.
James H. Zothantluanga, Neelutpal Gogoi, Anshul Shakya
et al.
Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in 2019 and is still an on-going pandemic. SARS-CoV-2 uses a human protease called furin to aid in cellular entry and its main protease (Mpro) to achieve viral replication. By targeting these proteins, scientists are trying to identify phytoconstituents of medicinal plants as potential therapeutics for COVID-19. Therefore, our study was aimed to identify promising leads as potential inhibitors of SARS-CoV-2 Mpro and furin using the phytocompounds reported to be isolated from Acacia pennata (L.) Willd. Results A total of 29 phytocompounds were reported to be isolated from A. pennata. Molecular docking simulation studies revealed 9 phytocompounds as having the top 5 binding affinities towards SARS-CoV-2 Mpro and furin. Among these phytocompounds, quercetin-3-O-α-L-rhamnopyranoside (C_18), kaempferol 3-O-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranoside (C_4), and isovitexin (C_5) have the highest drug score. However, C_18 and C_4 were not selected for further studies due to bioavailability issues and low synthetic accessibility. Based on binding affinity, molecular properties, drug-likeness, toxicity parameters, ligand interactions, bioavailability, synthetic accessibility, structure–activity relationship, and comparative analysis of our experimental findings with other studies, C_5 was identified as the most promising phytocompound. C_5 interacted with the active site residues of SARS-CoV-2 Mpro (GLU166, ARG188, GLN189) and furin (ASN295, ARG298, HIS364, THR365). Many phytocompounds that interacted with these amino acid residues were reported by other studies as potential inhibitors of SARS-CoV-2 Mpro and furin. The oxygen atom at position 18, the –OH group at position 19, and the 6-C-glucoside were identified as the pharmacophores in isovitexin (also known as apigenin-6-C-glucoside). Other in-silico studies reported apigenin as a potential inhibitor of SARS-CoV-2 Mpro and apigenin-o-7-glucuronide was reported to show stable conformation during MD simulations with SARS-CoV-2 Mpro. Conclusion The present study found isovitexin as the most promising phytocompound to potentially inhibit the cellular entry and viral replication of SARS-CoV-2. We also conclude that compounds having oxygen atom at position 18 (C-ring), –OH group at position 19 (A-ring), and 6-C-glucoside attached to the A-ring at position 3 on a C6–C3–C6 flavonoid scaffold could offer the best alternative to develop new leads against SARS-CoV-2.
Therapeutics. Pharmacology, Pharmacy and materia medica
Background: There are several studies reported on the association between blood groups and hemoglobin phenotypes. There are few older studies which have reported the higher incidence of hemolytic anemia in certain blood groups. Pernicious anemia is commoner in A blood group males and females.
Aim and Objective: The aim is to find the mean hemoglobin values for various blood groups and to find out if there are any significant differences in the values in different blood groups.
Materials and Methods: A total number of 269 subjects were recruited for the study. The randomly selected population consisted of 158 males and 111 females. The randomly selected population consisted of 158 males and 111 females. Blood hemoglobin levels were estimated using the instrument hemo control. Blood hemoglobin levels were estimated using the instrument hemo control.
Results: B+ve was the most common followed by O+ve blood group. O−ve, with around 0.4% prevalence, was the least of all blood groups. There was a significantly high value of hemoglobin occurring in the O+ve individuals (hemoglobin values of 1516.5 g/dL) as compared to the A+ve individuals. There was a significantly high value of hemoglobin occurring in the O+ve individuals (hemoglobin values of 1516.5 g/dL) as compared to the A+ve individuals.
Conclusion: Our study done on the rural population of Kancheepuram district showed significantly higher hemoglobin values in O blood group than the A and B blood groups. Rh-negative blood groups had low hemoglobin values when compared with Rh+ve blood groups. [Natl J Physiol Pharm Pharmacol 2020; 10(6.000): 495-498]
Therapeutics. Pharmacology, Pharmacy and materia medica
Meghan M Balough, Stephen Nwankpa, Elizabeth J Unni
Prescription opioid use disorder is a growing epidemic and pharmacists as the dispensers of prescription drugs can play a crucial role in the management of the opioid crisis. However, few studies have examined pharmacists’ perceptions of their role in it. The objective of this study was to evaluate the perceptions of pharmacists in Utah regarding their role in the opioid epidemic. The study utilized a cross sectional online survey design to understand the pharmacist knowledge and beliefs regarding pain management, opioids, naloxone, and the various opioid risk identification tools. Frequencies, t-tests, and chi-squared were used to describe and analyze the data. A total of 239 surveys were qualified for analysis. Analysis showed that pharmacists have positive attitudes towards opioid crisis management; however, this positive attitude was higher among newer pharmacists. Though the pharmacists were knowledgeable with the opioid pharmacotherapy and prescribing guidelines, they demonstrated education needs for hands-on training when faced with a situation of prescription opioid use disorder in their practice. The use of risk identification tools was not prevalent. Results show lack of active participation by pharmacists in this major public health challenge, and the need for education in several aspects of opioid dispensing, naloxone use, and efficient use of risk identification tools.
Enas J. Khadim, Alaa A. Abdulrasool, Zainab J. Awad
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms . They are a large family of compounds synthesized by plants in addition to the bacteria, fungi, and animals, they often have pharmacological effects. The aim of this study is to isolate and identified alkaloids in a newly studied, wild Iraqi plant named Echinops heterophyllus. The medicinal importance of alkaloids, on one hand and the absence of any phytochemical investigation on heterophyllus species of echinops genus on the other hand , acquired this study its importance. Three alkaloids (named E1, E2 and E3) were isolated from seed plant part by two chromatographic methods: Preparative high Performance Liquid Chromatography (PHPLC) and preparative thin layer chromatography (PTLC), one of them identified as(1-Methyl-2,3-dihydro-4(1H)-quinolinone by different chemical analysis like: ultra violet spectrum analysis (UV spectrum), Fourier transforms infrared spectra (FT-IR) , elemental microanalysis (CHN) and Proton1H-NMR and carbon 13C-NMR analysis.
Key words: Echinops, heterophyllus, quinoline alkaloids.
Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.