Pharmacological Research - Reports最新文献

{"title":"Exploring therapeutic potential of Carissa carandas for Typhoid: An integrated approach using molecular docking, MD simulation, MMGBSA, and ADMET analysis","authors":"Vanshika Chaudhary ,&nbsp;Indu Sharma ,&nbsp;Jayant Jagtap ,&nbsp;Mayank Bhushan","doi":"10.1016/j.prerep.2025.100057","DOIUrl":"10.1016/j.prerep.2025.100057","url":null,"abstract":"<div><div>Typhoid fever, caused by <em>Salmonella typhi</em>, continues to pose a significant global health challenge, particularly with the increasing prevalence of multidrug-resistant strains. Despite ongoing vaccination efforts, typhoid fever still accounts for over 9 million infections and more than 110,000 deaths annually, predominantly affecting low- and middle-income countries. This persistent burden, coupled with the rise of antibiotic resistance, underscores an urgent need for alternative therapeutic strategies. In response, this study investigates the therapeutic potential of phytochemicals derived from <em>Carissa carandas,</em> a novel and underexplored medicinal plant traditionally used in ethnomedicine, through an integrated computational approach. A comprehensive library of 143 phytochemicals was assembled and rigorously screened using Lipinski’s rule of five and ADMET parameters, which led to the identification of 42 promising candidates for further evaluation. Molecular docking studies revealed that key compounds including Ursolic acid, carissic acid, and 3-hydroxyurs-12-en-28-oic acid exhibited binding affinities of approximately –9.6, –9.4, and –9.6 kcal/mol, respectively, significantly outperforming ciprofloxacin, which showed a binding affinity of –7.0 kcal/mol. To further assess the stability of these interactions, molecular dynamics simulations were conducted over a 100 ns period. The results demonstrated outstanding structural stability of the Ursolic acid–OmpF complex, as evidenced by a strong network of hydrogen bonds throughout the simulation and minimal root-mean-square deviation (RMSD) fluctuations. Because Ursolic acid strongly interacts with the target protein, complementary MMGBSA analysis produced a total binding energy of –32.35 ± 2.87 kcal/mol. Furthermore, ADMET profiling confirmed that the lead compounds possess certain favorable pharmacokinetic properties and safety profiles and have improved drug-likeness scores relative to ciprofloxacin. These numerical outcomes suggest that C. carandas-derived compounds represent a promising phytotherapeutic approach for managing typhoid fever; therefore, further tests using both in vitro and in vivo setups are necessary to confirm this.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of cholecystokinin 2 receptor (CCK2R) in rectal cancer: Clinical relevance and in vitro targeting with a fluorescent CCK2R-binding peptide","authors":"Somayeh Rezaei ,&nbsp;Xi Zhang ,&nbsp;Ronald L.P. van Vlierberghe ,&nbsp;Amber Piet ,&nbsp;Elma Meershoek-Klein Kranenbarg ,&nbsp;Ajinkya Manelkar ,&nbsp;Yann Seimbille ,&nbsp;Peter Laverman ,&nbsp;Louise van der Weerd ,&nbsp;Alexander L. Vahrmeijer ,&nbsp;Peter J.K. Kuppen","doi":"10.1016/j.prerep.2025.100054","DOIUrl":"10.1016/j.prerep.2025.100054","url":null,"abstract":"<div><div>The cholecystokinin type 2 receptor (CCK2R), which mediates the effects of gastrin and cholecystokinin (CCK), is known to promote colorectal cancer (CRC) proliferation in advanced stages. Though well-studied in gastric and pancreatic cancers, the role of CCK2R in colorectal, especially rectal cancer (RC), is still emerging. In this research, we initially evaluated CCK2R expression across rectal and colorectal cancer cell lines using qRT-PCR to establish baseline expression patterns. To explore the potential for near-infrared (NIR) fluorescence-based tumor targeting, we synthesized a CCK2R-binding peptide conjugate, Cy5@PP-F11, and demonstrated its receptor-specific uptake in vitro through live-cell imaging microscopy. While these results suggest promise for tumor targeting, further studies are needed to assess its <em>in vivo</em> performance and utility in fluorescence-guided surgery. In addition, a cohort of 495 Stage I-IV rectal cancer patients was analyzed using tissue microarrays (TMAs) and immunohistochemistry (IHC) to assess CCK2R expression in both tumor and normal tissues. Expression patterns and their prognostic significance were evaluated in relation to clinicopathological parameters. CCK2R localization and expression levels were quantified in both the epithelial and stromal tumor compartments, with cytoplasmic and nuclear staining specifically analyzed in the epithelial compartment. Scoring data were assessed to determine their clinical relevance. Our findings revealed significant overexpression of CCK2R in both epithelial and stromal compartments of rectal cancer tissues compared to normal tissues, showing its high suitability as target for tumor imaging. While epithelial CCK2R expression showed no significant link to clinical staging, stromal expression was notably involved, indicating a role in tumor-stroma interactions and the tumor microenvironment.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nox4 inhibition with GKT137831 protects against diabetic cardiomyopathy: Insights from functional and transcriptomic analysis","authors":"Sivarupa Raji ,&nbsp;Rohini Dhat ,&nbsp;Sandhya L. Sitasawad","doi":"10.1016/j.prerep.2025.100053","DOIUrl":"10.1016/j.prerep.2025.100053","url":null,"abstract":"<div><h3>Objective</h3><div>NADPH oxidase 4 (Nox4) is abundantly expressed in the heart and is the primary source of reactive oxygen species (ROS) in the cardiac tissue associated with cardiovascular diseases. We sought to determine whether Nox4 plays a major role in modulating diabetic cardiomyopathy (DCM) and the mechanisms involved.</div></div><div><h3>Research design and methods</h3><div>Diabetes was induced in male Wistar rats with a single dose of streptozotocin, followed by a daily dose of GKT137831 for 3 months. The characteristics of DCM were evaluated by electrocardiography (ECG) and hemodynamic measurements. Western blot analysis, histopathological evaluation, and immunohistochemical staining were performed to assess ROS, fibrosis, and apoptosis. Additionally, transcriptome analysis via RNA sequencing was conducted to investigate the role of Nox4 in cardiac dysfunction in diabetic rats.</div></div><div><h3>Results</h3><div>Rats with DCM presented significant left ventricular dysfunction with elevated levels of cardiac damage markers, Nox4 expression, ROS, cardiac fibrosis markers, and apoptotic proteins. We found that treatment with the Nox4 specific inhibitor GKT137831 ameliorated effects in DCM. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, RNA sequencing revealed that GKT137831 treatment prevented the upregulation of genes associated with contractility abnormalities, such as <em>Myl4, Cacna2d2, Cacnb3, Atp2a1, Cox6b2, Cacnb1, and Cacna2d3</em> in the diabetic cardiac tissue.</div></div><div><h3>Conclusion</h3><div>Nox4 inhibition with GKT137831 may exert a protective effect on DCM by improving cardiac dysfunction, indicating its translational value in clinical settings.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin supplementation improves impairment in cognitive function in type 2 diabetes-induced rats","authors":"Azubuike Raphael Nwaji ,&nbsp;Kenneth Chiedozie Oparaji ,&nbsp;Chima Igwe ,&nbsp;Esther Onyinyechi Igwe ,&nbsp;Miracle Princess Okechukwu ,&nbsp;Joyful Idimmachi Esinulo ,&nbsp;Toochukwu Simon ,&nbsp;Kingsley Godspower Ogbonna","doi":"10.1016/j.prerep.2025.100055","DOIUrl":"10.1016/j.prerep.2025.100055","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) is a metabolic disorder facilitated by defective regulation of glucose and lipid metabolism. This glycemic fluctuation may be responsible for the alterations associated with diabetic brain.</div></div><div><h3>Aim</h3><div>The study aimed to investigate the impact of melatonin treatment on brain of alloxan-fructose-induced type 2 diabetic rat model.</div></div><div><h3>Materials and methods</h3><div>A single dose of alloxan (150 mg/kg, i.p.) was given to 14-day fructose solution (20 % w/v) pre-treated rats in drinking water. Rats with glucose levels above 200 mg/dL were classified as diabetic after three days post-induction. 20 rats were randomly assigned to four groups and treated as control, melatonin, diabetic untreated, and diabetic treated groups, respectively. Melatonin (10 mg/kg, p.o.) was given daily for 15 days after diabetic induction.</div></div><div><h3>Results</h3><div>Supplementation of diabetic rats with melatonin had an effect on the lipid profile by significantly decreasing TG and VLDL-c while no changes were observed in the TC, HDL-c and LDL-c. Melatonin also impacted neuroinflammatory markers by significantly (p &lt; 0.05) decreasing the brain level of TNF-α and decreasing NO with no changes observed in the CRP levels of the treated rats. There was a significant (p &lt; 0.05) increase in dopamine with no effect on serotonin levels. A protective effect against cognitive dysfunction is also shown by significantly increasing % alternation.</div></div><div><h3>Conclusion</h3><div>This study affirms the beneficial effects of melatonin in alloxan-fructose-induced type 2 diabetes by reducing lipid peroxidation, neuroinflammation, and improving cognitive functions. Thus, suggests that melatonin may be essential for defending the brain against cognitive alterations linked to DM.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory and antioxidant activities of a dibenzoylmethane derivative in experimental models of inflammation and pain","authors":"Matheus Brum Felício ,&nbsp;Caio de Castro Mello ,&nbsp;Marcela de Sá Hauck ,&nbsp;Tiago Antônio de Oliveira Mendes ,&nbsp;Virginia Ramos Pizziolo ,&nbsp;Maria do Carmo Pelusio ,&nbsp;Gaspar Diaz-Muñoz ,&nbsp;Leandro Licursi de Oliveira ,&nbsp;Marisa Alves Nogueira Diaz","doi":"10.1016/j.prerep.2025.100052","DOIUrl":"10.1016/j.prerep.2025.100052","url":null,"abstract":"<div><div>This study evaluated the anti-inflammatory, antinociceptive, and antioxidant activities of the synthetic compound 2-benzyl-1,3-diphenyl-1,3-propanedione (DPBP) in paw edema and inflammatory bowel disease models. Additionally, the pharmacokinetics of the compound were assessed following intraperitoneal and transdermal administration. The anti-inflammatory activity was evaluated through formalin-induced paw edema and by measuring levels of anti-inflammatory cytokines (IL-4, IL-10) and pro-inflammatory cytokines (IFN-γ). Antinociceptive activity was determined by assessing the reduction in time animals spent licking, shaking, or biting the injected paw, as well as by the reduction in abdominal writhing induced by intraperitoneal injection of acetic acid. Antioxidant activity was assessed by measuring the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), along with tissue concentrations of malondialdehyde (MDA) and nitric oxide (NO). DPBP was detected in serum for up to 12 h following both transdermal and intraperitoneal administration. Transdermal administration of DPBP demonstrated significant antioxidant activity, reducing nitric oxide levels in the colon and small intestine of animals with inflammatory bowel disease. These results show that the transdermal route is a viable alternative for this disease, especially considering the growing interest in alternative and innovative therapies for inflammatory bowel disease, with transdermal delivery emerging as a promising approach. Intraperitoneal administration reduced paw edema, decreased nociceptive behavior following formalin-induced pain, and reduced abdominal writhing caused by acetic acid. Furthermore, intraperitoneal administration increased the production of anti-inflammatory cytokines such as IL-4 and IL-10 and enhanced the activity of antioxidant enzymes (SOD and GST). These findings suggest that DPBP exhibits strong anti-inflammatory, antinociceptive, and antioxidant activities, making it a promising candidate for the treatment of inflammation and its associated symptoms.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxorubicin-mediated nephrotoxicity is associated with tubuloglomerular dysfunction accompanied with oxido-inflammatory stress: Implication of lutein, a natural carotenoid","authors":"Monalisa Oghenemarho Ataikiru ,&nbsp;Jerome Ndudi Asiwe ,&nbsp;John Chukwuka Igweh ,&nbsp;Alexander Obidike Naiho","doi":"10.1016/j.prerep.2025.100051","DOIUrl":"10.1016/j.prerep.2025.100051","url":null,"abstract":"<div><div>Renal toxicity is one of the pathological consequences of doxorubicin therapy in cancer patients. Meanwhile the renoprotective impact of lutein, a natural carotenoid widely known for its health benefits has not been fully studied. Hence, this study was designed to investigate the renal protective potential of lutein on doxorubicin induced renal toxicity. Animals were pretreated with lutein (40 mg/kg i.p) 25 days prior to doxorubicin (15 mg/kg i.p) exposure for 3 consecutive days. Following 28 days experimentation, animals were euthanized and kidney and blood samples were collected, processed for biochemical assay as well as histological evaluation. Our results showed that exposure to doxorubicin significantly increased serum creatinine, urea and elicited electrolyte imbalance accompanied with oxidative stress, inflammation, apoptosis and dysregulated autophagic process as well as distorted histoarchitecture. Interestingly, pretreatment with lutein offered renal protection by reversing these aberrant pathological changes caused by doxorubicin. Conclusively, lutein protects against doxorubicin-mediated nephrotoxicity via inhibition of oxidative stress, inflammation, apoptosis as well as suppression of tubuloglomerular dysfunction.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In human knee articular chondrocytic-spheroids, Orthogrit modulates TNF-α and IL-1β induced inflammation, oxidative stress, ECM catabolism, and improves locomotory behaviour in Caenorhabditis elegans","authors":"Acharya Balkrishna ,&nbsp;Vivek Gohel ,&nbsp;Nishit Pathak ,&nbsp;Meenu Tomer ,&nbsp;Rishabh Dev ,&nbsp;Anurag Varshney","doi":"10.1016/j.prerep.2025.100050","DOIUrl":"10.1016/j.prerep.2025.100050","url":null,"abstract":"<div><div>Osteoarthritis is a progressive chronic degenerative joint disease characterized by inflammation, pain, and articular cartilage deterioration. The current pharmacotherapies for osteoarthritis do not address the progression of osteoarthritis and are also associated with several adverse effects. Herbal medicines are emerging as potential source for the safe and effective treatment of osteoarthritis. Orthogrit, an herbo-mineral prescription medicine, has anti-oxidant, anti-inflammatory, and cartilage promoting properties that can potentially halt progression of osteoarthritis by its multifaceted bioactivities. The present study aimed to characterize the pharmacological effects of Orthogrit using 3D culture of human knee articular chondrocytes (NHAC-kn) and <em>Caenorhabditis elegans</em>. The chemical characterization of Orthogrit was performed by UHPLC analysis. The <em>in vitro</em> evaluation of Orthogrit was performed on TNF-α and IL-1β co-induced NHAC-kn spheroids; and <em>in vivo</em> analysis on LPS- exposed N2 (wild-type) strain of <em>C</em>. <em>elegans</em>. In chondrocytic spheroids, Orthogrit treatment reduced chondrotoxicity, ROS levels, and release of IL-6, PGE2, and CTXII, a marker of cartilage degradation. Treatment with Orthogrit normalized mitochondrial membrane potential; levels of aggrecan, and sulphated glycosaminoglycans; and reporter activity of IL-1β and NF-κB. In LPS-exposed <em>C</em>. <em>elegans</em>, Orthogrit treatment decreased nematode mortality, ROS levels and normalized locomotory behaviour (reversal and omega turns), SOD, Catalase and GSH levels. The mRNA expression analysis revealed that Orthogrit acts against progression of osteoarthritis by regulating inflammation mediators (<em>JAK2</em>, <em>COX2</em>), catabolic ECM enzymes (<em>MMP1</em>, <em>MMP3</em>, <em>ADAMTS-4</em>), redox homeostasis (<em>Nrf2</em>), p38 MAPK signalling (<em>PMK-1</em>, <em>SEK-1</em>) and apoptosis (<em>CED-3</em>). Taken together, Orthogrit is a potential therapeutic agent for management of osteoarthritis.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of paraquat-induced toxicity and the therapeutic potentials of Moringa oleifera and Moringa stenopetala leaf alkaloid extracts","authors":"Stephen Adeniyi Adefegha ,&nbsp;Opeyemi Babatunde Ogunsuyi ,&nbsp;Olayemi Philemon Aro ,&nbsp;Ganiyu Oboh","doi":"10.1016/j.prerep.2025.100049","DOIUrl":"10.1016/j.prerep.2025.100049","url":null,"abstract":"<div><div>Paraquat (PQ) exposure is a risk factor for Parkinson's disease (PD), motivating treatment investigations. The efficacy of Ayurveda moringa leaf alkaloids in treating Paraquat toxicity was investigated in <em>Drosophila</em> models. The study included 10 fruit fly groups, four groups of which received moringa leaf alkaloid samples alone, one group was Paraquat-induced, and others received both. The experiment was terminated on day 3, after which fly heads and bodies were homogenized. <em>Moringa oleifera</em> and <em>Moringa stenopetala</em> alkaloid extracts were tested on Paraquat-induced flies' survival, biochemical, and genetic markers of PQ-toxicity. Alkaloid extracts significantly improved paraquat-induced fly survivability. Both <em>Moringa</em> species exhibited a stronger inhibition of monoamine oxidase and acetylcholinesterase at 50 mg/ml. Both <em>Moringa</em> species increased tyrosine hydroxylase activity, with PQ+MSL (50 mg/ml) displaying a more pronounced ameliorative effect. In comparison with the Paraquat-induced group, <em>Moringa stenopetala</em> significantly increased both catalase and total thiol levels. At the genetic level, catalase and tyrosine hydroxylase mRNA levels were downregulated in paraquat-induced flies. <em>Moringa stenopetala</em> exhibited a higher upregulation of tyrosine hydroxylase mRNA expression compared to <em>Moringa oleifera</em>, while <em>Moringa oleifera</em> upregulated catalase mRNA expression more than <em>Moringa stenopetala</em>. In conclusion, alkaloid extracts from moringa leaves demonstrated neuroprotective effects against paraquat-induced neurotoxicity in fruit flies. However, <em>Moringa stenopetala</em> exhibited superior medicinal properties compared to <em>Moringa oleifera</em>, as observed from this study. These findings support the antioxidant potential of Moringa extracts in counteracting environmental toxicant-induced stress. Future studies using non-lethal, neurodegeneration-focused Paraquat exposure models may further elucidate their neuroprotective potential.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping research trends and hotspots of artificial intelligence, and machine learning in medicine and health within the Eastern Mediterranean region‎: A comprehensive bibliometric analysis","authors":"Arwa M. Al-Dekah","doi":"10.1016/j.prerep.2025.100048","DOIUrl":"10.1016/j.prerep.2025.100048","url":null,"abstract":"<div><h3>Background</h3><div>Artificial Intelligence (AI) and Machine Learning (ML) literature on medicine and healthcare within the Eastern Mediterranean Region (EMR) is proliferating, and the volumes of scientific data are getting increasingly complex to analyze. It is essential to comprehensively analyze the current state of research in this area. This study performs comprehensive bibliometric analysis to evaluate the productivity and impact of publications on AI and ML in medicine and health within the EMR and to anticipate future research directions in the field.</div></div><div><h3>Methods</h3><div>The literature between 1996 and 2024 was retrieved from Scopus and Web of Science (WoS) databases. Microsoft Excel, the R package \"bibliometrix\" and VOSviewer were employed to perform bibliometric analysis and to map the landscape research, identify key themes, and explore trends.</div></div><div><h3>Results</h3><div>A total of 2365 eligible publications were identified, showing an average annual growth rate of 22.92 % over the past two decades. Iran (37.1 %), Saudi Arabia (25.1 %) were the most productive countries in this field. The author with the most publications was Leili Tapak. The journal with the most publications was Scientific Reports, and the most active affiliation was Tehran University of Medical Sciences. The most frequent keywords were \"<em>machine learning</em>\", \"<em>COVID-19</em>\", and \"<em>artificial intelligence</em>\".</div></div><div><h3>Conclusion</h3><div>AI/ML research in the EMR is expanding rapidly, driven by a few high-output countries and concentrated around clinical and diagnostic themes. The findings underscore the need for enhanced intra-regional collaboration, strategic investment in AI infrastructure, and the inclusion of underrepresented countries to ensure equitable AI development across the region.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetaminophen and acetaminophen-opioid combination prescribing trends among hospitalized children, adolescents, and young adults with cancer","authors":"Cheryl L. Mathis ,&nbsp;Huong D. Meeks ,&nbsp;Kevin M. Watt ,&nbsp;Luke D. Maese ,&nbsp;Jonathan E. Constance","doi":"10.1016/j.prerep.2025.100047","DOIUrl":"10.1016/j.prerep.2025.100047","url":null,"abstract":"<div><div>Acetaminophen (<strong>APAP</strong>) is a ubiquitous antipyretic and analgesic used in children in the United States (<strong>US</strong>), including those with cancer. The effects of US Food &amp; Drug Administration (<strong>FDA</strong>) guidance on APAP prescribing have been described for healthy adults and children; however, APAP use patterns in neonates, infants, children, adolescents, and young adults (<strong>CAYA</strong>) with cancer are unknown. Considering their increased risk of liver injury, APAP’s potential for causing hepatoxicity, and FDA guidance changes, this study examined the recent evolution of APAP use in CAYA with cancer. This retrospective, multi-center analysis extracted APAP prescribing data from the Pediatric Health Information System® (<strong>PHIS</strong>). Eligible patients were aged 0–26 years, had a cancer diagnosis per International Classification of Diseases (<strong>ICD</strong>) codes, and were prescribed a chemotherapeutic. APAP and APAP-opioid combination prescribing were assessed at hospital, regional, and national levels. APAP and APAP-opioid combination use changes were assessed using the non-parametric Mann-Kendall test. PHIS records for the complete years of 2004–2021 yielded 388,364 inpatient encounters for 50,779 unique patients. Of these, 87.3 % of patients received APAP. Although APAP-opioid combination use was infrequent overall, CAYA receiving APAP were more likely to receive APAP-opioid combination medications (N = 25,880, 13.4 %, p &lt; 0.001) compared to those not receiving APAP. Among specialty children’s hospitals, national APAP use was stable over the study period. Regionally, APAP use increased among Northeastern hospitals. APAP-opioid combination use decreased nationally with regional variation. In contrast to the steady decline in other regions, Southern APAP-opioid combination use was consistently elevated before declining in 2014.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}