Pharmaceuticals最新文献

{"title":"Metformin Treatment Shows Beneficial Effects on RTT-Associated Phenotypical Deficits in <i>Mecp2</i> T158M Male Mice.","authors":"Khatereh Saei Arezoumand, Ghanan Bin Akhtar, Ashraf Kadar Shahib, Jessica S Jarmasz, Chris-Tiann Roberts, Abbas Rezaeian Mehrabadi, Carl O Olson, Mojgan Rastegar","doi":"10.3390/ph19040621","DOIUrl":"10.3390/ph19040621","url":null,"abstract":"<p><p><b>Background</b>: Rett Syndrome (RTT) is a progressive neurodevelopmental disorder caused by <i>MECP2</i> gene mutations. MeCP2 protein binding to methylated DNA is involved in normal brain development and function. T158M is a common RTT-associated mutation, where a threonine is replaced with a methionine, affecting protein function and stability. RTT has recently been identified as a neurometabolic disorder, with metformin emerging as a potential candidate drug. Metformin is a safe and accessible drug, commonly used for Type 2 diabetes. Our team previously studied the regulatory role of metformin on the expression of RTT-related genes/proteins using in vitro and in vivo approaches. However, the phenotypical and behavioral impact of metformin in transgenic mice carrying the common T158M mutation was not explored. <b>Methods</b>: Wild type (WT) and mutant <i>Mecp2^T158M</i> (<i>Mecp2^tm4.1Bird</i>) male mice were subjected to daily intraperitoneal injection of metformin for 20 days. The control mice received a daily intraperitoneal injection of the solvent. The main RTT-like phenotypical criteria were assessed daily. Behavioral tests included the open field test and elevated plus maze. <b>Results</b>: Behavioral tests indicated no significant effect of metformin on the anxiety levels, locomotion, and exploratory behaviors in the hemizygous male <i>Mecp2^T158M</i> mice, despite our observation of increased anxiety levels in the WT counterparts. In hemizygous male <i>Mecp2^T158M</i> mice, metformin treatment showed beneficial effects on RTT-like phenotypes, including breathing irregularities, gait abnormalities, hindlimb clasping, and overall total score. The positive effect of metformin was also observed on the body weight in the hemizygous male <i>Mecp2^T158M</i> mice. <b>Conclusions</b>: Our findings provide evidence for potential therapeutic effects of metformin for MeCP2-associated neurological disorders.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Pain and Depression in Alzheimer's Disease: Translational Insights and Emerging Treatments.","authors":"Ivona Costachescu, Gabriela-Dumitrita Stanciu, Raluca Maria Gogu, Bogdan-Ionel Tamba","doi":"10.3390/ph19040626","DOIUrl":"10.3390/ph19040626","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is primarily recognized for progressive cognitive decline driven by beta-amyloid accumulation and tau pathology. However, many individuals with AD also experience chronic pain and depressive symptoms, which significantly impair daily functioning and quality of life and increase caregiver burden. These non-cognitive features are frequently underrecognized, despite evidence suggesting they share overlapping biological pathways with neurodegeneration. Emerging data highlight the role of neuroinflammation, oxidative stress, hypothalamic-pituitary-adrenal axis dysregulation, and endocannabinoid system alterations in linking AD pathology to disturbances in pain processing and mood regulation. Persistent microglial activation, cytokine imbalance, redox disruption, and chronic stress signaling may simultaneously promote neuronal vulnerability while shaping affective and nociceptive responses. This review synthesizes current preclinical and clinical evidence on the interplay between pain, depression, and AD, emphasizing their shared pathophysiological mechanisms and clinical relevance. Recognizing these symptoms as integral components of disease progression, rather than isolated comorbidities, can inform the development of integrated, multidimensional therapeutic strategies in AD care.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewing the Implication of Aldehyde Dehydrogenases in Male Reproduction: Prospects for New Therapeutic Approaches.","authors":"Foteini Gkaitatzi, Ilias Tsochantaridis, Olga Pagonopoulou, Georgia-Persephoni Voulgaridou","doi":"10.3390/ph19040617","DOIUrl":"10.3390/ph19040617","url":null,"abstract":"<p><p>The World Health Organization (WHO) defines infertility as the inability of a couple to conceive after at least 12 months of regular, unprotected sexual intercourse. The male factor appears to be contributing, solely or in combination with other causes, to approximately 50% of all infertility cases. Several etiological factors of male infertility have been identified; however, the exact molecular mechanisms underlying sperm dysfunction are not yet fully understood. Aldehyde dehydrogenases (ALDHs) are multifaceted metabolic enzymes that catalyze the detoxification of several aldehydes, thus acting as antioxidants, while they regulate additional homeostatic functions by contributing to retinoic acid (RA) synthesis. Consequently, they have been identified as crucial factors in various pathogenetic mechanisms. ALDHs hold physiological roles in the testis through supporting the Sertoli cell function, the steroidogenesis in Leydig cells, and the maintenance of sperm integrity. Current evidence supports that dysregulation of specific ALDHs isoforms could be associated with disrupted testicular cell function, including oxidative imbalance and altered RA synthesis. These irregularities could interfere with germ cell development and, subsequently, contribute to decline in reproductive function. In this paper, we are reviewing the role of ALDHs in male reproduction and how their dysregulation could be implicated in male infertility. Unraveling the mechanisms underlying the association of ALDHs with male reproductive function could hold clinical interest regarding the development of novel approaches for enhancing male fertility.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effects of Gyeongok-go on Lung Injury in a Chronic Obstructive Pulmonary Disease Mouse Model.","authors":"Won-Kyung Yang, Jin Kwan Choi, Seung-Hyung Kim, Su Won Lee, Yee Ran Lyu, Yang-Chun Park","doi":"10.3390/ph19040618","DOIUrl":"10.3390/ph19040618","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Chronic obstructive pulmonary disease (COPD) is characterized by incomplete recovery of airflow blockage; however, effective therapeutic agents that can prevent lung function deterioration are limited. East Asian herbal treatments have gained attention for their potential benefits in managing COPD. This study aimed to evaluate the inhibitory effects of Gyeongok-go (GOG) on lung injury in a COPD mouse model. <b>Methods:</b> Lipopolysaccharide (LPS)-induced alveolar macrophage (MH-S) cells were treated with GOG (50, 100, 200, and 400 μg/mL), and analyzed using enzyme-linked immunosorbent assay (ELISA). C57BL/6 mice were challenged with cigarette smoke extract and LPS and then treated with vehicle only, dexamethasone (3 mg/kg), or GOG (100, 200, or 400 mg/kg). Bronchoalveolar lavage fluid (BALF) or lung tissues were analyzed using cytospin, ELISA, real-time PCR, flow cytometry, hematoxylin and eosin, and Masson's trichrome staining. <b>Results:</b> Treatment with GOG decreased tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 expression in LPS-challenged MH-S cells. In COPD mice, GOG significantly decreased the elevated numbers of neutrophils, total cells, macrophages, and Gr-1⁺/Siglec-F, Gr-1⁺/CD11b⁺, and CD44^high/CD62L^- cells. It also downregulated the expression of TNF-α, IL-17A, macrophage inflammatory protein-2 (MIP2), and CXC chemokine ligand-1 in BALF. GOG also inhibited the increase in <i>Mip2</i>, <i>Cox-2</i>, and <i>Trpv1</i> mRNA expression. Moreover, GOG prevented the increase in the number of total cells, neutrophils, Gr-1⁺/Siglec-F, Gr-1⁺/CD11b⁺, CD44^high/CD62L^-, and CD21⁺/CD35⁺/B220⁺ cells in lung tissues. Notably, GOG decreased the severity of lung injury. <b>Conclusions:</b> Overall, these findings indicate that GOG alleviates lung injury, suggesting its potential in the treatment of COPD.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for Selective Anticancer Activity of Extracts from 59 Plant Species Collected in Southern Spain (Andalusia).","authors":"Víctor Jiménez-González, Guillermo Benítez, Julio Enrique Pastor, Miguel López-Lázaro, José Manuel Calderón-Montaño","doi":"10.3390/ph19040616","DOIUrl":"10.3390/ph19040616","url":null,"abstract":"<p><p><b>Background:</b> Despite pharmacological advances, many cancer therapies provide only limited clinical benefits while often inducing significant toxicity. Therefore, the search for more effective and safer anticancer drugs remains an urgent priority. This study aimed to identify plant extracts from the Andalusian flora (Southern Spain) with selective anticancer potential. <b>Methodology:</b> A total of 67 extracts from 59 plant species were screened for selective cytotoxicity using A549 lung adenocarcinoma and HaCaT non-malignant cells. The most promising candidates, extracts from <i>Thymelaea lanuginosa</i> and <i>Daphne oleoides</i>, were further evaluated through fluorescence-based co-cultures, cell cycle analysis, and redox-mechanism assay. These extracts were also tested against a panel of cancer cells derived from different tissues (MDA-MB-231, T24, KATO-III, SK-OV-3, and MeWo). <b>Results:</b> Several extracts exhibited selective activity against A549 cancer cells, including extracts from <i>Chamaeiris foetidissima</i> (L.) Medik. (=<i>Iris foetidissima</i> L.), <i>Daphne oleoides</i> Schreb, <i>Iberodes linifolia</i> (L.) M. Serrano, R. Carbajal & S. Ortiz, <i>Reseda media</i> Lag., <i>Saxifraga hirsuta</i> L., <i>Seseli montanum</i> subsp. <i>granatense</i> (Willk.) C. Pardo, <i>Thymelaea lanuginosa</i> (Lam.), and <i>Tordylium officinale</i> L. The extracts from <i>D. oleoides</i> and <i>T. lanuginosa</i> were over 1000 times more active against lung cancer cells than non-malignant cells. These extracts induced a specific G1-phase arrest in A549 cells. Both extracts showed also selective activity against triple-negative breast cancer cells (MDA-MB-231) and bladder cancer cells (T24). <b>Conclusions:</b> These findings highlight <i>Daphne</i> and <i>Thymelaea</i> species as valuable sources for discovering novel selective anticancer agents. Future research should focus on bio-guided fractionation and in vivo validation to fully delineate their therapeutic potential.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Aspects of ¹⁶¹Tb Production.","authors":"Marie Skálová, Tereza Janská, Matěj Štíbr, Martin Vlk, Jaroslav Šoltés, Miroslav Vinš, Sindre Hassfjell, Jiri Muller, Ján Kozempel","doi":"10.3390/ph19040619","DOIUrl":"10.3390/ph19040619","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: Terbium-161 is an interesting and promising theranostic radionuclide, thanks to its decay characteristics (T&lt;sub&gt;1/2&lt;/sub&gt; = 6.95 d, E(β)&lt;sub&gt;max&lt;/sub&gt; = 593 keV, E(β)&lt;sub&gt;av&lt;/sub&gt; = 154 keV, E(γ) = 74.6 keV (10.2%)). Having similar chemical properties, it is considered as an alternative to currently used &lt;sup&gt;177&lt;/sup&gt;Lu. In addition, &lt;sup&gt;161&lt;/sup&gt;Tb emits a significant amount of conversion and Auger electrons, which contribute to the enhancement of localised therapeutic effect. The aim of this paper is to describe the preparation of &lt;sup&gt;161&lt;/sup&gt;Tb in quantity and quality relevant for preclinical and early clinical studies and to provide practical notes on the preparation. &lt;b&gt;Methods&lt;/b&gt;: No-carrier-added &lt;sup&gt;161&lt;/sup&gt;Tb has been repeatedly prepared by neutron irradiation of highly enriched &lt;sup&gt;160&lt;/sup&gt;Gd targets (up to 98 mg of &lt;sup&gt;160&lt;/sup&gt;Gd&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;) at nuclear reactor LVR-15 (CV Řež, Czech Republic) in four different irradiation positions. The separation and purification process of &lt;sup&gt;161&lt;/sup&gt;Tb from the bulk of &lt;sup&gt;160&lt;/sup&gt;Gd target was performed by cation exchange chromatography with Dowex 50 W × 8 (H&lt;sup&gt;+&lt;/sup&gt; cycle, 200-400 mesh). Terbium-161 was obtained in &lt;sup&gt;161&lt;/sup&gt;TbCl&lt;sub&gt;3&lt;/sub&gt; form and formulated into 0.1 M HCl solution. The γ-ray spectrometry was used for radionuclide identification and radionuclidic purity and the ICP-MS method for chemical purity measurements and specific activity determination. The DOTA labelling assay was performed, as described by Gracheva et al., providing an assessment of the apparent molar activity of the preparation in terms of its competitive interaction with stable daughter nuclide &lt;sup&gt;161&lt;/sup&gt;Dy. &lt;b&gt;Results&lt;/b&gt;: Irradiations (59.2 h to 421.52 h) of enriched &lt;sup&gt;160&lt;/sup&gt;Gd targets with mass ranging from 43.4 to 144.0 mg for &lt;sup&gt;160&lt;/sup&gt;Gd(NO&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;3&lt;/sub&gt; and from 12.5 to 98.3 mg for &lt;sup&gt;160&lt;/sup&gt;Gd&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; yielded 1.3-23.7 GBq of &lt;sup&gt;161&lt;/sup&gt;Tb. The separation yields of purified &lt;sup&gt;161&lt;/sup&gt;Tb varied from 85 to 99%, with the activities of 9.9-22.1 GBq and the highest achieved specific activity of the final product was 4.1 GBq/μg (of Tb). The DOTA chelator was radiolabelled with &lt;sup&gt;161&lt;/sup&gt;Tb at time points from 2 to 14 days after the end of separation (EOS). &lt;b&gt;Conclusions&lt;/b&gt;: Based on our results, we describe practical aspects of terbium production at the laboratory scale with a particular focus on practical aspects and issues arising during the process that may surprise even experienced radiochemists, as lanthanoid separation is not always straightforward, even though it is well-known and has been extensively studied. The preparation of &lt;sup&gt;161&lt;/sup&gt;Tb in a n.c.a. form proceeds, according to the reported data, with high reproducibility and achieves significant activity levels suitable for both preclinical and clinical investigations by irradiation of highly enriched &lt;sup&gt;160&lt;/sup&gt;Gd ta","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Cannabidiol on Cancer-Pathway Genes in Doxorubicin-Sensitive and Resistant Breast Cancer Cells.","authors":"Kezban Uçar Çifçi, Ayşe Büşranur Çelik, Ebru Güçlü, Nisanur Şahinoğlu, Levent Gülüm, Emir Çapkınoğlu, Yusuf Tutar","doi":"10.3390/ph19040615","DOIUrl":"10.3390/ph19040615","url":null,"abstract":"<p><p><b>Purpose</b>: Cannabidiol (CBD) is a primary bioactive, non-intoxicating cannabinoid found in the cannabis plant. Studies have shown that CBD causes anticancer activity by inhibiting the expression of growth factors and inducing apoptosis, leading to cell cycle arrest. In this study, we aimed to determine how CBD influences the expression of genes that affect cancer pathways in doxorubicin-sensitive (MCF-7) and doxorubicin-resistant (MCF-7/Adr) breast cancer cells. <b>Materials and Methods</b>: IC₅₀ concentrations of CBD in MCF-7 and MCF-7/Adr cell lines were determined by the MTT cell cytotoxicity assay. RNA isolation and subsequent cDNA synthesis were performed for qPCR experiments with the determined IC₅₀ values. The effects of CBD on the cell cycle and apoptosis were studied using flow cytometry. IC₅₀ values of CBD were determined in MCF-7 and MCF-7/Adr breast cancer cell lines at eight different concentrations and at three different incubation periods (24 h, 48 h, and 72 h) with different doses. RT-qPCR was used to investigate the molecular mechanisms underlying the expression of genes involved in cancer pathway analysis. <b>Results</b>: Treatment with CBD at concentrations of 17.57 μM (MCF-7) and 11.41 μM (MCF-7/Adr) for 48 h decreased colony formation, induced apoptosis, and inhibited cell invasion in both cell lines. In addition, we observed significant alterations of angiogenesis, apoptosis, cell cycle, cellular senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, metabolism, telomeres, and telomerase in both cell lines. <b>Conclusions</b>: Our research indicates that CBD could be an effective natural bioactive compound for breast cancer treatment, inhibiting tumor cell proliferation and inducing apoptosis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Tribenoside/Lidocaine Rectal Cream (Procto-Glyvenol^®) Promotes Tissue Repair in a Preclinical Model of Acute Complicated Anal Fissure.","authors":"Ganna Zaychenko, Nazarii Kobyliak, Larysa Natrus, Maksym Tymofieiev, Patrizia Angelico, Stefano Biondi, Matteo Malinverno","doi":"10.3390/ph19040612","DOIUrl":"10.3390/ph19040612","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The objective of this study was to evaluate the efficacy of a rectal cream containing tribenoside and lidocaine (TL) in a rat model of anal fissure (AF) and to investigate the potential mechanisms of its therapeutic action compared with those of a standard care rectal cream containing 2% diltiazem (D). <b>Methods</b>: Treatment efficacy was assessed via macroscopic methods. The levels of the inflammatory factors IL-6 and IL-10 in the tissues were measured via ELISA. Histology assessment was performed with standard hematoxylin/eosin stain, Masson's trichrome method and picrosirius stain. The levels of NF-κB, VEGF, TGF-beta 1, HIF-1α and E-cadherin were measured via densitometric immunoblot analysis. <b>Results</b>: The results of this study show that the medical product TL has therapeutic efficacy in a preclinical model of acute complicated AF, which is likely related to its complex composition. The severity of pathology in the TL group was significantly lower than that in the control pathology (CP) group on the eighth day of treatment and remained significantly lower on the 11th and 12th days. There was no statistically significant difference between the TL group and the CP group (<i>p</i> = 0.186 for IL-6 and <i>p</i> = 0.078 for IL-10). The efficacy of TL and D groups showed no statistically significant difference. At the end of the experiment, after 12 days of treatment, the level of the proinflammatory marker NF-κB in the CP group was greater than that in the intact control (IC) group. In turn, the NF-κB level in the TL group was lower than that in the CP group and significantly lower than that in the D group. Other important markers evaluated in this study demonstrated a similar tendency. The histopathological analysis showed that TL ointment promoted superior tissue repair, resulting in healthier anodermal architecture with minimal scarring and reduced fibrosis. <b>Conclusions</b>: This study confirms the potential for conducting further pharmacological studies of the mechanism of action and further clinical trials of the rectal cream TL, which has certain advantages in terms of effectiveness in a model of acute complicated AF.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine as a Multifunctional Adjuvant in Cancer Therapy: Mechanistic Insights, Nanotechnological Strategies, and Translational Challenges.","authors":"Yıldız Özalp, Tarek Alloush, Nedime Serakıncı, Murat Kartal","doi":"10.3390/ph19040613","DOIUrl":"10.3390/ph19040613","url":null,"abstract":"<p><p>Multidrug resistance (MDR) and chemotherapy-associated toxicity remain major challenges limiting the success of cancer treatments. In this context, berberine (BBR), an isoquinoline derivative belonging to the barberry family, has emerged as a promising adjuvant that can enhance the efficacy of chemotherapy while potentially mitigating its side effects. The findings indicate that berberine enhances the therapeutic effect of several drugs, such as doxorubicin, cisplatin, tamoxifen, and 5-fluorouracil, through multiple mechanisms including the inhibition of ABC transporters, regulation of autophagy, and synergistic enhancement of reactive oxygen species generation. Advanced pharmaceutical and nanotechnological formulations, including cyclodextrin complexes, solid dispersions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, chitosan-based systems, and inorganic nanoplatforms, have demonstrated significant improvements in the solubility, stability, cellular uptake, and oral bioavailability of berberine. However, knowledge gaps remain regarding optimal dosage determination, safety assessment in combination therapy, and establishing efficacy in large-scale clinical trials. Incorporating berberine into combination therapy strategies may improve treatment outcomes, overcome drug resistance, and potentially reduce the toxic burden associated with chemotherapy. Therefore, this review provides a comprehensive analytical framework for berberine's potential as an adjuvant, elucidates its mechanistic synergistic interactions with standard therapies, explores pharmaceutical strategies to overcome bioavailability limitations, and suggests future research avenues to further its clinical development.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generative Artificial Intelligence Transitions Pharmaceutical Development from Empirical Screening to Predictive Molecular Design and Clinical Trial Optimization.","authors":"Ghaith K Mansour, Hatouf H Sukkarieh","doi":"10.3390/ph19040614","DOIUrl":"10.3390/ph19040614","url":null,"abstract":"<p><p>The traditional paradigm of pharmaceutical research is characterized by substantial inefficiency, requiring extensive timelines and billions of dollars while suffering from high clinical attrition rates. The integration of generative artificial intelligence (AI) is driving a paradigm shift from empirical experimentation toward predictive, data-driven innovation. This review evaluates state-of-the-art applications of these technologies across the drug discovery and development pipeline. By analyzing multi-omics data streams, AI models can elucidate complex disease mechanisms and identify novel therapeutic targets. Deep generative architectures facilitate the algorithmic creation of novel molecular entities, enabling the design of therapeutics with complex polypharmacological profiles. Furthermore, AI is enhancing the clinical testing phase through large language models (LLMs) that improve patient enrollment and through synthetic control arms (SCAs) that provide computational alternatives to traditional placebo groups. Despite these advances, the scientific community must address inherent algorithmic biases stemming from demographic underrepresentation and mitigate the risks of data hallucinations. Ultimately, realizing the full translational potential of generative AI in precision medicine may require the widespread adoption of explainable AI (XAI) frameworks and rigorous data standards.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}