Pharmaceuticals最新文献

{"title":"Current Status of Drug Treatment of Cholangiocarcinoma-Updated Progress and Critical Limitations.","authors":"Jennifer Cillis, Courtney Chen, Supriya Deshpande, Yuman Fong, Shyambabu Chaurasiya","doi":"10.3390/ph19040554","DOIUrl":"10.3390/ph19040554","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is a highly lethal, heterogeneous malignancy arising from the biliary tract. Although the prevalence of CCA is relatively low, its incidence has increased in the last few decades, and the overall prognosis is poor. Surgical resection remains the most efficacious treatment modality for CCA. However, due to its aggressive nature and often asymptomatic presentation, most patients are first diagnosed with advanced disease, precluding them from curative intervention. Moreover, due to its heterogeneity at the molecular, genomic, and epigenetic levels, drug treatment of CCA remains challenging. In this review, we discuss the current standard drug treatment approaches, recent breakthroughs, and promising new therapeutics for CCA. We summarize key clinical data for the standard first-line chemotherapy regimen and its efficacy and resistance mechanisms, along with more recent studies supporting or proposing second-line treatments. We highlight landmark clinical trials, including ABC-02, which established gemcitabine-cisplatin (GC) as the first-line regimen against biliary cancers. Additionally, we discuss recent findings on the susceptibility of CCA against targeted therapies and other immunologic molecules, including results from the KEYNOTE-966 and TOPAZ-1 clinical trials. Finally, we critically analyze new therapeutics in the preclinical and clinical space, such as CAR-T cells and oncolytic viruses that may be effective against CCA.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819910","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":"A Standard Herbal Formula, CGAC, Attenuates Bone Loss by Normalizing Low-Bone Turnover Stagnation in an Orchiectomy-Induced Mouse Model.","authors":"Dong-Cheol Baek, Min-Young Chae, Tae-Wook Woo, Chang-Gue Son, Eun-Jung Lee","doi":"10.3390/ph19040555","DOIUrl":"10.3390/ph19040555","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Osteoporosis is a progressive systemic skeletal disease, with male osteoporosis emerging as a critical global concern due to high morbidity and mortality from fractures. This study investigated the anti-osteoporotic potential of CGAC-a herbal mixture of <i>Cervus elaphus Linnaeus</i>, <i>Glycine max</i> (L.) Merr., <i>Angelica gigas</i> Nakai, and <i>Cnidium officinale</i> Makino-and its underlying mechanisms in an orchiectomized (ORX) mouse model. <b>Methods</b>: C57BL/6J mice underwent ORX for 8 weeks, followed by CGAC administration (250 and 500 mg/kg) for an additional 8 weeks. Molecular mechanisms were further validated using MG63 osteoblastic and RAW 264.7 osteoclast assays. <b>Results</b>: ORX induced severe osteoporotic phenotypes, including significant reductions in bone mineral density (BMD) and trabecular microarchitecture. Notably, at the time point examined, ORX was associated with a suppressed bone remodeling state, reflected by reductions in both TRAP-positive osteoclasts and ALP-positive osteoblasts, together with lower serum BALP, CTX-1, and Gla/Glu-OC ratio. Conversely, CGAC normalized this stagnant state and restored physiological remodeling. This was accompanied by reduced marrow fat accumulation through the AMPK signaling axis, which upregulated Runx2 and downregulated PPAR-γ. In vitro results confirmed that CGAC promoted osteoblast differentiation and mineralization while suppressing RANKL-induced osteoclastogenesis. These actions suggest that CGAC may be involved in regulating Wnt/β-catenin signaling. <b>Conclusions</b>: Overall, CGAC is a promising therapeutic candidate for male osteoporosis, offering pharmacological benefits particularly relevant to aging populations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819649","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":"Revisiting the F3 Peptide: In Vitro Investigations of C- and N-Terminally Modified Peptide Conjugates for Radiotracer Development.","authors":"Maximilian Anderla, Marlene Grillmayr, Katharina Huemer, Thomas L Mindt","doi":"10.3390/ph19040558","DOIUrl":"10.3390/ph19040558","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (¹¹¹In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. <b>Methods</b>: N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. <b>Results</b>: In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca²⁺ and Mg²⁺ had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, ¹¹¹In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). <b>Conclusions</b>: A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819794","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":"Unraveling the Mechanisms of Wuling Powder Against MASLD by Integrated Metabolomics-Gut Microbiota-Serum Pharmacochemistry.","authors":"Huan Yang, Yan-Mei Tang, Shao-Cong Han, Peng-Quan Wang, Yu-Xuan Tao, Hui-Qiong Yang, Min Zhang, Min Li, Jie Yu, Xing-Xin Yang","doi":"10.3390/ph19040557","DOIUrl":"10.3390/ph19040557","url":null,"abstract":"<p><p><b>Background/Objective:</b> Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease with no specific therapeutics. Wuling Powder (WLP) is a classic traditional Chinese medicine prescription with therapeutic potential against MASLD, yet its molecular mechanism remains unclear. This study aims to elucidate the mechanism and possible effective substances of WLP in the treatment of MASLD. <b>Methods:</b> A rat MASLD model was established via high-fat diet feeding to evaluate WLP's efficacy. Untargeted metabolomics and 16S rRNA sequencing were used to explore the effects of WLP on metabolism and gut microbiota in vivo. Serum pharmacochemistry combined with metabolomics was used to analyze the key active components and core targets of WLP against MASLD, and molecular docking and cell experiments were used to verify the relationship between them. <b>Results:</b> WLP reduced hepatic lipid accumulation and pathological damage, improved lipid levels in blood liver, enhanced antioxidant capacity, and alleviated inflammation in MASLD rats. Mechanistically, WLP regulated 19 metabolic pathways. It also decreased the Firmicutes/Bacteroidota ratio and reduced the abundance of potential pathogenic bacteria (<i>Romboutsia</i> and <i>Turicibacter</i>). Thirty-one WLP-derived components were identified in serum, 13 of which were key active components for treating MASLD. These components, especially 11-deoxyalisol A and 8β-methoxyatractylenolide I, alleviated hepatic steatosis by downregulating NOS2 and PLA2G2A expression. <b>Conclusions:</b> The alleviation of MASLD by WLP was mediated by the regulation of 8 metabolic pathways, alterations in the abundance of <i>Romboutsia</i> and <i>Turicibacter</i>, and the restoration of 20 metabolite levels, an effect primarily ascribed to 13 distinct pharmacodynamic components derived from WLP.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819889","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":"Evaluation of the Pharmacological Potential of <i>Psidium guajava</i> (Guava) and Its Anticancer Effect.","authors":"Mariana Toma, Laura Ancuta Pop, Ioana Berindan-Neagoe, Ancuta Jurj, Lajos Raduly, Dorel Hoza, Vasilica Luchian, Ligia Ion, Radu Burlacu, Floricuta Ranga","doi":"10.3390/ph19040561","DOIUrl":"10.3390/ph19040561","url":null,"abstract":"<p><p><b>Background</b>: <i>Psidium guajava</i> L. (<i>Psidium guajava</i>) is an edible plant; its parts are widely used to cure and prevent many health disorders. <i>Psidium guajava</i> leaves contain a wide array of polyphenols that inhibit peroxidation and may play a role in the prevention and treatment of common, degenerative chronic disorders such as diabetes, cardiovascular disease, and cancer. Colon cancer is the third most common type of cancer diagnosed and the second most common cause of cancer-related deaths globally. In contrast, prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer-related death worldwide. This study aims to evaluate the pharmacological potential of the <i>Psidium guajava</i> plants cultivated in Romania on colon and prostate cancer cell lines. <b>Methods</b>: Phenolic compounds extraction was made using an average sample of all nine <i>Psidium guajava</i> varieties. Analyses were carried out using a HP-1200 liquid chromatograph. The effect of the alcoholic extract of <i>Psidium guajava</i> leaves was tested on two colon cancer and one prostate cancer cell line as in vitro models. <b>Results</b>: The <i>Psidium guajava</i> leaf extract exhibited anticancer activity against the tested cell lines, with decreased proliferation, increased apoptosis, and cell cycle arrest. The extract reduced the cancer cell line's migration and invasion capacity, demonstrating greater selectivity for the colon cancer cell line than for the prostate cancer cell lines. <b>Conclusions</b>: This study provides further proof of the <i>Psidium guajava</i> plant's anticancer properties against colon cancer cell lines. Further studies are needed to confirm its use either alone or in conjunction with conventional cancer treatments as an alternate treatment for certain kinds of malignancies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819185","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":"Rebamipide Reprograms Hepatic Networks to Prevent and Reverse Metabolic-Dysfunction-Associated Steatotic Liver Disease: Multi-Omics Insights and Histological Validation.","authors":"Hebatallah H Abo Nahas, Abdullah Al-Dakhil, Doaa I Mohamed, Tarek A Yousef, Ali H Abu Almaaty, Ibrahium M El-Deen, Hatem Adel M Sembawa, Essa M Saied","doi":"10.3390/ph19040559","DOIUrl":"10.3390/ph19040559","url":null,"abstract":"<p><p><b>Background:</b> Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden, yet no approved pharmacological therapy currently exists. Purpose: The purpose of this study is to investigate the prophylactic and therapeutic potential of Rebamipide, a mucosal-protective and anti-inflammatory drug, in a high-fat diet (MHFD)-induced MASLD rat model, integrating quantitative liver proteomics, network analysis, and histopathology. <b>Methods:</b> Male Wistar rats were fed MHFD for 16 weeks and treated with Rebamipide either prophylactically (Reb T1, co-administered with diet) or therapeutically (Reb T2, administered post-NASH onset). Label-free LC-MS/MS proteomics combined with principal component analysis (PCA), partial squares discriminant analysis (PLS-DA), and enrichment analyses (including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome via g: Profiler, network mapping, and Rat Genome Database (RGD) mining) revealed that MHFD had the following impacts: it induced the profound suppression of mitochondrial chaperones (Hspa9), microsomal triglyceride transfer protein (Mttp), and cytochrome P450 isoforms (Cyp2c6); it disrupted lipid trafficking, oxidative stress defense, and xenobiotic metabolism. <b>Results:</b> Rebamipide prophylaxis preserved lipid-handling proteins, prevented glycogen loss, and maintained antioxidant defenses. In contrast, therapeutic administration reversed established steatosis and remodeled metabolic pathways, enhancing fatty acid β-oxidation, detoxification, and mitochondrial protein import. Nine shared proteins across all comparisons, including MTTP and multiple Stress-70 mitochondrial isoforms, mapped to three core genes (Mttp, Cyp2c6, Hspa9) central to lipid transport, protein import, and metabolic stress adaptation. KEGG and Reactome analyses highlighted Rebamipide's modulation of bile acid synthesis, ceramide and phosphatidylcholine metabolism, lipoprotein remodeling, and MAPK signaling. Histopathological evaluation confirmed Rebamipide's efficacy, showing reduced steatosis and the normalization of the hepatocyte structure, with near-complete restoration in the therapeutic (Reb T2) group compared to partial protection in the Reb T1 group. <b>Conclusions:</b> These findings demonstrate Rebamipide's dual-phase, multi-targeted mechanism: early protection against diet-induced metabolic injury and robust reversal of established MASLD pathology. The identified protein triad (Mttp, Cyp2c6, Hspa9) and associated pathways provide novel biomarker candidates and mechanistic insight supporting Rebamipide's repurposing as a therapeutic for metabolic liver disease.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819758","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":"Cannabigerol (CBG) Modulates Neutrophil Activity and Ameliorates Rheumatoid Arthritis Pathogenesis.","authors":"Miran Aswad, Antonina Pechkovsky, Haya Hamza, Igal Louria-Hayon","doi":"10.3390/ph19040560","DOIUrl":"10.3390/ph19040560","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. <b>Methods</b>: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. <b>Results</b>: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-α and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1β by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1β cytokines in the joints by 22% and 38%, respectively. <b>Conclusions:</b> These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819522","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":"Antiviral Potential Efficacy of Green-Synthesized Silver and Titanium Dioxide Nanoparticles Against Rotavirus, Cytomegalovirus, and Human Papillomavirus.","authors":"Mohamed Z Sayed-Ahmed, Mohamed A Rizk, Soheir A A Hagras, Moaddey Alfarhan, Ayed A Alshamrani, Ahmed H Albariqi, Amal A Mohamed, Mostafa A Abdel-Maksoud, Wahidah H Al-Qahtani, Bushra Hafeez Kiani, Atef S Elgebaly","doi":"10.3390/ph19040556","DOIUrl":"10.3390/ph19040556","url":null,"abstract":"<p><p><b>Background:</b> Viral infections represent a major challenge in modern medicine, including diseases caused by human papillomavirus (HPV), cytomegalovirus (CMV), and rotavirus, which are among the most prevalent viral pathogens. The rapid transmission and high mutation rates of these viruses contribute to substantial health burdens and socio economic consequences. Silver nanoparticles (Ag NPs) and titanium dioxide nanoparticles (TiO₂-NPs) are effective antiviral agents. The major objective of this investigation was to measure the antiviral activity of titanium dioxide nanoparticles (TiO₂-NPs) and green-produced silver nanoparticles (Ag NPs) against rotavirus, HPV, and CMV. <b>Methods:</b> UV-Vis spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) were used to characterize the nanoparticles. Cytotoxicity and antiviral activity were evaluated using a crystal violet assay in infected cell cultures. <b>Results:</b> The main findings indicate that both Ag NPs and TiO₂-NPs exhibited pronounced antiviral activity against HPV, CMV, and rotavirus. Ag NPs exhibited strong antiviral activity, with lower IC₅₀ values against HPV and CMV; however, this effect was associated with lower cytotoxic concentration (CC₅₀) and selectivity index (SI) values, indicating higher cytotoxicity. In contrast, TiO₂-NPs demonstrated a favorable safety profile, as indicated by higher CC₅₀ value particularly against CMV (863.90 µg/mL) and rotavirus (386.84 µg/mL)-and low cytotoxicity toward host cells-highlighting their strong antiviral selectivity and therapeutic potential. <b>Conclusions:</b> Overall, these findings suggest that, while Ag-NPs possess strong antiviral efficacy, TiO₂ NPs offer a more balanced combination of antiviral effectiveness and biosafety and may therefore be more promising candidates for antiviral applications.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818942","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":"Adjunctive Pentoxifylline Enhances Clinical Remission and Reduces Inflammatory Biomarkers in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-Controlled Pilot Trial.","authors":"Mohannad O Khrieba, Furqan M Abdulelah, Amal Mohammed Badawoud, Eman Hamza, Reham A Al-Dhelaan, Tarek I Ahmed, Ahmed G Abdelhameed, Nora Elshorbagi, Doaa A El-Hanafy, Nashwa Eltantawy, Muhammed M Salahuddin, Noha M Elkhodary, Kholoud H Radwan, Khaled Abo Bakr Khalaf Ali, Abeer A El-Sayed, Marwa Kamal","doi":"10.3390/ph19040552","DOIUrl":"10.3390/ph19040552","url":null,"abstract":"<p><p><b>Background</b>: Despite mesalamine's efficacy in mild-to-moderate ulcerative colitis (UC), many patients fail to achieve complete clinical or biochemical remission. Pentoxifylline (PTX) may act as an adjunct therapy by modulating cytokine production and oxidative stress. <b>Aim</b>: To evaluate the therapeutic effect of adding PTX in patients with UC. <b>Methods</b>: In this randomized, double-blind, placebo-controlled pilot study, 60 patients with UC were assigned to mesalamine plus placebo (Group 1) or mesalamine plus PTX 400 mg BID (Group 2) for 24 weeks. The primary outcome was changes in the partial Mayo score (PMS). Clinical remission was defined as PMS ≤ 2 with no subscore > 1; clinical response as a reduction in PMS ≥ 2 points. Quality of life (QoL) was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ-32). Serum TNF-α, fecal calprotectin, and erythrocyte sedimentation rate (ESR) were assessed. Analyses were performed using intention-to-treat (ITT) and per-protocol (PP) approaches. Subgroup analyses stratified by prior mesalamine exposure, and multivariable regression adjusted for age, sex, disease duration, smoking, and disease extent. <b>Results</b>: PTX significantly improved PMS compared to placebo in both ITT and PP analyses. Clinical response and remission rates were higher with PTX. IBDQ-32 scores increased, and TNF-α, calprotectin, and ESR decreased significantly more with PTX. Improvements were consistent across mesalamine-naïve and experienced patients. Multivariable regression confirmed that these effects were independent of demographic or disease-related confounders. <b>Conclusions</b>: Adjunctive PTX significantly enhanced clinical outcomes, reduced inflammation, and improved QoL in UC patients, supporting its potential as an effective add-on therapy to mesalamine.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819675","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":"A Narrative Review of Augmentation Strategies in Obsessive-Compulsive Disorder: Antipsychotics as Mainstay and Emerging Role of Extended-Release Methylphenidate.","authors":"Julija Grigaitytė, Robertas Strumila","doi":"10.3390/ph19040551","DOIUrl":"10.3390/ph19040551","url":null,"abstract":"<p><p>Obsessive-compulsive disorder (OCD) is a chronic mental disorder characterized by distressing thoughts and repetitive behaviors that significantly impair daily functioning and quality of life. Many patients fail to achieve sufficient symptom relief with first-line treatments, such as cognitive-behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs). Dopaminergic dysregulation has been implicated in the pathophysiology of OCD, providing a rationale for pharmacological augmentation strategies. This article presents a narrative review of the evidence regarding the efficacy, safety, and clinical applicability of antipsychotic agents and emerging pharmacological augmentation approaches, including extended-release methylphenidate (MPH-ER), in SSRI-resistant OCD. A literature search was conducted using PubMed, EBSCO, and Embase databases, with an additional search of Google Scholar, focusing on studies examining pharmacological augmentation in treatment-resistant OCD. Overall, the evidence base is limited by small sample sizes, short follow-up durations, heterogeneous response criteria, and a lack of head-to-head comparisons versus CBT augmentation, which constrains the generalizability of conclusions. Dopamine receptor antagonists, particularly risperidone, as well as the partial agonist aripiprazole, remain the most consistently supported augmentation strategies, while olanzapine and quetiapine may be considered in selected cases. Evidence for MPH-ER is currently limited-supported by one small RCT and two recent case series-and may be considered in carefully selected adults with comorbid ADHD or marked executive dysfunction, although larger controlled studies and long-term safety data are required before firm clinical recommendations can be made.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819625","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}