Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Gallic acid serves as an effective therapeutic agent of inflammatory bowel disease: Pharmacological impacts on tight junction-dependent intestinal permeability in vivo and its related intracellular signaling","authors":"Apiwan Arinno ,&nbsp;Pichayapa Sukmak ,&nbsp;Purisha Kulworasreth ,&nbsp;Thaniya Sricharunrat ,&nbsp;Chutima S. Vaddhanaphuti ,&nbsp;Pawin Pongkorpsakol","doi":"10.1016/j.crphar.2025.100223","DOIUrl":"10.1016/j.crphar.2025.100223","url":null,"abstract":"<div><div>Intestinal tight junction disruption contributes to the pathogenesis of inflammatory bowel diseases (IBD). We have recently reported that gallic acid was able to enhance intestinal tight junction assembly via CaMKK-β/AMPK/SIRT-1/ERK-dependent mechanisms with unknown possible therapeutic applications in IBD. The main aims of this study are to investigate the <em>in vivo</em> effects of gallic acid in experimental colitis mice and to search for feasible mechanisms of action. Here, we found that gallic acid attenuated weight loss, reduced disease activity index, and reversed colon length shortening in DSS-induced colitis mice. Importantly, gallic acid also significantly increased survival rates of DSS-induced colitis mice. Based on histopathological analyses, gallic acid diminished immune cell infiltration and neutrophil activity in colitis tissues. Of particular interest, gallic acid significantly reduced gene expressions of proinflammatory cytokines, including TNF, IFN-γ, IL-1β, IL-6, and IL-8. In addition, gallic acid suppressed MLCK gene transcription and protein expression in DSS-induced colitis mice. Furthermore, gallic acid also enhanced the expression of tight junction proteins, including ZO-1 and occludin. Consistently, gallic acid reduced tight junction-dependent leak pathway permeability and was shown to increase SIRT-1 activity, AMPK, and ERK phosphorylation in colon tissues of DSS-induced colitis mice. This study not only explores anti-colitogenic impacts of gallic acid, but also sheds some light on the mechanisms of its action. According to our findings, gallic acid may be useful as an anti-colitogenic nutraceutical.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100223"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099671","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 concern regarding the article titled “Variability in the serum and tissue concentrations of pre-incisional ceftriaxone for surgery in paediatric population and outcome of surgical-site infections; An open labelled, prospective, non-randomized, analytical study”","authors":"Luigino Calzetta","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carnosine modulates Aβ-induced transcriptional aberrations in murine microglial cells","authors":"Veronica Rivi ,&nbsp;Giuseppe Carota ,&nbsp;Fabio Tascedda ,&nbsp;Johanna M.C. Blom ,&nbsp;Filippo Caraci ,&nbsp;Cristina Benatti ,&nbsp;Giuseppe Caruso","doi":"10.1016/j.crphar.2025.100221","DOIUrl":"10.1016/j.crphar.2025.100221","url":null,"abstract":"<div><div>Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide known for its anti-inflammatory and antioxidant effects, making it a promising agent for neurodegenerative diseases like Alzheimer's disease (AD). Carnosine has shown protective effects against amyloid beta (Aβ)-induced oxidative stress and inflammation in murine microglial cells, yet its full immunomodulatory impact on these cells, particularly in terms of transcriptional regulation and cytokine interplay, remains underexplored. This study examined carnosine's effects on immune response markers in BV-2 cells exposed to Aβ oligomers. Specifically, gene expression changes in anti-inflammatory mediators (CXCL2 and IL-10) and phagocytic markers (CD11b, CD68, TNFα, IL-1β) were assessed. Notably, carnosine increased CXCL2 and IL-10 expression, promoting an anti-inflammatory response and enhancing microglial phagocytosis. Additionally, carnosine restored CX3CR1 expression, a receptor implicated in Aβ- effects in murine macrophages, and upregulated TGF-β1 and its receptor, supporting its neuroprotective role. These results underscore carnosine's potential to modulate immune responses, enhance microglial activity, and provide neuroprotection in Aβ-induced conditions. The findings highlight carnosine's therapeutic promise for AD treatment, offering a pathway for future research on its use in neurodegenerative disease interventions.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100221"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943643","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":"Folic acid supplementation on congenital heart disease and its dual character","authors":"Yanli Wang ,&nbsp;Zhengpei Cheng ,&nbsp;Mingfang He ,&nbsp;Rui Gu ,&nbsp;Harvest F. Gu","doi":"10.1016/j.crphar.2025.100222","DOIUrl":"10.1016/j.crphar.2025.100222","url":null,"abstract":"<div><div>Pregnant women are vulnerable to folate deficiency as its requirement is substantially greater than folate requirements for non-pregnant women. Folic acid is a synthetic form of folate and has been used in the fortified foods and nutritional supplements. Since the 1990s, maternal folic acid supplementation has been adopted by the governments and health organizations around the world as the policy to prevent the birth defects, especially neural tube defects. Under the promotion of folic acid supplementation, however, the global prevalence of congenital heart disease continues to be increased. In the recent years, our research group has evaluated that the heterogeneity concerning the association between folic acid supplementation and congenital heart disease is high. Based on experiments with animal models such as zebrafish and mice, we have demonstrated that excessive folic acid supplementation led to cardiovascular development disorders and even early embryo death. In this review article, we first summarize the discovery of folic acid and the achievement of folic acid supplementation in the prevention of congenital diseases. We then discuss the transport and metabolism of folic acid particularly in the form of unmetabolized folic acid. Finally, we comment on the association of folic acid supplementation with congenital heart disease. Better understanding the dual character of folic acid supplementation on congenital heart disease may provide new insights into the potential role of folic acid and offer a fresh perspective on the prevention of congenital heart disease.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"8 ","pages":"Article 100222"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946554","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":"Quercetin prevents rats from type 1 diabetic liver damage by inhibiting TGF-ꞵ/apelin gene expression","authors":"Gholampour Firouzeh ,&nbsp;Abbasi Susan ,&nbsp;Karimi Zeinab","doi":"10.1016/j.crphar.2024.100201","DOIUrl":"10.1016/j.crphar.2024.100201","url":null,"abstract":"<div><h3>Background</h3><p>Hyperglycemia-induced oxidative stress is a significant contributor to diabetic complications, including hepatopathy. The current survey aimed to evaluate the ameliorative effect of quercetin (Q) on liver functional disorders and tissue damage developed by diabetes mellitus in rats.</p></div><div><h3>Methods</h3><p>Grouping of 35 male Wistar rats was performed as follows: sham; sham + quercetin (sham + Q: quercetin, 50 mg/kg/day in 1 ml 1% DMSO for 6 weeks, by gavage); diabetic control (Diabetes: streptozotocin (STZ), 65 mg/kg, i.p.); diabetic + quercetin 1 (D + Q1: quercetin, 25 mg/kg/day in 1 ml 1% DMSO for 6 weeks, by gavage after STZ injection); and diabetic + quercetin 2 (D + Q2: quercetin, 50 mg/kg/day in 1 ml 1% DMSO for 6 weeks, by gavage after STZ injection). Body weight, food intake, and water intake were measured. Ultimately, the samples of plasma and urine, as well as tissue samples of the liver and pancreas were gathered for later assays.</p></div><div><h3>Results</h3><p>STZ injection ended in elevated plasma blood glucose levels, decreased plasma insulin levels, liver dysfunction (increased activity levels of AST, ALT, and ALP, increased plasma levels of total bilirubin, cholesterol, LDL, triglyceride, decreased plasma levels of total protein, albumin and HDL), enhanced levels of malondialdehyde, diminished activities of antioxidant enzymes (superoxide dismutase, and catalase), reduced level of glutathione (GSH) increased gene expression levels of apelin and TGF-ꞵ, plus liver histological destruction. All these changes were diminished by quercetin. However, the measure of improvement in the D + Q2 group was higher than that of the D + Q1 group.</p></div><div><h3>Conclusions</h3><p>Quercetin improved liver function after diabetes mellitus type 1, possibly due to reduced lipid peroxidation, increased antioxidant systems, and inhibiting the apelin/TGF-ꞵ signaling pathway.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100201"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000282/pdfft?md5=7e3380387bfbea656bb9d299b057e0f1&pid=1-s2.0-S2590257124000282-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective effect of Nobiletin against 5-fluorouracil induce hepatotoxicity","authors":"Safa A. Yahya,&nbsp;Nada N. Al-Shawi","doi":"10.1016/j.crphar.2024.100199","DOIUrl":"10.1016/j.crphar.2024.100199","url":null,"abstract":"<div><div>5-florouracil is a widely used anticancer/anti-metabolite drug used to treat solid tumor like colon cancer, head and neck, rectum, stomach, pancreas and breast cancer; but, it can cause hepatotoxicity by induction of apoptosis through activation of caspases enzymes and oxidative stress. Nobiletin is a citrus fruit-derived flavonoid that possess significant biological activity, including anticancer, and anti-inflammatory. This study was design to investigate the effects of nobiletin against 5-florouracil-indcued hepatotoxicity in male rats through the measurement of selected -inflammatory, -apoptosis, and -oxidative stress markers. By use male Albino rats weighing 150-250gm around 28 animals; giving them tap water ad libitum and fed commercial pellets; and randomized into four groups (7animals/group) as following arrangement: Group I oral administered only corn oil for rats 1 ml for each kilogram for day by using of oral gavage for rat for 14 days. Group II: oral administered Nobiletin at dose 10 mg for each kilogram for each day (dissolved in corn oil) via oral gavage for 14 days. Group III: oral administered corn oil via oral gavage for 14 days after that single IP injection of 5-FU (150 mg/kg) on the day fourteenth (14). Group VI: Rats oral administered nobiletin dissolved in corn oil daily by oral gavage at a dose 10 mg/kg for each day for 14 days and a single IP injection of (150 mg/kg) 5-florouracil was given on day 14. All groups, seven animals of each group were sacrificed at day fifteenth (15); and, serum was collected to measure inflammatory and anti-inflammatory markers (interlukin-6 and interlukin-10) and liver function tests(ALT, LDH and AST); furthermore, liver tissue samples were collected to measure level of caspase-3, malondialdehyde and reduced form of glutathione, assessment of Hemeoxygenase-1 and NADPH quinone dehydrogenase-1 enzymes. In addition, histopathological study of the liver tissue of rats was perform to detect difference between architecture of liver cells in all rats’ groups. The protective effect of Nobiletin noted by decrease in apoptosis of hepatocytes by decreasing of caspase-3 and reduction on free radical through reduce in malondialdehyde level, also increase in Hemeoxygenase-1gene expression. Increase in NADPH quinone dehydrogenase-1 dehydrogenase enzyme. On histopath reduce in congestion and some inflammatory infiltration by using of nobiletin prior to give 5-florouracil.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids","authors":"Kingsley C. Mbara ,&nbsp;Marthe C.D. Fotsing ,&nbsp;Derek T. Ndinteh ,&nbsp;Claudine N. Mbeb ,&nbsp;Chinekwu S. Nwagwu ,&nbsp;Rene Khan ,&nbsp;Kopang C. Mokhetho ,&nbsp;Himansu Baijnath ,&nbsp;Manimbulu Nlooto ,&nbsp;Shoeshoe Mokhele ,&nbsp;Carmen M. Leonard ,&nbsp;Vuyelwa J. Tembu ,&nbsp;Clemence Tarirai","doi":"10.1016/j.crphar.2024.100184","DOIUrl":"10.1016/j.crphar.2024.100184","url":null,"abstract":"<div><p>Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic β-cells. In pancreatic β-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to β-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic β-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic β-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic β-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic β-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic β-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"6 ","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000117/pdfft?md5=e9be6bef98dc4f953504348decab6dff&pid=1-s2.0-S2590257124000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141135981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaling approaches for the prediction of human clearance of LNA-i-mir-221: A retrospective validation","authors":"Massimiliano Fonsi ,&nbsp;Jacques Fulbert ,&nbsp;Pierre-Andre Billat ,&nbsp;Mariamena Arbitrio ,&nbsp;Pierosandro Tagliaferri ,&nbsp;Pierfrancesco Tassone ,&nbsp;Maria Teresa Di Martino","doi":"10.1016/j.crphar.2024.100197","DOIUrl":"10.1016/j.crphar.2024.100197","url":null,"abstract":"<div><p>LNA-i-miR-221 is a novel microRNA(miRNA)-221 inhibitor designed for the treatment of human malignancies. It has recently undergone phase 1 clinical trial (P1CT) and early pharmacokinetics (PKs) data in cancer patients are now available. We previously used multiple allometric interspecies scaling methods to draw inferences about LNA-i-miR-221 PKs in humans and estimated the patient dose based on the safe and pharmacodynamic (PD) active dose observed in mice, therefore providing a framework for the definition of safe starting and escalation doses for the P1CT. The preliminary data collected during the P1CT showed that the LNA-i-miR-221 anticipated doses, according to our human PK estimation approach, were indeed well tolerated and effective. PD data demonstrated concentration-dependent downregulation of miR-221 and upregulation of its CDKN1B/p27 and PTEN canonical targets as well as stable disease in 8 (50.0%) patients and partial response in 1 (6.3%) colorectal cancer case. Here, we detail the experimentally evaluated PK parameters of LNA-i-miR-221 in human, using both a non-compartmental and a population PKs approach. The population approach was adequately described by a three-compartments model with first-order elimination. The recorded age, sex and body weight of patients were evaluated as potential covariates. The estimated typical population parameter values were clearance (CL = 200 mL/h/kg), central volume of distribution (V1 = 45 mL/kg), peripheral volume of distribution (V2 = 200 mL/kg, volume of the second peripheral compartment V3 = 930 mL/h/kg) and inter-compartmental clearance (Q2 = 480 mL/h/kg and Q3 = 68 mL/h/kg). Age was found to be a predictor of Q3, with a statistically significant correlation. This work aimed also at retrospectively comparing the measured plasmatic clearance values with those predicted by different allometric scaling approaches. Our comparative analysis showed that the most accurate prediction was achieved by applying the single species allometric scaling approach and that the use of more than one species in allometric scaling to predict therapeutic oligonucleotides PKs would not necessarily generate the best prediction. Finally, our predictive approach was found accurate not only in predicting the main PK parameters in human but suggesting the range of effective and safe dose to be applied in the next clinic phase 2.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"7 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000245/pdfft?md5=14be37eb3e3e1daad2b299ed49e09672&pid=1-s2.0-S2590257124000245-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients","authors":"Simone Parisi ,&nbsp;Becciolini Andrea ,&nbsp;Ditto Maria Chiara ,&nbsp;Lo Gullo Alberto ,&nbsp;Larosa Maddalena ,&nbsp;Scolieri Palma ,&nbsp;Addimanda Olga ,&nbsp;Reta Massimo ,&nbsp;Paroli Marino (Prof) ,&nbsp;Caccavale Rosalba ,&nbsp;Visalli Elisa ,&nbsp;Foti Rosario ,&nbsp;Amato Giorgio ,&nbsp;De Lucia Francesco ,&nbsp;Dal Bosco Ylenia ,&nbsp;Foti Roberta ,&nbsp;Farina Antonella ,&nbsp;Girelli Francesco ,&nbsp;Bernardi Simone ,&nbsp;Camellino Dario ,&nbsp;Fusaro Enrico","doi":"10.1016/j.crphar.2024.100178","DOIUrl":"https://doi.org/10.1016/j.crphar.2024.100178","url":null,"abstract":"<div><h3>Objectives</h3><p>The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate.</p></div><div><h3>Methods</h3><p>This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence.</p></div><div><h3>Results</h3><p>Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006.</p></div><div><h3>Conclusion</h3><p>Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"6 ","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000051/pdfft?md5=de00ff9c3ff118ac9487540fc26e78bb&pid=1-s2.0-S2590257124000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139935265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The polyphenolic compound punicalagin protects skin fibroblasts from UVA radiation oxidative damage","authors":"Giada Bianchetti ,&nbsp;Patrizia Bottoni ,&nbsp;Giuseppe Tringali ,&nbsp;Giuseppe Maulucci ,&nbsp;Elisabetta Tabolacci ,&nbsp;Maria Elisabetta Clementi","doi":"10.1016/j.crphar.2024.100186","DOIUrl":"10.1016/j.crphar.2024.100186","url":null,"abstract":"<div><p>Polyphenols are a class of natural compounds that act as antioxidants, neutralising harmful free radicals that would damage cells and increase the risk of diseases such as cancer, diabetes and heart disease. They also reduce inflammation, which is thought to be at the root of many chronic diseases.</p><p>We are investigating the photoprotective effects of punicalagin, a type of polyphenolic compound mainly found in pomegranates, against UVA-induced damage in human skin fibroblasts. Punicalagin increases cell viability and reduces the high levels of ROS generated by photooxidative stress through its ability to modulate the Nrf2 transcriptional pathway. Interestingly, activation of the Nrf2 pathway results in an increase in reduced glutathione, NADH, and subsequently protects mitochondrial respiratory capacity. Integrating molecular and imaging approaches, our results demonstrate a potential cytoprotective effect of punicalagin against UVA-induced skin damage through an anti-apoptotic mechanism.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"6 ","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257124000130/pdfft?md5=d12cefebb62aea6cad9d5e2fd6a20512&pid=1-s2.0-S2590257124000130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}