Search Results (105)

The 33^rd Annual Conference of the Group for the Promotion of Pharmaceutical Chemistry in Academia (GP₂A), held in Nantes from 11 to 13 June 2025, marked a significant expansion of the organization’s scope and collaborative efforts. Building on the success of the previous meeting in Coimbra, the 2025 edition brought together 168 participants and featured a comprehensive scientific programme comprising 102 abstracts. A key highlight of this year’s conference was the collaboration with COST Action OneHealthdrugs and the Paul Ehrlich (PE) Euro-PhD Network, fostering interdisciplinary exchange and identifying future research synergies. The event included 1 computational workshop and 8 keynote lectures by international experts, alongside a strong emphasis on early-career researchers, with 25 oral presentations and 25 flash poster communications. In addition, 77 posters were presented across three dedicated sessions. All the presentations were eligible for 18 conference awards. Staying true to the GP₂A and PE mission, the conference provided a dynamic platform for young scientists to engage with established researchers. Full article

Objectives: Pulmonary metastasectomy is not a standardised procedure, with no consensus regarding the optimal extent of lung resection. This international multicentre study aimed at comparing short and long-term outcomes of anatomical versus non-anatomical pulmonary metastasectomy. Methods: Retrospective database including 1647 patients aged ≥18 years, who underwent curative intent pulmonary metastasectomy between January 2010 and December 2018 at 15 European centres. Patients who underwent pneumonectomy, previous metastasectomies, and/or suffered from extrapulmonary recurrence at the time of lung surgery were excluded. Primary endpoint was overall survival. Secondary endpoints were recurrence-free survival and 30-day morbidity. Differences between the two groups were analysed using 3:1 matching. Results: In the matched cohort, 324 patients underwent anatomical resection, and 830 patients underwent non-anatomical resection. Five-year overall survival was 62.0%. Averaged over the entire follow-up, there was no significant difference in overall survival between the two groups (HR = 1.122, 95% CI = 0.909–1.385, p = 0.283). In the early period following pulmonary metastasectomy, anatomical resections were associated with worse overall survival (HR = 1.549, 95% CI = 1.135–2.114, p = 0.006). The difference in any-site recurrence-free survival between the two groups was not significant (HR = 0.832, 95% CI = 0.690–1.002, p = 0.053). Locoregional recurrence-free survival was significantly longer after anatomical resection (HR = 0.651, 95% CI = 0.520–0.817, p < 0.001). Thirty-day morbidity was significantly higher after anatomical resection (22.2% versus 13.7% for non-anatomical resections, p = 0.001). Conclusions: In a highly selected cohort, non-anatomical resection showed comparable survival and lower morbidity compared to anatomical resections, supporting the surgical strategy of favouring limited resections whenever technically and oncologically feasible. Anatomical resections remain a valid option in selected cases with acceptable outcomes. Full article

The genus Psiadia (Asteraceae), widely distributed in Madagascar and the Mascarene Islands (Mauritius, La Réunion, Rodrigues), is traditionally used to treat bronchitis, asthma, colds, abdominal pain, and other inflammatory disorders. However, few studies have scientifically validated these traditional medicinal uses. To assess P. dentata as a valuable source of bioactive natural products, a combined ¹H NMR-based metabolomic, molecular networking, and phytochemical study was conducted. Multivariate analysis (PLS-DA) of crude extracts from Psiadia species collected on Reunion Island enabled rapid discrimination of active extracts from P. dentata and revealed two methoxylated flavonoids and one coumarin as metabolites correlated with its antiplasmodial and anti-inflammatory activities. Additionally, UHPLC-DAD-ESI-QTOF-MS/MS molecular networking approach enabled detailed chemical profiling of this species, allowing the annotation of 25 compounds (1–25) in this species. Subsequent phytochemical investigation of P. dentata leaves led to the isolation and identification of 25 metabolites, including nine new diterpenes (26–34), one new coumarin (35), and 15 known compounds (1–8, 11, 18, 19 and 36–39) from the diterpenoid, flavonoid, and coumarin families. The structures of the new compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR and HRESIMS analyses. Biological evaluation of the isolated compounds showed that compounds 1, 7, 26 and 27 showed antiplasmodial activity against Plasmodium falciparum (3D7 strain, IC₅₀ = 7.25–13.46 μM). Compounds 7, 26, 27, 31 and 32 inhibited nitric oxide production (IC₅₀ = 0.87–27.71 μM), indicating potential anti-inflammatory effects. Only compound 1 displayed moderate cytotoxicity against HepG2 and HT29 cancer cell lines (IC₅₀ = 25.67 and 18.35 μM, respectively). Full article

Background: Oncological treatment remains a major clinical challenge. Despite therapeutic advances and the diversity of available approaches, many tumors continue to exhibit limited responsiveness to chemotherapy. In this context, nutrition has emerged as a promising complementary strategy to support cancer therapy. In particular, interventions based on nutritional deprivation have gained prominence due to their ability to modulate tumor metabolism, inducing alterations that may increase the sensitivity of cancer cells to conventional treatments. Accordingly, the present study aimed to evaluate the safety and efficacy of caloric restriction combined with chemotherapy in a Sarcoma-180 model, investigating its effects on immunological and hematological parameters, antioxidant activity, oxidative stress, and tumor and liver morphology, as well as DNA damage. Methods: Mice bearing Sarcoma-180 were randomly assigned to four groups: Ad Libitum (AL), Ad Libitum + Doxorubicin (ALDOX), Caloric Restriction (CR), and Caloric Restriction + Doxorubicin (CRDOX). Assessment included tumor weight and volume, food and caloric intake, hematotoxicity, lipid metabolism, oxidative stress and antioxidant markers, genotoxicity, morphological alterations in the tumor and liver, and overall survival. Results: The data obtained demonstrate that caloric restriction combined with doxorubicin is both safe and feasible, as it preserves body weight and does not induce metabolic disturbances. Importantly, this combined strategy produced a marked reduction in tumor volume and mass while also mitigating the hematotoxicity typically associated with doxorubicin. In peripheral blood, the regimen decreased chemotherapy-induced DNA damage, supporting a systemic protective effect. Consistently, the combination reduced oxidative stress markers (NOx and MDA) and enhanced antioxidant activity within the tumor. Histological analyses further confirmed these outcomes, showing tumor cell death with features compatible with apoptosis and reduced local invasion. Together, these data indicate that caloric restriction enhances the antitumor efficacy of doxorubicin while simultaneously improving treatment tolerance. Conclusions: This study demonstrates that caloric restriction, combined with doxorubicin, is safe, well-tolerated, and enhances the antitumor response in the Sarcoma-180 model. Full article

Gastric cancer (GC) often presents a poor prognosis due to its asymptomatic phenotype at early stages. Upper endoscopy, which is the current gold standard to diagnose GC, is invasive with limited sensitivity for detecting gastric preneoplasia. Non-invasive biomarkers, such as blood circulating proteins, offer a promising alternative for the early detection of gastric lesions. In this prospective study, we identified plasma protein biomarkers for gastric preneoplasia and cancer using mass spectrometry-based proteomics in an exploratory cohort (n = 39). Fifteen promising protein candidates emerged to distinguish patient categories and were further confirmed by enzyme-linked immunosorbent assays (ELISA) in plasma samples from a validation cohort of 138 participants. Our predictive models demonstrated high classification performance with a minimal set of biomarkers. A four-protein panel (ARG1, CA2, F13A1, S100A12) achieved 94.1–98.2% AUROC (95% CI) for distinguishing cancer from non-cancer cases, while a five-protein panel (ARG1, CA2, HPT, MAN2A1, LBP) reached 97.3–99.5% AUROC (95% CI) for distinguishing cancer or preneoplasia from healthy or non-atrophic gastritis cases on the full cohort. Leveraging simple blood sampling, this strategy holds promise to detect high-risk gastric lesions, even at asymptomatic stages. Such an approach could significantly improve early detection and clinical management of GC, offering direct benefit for patients. Full article

Background: Irreversible electroporation (IRE) is a novel ablative treatment modality for localized prostate cancer and aims at achieving oncological control while minimizing the related side effects. We present the functional and oncological outcomes of focal IRE ablation versus hemi-ablation from a single-center patient series. Methods: Men with histologically confirmed low–intermediate risk prostate cancer received focal IRE ablation or hemi-ablation. All the patients were recommended an MRI-targeted fusion biopsy plus systematic biopsy at 1 year post-IRE ablation. The functional outcomes were measured by the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) questionnaires. Results: In total, 106 patients were recruited in this study. The median follow-up time was 24 months (IQR 15–36). Overall, 94 patients underwent repeat prostate biopsy at 12 months after IRE. Persistent tumor was detected in 72.2% in the focal ablation group and in 31% in the hemi-ablation group (p < 0.001). Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 25% in the focal ablation group and in 8.6% in the hemi-ablation group (p = 0.003). There was no significant difference between the two groups in terms of IPSS and IIEF at each follow-up time point. Conclusion: For men with localized low–intermediate risk prostate cancer, hemi-IRE ablation treatment displayed better oncological control than focal ablation without compromising on functional or sexual outcomes. Full article

Youth exposed to early-life adversity (ELA) are at greater risk for poorer physical and mental health outcomes in adolescence and adulthood. Although the biological mechanisms underlying these associations remain elusive, DNA methylation (DNAm) has emerged as a potential pathway. DNAm-based measures of epigenetic age have been associated with ELA, indicating accelerated aging. According to the stress sensitization hypothesis, prenatal adversity may further heighten sensitivity to subsequent stressors in childhood and adolescence. This study examined the associations between ELA and six epigenetic aging measures, considering both the timing of adversity and the participant’s sex. Data were drawn from the Quebec Longitudinal Study of Child Development, with two cumulative indices of ELA derived from prospectively collected data: the Perinatal Adversity and the Child and Adolescent Adversity indices. Higher Perinatal Adversity scores were associated with accelerated DunedinPACE scores. No significant associations were found between ELA and the other epigenetic clocks, nor did we find support for the stress sensitization hypothesis—though a sex-specific trend emerged among girls. The findings suggest that DunedinPACE may be more sensitive to variations in ELA than other clocks. Future research should systematically investigate sex-dimorphic associations between ELA and epigenetic aging, with particular attention to the impact of perinatal adversity. Full article

Mother’s own milk (MOM) offers the highest protection for preterm and low birth weight infants. However, breastfeeding can be challenging during neonatal hospitalization. When MOM is unavailable, donor human milk (DHM) is the recommended alternative for feeding vulnerable neonates. Human milk banks (HMBs) collect, process, and deliver DHM, playing a key role in lactation support and promoting MOM availability. Although HMBs are expanding globally, scale-up remains hindered, restricting equitable DHM access. In Switzerland, despite the existence of eight HMBs, the western region lacked such a facility until 2022. To address this gap, an interdisciplinary team from the Lausanne University Hospital (CHUV) and the Swiss Red Cross Interregional Blood Transfusion Centre (TIR) collaborated to establish a regional HMB. This partnership leveraged both institutions’ available expertise, infrastructure, and resources. After two years of preparation, the CHUV Lactarium launched in 2022 with the support of the Department of Health and Social Action (DSAS) of the Canton of Vaud. This novel human milk bank–blood bank model is fully integrated into the hospital’s neonatal care, nutrition, and breastfeeding programs, operating under a strict quality and coordination system. Since its implementation, the HMB has met 100% of DHM needs, with an 80% breastfeeding bridging rate. It has had a positive impact on neonatal care, family engagement, professional interest, and community awareness of human milk. This case study illustrates how synergistic collaboration can help bridge gaps in establishing a safe, efficient, and equitable HMB model. It also offers a scalable framework adaptable to other settings. Full article

Background: Women with a familial predisposition to breast cancer (BC) are offered screening at earlier ages and more frequently than women from the general population. Methods: We evaluated the effect of screening mammography in 1552 BC cases with a hereditary predisposition to BC unexplained by BRCA1 or BRCA2 and 1363 unrelated controls. Participants reported their lifetime mammography exposures in a detailed questionnaire. Germline rare deleterious or predicted deleterious variants (D-PDVs) in 113 DNA repair genes were investigated in 82.5% of the women and classified according to the strength of their association with BC. Genes with an odds ratio (OR) < 0.9 was assigned to the Gene Group “Reduced”, those with OR ≥ 0.9 and ≤1.1 to Group “Independent”, and those with OR > 1.1 to Group “Increased”. Results: Overall, having been exposed to mammograms (never vs. ever) was not associated with BC risk. However, an increase in BC risk of 4% (95% CI: 1–6%) per additional exposure was found under the assumption of linearity. When grouped according to D-PDV carrier status, mammograms doubled the BC risk of women carrying a D-PDV in Group “Reduced”, as compared to those carrying a D-PDV in Group “Increased”. Conclusions: Our study is the first to investigate the joint effect of mammogram exposure and variants in DNA repair genes other than BRCA1 and BRCA2 in women at high risk of BC; therefore, further studies are needed to verify our findings. Even though mammographic screening reduces the risk of mortality from BC, the identification of populations that are more or less susceptible to ionizing radiation may be clinically relevant. Full article

Objectives: Perfusion strategy is crucial for the outcome of neonatal aortic arch surgery. This study investigates Whole-Body Perfusion to potentially improve postoperative outcomes for neonates, addressing a significant gap in current research. Methods: Retrospective analysis was conducted for neonates receiving aortic arch reconstruction in our institution: 33 patients were treated with Antegrade Cerebral Perfusion (ACP, 2014–2017) and 61 patients with Whole-Body Perfusion (WBP, 2017–2022). After strict Propensity Score Matching, 20 patients were analyzed in each group. WBP consists of ACP and Lower Body Perfusion (LBP), achieved through a femoral arterial sheath. Results: Patients with WBP had a shorter time on Cardiopulmonary Bypass (86.65 ± 25.47 vs. 172.95 ± 60.12 min) and Cross-Clamp time (46.70 ± 18.48 vs. 91.30 ± 40.10 min) (p ≤ 0.001). Lactate at the time of reperfusion and after 24 h was lower in the WBP group (1.73 ± 0.63 vs. 4.29 ± 1.61, p < 0.001; 1.45 ± 0.57 vs. 2.09 ± 0.96 mmol/L, p = 0.026). Patients with WBP needed significantly fewer intraoperative transfusions of Red Blood Cells, Fresh Frozen Plasma and Platelets (p ≤ 0.001). WBP patients had a shorter time on ventilator (5.15 ± 4.05 vs. 10.00 ± 8.72 days, p = 0.01) and a higher urine output after 24 h (200.85 ± 100.87 vs. 118.10 ± 82.33 mL, p = 0.002). Conclusions: Patients treated with WBP received significantly fewer intraoperative transfusions and had a shorter time on extracorporeal circulation and ventilator. Furthermore, there was a trend for reduced multiorgan dysfunction. Full article

Background: Choroidal involution is a common feature of age-related ischemic retinopathies such as age-related macular degeneration (AMD). It is now well recognized that endothelial progenitor cells (EPCs) are essential to endothelial repair processes and in maintaining vascular integrity. However, the contribution of EPCs and the role of senescence in age-related choroidal vascular degeneration remain to be investigated. In this study, we compared the senescent phenotype of EPCs in the choroid and performed whole-genome profiling of EPCs derived from young versus old rats. Methods and Results: We isolated and compared the retinas of young (6-weeks-old) and old (16–18-month-old) rats. The thickness of the choroid and outer nuclear layer (ONL), along with local quantification of CD34+ EPCs, was performed. Compared to young rats, older rats displayed a significant reduction in choroidal and ONL thickness associated with markedly fewer choroid-localized EPCs; this was attested by lower expression of several EPC markers (CXCR4, CD34, CD117, CD133, and KLF-2). Choroid and choroid-localized EPCs displayed abundant senescence as revealed by increased β-gal and P53 expression and decreased Lamin-B1 (immunostaining and RT-qPCR). Concordantly, choroidal cells and EPCs isolated from older rats were unable to form vascular networks ex vivo. To better understand the potential mechanisms associated with the dysfunctional EPCs linked to age-related choroidal involution, we performed whole-genome profiling (mRNA and miRNA) of EPCs derived from old and young rats using next-generation sequencing (NGS); 802 genes were significantly modulated in old vs. young EPCs, corresponding to ~2% of total genes expressed. Using a bioinformatic algorithm, the KEGG pathways suggested that these genes participate in the modulation of several key signaling processes including inflammation, G protein-coupled receptors, and hematopoietic cell lineages. Moreover, we identified 13 miRNAs involved in the regulation of immune system processes, cell cycle arrest and senescence, which are significantly modulated in EPCs from old rats compared to young ones. Conclusions: Our results suggest that age-related choroidal involution is associated with fewer EPCs, albeit displaying a senescence-like phenotype. One would be tempted to propose that biological modification of native EPCs (such as with senolytic agents) could potentially provide a new strategy to preserve the vascular integrity of the aged choroid, and evade progression to degenerative maculopathies. Full article

Background: Neonatal aortic arch surgery remains one of the most challenging procedures in congenital cardiac surgery. In recent years, there has been a trend away from selective cerebral perfusion (SCP) and arrest of body circulation towards whole-body perfusion (WBP), a combination of SCP and lower-body perfusion (LBP), to facilitate arch surgery and preserve organ function. Methods: Retrospective, single-centre analysis was conducted of patients under one year of age undergoing aortic arch surgery from January 2014 until December 2022. SCP was used from January 2014—December 2017; WBP was implemented from January 2017—December 2022. Patients were separated according to the type of perfusion used during surgery, SCP or WBP. The cohort consisted of a total of 95 patients, 34 in the SCP group and 61 in the WBP group. Results: Patients in the WBP group showed significantly lower rates of intraoperative transfusions, namely red blood cells, fresh-frozen plasma and thrombocytes (p-value < 0.01, <0.01, and <0.01, respectively). The WBP group showed significantly lower creatinine and higher urine output values 24 and 72 h after surgery (p-value = 0.02, <0.01, respectively). The WBP group showed a significant lower incidence of major neurological complications (p-value 0.01). Binary logistic regression analyses showed favourable outcomes for the WBP group regarding 30-day mortality (OR = 0.03, CI = 0.003–0.391, p-value = <0.01), multiorgan failure (OR = 0.002, CI = 0–0.275, p-value = 0.01), neurological complications (OR = 0.994, CI = 0.998–1, p-value = 0.06) and postoperative renal replacement therapy (RRT) (OR = 0.989, CI = 0.983–0.995, p-value = <0.01). Conclusions: Patients with WBP received fewer intraoperative transfusions, showed improved postoperative renal function and suffered significantly fewer neurological complications. Full article

Delayed therapy escape (DTE) is frequent after thalamic deep brain stimulation for essential tremor, leading to reduced quality of life, often with ataxic symptoms, and early recognition is challenging. Our goal was to examine whether a low-frequency rebound tremor of the left hand after switching off stimulation is useful as a diagnostic marker for DTE. In this cross-sectional study with additional retrospective analysis, we examined 31 patients with bilateral thalamic DBS ≥ 12 months for essential tremor, using quantitative assessments including video-based motion capture, Fahn–Tolosa–Marin Tremor Rating Scale (FTMTRS), and scale for the assessment and rating of ataxia (SARA). If available, preoperative (preOP) and 12-month postoperative assessments were included in the analysis. Evaluations occurred with DBS activated (ON) and deactivated (OFF). A higher ratio FTMTRS now_ON/preOP indicated DTE. Preoperative FTMTRS scores were available for 16 patients, including 5 patients with DTE. The receiver operating characteristic analysis found an area under the curve of 0.86 (p = 0.024) for identification of DTE by low-frequency rebound tremor (i.e., OFF) on the left. In conclusion, it could serve as a potential diagnostic marker. Full article

Leber congenital amaurosis (LCA)/early-onset severe retinal dystrophy (EOSRD) stand as primary causes of incurable childhood blindness. This study investigates the clinical and molecular architecture of syndromic and non-syndromic LCA/EOSRD within a Chilean cohort (67 patients/60 families). Leveraging panel sequencing, 95.5% detection was achieved, revealing 17 genes and 126 variants (32 unique). CRB1, LCA5, and RDH12 dominated (71.9%), with CRB1 being the most prevalent (43.8%). Notably, four unique variants (LCA5 p.Glu415*, CRB1 p.Ser1049Aspfs*40 and p.Cys948Tyr, RDH12 p.Leu99Ile) constituted 62.7% of all disease alleles, indicating their importance for targeted analysis in Chilean patients. This study underscores a high degree of inbreeding in Chilean families affected by pediatric retinal blindness, resulting in a limited mutation repertoire. Furthermore, it complements and reinforces earlier reports, indicating the involvement of ADAM9 and RP1 as uncommon causes of LCA/EOSRD. These data hold significant value for patient and family counseling, pharmaceutical industry endeavors in personalized medicine, and future enrolment in gene therapy-based treatments, particularly with ongoing trials (LCA5) or advancing preclinical developments (CRB1 and RDH12). Full article