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Although the intake of nonsteroidal anti-inflammatory drugs ( NSAIDs) intake by athletes prevents soreness, little is known concerning their role in exercise performance. This study assessed the effects of ibuprofen intake on an exhaustive protocol test after 6 weeks of swimming training in rats. Animals were divided into sedentary and training groups. After training, animals were subdivided into two subsets: saline or ibuprofen. Afterwards, three repeated swimming bouts were performed by the groups. Ibuprofen (15 mg/kg) was administered once a day. Pain measurements were performed and inflammatory and oxidative stress parameters were assayed in cerebral cortex and gastrocnemius muscle. Training, ibuprofen administration, or both combined ( P < 0.05; 211 ± 18s, 200 ± 31s, and 279 ± 23s) increased exercise time to exhaustion. Training decreased the acetylcholinesterase ( AChE) activity ( P < 0.05; 149 ± 11) in cerebral cortex. Ibuprofen intake decreased the AChE activity after exhaustive protocol test in trained and sedentary rats ( P < 0.05; 270 ± 60; 171 ± 38; and 273 ± 29). It also prevented neuronal tumor necrosis factor-α ( TNF-α) and interleukin ( IL 1β) increase. Fatigue elicited by this exhaustive protocol may involve disturbances of the central nervous system. Additive anti-inflammatory effects of exercise and ibuprofen intake support the hypothesis that this combination may constitute a more effective approach. In addition, ergogenic aids may be a useful means to prevent exercise-induced fatigue. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the impact of moderate aerobic training on functional, anthropometric, biochemical, and health-related quality of life (HRQOL) parameters on women with metabolic syndrome (MS). Fifteen untrained women with MS performed moderate aerobic training for 15 weeks, without modifications of dietary behaviours. Functional, anthropometric, biochemical, control diet record and HRQOL parameters were assessed before and after the training. Despite body weight maintenance, the patients presented decreases in waist circumference (P=0.001), number of MS components (P=0.014), total cholesterol (P=0.049), HDL cholesterol (P=0.004), LDL cholesterol (P=0.027), myeloperoxidase activity (P=0.002) and thiobarbituric acid-reactive substances levels (P=0.006). There were no differences in total energy, carbohydrate, protein and lipid intake pre- and post-training. Furthermore, improvements in the HRQOL subscales of physical functioning (P=0.03), role-physical (P=0.039), bodily pain (P=0.048), general health (P=0.046) and social functioning scoring (P=0.011) were reported. Despite the absence of weight loss, aerobic training induced beneficial effects on functional, anthropometric, biochemical and HRQOL parameters in women with MS. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to determine if the critical swimming velocity (CSV), defined as the theoretical maximal swimming velocity that could be maintained for a long period of time without exhaustion, corresponds to the exercise intensity at onset blood lactate accumulation (OBLA), and if it could be utilized as a practical index for assessing endurance performance in elite physically disabled swimmers. Eight elite physically disabled swimmers swam four different distances (50, 100, 200 and 400 m) at maximal effort. The swimming time was taken during each trial. The CSV was expressed as the slope of a regression line between the covered swimming distance and the corresponding times of all possible combinations of 2 or 4 time trials. Results indicate that all the CSVs calculated were similar independently of the distances utilized for their calculation. Afterwards, a CSV confirmation test consisting of 3 x 10-min trials at 95, 100, 105% of the CSV was carried out. The lactate concentration at the end of each trial was 3.32, 4.03 and 5.73 mmol x l(-1), respectively. Lactate concentration at 100% CSV approached the value of 4 mmol x l(-1), which is considered the exercise intensity at OBLA. We conclude that the CSV corresponds with the OBLA intensity and could be a valuable index to plan a training schedule for physically disabled swimmers. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a common retinal pathology characterized by degeneration of macula's retinal pigment epithelium (RPE) and photoreceptors, visual impairment, or loss. Compared to wet AMD, dry AMD is more common, but lacks cures; therefore, identification of new potential therapeutic targets and treatments is urgent. Increased oxidative stress and declining antioxidant, detoxifying systems contribute to the pathophysiologic mechanisms underlying AMD. The present work shows that the Embryonic Lethal Abnormal Vision-Like 1/Human antigen R (ELAVL1/HuR) and the Vascular Endothelial Growth Factor (VEGF) protein levels are higher in the RPE of both dry and wet AMD patients compared to healthy subjects. Moreover, increased HuR protein levels are detected in the retina, and especially in the RPE layer, of a dry AMD model, the nuclear factor erythroid 2-related factor 2 (Nrf2) / peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) double knock-out mouse. The crosstalk among Nrf2, HuR and VEGF has been also studied in ARPE-19 cells in basal and stressful conditions related to the AMD context (i.e., oxidative stress, autophagy impairment, Nrf2 deficit), offering new evidence of the mutual influence between Nrf2 and HuR, of the dependence of VEGF expression and secretion by these two factors, and of the increased susceptibility of cells to stressful conditions in Nrf2- or HuR-impaired contexts. Overall, this study shows evidence of the interplay among Nrf2, HuR and VEGF, essential factors for RPE homeostasis, and represents an additional piece in the understanding of the complex pathophysiologic mechanisms underlying AMD., Competing Interests: Declaration of Competing Interest I declare that potential competing interests do not exist and there is no financial/personal interest, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Among the tumors with the highest lethality, gliomas are primary brain tumors associated with common recurrence inclined to metastasize along the neuraxis and occasionally out of the central nervous system. Even though metastasis is the main responsible for death in oncological patients, few dedicated treatments are approved. Therefore, the establishment of effective anti-metastasis agents is the final frontier in cancer research. Interestingly, some copper complexes have demonstrated promising efficacy as antimetastatic agents, but they may cause off-site effects such as the alteration of copper homeostasis in healthy tissues. Thus, the incorporation of copper-based antimetastatic agents in rationally designed nano-architectures can increase the treatment localization reducing the side effects. Here, copper complex loaded hybrid nano-architectures (CuLNAs) are presented and employed to assess the impact of an intracellular copper source on glioma cell invasiveness. The novel CuLNAs are fully characterized and exploited for cell migration modulation in a glioma cell line. The results demonstrate that CuLNAs significantly reduce cell migration without impairing cell proliferation compared to standard gold and copper NAs. A concomitant antimigratory-like regulation of the epithelial-to-mesenchymal transition genes confirmed these results, as the gene encoding for the epithelial protein E-cadherin was upregulated and the other explored mesenchymal genes were downregulated. These findings, together with the intrinsic behaviors of NAs, demonstrate that the inclusion of metal complexes in the nano-architectures is a promising approach for the composition of a family of agents with antimetastatic activity., Competing Interests: Declaration of Competing Interest The Authors declare no competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the synthesis of metal-organic frameworks (MOFs), the choice of the metal precursor plays a key role because of the influence that it can exert on the crystallization kinetics. The present work explores the use of metal-carbamato complexes for the synthesis of benchmark MOFs, namely HKUST-1 and UiO-66. Cu 2 (O 2 CNEt 2 ) 4 ·2NHEt 2 and Zr(O 2 CNEt 2 ) 4 , prepared using straightforward CO 2 fixation reactions starting from the corresponding metal chlorides and diethylamine, were employed as metal precursors for MOF formation. The synthesis conditions, including the solvent, temperature, and ligand protonation degree, were systematically investigated, revealing metal carbamates as highly reactive precursors due to their prompt release of CO 2 and amine upon reaction with protic species, i.e. , the polycarboxylic linkers. This property of metal carbamates allowed us to identify room temperature protocols to achieve MOFs with comparable properties to those obtained using traditional metal precursors. Subsequent optimization of the reaction conditions led to the design of a one-pot synthetic strategy for HKUST-1, starting directly from copper(II) chloride and diethylamine under a CO 2 atmosphere. The MOFs were characterized using various techniques, including powder X-ray diffraction, N 2 sorption analysis, 1 H nuclear magnetic resonance spectroscopy, and CHN elemental analysis, and compared to reference samples prepared according to literature procedures.

Primary cilia are sensory organelles that extend from the cellular membrane and are found in a wide range of cell types. Cilia possess a plethora of vital components that enable the detection and transmission of several signaling pathways, including Wnt and Shh. In turn, the regulation of ciliogenesis and cilium length is influenced by various factors, including autophagy, organization of the actin cytoskeleton, and signaling inside the cilium. Irregularities in the development, maintenance, and function of this cellular component lead to a range of clinical manifestations known as ciliopathies. The majority of people with ciliopathies have a high prevalence of retinal degeneration. The most common theory is that retinal degeneration is primarily caused by functional and developmental problems within retinal photoreceptors. The contribution of other ciliated retinal cell types to retinal degeneration has not been explored to date. In this review, we examine the occurrence of primary cilia in various retinal cell types and their significance in pathology. Additionally, we explore potential therapeutic approaches targeting ciliopathies. By engaging in this endeavor, we present new ideas that elucidate innovative concepts for the future investigation and treatment of retinal ciliopathies., (© 2024. The Author(s).)

Parents and caregivers may seek help with different questions or concerns on how to handle the diverse gender expressions of their children. Sometimes the issue may be evident while seeking medical advice for other concerns. Because of the many uncertainties around this topic, clinicians need to know what to say and what can be done to provide the best possible care for gender-diverse children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

We present a new synthetic strategy for obtaining mixed-valence triiron complexes where the metal centers are bridged by a novel, highly functionalized hydrocarbyl ligand. The alkynyl-vinyliminium complexes [Fe 2 Cp 2 (CO)(μ-CO){μ-η 1 :η 3 -C(X-CCH)CHCNMe 2 }]CF 3 SO 3 (X = 4-C 6 H 4 , [2a1]CF3SO3; X = (CH 2 ) 3 , [2a2]CF3SO3) were synthesized in almost quantitative yields from the aminocarbyne precursor [Fe 2 Cp 2 (CO) 2 (μ-CO){μ-CNMe 2 }]CF 3 SO 3 , [1a]CF3SO3, and the di-alkynes HCC-X-CCH. Then, the ferracycle [Fe(Cp)(CO){C(NMe 2 )CHC(4-C 6 H 4 CCH)C(O)}], 4a1, was produced in 47% yield from the cleavage of [2a1]CF3SO3 promoted by pyrrolidine. Subsequent reactions of the acetonitrile adducts [Fe 2 Cp 2 (CO)(μ-CO)(NCMe){μ-CNMe(R)}]CF 3 SO 3 (R = Me, [1aACN]CF3SO3; R = Xyl, [1bACN]CF3SO3) ([Fe I Fe I ]) with 4a1 ([Fe II ]) at room temperature resulted in the formation of [Fe I Fe I Fe II ] complexes [Fe 2 Cp 2 (CO)(μ-CO){μ-η 1 :η 3 -C(X-CCHC(NMe 2 )FeCp(CO)CO)CHCNMe(R)}]CF 3 SO 3 (R = Me, [5a1]CF3SO3; R = Xyl, [5b1]CF3SO3) in yields ranging from 56% to 64%. The new products were characterized by IR and multinuclear NMR spectroscopy, and the structures of [2a2]CF3SO3 and 4a1 were confirmed by single crystal X-ray diffraction. Cyclic voltammetry and spectroelectrochemical studies on [5a1]+ have revealed that reduction and oxidation events occur almost independently at the [Fe I Fe I ] and [Fe II ] units, respectively. This observation underscores a minimal electronic interaction between the two fragments within the triiron complex. Accordingly, DFT studies pointed out that the HOMO and LUMO orbitals are predominantly localized in the two distinct compartments of [5a1]+.

Objectives: This study aimed to investigate the dynamic patterns of perception and expectations among COPD patients. Methods: Conducted at the Heart-Respiratory Rehabilitation Unit, IRCCS Fondazione Don Carlo Gnocchi, in Milan, Italy, the research involved 28 participants (16 males; mean age 72.8 ± 9.9) in face-to-face interviews. Utilizing a Grounded Theory approach, complemented by clinical data, recorded, and transcribed interviews underwent enhancement through the integration of two pictorial tools. Results: The central theme that emerged was a profound sense of responsibility toward their condition, perceived as a significant threat to life. Key symptoms, such as shortness of breath, coupled with negative expectations about their condition, contributed to depressive mood and avoidance behaviors. A notable proportion ( N = 17; 60.71%) of participants struggled to envision a positive future, expressing a pervasive sense of hopelessness, which significantly influenced their health behaviors and adherence to medical recommendations. Conversely, individuals who felt supported and optimistic about treatment efficacy exhibited more positive expectations and adopted proactive coping strategies. Discussion: Recognizing the dynamic nature of patients' perceptions and negative illness expectations is essential to create personalized therapeutic interventions and meet the specific needs of COPD patients, ultimately improving the overall effectiveness of their care journey., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The indole scaffold has been established as a key organic moiety for developing new drugs; on the other hand, a range of diiron bis-cyclopentadienyl complexes have recently emerged for their promising anticancer potential. Here, we report the synthesis of novel diiron complexes with an indole-functionalized vinyliminium ligand (2-5) and an indole-lacking analogue for comparative purposes (6), which were characterized by analytical and spectroscopic techniques. Complexes 2-6 are substantially stable in DMSO‑d 6 and DMEM-d solutions at 37 °C (8% average degradation after 48 h) and display a balanced hydrophilic/lipophilic behaviour (LogP ow values in the range -0.32 to 0.47), associated with appreciable water solubility. The complexes display selective antiproliferative potency towards several cancer cells in monolayer cultures, mainly in the low micromolar range, with reduced toxicity towards noncancerous epithelial cells. Thus, the cytotoxicity of the complexes is comparable to or better than clinically used metallopharmaceutical cisplatin. Comparing the antiproliferative activity obtained for complexes containing different ligands, we confirmed the importance of the indolyl group in the mechanism of antiproliferative activity of these complexes. Cell-based mechanistic studies suggest that the investigated diiron vinyliminium complexes (DVCs) show cytostatic rather than cytotoxic effects and subsequently induce a population of cells to undergo apoptosis. Furthermore, the molecular mechanism of action involves interactions with mitochondrial DNA and proteins, the reactive oxygen species (ROS)-scavenging properties and antioxidant activity of these complexes in cancer cells. This study highlights the importance of DVCs to their cancer cell activity and reinforces their prospective therapeutic potential as anticancer agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diruthenacyclopentenone complexes of the general composition [Ru 2 Cp 2 (CO) 2 {μ-η 1 :η 3 -CH═C(C(OH)(R))C(═O)}] ( 2a - c ; Cp = η 5 -C 5 H 5 ) were synthesized in 94-96% yields from the reactions of [Ru 2 Cp 2 (CO) 2 {μ-η 1 :η 3 -C(Ph)═C(Ph)C(═O)}] ( 1 ) with 1-ethynylcyclopentanol, 17α-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a - c by HBF 4 afforded the corresponding allenyl derivatives [Ru 2 Cp 2 (CO) 3 {μ-η 1 :η 2 -CH═C═R}]BF 4 ( 3a - c ) in 85-93% yields. All products were thoroughly characterized by elemental analysis, mass spectrometry, and IR, UV-vis, and nuclear magnetic resonance spectroscopy. Additionally, 2a and 3a were investigated by cyclic voltammetry, and the single-crystal diffraction method was employed to establish the X-ray structures of 2b and 3a . The cytotoxicity in vitro of 2b and 3a - c was evaluated against nine human cancer cell lines (A2780, A2780R, MCF-7, HOS, A549, PANC-1, Caco-2, PC-3, and HeLa), while the selectivity was assessed on normal human lung fibroblast (MRC-5). Overall, complexes exert stronger cytotoxicity than cisplatin, and 3b (comprising 17α-estradiol derived ligand) emerged as the best-performing complex. Inductively coupled plasma mass spectrometry cellular uptake studies in A2780 cells revealed a higher level of internalization for 3b and 3c compared to 2b , 3a, and the reference compound RAPTA-C. Experiments conducted on A2780 cells demonstrated a noteworthy impact of 3a and 3b on the cell cycle, leading to the majority of the cells being arrested in the G0/G1 phase. Moreover, 3a moderately induced apoptosis and oxidative stress, while 3b triggered autophagy and mitochondrial membrane potential depletion.

Dimethyl fumarate (DMF) is an FDA-approved drug for the treatment of psoriasis and multiple sclerosis. DMF is known to stabilize the transcription factor Nrf2, which in turn induces the expression of antioxidant response element genes. It has also been shown that DMF influences autophagy and participates in the transcriptional control of inflammatory factors by inhibiting NF-κB and its downstream targets. DMF is receiving increasing attention for its potential to be repurposed for several diseases. This versatile molecule is indeed able to exert beneficial effects on different medical conditions through a pleiotropic mechanism, in virtue of its antioxidant, immunomodulatory, neuroprotective, anti-inflammatory, and anti-proliferative effects. A growing number of preclinical and clinical studies show that DMF may have important therapeutic implications for chronic diseases, such as cardiovascular and respiratory pathologies, cancer, eye disorders, neurodegenerative conditions, and systemic or organ specific inflammatory and immune-mediated diseases. This comprehensive review summarizes and highlights the plethora of DMF's beneficial effects and underlines its repurposing opportunities in a variety of clinical conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bresciani, Manai, Davinelli, Tucci, Saso and Amadio.)

We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds ( 2 - 4 ) were obtained (45-92% yields) from the thermal reaction (PhCCPh exchange) of [Ru 2 Cp 2 (CO)(μ-CO){μ-η 1 :η 3 -C(Ph)═C(Ph)C(═O)}], 1 , with alkynes HCCR [R = C 5 H 4 FeCp (Fc), 3-C 6 H 4 (Asp), 2-naphthyl; Cp = η 5 -C 5 H 5 , Asp = OC(O)-2-C 6 H 4 C(O)Me]. Protonation of 1 - 3 by HBF 4 afforded the corresponding μ-alkenyl derivatives 5 - 7 , in 40-86% yields. All products were characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry ( 1 , 2 , 5 , 7 ) and single-crystal X-ray diffraction ( 5 , 7 ) analyses were performed on representative compounds. Complexes 5 - 7 revealed a cytotoxic activity comparable to that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma), and ovarian (A2780) cancer cell lines, and 2 , 5 , 6 , and 7 overcame cisplatin resistance in A2780cis cells. Complexes 2 , 5 , and 7 (but not the aspirin derivative 6 ) induced an increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus, CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 is ineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity for this nucleic acid. Complexes 5 - 7 can interact with the albumin protein with a thermodynamic signature dominated by hydrophobic interactions. Overall, we show that organometallic species based on the Ru 2 Cp 2 (CO) x scaffold ( x = 2, 3) are active against cancer cells, with different incorporated fragments influencing the interactions with nucleic acids and the production of ROS.

Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries ( n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.