Search Results (655)

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article

Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadustat causing the strongest transcriptional changes. However, Roxadustat-induced angiogenic signals did not promote endothelial tube formation. Moreover, it did not induce oxidative stress, inflammation, or significant antioxidant gene responses in ARPE-19 cells. Roxadustat also reduced the inflammatory cytokine response to tumor necrosis factor-α, including IL-6, IL-8, and MCP-1, and did not exacerbate VEGF expression under high-glucose conditions. Overall, Roxadustat triggered complex gene expression changes without promoting inflammation or oxidative stress in RPE cells. Despite these findings, ophthalmologic monitoring is advised during PHI treatment in CKD patients receiving HIF-PHIs. Full article

Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients. Full article

The aim of this study is to evaluate the effectiveness of deacidifying treatments for the restoration of textiles used as supports for works of art, with particular attention to the chemical stability, colour variation and mechanical resistance of the materials over time. The present study involved the analysis of two products: Bookkeeper^TM, containing magnesium oxide, and Nanorestore^TM, a dispersion of calcium hydroxide in alcoholic solutions of ethanol and 2-propanol. The products were applied to a series of tests on cotton, linen and jute fabrics. The experimental approach comprised an artificial degradation process of the fabrics, followed by the application of the treatments and an accelerated ageing cycle. A series of parameters were monitored throughout the experiment, encompassing surface pH, chromatic shifts ascertained through colorimetric measurements and the morphological transformations of the fabrics, as elucidated by scanning electron microscopy (SEM-EDS). The findings yielded from this study have enabled the delineation of the behaviour exhibited by the treated materials over an extended timeframe. This underscores the significance of a judicious selection of treatments, contingent upon the particular chemical and physical attributes inherent to the fabrics in question. Full article

Plasma electrolytic oxidation (PEO) is an advanced electrochemical surface treatment technology. It can effectively improve the corrosion resistance of magnesium and its alloys. This paper aims to form protective PEO coatings on an AZ31 substrate with different electrolytes, while monitoring the micro-discharge evolution by noise intensity and morphology analysis. By setting the PEO parameters and monitoring process characteristics, such as current density, spark appearance, and noise intensity, it was deduced that the PEO process consists of the following three stages: anodic oxidation, spark discharge, and micro-arc discharge. The PEO oxide coating formed on the AZ31 alloy exhibits various irregular volcano-like structures. Oxygen species are uniformly distributed along the coating cross-section. Phosphorus species tend to be enriched inwards to the coating/magnesium substrate interface, while aluminum piles up towards the surface region. Surface roughness of the PEO coating formed in the silicate-based electrolyte was the lowest in an arithmetic average height (Sa) of 0.76 μm. Electrochemical analysis indicated that the corrosion current density of the PEO coating decreased by about two orders of magnitude compared to that of untreated blank AZ31 substrate, while, at the same time, the open-circuit potential shifted significantly to the positive direction. The corrosion current density of the 10 min/400 V coating was 1.415 × 10⁻⁶ A/cm², approximately 17% lower than that of the 2 min/400 V coating (1.738 × 10⁻⁶ A/cm²). For a fixed 10 min treatment, the longer the PEO duration time, the lower the corrosion current density. Finally, the tested potentiodynamic polarization curve reveals the impact of different types of PEO electrolytes and different durations of PEO treatment on the corrosion resistance of the oxide coating surface. Full article

Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the AGE-RAGE-NF-κB axis, increases oxidative stress, and impairs macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, collectively disrupting normal wound healing processes. The local wound environment is further worsened by antibiotic-resistant polymicrobial infections, which sustain inflammatory signaling and promote extracellular matrix degradation. The rising threat of antimicrobial resistance complicates infection management even further. Recent studies emphasize that optimal glycemic control using antihyperglycemic agents such as metformin, Glucagon-like Peptide 1 receptor agonists (GLP-1 receptor agonists), and Dipeptidyl Peptidase 4 enzyme inhibitors (DPP-4 inhibitors) improves overall metabolic balance. These agents also influence angiogenesis, inflammation, and tissue regeneration through pathways including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and vascular endothelial growth factor (VEGF) signaling. Evidence indicates that maintaining glycemic stability through continuous glucose monitoring (CGM) and adherence to antihyperglycemic treatment enhances antibiotic effectiveness by improving immune cell function and reducing bacterial virulence. This review consolidates current molecular evidence on the combined effects of glycemic and antibiotic therapies in DFUs. It advocates for an integrated approach that addresses both metabolic and microbial factors to restore wound homeostasis and minimize the risk of severe outcomes such as amputation. Full article

Hypochlorous acid (HClO) serves as a biological mediator and is widely utilized as a disinfectant in food processing and water treatment. However, excessive HClO residues in food and environmental water raise concerns due to the potential formation of carcinogenic chlorinated byproducts and disinfection byproducts (DBPs). Despite its importance, traditional methods for HClO detection often involve complex sample preparation, sophisticated instrumentation, and skilled operators. Herein, we report an aggregation-induced emission (AIE) small molecule fluorescent probe (NYV) that integrates colorimetric and ratiometric fluorescence responses for the detection of HClO. This probe exhibits high sensitivity, with a detection limit of 0.35 $\mathsf{\mu }$M, a rapid response time of 1 min, and a wide linear range (0–142.5 $\mathsf{\mu }$M), along with anti-interference capabilities, making it suitable for real-time monitoring. Furthermore, we have developed a portable solid-state sensor based on probe NYV for the rapid visual detection of HClO. The potential applications of this probe in real sample analysis and bioimaging experiments are demonstrated. Our findings contribute to the development of innovative fluorescent probes for HClO detection, with broad applications in food safety, environmental monitoring, and biomedical research on oxidative stress and ferroptosis. Full article

We present a miniaturized, inexpensive, and user-friendly microfluidic platform to support biological applications. The system integrates a mini-incubator providing controlled environmental conditions and housing a microfluidic device for long-term cell culture experiments. The incubator is designed to be compatible with standard inverted optical microscopes and Raman spectrometers, allowing for the non-invasive imaging and spectroscopic analysis of cell cultures in vitro. The microfluidic device, which reproduces a dynamic environment, was optimized to sustain a passive, gravity-driven flow of medium, eliminating the need for an external pumping system and reducing mechanical stress on the cells. The platform was tested using Raman analysis and adherent tumoral cells to assess proliferation prior and subsequent to hydrogen peroxide treatment for oxidative stress induction. The results demonstrated a successful adhesion of cells onto the substrate and their proliferation. Furthermore, the platform is suitable for carrying out optical monitoring of cultures and Raman analysis. In fact, it was possible to discriminate spectra deriving from control and hydrogen peroxide-treated cells in terms of DNA backbone and cellular membrane modification effects provoked by reactive oxygen species (ROS) activity. The 800–1100 cm⁻¹ band highlights the destructive effects of ROS on the DNA backbone’s structure, as its rupture modifies its vibration; moreover, unpaired nucleotides are increased in treated sample, as shown in the 1154–1185 cm⁻¹ band. Protein synthesis deterioration, led by DNA structure damage, is highlighted in the 1257–1341 cm⁻¹, 1440–1450 cm⁻¹, and 1640–1670 cm⁻¹ bands. Furthermore, membrane damage is emphasized in changes in the 1270, 1301, and 1738 cm⁻¹ frequencies, as phospholipid synthesis is accelerated in an attempt to compensate for the membrane damage brought about by the ROS attack. This study highlights the potential use of this platform as an alternative to conventional culturing and analysis procedures, considering that cell culturing, optical imaging, and Raman spectroscopy can be performed simultaneously on living cells with minimal cellular stress and without the need for labeling or fixation. Full article

Nanoradiopharmaceuticals integrate nanotechnology with nuclear medicine to enhance the precision and effectiveness of radiopharmaceuticals used in diagnostic imaging and targeted therapies. Nanomaterials offer improved targeting capabilities and greater stability, helping to overcome several limitations. This review presents a comprehensive overview of the fundamental design principles, radiolabeling techniques, and biomedical applications of nanoradiopharmaceuticals, with a particular focus on their expanding role in precision oncology. It explores key areas, including single- and multi-modal imaging modalities (SPECT, PET), radionuclide therapies involving beta, alpha, and Auger emitters, and integrated theranostic systems. A diverse array of nanocarriers is examined, including liposomes, micelles, albumin nanoparticles, PLGA, dendrimers, and gold, iron oxide, and silica-based platforms, with an assessment of both preclinical and clinical research outcomes. Theranostic nanoplatforms, which integrate diagnostic and therapeutic functions within a single system, enable real-time monitoring and personalized dose optimization. Although some of these systems have progressed to clinical trials, several obstacles remain, including formulation stability, scalable manufacturing, regulatory compliance, and long-term safety considerations. In summary, nanoradiopharmaceuticals represent a promising frontier in personalized medicine, particularly in oncology. By combining diagnostic and therapeutic capabilities within a single nanosystem, they facilitate more individualized and adaptive treatment approaches. Continued innovation in formulation, radiochemistry, and regulatory harmonization will be crucial to their successful routine clinical use. Full article

Aquaculture expansion to meet global protein demand has intensified concerns over nutrient pollution and greenhouse gas (GHG) emissions. While floating treatment wetlands (FTWs) are proven for water quality improvement, their potential to mitigate GHG emissions in marine aquaculture remains poorly understood. This study quantitatively evaluated the dual capacity of Sesuvium portulacastrum FTWs to (a) regulate dissolved inorganic nitrogen (DIN) and (b) reduce CO₂/N₂O emissions in grouper aquaculture systems. DIN speciation (NH₄⁺, NO₂⁻, NO₃⁻) and CO₂/N₂O fluxes of six controlled ponds (three FTW and three control) were monitored for 44 days. DIN in the FTW group was approximately 90 μmol/L lower than that in the control group, and the water in the plant group was more “oxidative” than that in the control group. The former groups were dominated by NO₃⁻, with lower dissolved inorganic carbon (DIC) and N₂O concentrations, whereas the latter were dominated by NH₄⁺ during the first 20 days of the experiment and by NO₂⁻ at the end of the experiment, with higher DIC and N₂O concentrations on average. Higher primary production may be the reason that the DIC concentration was lower in the plant group than in the control group, whereas efficient nitrification and uptake by plants reduced the availability of NH₄⁺ in the plant group, thereby reducing the production of N₂O. A comparison of the CO₂ and N₂O flux potentials in the plant group and control group revealed that, in the presence of FTWs, the CO₂ and N₂O emissions decreased by 14% and 36%, respectively. This showed that S. portulacastrum FTWs effectively couple DIN removal with GHG mitigation, offering a nature-based solution for sustainable aquaculture. Their low biomass requirement enhances practical scalability. Full article

This study combines machine vision technology and deep learning models to rapidly assess the activity of anaerobic ammonium oxidation (Anammox) granular sludge. As a highly efficient nitrogen removal technology for wastewater treatment, the Anammox process has been widely applied globally due to its energy-saving and environmentally friendly features. However, existing sludge activity monitoring methods are inefficient, costly, and difficult to implement in real-time. In this study, we collected and enhanced 1000 images of Anammox granular sludge, extracted color features, and used machine learning and deep learning training methods such as XGBoost and the ResNet50d neural network to construct multiple models of sludge image color and sludge denitrification efficiency. The experimental results show that the ResNet50d-based neural network model performed the best, with a coefficient of determination (R²) of 0.984 and a mean squared error (MSE) of 523.38, significantly better than traditional machine learning models (with R² up to 0.952). Additionally, the experiment demonstrated that under a nitrogen load of 2.22 kg-N/(m³·d), the specific activity of Anammox granular sludge reached its highest value of 470.1 mg-N/(g-VSS·d), with further increases in nitrogen load inhibiting sludge activity. This research provides an efficient and cost-effective solution for online monitoring of the Anammox process and has the potential to drive the digital transformation of the wastewater treatment industry. Full article

Oxidative stress and hypoxia-induced inflammation contribute to benign prostatic hyperplasia (BPH) progression. This study investigated the roles of urinary inflammatory and oxidative stress biomarkers in BPH patients. This prospective study enrolled 62 clinical BPH patients (33 treated medically, 29 surgically) and 20 controls. Symptom scores, uroflowmetry, and urinary biomarker levels were assessed at baseline and three months post-treatment. Before treatment, BPH patients exhibited elevated urinary levels of total antioxidant capacity (TAC), PGE2, IL-1β, and IL-6. Post-treatment, successful outcomes were reported in 63.6% of the medical treatment group and 86.2% of the surgical treatment group, with improvements in symptom scores and urinary flow rate, along with reductions in urinary 8-isoprostane, TAC, and IL-1β. Prior to treatment, voiding efficiency (VE) was negatively correlated with urinary IL-1β, IL-6, and IL-8 levels, while bladder wall thickness was positively correlated with TAC. After treatment, changes in VE were negatively correlated with changes in IL-1β, and changes in post-void residual urine were positively correlated with changes in IL-1β, IL-6, IL-8, and TNF-α. Urinary inflammatory and oxidative stress biomarkers may serve as non-invasive indicators of disease severity and treatment response in clinical BPH. Their significant correlations with clinical improvements underscore their potential utility in monitoring treatment efficacy. Full article

This study investigated the enhancement in lipid accumulation in Chlorella sp. using non-thermal atmospheric pressure plasma as a pretreatment strategy for the production of value-added products. The plasma treatment was optimized by varying discharge times (0–16 min) using argon gas at a flow rate of 4 L/min. Lipid productivity was assessed through gravimetric analysis and profiling of fatty acid methyl ester using gas chromatography−mass spectrometry (GC-MS). The growth rate and pH of the treated cells were monitored. The findings demonstrated that the 4-min plasma exposure maximized the efficiency of lipid recovery, achieving a 35% of the dry cell weight and a 34.6% increase over untreated control. However, longer plasma treatment times resulted in a comparative decrease in lipid yield, as the decline is possibly due to oxidative degradation. The findings highlight the role of plasma treatment, which significantly boosts lipid yield and gives complementary optimization of downstream processes to improve biodiesel production. The accumulation of lipids in terms of size and volume in the algal cells was assessed by confocal laser scanning microscopy. The GC–MS results of the control revealed that lipids comprised primarily mixed esters such as 2H Pyran 2 carboxylic acid ethyl esters, accounting for 50.97% and 20.52% of the total peak area. In contrast, the 4-min treated sample shifted to saturated triacylglycerols (dodecanoic acid, 2,3 propanetriyl ester), comprising 85% of the total lipid content, which efficiently produced biodiesel. Thus, the non-thermal plasma-based enhancement of lipids in the algal cells has been achieved. Full article