Search Results (4,364)

Pyrethroids, synthetic analogues of natural pyrethrins, are extensively used in agriculture and household pest control due to their high insecticidal activity and relatively low toxicity to mammals. Due to the presence of multiple chiral centres, many pyrethroids exist as complex mixtures of stereoisomers with significantly different biological activities, toxicities, and environmental behaviours. Consequently, accurate determination of these stereoisomeric forms, particularly compounds such as cypermethrin, is critical for food safety monitoring. Determining pyrethroid residues in food matrices presents a significant analytical challenge due to the structural diversity and stereochemical complexity of these compounds. This study presents the development of an analytical method for determining the stereoisomeric forms of cypermethrin and other synthetic pyrethroids in food matrices using both LC-MS/MS and GC-MS/MS techniques. The method meets the performance criteria outlined in SANTE/11312/2021 v2, demonstrating satisfactory recovery rates (91.6%), precision (RSDR 1.9%), and low limits of quantification (LOQ 0.010 µg/kg) for the quantification of alpha-cypermethrin. This approach offers a reliable tool for regulatory monitoring and risk assessment of pyrethroid residues, especially those with complex stereochemistry. Full article

Prostate cancer is one of the most common malignancies in men, and advanced or metastatic disease remains associated with substantial morbidity and mortality. Therapeutic progress in recent years has been driven by the introduction of targeted treatment strategies, notably poly (ADP-ribose) polymerase (PARP) inhibitors, prostate-specific membrane antigen (PSMA)–directed radioligand therapy (RLT), and androgen receptor pathway inhibitors (ARPIs). This review summarizes evidence from phase II and III clinical trials, meta-analyses, and real-world studies evaluating the efficacy, safety, and clinical integration of olaparib, lutetium (¹⁷⁷Lu) vipivotide tetraxetan, and abiraterone in advanced prostate cancer. Emphasis is placed on the practical clinical application of these agents, including patient selection, treatment sequencing, and combination strategies. PARP inhibition with olaparib has demonstrated clear benefits in metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) mutations, particularly BRCA1/2 alterations. PSMA-directed RLT offers a survival advantage in PSMA-positive mCRPC following AR pathway inhibition, with distinct toxicity considerations that influence patient selection. Abiraterone remains a cornerstone therapy across disease stages and plays an important role both as monotherapy and as a combination partner. Emerging data suggest a potential synergy between PARP inhibitors and AR-targeted agents, while also highlighting the limitations of biomarker-unselected approaches. We conclude that the optimal use of PARP inhibitors, PSMA-targeted RLT, and ARPIs requires a personalized strategy guided by molecular profiling, functional imaging, prior treatment exposure, and safety considerations. This clinically focused overview aims to support evidence-based decision-making in an increasingly complex treatment landscape. Full article

The pharmacological effects of ginger extract from Zingiber officinale Roscoe are well-established; however, more refined extraction methods for higher-quality yields are needed. This study isolated and evaluated 6-, 8-, and 10-shogaol and 6-, 8-, and 10-gingerol from ginger extract, assessing their effects on glucose-stimulated insulin secretion (GSIS). To ensure safety, non-toxic concentrations were determined for pancreatic β-cells. Both non-processed and microwave-processed ginger extracts enhanced GSIS, with microwave-treated extracts exhibiting the strongest effect. Specifically, the microwave-processed ginger extract increased the glucose stimulation index (GSI) to 12.4 ± 0.4 at 5 μg/mL, compared to a GSI of 7.7 ± 0.2 observed for the non-processed ginger extract. Notably, fraction F4 of the microwave-processed extract demonstrated superior GSIS activity. In contrast, steam-processed ginger extract induced only a modest increase in GSI under limited exposure conditions. Furthermore, 6-shogaol emerged as a key compound, correlating with increased expression of proteins crucial for pancreatic β-cell regulation. Microwave-assisted processing notably altered the content and proportion of shogaols and gingerols, significantly impacting GSIS activity. These findings underscore the importance of extraction methods in enhancing ginger’s pharmacological potential in regulating insulin secretion and pancreatic β-cell function. Full article

Background/Objectives: Ash made from juniper trees and added to cornmeal-based dishes may have provided calcium (Ca) to traditional Indigenous diets. Few studies have quantified the mineral content of juniper ash, including its Ca content. The objective of this study was to determine whether juniper ash could serve as a safe source of non-dairy Ca in an intervention study. Methods: Branches from two varieties of Juniper (Rocky Mountain Juniper, or Juniperus scopulorum and Eastern Red Cedar, or Juniperus virginiana) were harvested and burned to ash in a laboratory setting. Juniper ash from the southwestern U.S. available for retail purchase was used for comparison. All samples were tested for content of 10 nutritive elements (Ca, copper, iron, potassium, magnesium, manganese, sodium, phosphorus, selenium, and zinc) and 20 potentially toxic elements (silver, aluminum, arsenic, barium, beryllium, cadmium, cobalt, chromium, mercury, lithium, molybdenum, nickel, lead, antimony, tin, strontium, thallium, uranium, and vanadium) as well as n = 576 pesticide residues. Results: All samples contained both nutritive and potentially toxic elements. Each teaspoon of ash contained an average of 445 ± 141 mg Ca. However, the samples also contained lead in amounts ranging from 1.09 ppm to 15 ppm. Conclusions: Information on the nutritive and potentially toxic elemental content of juniper ash and how it may interact within a food matrix is insufficient to determine its safety as a Ca source. Further investigation is needed on the bioavailability of calcium oxide and its interaction with other dietary components to clarify the potential role of juniper ash in contemporary food patterns. Full article

Subcutaneous mycoses are a heterogeneous group of chronic fungal infections, usually acquired through traumatic inoculation of environmental fungi and particularly severe in immunocompromised and critically ill patients. These infections involve pathogens with marked morphological and physiopathological diversity, resulting in significant diagnostic and therapeutic challenges. Conventional treatment relies on systemic antifungals such as amphotericin B, itraconazole, and other azoles; however, these therapies are often limited by poor tissue penetration, adverse effects, and prolonged treatment regimens, especially in vulnerable patient populations. In this context, nanodrugs have emerged as promising alternatives by improving solubility, stability, bioavailability, and targeted delivery to infection sites. This review conducted a comprehensive literature search in PubMed, SciELO, ScienceDirect, Web of Science, and Scopus, identifying 31 eligible studies that developed and evaluated antifungal nanosystems using in vitro, ex vivo, and/or in vivo models. Quantitative outcomes included minimum inhibitory concentration (MIC), colony-forming units (CFU), inhibition halo diameter, and survival assays. Overall, the evidence indicates that several nanosystems may overcome key pharmacological limitations of conventional antifungals and enhance therapeutic outcomes. Nevertheless, important translational challenges remain, including toxicity, long-term safety, scalability, and regulatory approval, which must be addressed before clinical implementation. Full article

The discovery and development of new drugs is a lengthy, complex, and costly process, often requiring 10–20 years to progress from initial concept to market approval, with clinical trials representing the most resource-intensive stage. In recent years, Artificial Intelligence (AI) has emerged as a transformative technology capable of reshaping the entire pharmaceutical research and development (R&D) pipeline. The purpose of this narrative review is to examine the role of AI in drug discovery and development, highlighting its contributions, challenges, and future implications for pharmaceutical sciences and global public health. A comprehensive review of the scientific literature was conducted, focusing on published studies, reviews, and reports addressing the application of AI across the stages of drug discovery, preclinical development, clinical trials, and post-marketing surveillance. Key themes were identified, including AI-driven target identification, molecular screening, de novo drug design, predictive toxicity modelling, and clinical monitoring. The reviewed evidence indicates that AI has significantly accelerated drug discovery and development by reducing timeframes, costs, and failure rates. AI-based approaches have enhanced the efficiency of target identification, optimized lead compound selection, improved safety predictions, and supported adaptive clinical trial designs. Collectively, these advances position AI as a catalyst for innovation, particularly in promoting accessible, efficient, and sustainable healthcare solutions. However, substantial challenges remain, including reliance on high-quality and representative biomedical data, limited algorithmic transparency, high implementation costs, regulatory uncertainty, and ethical and legal concerns related to data privacy, bias, and equitable access. In conclusion, AI represents a paradigm shift in pharmaceutical research and drug development, offering unprecedented opportunities to improve efficiency and innovation. Addressing its technical, ethical, and regulatory limitations will be essential to fully realize its potential as a sustainable and globally impactful tool for therapeutic innovation. Full article

Metastatic uveal melanoma (MUM) remains largely refractory to immune-checkpoint inhibition, so recent research has turned to bispecific T-cell engagers (BTCEs), adoptive-cell therapies (ACTs), and oncolytic viruses (OVs). To summarize the available clinical evidence, we performed a structured literature search across PubMed, Scopus, and Europe PMC for primary studies published between 1 January 2010 and 31 May 2025 that enrolled at least three adults with MUM, treated with one of these modalities, and that reported efficacy or grade-3+ safety outcomes; two reviewers independently performed screening, data extraction, and risk-of-bias assessment, and because of notable heterogeneity, we synthesized the findings narratively. Twenty-two studies met the criteria—thirteen phase I–III trials, eight observational cohorts, and one case series—covering fifteen BTCE cohorts, four ACT cohorts, and three OV cohorts. Tebentafusp, the dominant BTCE evaluated in roughly 1150 HLA-A*02:01-positive patients, extended median overall survival from 16.0 to 21.7 months (hazard ratio 0.51, with three-year follow-up HR 0.68) in its pivotal phase-III trial despite objective response rates of only 5–12%, with early skin rash and week-12 circulating-tumor-DNA clearance emerging as consistent markers of benefit. Tumor-infiltrating lymphocyte therapy, administered to about thirty patients, produced objective responses in 11–35% and occasional durable complete remissions, although median progression-free survival remained 2–6 months and severe cytopenias were universal. Three early-phase OV studies, totaling twenty-nine patients, yielded no radiographic responses but showed tumor-specific T-cell expansion and transient disease stabilization. Safety profiles reflected the mechanism of action: tebentafusp most often caused rash, pyrexia, and usually manageable cytokine-release syndrome with grade-3+ events in 40–70% yet discontinuation in roughly 2%; TIL therapy toxicity was driven by lymphodepleting chemotherapy and high-dose interleukin-2 with one treatment-related death; and OVs were generally well tolerated with no more than 20% grade-3 events. Full article

Background: Triple-negative breast cancer (TNBC) remains primarily treated with chemotherapy due to the lack of effective therapeutic targets, but this approach carries significant systemic toxicity and a high risk of drug resistance. Curcumin (Cur), despite its multifaceted antitumor activity, faces limitations in clinical application due to poor water solubility and weak targeting properties. This study aims to develop a folate/mitochondria dual-targeted curcumin–copper chelate liposome (Cu-Cur DTLPs) formulation that enables copper accumulation within tumor cells and induces copper-mediated cell death, thereby providing an effective and relatively low-toxicity therapeutic strategy for triple-negative breast cancer. Methods: Curcumin–copper chelates (Cu-Cur) were first synthesized and characterized using mass spectrometry, NMR, and infrared spectroscopy. Subsequently, dual-targeted liposomes (Cu-Cur DTLPs) were prepared via the thin-film dispersion method, with systematic evaluation of particle size, zeta potential, encapsulation efficiency, and in vitro release profiles. In vitro cytotoxicity was assessed against 4T-1 and MDA-MB-231 cells using the MTT assay. In a 4T-1 tumor-bearing BALB/c mouse model, comprehensive evaluation of targeting efficiency, antitumor efficacy, and mechanisms of action was conducted via in vivo imaging, tumor volume monitoring, immunohistochemistry (detecting FDX1 and DLAT proteins), and TUNEL staining. Results: Cu-Cur DTLPs with a uniform particle size of approximately 104.4 nm were successfully synthesized. In vitro and in vivo studies demonstrated that compared to free curcumin and conventional liposomes, Cu-Cur DTLPs significantly enhanced drug accumulation in tumor tissues and exhibited effective tumor growth inhibition. Mechanistic studies confirmed that this formulation specifically accumulates copper ions within tumor cells, upregulates FDX1, promotes DLAT oligomerization, and induces mitochondrial dysfunction, thereby driving copper death. TUNEL staining ruled out apoptosis as the primary mechanism. Safety evaluation revealed no significant toxicity in major organs. Conclusions: The Cu-Cur DTLPs developed in this study effectively induce copper-mediated death in TNBC through a dual-targeted delivery system, significantly enhancing antitumor activity with favorable safety profiles. This establishes a highly promising novel nanotherapeutic strategy for TNBC treatment. Full article

Anthropogenic climate change represents a critical and complex threat to the health and resilience of aquatic ecosystems. This review aims to critically synthesise and evaluate the synergetic and antagonistic mechanisms through which rising water temperature, the most prominent climatic factor, modulates the host–parasite relationship. The systematic literature review was conducted across a high-impact database (Web of Science), focusing on the extraction and qualitative analysis of data concerning infection dynamics and both host and parasite interactions. The findings demonstrate that thermal stress imposes a dual penalty on host–parasite systems: (1) it confers a critical thermal advantage to direct-life cycle parasites, significantly accelerating their virulence, reproduction, and infective capacity; (2) simultaneously, it severely compromises the immunocompetence and physiological resilience of piscine hosts, often through immunometabolic trade-offs and inflammatory dysfunction. This toxic synergy is the root cause of the exponential disease prevalence/intensity of parasites and fish mass mortality events, directly impacting biodiversity and global aquaculture sustainability. In contrast, it may also cause the disruption of the transmission chains to threaten complex life cycle parasites with localised extinction. We conclude that climate mitigation must be urgently recognised and implemented as a primary strategy for biological risk management to secure aquatic health and global food safety. Full article

Background: As a widely used chemotherapeutic agent, cisplatin frequently induces acute kidney injury (AKI), which severely compromises patient survival and limits its clinical use. While the natural flavonoid diosmetin (Dio) shows promise in mitigating cisplatin-induced nephrotoxicity, its clinical translation is challenged by poor solubility, low bioavailability, and incompletely elucidated mechanisms. This study aimed to overcome these limitations by developing a novel drug delivery system using the microalgae Dunaliella salina (D. salina, Ds) to load Dio (Ds-Dio), thereby enhancing its efficacy and exploring its therapeutic potential. Methods: We first characterized the physicochemical properties of Ds and Dio, and then Ds-Dio complex was synthesized via co-incubation. Its nephroprotective efficacy and safety were systematically evaluated in a cisplatin-induced mouse AKI model by assessing renal function (serum creatinine, blood urea nitrogen), injury biomarkers, histopathology, body weight, and organ index. The underlying mechanism was predicted by network pharmacology and subsequently validated experimentally. Results: The novel Ds-Dio delivery system has been successfully established. In the AKI model, Ds-Dio significantly improved renal function and exhibited a superior protective effect over Dio alone; this benefit is attributed to the enhanced bioavailability provided by Ds carrier. In addition, Ds-Dio also demonstrated safety performance, with no evidence of toxicity to major organs. Network pharmacology analysis predicted the involvement of PI3K/AKT pathway, which was experimentally verified. Specifically, we confirmed that Ds-Dio alleviates AKI by modulating the PI3K/AKT pathway, resulting in concurrent suppression of NF-κB-mediated inflammation and activation of NRF2-dependent antioxidant responses. Conclusions: This study successfully developed a microalgae-based drug delivery system, Ds-Dio, which significantly enhances the nephroprotective efficacy of Dio against cisplatin-induced AKI. The nephroprotective mechanism is associated with modulation of the PI3K/AKT pathway, resulting in the simultaneous attenuation of oxidative stress and inflammation. Full article

Deep Eutectic Solvents (DESs), particularly Naturally Available Deep Eutectic Solvents (NADESs), are increasingly regarded as green solvents due to their low vapor pressure, non-flammability, thermal stability, strong solvent power, and low toxicity. In line with Green Chemistry principles, the use of renewable and biocompatible components such as amino acids, lipids, and naturally derived acids enables the development of more sustainable solvent systems. This study addresses the need for environmentally safer NADESs by evaluating their physico-chemical suitability and environmental impact. Fifteen NADESs were prepared using naturally derived components and assessed for environmental safety. Biodegradability was evaluated using the OECD 301D Closed Bottle Test (CBT), while toxicity toward Raphidocelis subcapitata was examined to characterize ecotoxicological behavior. The results demonstrated that the synthesized NADESs exhibit high biodegradability levels and low toxicity toward microalgae. Toxicity control indicated no significant inhibition of microbial activity during biodegradation, suggesting favorable environmental compatibility. Overall, the findings indicate that the NADESs represent more sustainable solvent alternatives with low toxicological profiles. However, the potential role of these compounds in enhancing eutrophication processes cannot be excluded and warrants further investigation. Full article

BTK (Bruton’s tyrosine kinase) has become a key therapeutic target across several hematologic diseases, beginning with its original use in CLL/SLL. As a central mediator of B-cell receptor signaling and microenvironment interactions, BTK supports survival, proliferation, and trafficking in multiple mature B-cell malignancies (mantle cell lymphoma, marginal zone lymphoma, Waldenström macroglobulinemia, and other indolent/aggressive lymphomas) and in selected immune-mediated conditions such as chronic graft-versus-host disease. Covalent BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib) irreversibly bind the C481 residue and have produced high response rates and durable disease control, often replacing chemoimmunotherapy in the relapsed setting and, for some entities, even in the first line. Differences in kinase selectivity lead to different safety profiles: second-generation covalent agents generally maintain efficacy while reducing significant off-target toxicities, especially atrial fibrillation and hypertension. Resistance to covalent BTK inhibitors most commonly develops through BTK C481 substitutions and activating PLCG2 mutations, with other kinase-domain variants increasingly recognized. Non-covalent BTK inhibitors (e.g., pirtobrutinib) bind BTK independently of C481, can overcome classic C481-mediated resistance, and extend BTK pathway targeting into later lines of therapy. Overall, BTK inhibition has evolved into a versatile platform enabling long-term, often chemo-free management strategies. Full article

Objective: Cosmetic products are widely used, yet public awareness of their potential health risks and of cosmetovigilance remains limited. Given that studies increasingly highlight chemical exposure associated with cosmetics, this study aimed to assess public knowledge, attitudes, and behaviours regarding cosmetic use, toxicity, and cosmetovigilance in Türkiye. Methods: A cross-sectional study was conducted among the general population living in Türkiye, consisting of 700 people between January and May 2024. The study was conducted using a Google survey form. Results: Among 700 participants, 91.6% reported regular cosmetic use and 47.6% experienced at least one adverse effect, most commonly redness, itching, and burning. Adverse effects were more frequently associated with products purchased from shopping malls/cosmetic stores. Education level was significantly linked to awareness of cosmetovigilance and product preferences, with university graduates showing higher awareness and favoring both local and international brands. Conclusion: The study revealed that although cosmetic use is common in Türkiye, awareness of cosmetovigilance remains low, even among well-educated consumers. Many participants reported adverse effects but did not seek professional consultation, indicating gaps in safety practices and reporting. Strengthening public awareness and establishing effective cosmetovigilance systems are essential to ensure safer cosmetic use and protect public health. Full article

Atractylenolides (ATs; mainly AT-I, II, and III), as one of the primary active components of the traditional Chinese medicine Atractylodes macrocephala, have demonstrated significant antitumorigenic effects against various cancer cells in both in vitro and in vivo studies. This review aims to systematically review the antitumorigenic effects, mechanisms, pharmacokinetics, and safety profile of ATs, aiming to contribute to clinical research and applications. To achieve this, a systematic literature search was conducted across multiple databases, and findings were synthesized narratively to provide a comprehensive overview of the current evidence. This review comprehensively discusses the antitumorigenic effects and mechanisms of ATs, including arresting tumor cell cycle progression, inducing programmed cell death (apoptosis, autophagy, and ferroptosis), inhibiting tumor angiogenesis, suppressing tumor migration and invasion, modulating the tumor immune microenvironment, and enhancing the efficacy of combination therapies. Additionally, their pharmacokinetic properties and safety profile are summarized, with a focus on their research and application prospects. ATs appear to be safe and reliable candidate anticancer agents in preclinical models, exhibiting potent antitumor efficacy both as monotherapy and in combination regimens. Preliminary clinical data from a small pilot study also indicated no signs of toxicity, but more extensive trials are needed to confirm their safety profile in humans. Further studies on their mechanisms are warranted to facilitate their development into clinically effective antitumor agents. Full article

Background: The UGT1A1 gene is associated with the toxicity caused by SN38, the cytotoxic component of Sacituzumab govitecan (SG) used in the treatment of metastatic triple-negative breast cancer (mTNBC), among other approved indications. In this study, we aimed to analyze the effect of UGT1A1*28 allele on the safety and, secondarily, the effectiveness of SG in mTNBC. Methods: This was a multicenter, ambispective study that included patients treated with SG for mTNBC. Genotyping for UGT1A1*28 was performed using real-time polymerase chain reaction (PCR). Adverse events (AEs) of grade ≥ 2 during the first three cycles were compared between patients who were homozygous mutant (UGT1A1*28/*28) and those with wild-type (WT) or heterozygous genotypes. Effectiveness between the two groups was also compared using progression-free survival (PFS) and overall survival (OS) assessed with the Kaplan–Meier method. Results: A total of 81 patients were included: 37.0% were WT, 55.6% heterozygous, and 7.4% homozygous mutant. All UGT1A1 *28/*28 patients experienced grade ≥ 2 AEs (100% vs. 69.3%; p = 0.109), with a statistically significant association in the case of febrile neutropenia (33.3% vs. 6.7%; p = 0.025), and a trend towards higher rates of anemia and diarrhea (50.0% vs. 17.3%; p = 0.053). Genotype did not influence PFS or OS; however, dose reductions were associated with better survival outcomes. Conclusions: This real-world study shows a correlation between toxicity and the presence of the UGT1A1*28 mutation in patients treated with SG for mTNBC. Improving treatment tolerability through dose reductions may enhance SG effectiveness. These findings support the implementation of UGT1A1 genotyping in routine clinical practice. Full article