Search Results (1,247)

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article

Objectives: Parental exposure to tobacco smoke is a significant public health concern, with over 1.1 billion smokers worldwide. The aim of this systematic review was to evaluate the impact of maternal, paternal, and dual-parental cigarette smoke exposure on offspring reproductive health. Methods: Original human clinical and animal research studies were included; titles and abstracts were manually scanned for relevance to the effect of parental smoking on offspring reproductive outcomes (Date of search:18/03/2025). Results: This systematic review incorporates 30 studies identified from three databases (PubMed, Web of Science, and Scopus). The results indicate that male offspring exhibit reduced spermatogenic capacity, characterized by decreased testicular size, lower sperm count, and impaired hormonal biosynthesis, with reductions of 30–40% in sperm production. Dual-parental smoking exacerbates these effects, with sperm counts averaging 85 million per ml in human male offspring from dual-smoking households, compared to 111 million per ml in single-smoking households. Animal studies provide mechanistic insights, revealing reduced testis weight in nicotine-exposed male rats and increased oxidative stress in offspring. Conclusions: This review highlights the dose-dependent and sex-specific effects of smoking on the fertility of offspring and underscores the need for standardized protocols to enhance the consistency and comparability of future research in both human and animal studies. Full article

Background: Understanding the origin and natural organization of early infant vocalizations is important for predicting communication and language abilities in later years. The very frequent production of speech-like vocalizations (hereafter “protophones”), occurring largely independently of interaction, is part of this developmental process. Objectives: This study aims to investigate the gap durations (time intervals) between protophones, comparing typically developing (TD) infants and infants later diagnosed with autism spectrum disorder (ASD) in a naturalistic setting where endogenous protophones occur frequently. Additionally, we explore potential age-related variations and sex differences in gap durations. Methods: We analyzed ~1500 five min recording segments from longitudinal all-day home recordings of 147 infants (103 TD infants and 44 autistic infants) during their first year of life. The data included over 90,000 infant protophones. Human coding was employed to ensure maximally accurate timing data. This method included the human judgment of gap durations specified based on time-domain and spectrographic displays. Results and Conclusions: Short gap durations occurred between protophones produced by infants, with a mode between 301 and 400 ms, roughly the length of an infant syllable, across all diagnoses, sex, and age groups. However, we found significant differences in the gap duration distributions between ASD and TD groups when infant-directed speech (IDS) was relatively frequent, as well as across age groups and sexes. The Generalized Linear Modeling (GLM) results confirmed these findings and revealed longer gap durations associated with higher IDS, female sex, older age, and TD diagnosis. Age-related differences and sex differences were highly significant for both diagnosis groups. Full article

Medicinal plants have been used in traditional medicines all over the world to treat human diseases throughout human history. Many of the medicinal plants have frequently become food and nutrition plants. A more sophisticated investigation resulted in discovering numbers of biologically important secondary metabolites of plants. Pentacyclic triterpenoids represent an important group of the plant secondary metabolites that have emerged as having top biological importance. While the most widespread plant triterpenoids and a majority of their semisynthetic derivatives have been reviewed quite often, other plant pentacyclic triterpenoids and their derivatives have so far been less frequently studied. Therefore, attention has been focused on selected pentacyclic triterpenoids, namely on arjunolic acid, asiatic acid, α- and β-boswellic acids, corosolic acid, maslinic acid, morolic acid, moronic acid, and the friedelane triterpenoids, and on different derivatives of the selected triterpenoids in this review article. A literature search was made in the Web of Science for the given keywords, covering the required area of secondary plant metabolites and their semisynthetic derivatives starting in 2023 and ending in February 2025. The most recently published findings on the biological activity of the selected triterpenoids, and on the structures and the biological activity of their relevant derivatives have been summarized therein. Even if cytotoxicity of the compounds has mainly been reviewed, other biological effects are mentioned if they appeared in the original articles in connection with the selected triterpenoids and their derivatives, listed above. A comparison of the effects of the parent plant products and their derivatives has also been made. Full article

Acute lymphoblastic leukemia (ALL) is the most common cancer affecting children, making up about 80% of all acute leukemia cases in the pediatric population. While treatment with L-asparaginase (ASNase) has greatly improved survival rates, its bacterial origin often causes immune reactions in some patients, which can reduce how well the therapy works. To overcome this challenge, previous in silico studies designed a humanized chimeric ASNase by swapping out the predicted immunogenic parts of the bacterial enzyme with similar, less immunogenic segments from the human version—while keeping the enzyme’s active site intact. In this study, the chimeric L-asparaginase designed was successfully cloned, expressed, and purified using the Escherichia coli Rosetta strain. The production conditions (37 °C, 0.01 mM IPTG, 2–4 h) were optimized, and we purified the enzyme in a single step with nickel-affinity chromatography. The enzyme’s activity was confirmed in vitro, showing that it is possible to produce a functional humanized variant in a bacterial system. These results lay important groundwork for future research to assess the immune response and therapeutic potential of this novel chimeric enzyme. Full article

Mycotoxins are secondary metabolites produced by various fungal species that can contaminate food and feed, posing significant risks to human and animal health. In aquaculture, the replacement of fishmeal with alternative protein sources has increased the risk of mycotoxin contamination, becoming a major challenge in fish feed production. Current data highlights that fish are exposed not only to common mycotoxins but also to emerging ones, raising concerns about human exposure through fish consumption. In this review, we draw attention to the toxicity data of key emerging mycotoxins from Fusarium (enniatins, ENNs; beauvericin, BEA) and Alternaria (alternariol monomethyl ether, AME; alternariol, AOH), their occurrence in aquafeeds and in commercially relevant fish species in Europe, and potential biocontrol approaches to prevent/mitigate contaminations. From the present review, it emerged that these mycotoxins exhibit in vitro cytotoxic properties. Their prevalence and concentrations vary widely both among aquafeeds, depending on the sample’s origin, and among fish species. Biocontrol approaches using microorganisms or natural compounds show promise as sustainable solutions to limit contamination. However, further research is essential to address data gaps and to allow for a proper risk assessment and, if necessary, the implementation of effective management measures. Full article

Background/Objectives: In the context of preclinical studies, we have hitherto showcased that a low-molecular-weight ruthenium(III) complex we named AziRu holds significant potential for further developments as an anticancer candidate drug. When appropriately converted into stable nanomaterials and delivered into tumor cells, AziRu exhibits superior antiproliferative activity, benefiting from a multimodal mechanism of action. The activation of regulated cell death (RCD) pathways (i.e., apoptosis and autophagy) has been proved in metastatic phenotypes, including triple-negative breast cancer (TNBC) cells. This study focuses on a bioengineered lipophilic derivative of AziRu, named PalmiPyRu, that we are currently developing as a potential anticancer drug in preclinical studies. When delivered in this way, AziRu confirms a multimodal mechanism of action in effectively blocking the growth and proliferation of TNBC phenotypes. Special focus is reserved for the activation of the ferroptotic pathway as a consequence of redox imbalance and interference with iron homeostasis, as well as the glutathione biosynthetic pathway. Methods: Human preclinical models of specific TNBC phenotypes and healthy cell cultures of different histological origin were selected. After in vitro treatments, cellular responses were carefully analyzed, and targeted biochemical and molecular biology experiments coupled to confocal microscopy allowed us to explore the antiproliferative effects of PalmiPyRu. Results: In this study, we unveil that PalmiPyRu can enter TNBC cells and interfere with both the iron homeostasis and the cystine-glutamate antiporter system Xc-, causing significant oxidative stress and the accumulation of lipid oxidation products. The increase in intracellular reactive free iron and depletion of glutathione engender a lethal condition, driving cancer cells toward the activation of ferroptosis. Conclusions: Overall, these outcomes allow us, for the first time, to couple the antiproliferative effect of a ruthenium-based candidate drug with the inhibition of the Xc- antiporter system and Fenton chemistry, thereby branding PalmiPyRu as an effective multimodal inducer of ferroptosis. Molecular mechanisms of action deserve further investigations, and new studies are underway to uncover how interference with Xc- controls cell fate, allowing us to explore the connection between iron metabolism regulation, oxidative stress and RCD pathways activation. Full article

Sulfate as a potential pollution source in the water environment of the basin, identifying sulfate sources and migration mechanisms is essential for protecting the water environment and ensuring sustainable water management. Liuyang River is a primary tributary of the Xiangjiang River. It has experienced progressively intensifying anthropogenic influences in recent decades, manifested by sustained sulfate concentration increases. However, the sulfate sources and their contributions were not clear. This study used hydrochemistry and multi-isotopes methods combined with Simmr model to study the hydrochemical characteristics, sulfate sources, and migration–transformation processes of surface water and groundwater. The results showed that the hydrochemical types of surface water were HCO₃-Ca and HCO₃·SO₄-Ca·Mg, and groundwater were HCO₃-Ca, HCO₃-Ca·Mg, and HCO₃·SO₄-Ca. Ions in the water primarily originated from carbonate and silicate rocks dissolution and sulfide oxidation, augmented by mining operations, sewage discharge, and chemical production. The analyses of hydrochemistry, isotopes, and Simmr model revealed that surface water sulfate originated from soil sulfate (35.70%), sulfide oxidation (26.56%), sewage (16.58%), and atmospheric precipitation (12.45%). Groundwater sulfate was derived predominantly from sewage (34.96%), followed by soil sulfate (28.09%), atmospheric precipitation (17.35%), and sulfide oxidation (12.25%). Sulfate migration and transformation were controlled by the natural environment and anthropogenic impacts. When unaffected by human activities, sulfate mainly originated from soil and atmospheric precipitation, relating to topography, geological conditions, agricultural activities, and precipitation intensity. However, in regions with intense human activities, contributions from sewage and sulfide oxidation significantly increased due to the influences of mining and industrial activities. Full article

The singular biodiversity of the Brazilian Caatinga inspires innovative solutions in food science. In this study, we evaluated the prebiotic potential of honeys produced by Apis mellifera in the Pajeú hinterland, Pernambuco, Brazil (Caatinga Biome), with different floral origins: Mastic (Aroeira), Mesquite (Algaroba), and mixed flowers. These were used to formulate synbiotic and alcoholic beverages fermented by Saccharomyces boulardii CNCM I-745. Static and dynamic simulations of the human gastrointestinal tract (GIT) were used, as well as physicochemical, rheological, and microbiological analyses. The results revealed that honey positively influences the viability and resilience of probiotic yeast, especially honey with a predominance of Algaroba, which promoted the highest survival rate (>89%) even after 28 days of refrigeration and in dynamic in vitro simulation of the GIT (more realistic to human physio-anatomical conditions). The phenolic composition of the honeys showed a correlation with this tolerance. The use of complementary methodologies, such as flow cytometry, validated the findings and highlighted the functional value of these natural matrices, revealing an even greater longevity potential compared to conventional microbiological methodology. The data reinforces the potential of the Caatinga as a source of bioactive and sustainable compounds, proposing honey as a promising non-dairy synbiotic vehicle. This work contributes to the appreciation of the biome and the development of functional food products with a positive social, economic, and ecological impact. Full article

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article

Nowadays, food traceability represents an important issue in the current context of trade agreements, which influence global food prices. Many consumers prefer to pay a higher price for a traditional cultivation regime of a certain food product that comes from a certain region, appreciating the taste of the respective foodstuff. The potato is now the world’s fourth most important food crop in terms of human consumption, after wheat, maize, and rice. In this context, 100 potato samples from the Romanian market were collected. While 68 samples came from Romania, the rest of the 32 were from abroad (Hungary, France, Greece, Italy, Germany, Egypt, and Poland). The countries selected for potato sample analysis are among the main exporters of potatoes to the Romanian market. The samples were investigated by their multi-elemental and isotopic (²H, ¹⁸O and ¹³C) fingerprints, using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Isotope Ratio Mass Spectrometry (IRMS). Then, to distinguish the geographical origin, the experimental results were statistically processed using linear discriminant analysis (LDA). The best markers that emphasize Romanian potatoes were identified to be δ¹³C_bulk, δ²H_water, and Sr. Full article

Cryptosporidium spp. are protozoan parasites that cause cryptosporidiosis, an enteric disease that can affect a wide range of vertebrate hosts. Pigs play a potential role in the transmission of Cryptosporidium spp. to humans, although infections are most often subclinical. This study aimed to assess the occurrence and molecular characterization of Cryptosporidium spp. in swine farms located in Aragón, northeastern Spain. Fecal samples (n = 72) were collected from 10 breeding farms, encompassing various production stages (lactation, nursery, fattening, and/or wean-to-finish). Data regarding the type of production system (two- or three-stage), production stages, and farming facilities (the type of flooring and water source) associated with the parasite presence were also analyzed using a questionnaire. The results showed that Cryptosporidium spp. were more frequently detected in fecal samples originating from three-stage production systems (21.9%) compared to two-stage systems (12.5%). Samples from the fattening stage exhibited the highest positivity rate and estimated oocyst count (3.0 oocyst/microscopic field). Furthermore, the molecular characterization of Cryptosporidium spp. revealed the circulation of multiple species both among farms and within the same pig production flow, with Cryptosporidium scrofarum being the most prevalent species (7/72; 9.7%), followed by Cryptosporidium suis (1/72; 1.4%). These findings underscore the importance of the surveillance and molecular characterization of Cryptosporidium spp. for controlling infections in pigs, considering the potential for the zoonotic transmission of this parasite to humans. Full article

In recent years, there has been growing consumer interest in foods and cosmetics containing ingredients of natural origin. During the production process, a by-product of pomace is generated, which is regarded as a dispensable product by the food industry. However, studies have clearly indicated that fruit and vegetable pomace is a valuable source of many nutrients, whose beneficial effects on human health and appearance may represent an added value in its secondary use. Incorporating pomace into cosmetic products enhances their aesthetic value and can enrich them with naturally occurring polyphenols, which is in line with the circular economy model. In the present study, we determined selected mechanical properties of lip balms containing different amounts of grape pomace, for example, the kinetic friction against artificial leather, hardness, penetration performance, maximum shear force, and sample penetration resistance. Moreover, the antiradical activity against DPPH and the total phenolic content were determined, and the colour parameters were analyzed. All tests were conducted on lip balm samples containing 1, 3, and 5% fruit pomace and a control sample. Analysis of the penetration performance showed no statistically significant differences between the individual samples. However, differences in the values of other physical properties were noted. Moreover, the antiradical activity against the synthetic radical DPPH and the total phenolic content increases the value of lip balms with increasing amounts of pomace added. The colour of the lip balms also darkens with increasing amounts of pomace added. The innovative use of grape pomace is in line with sustainable development, and its properties enhance the effects of lip balms. Full article

The evolution of global agriculture encourages the extensive use of pesticides although significant concerns regarding their impact on human health and the environment must be considered. The present paper highlights the presence and concentrations of various pesticide residues in fruits and vegetables available on Romanian markets. A total of 74 pesticide compounds authorized for agricultural use were identified and quantified in 620 randomly selected samples spanning a wide range of horticultural products by employing the QuEChERS extraction method and liquid chromatography–mass spectrometry (LC-MS/MS). The most often detected pesticides comprised boscalid and azoxystrobin, present in 42% and 37% of apple and strawberry samples, respectively, with mean concentrations of 0.12 mg/kg and 0.09 mg/kg. In cucumbers and tomatoes, difenoconazole and acetamiprid were predominant, detected in 35% and 40% of samples, with average residue amounts of 0.08 mg/kg and 0.07 mg/kg, respectively. Statistical analysis, achieved with Python 3.13.2, the pandas library (alongside descriptive statistics), and ANOVA, revealed significant variations in residue levels based on the product type and geographic origin. Boscalid and azoxystrobin were commonly encountered in apples and strawberries while difenoconazole and acetamiprid predominated in cucumbers and tomatoes. Even though the majority of pesticide residues conformed to EU maximum residue limits (MRLs), about 6% of samples, generally from imported products, displayed some residue concentrations approaching critical thresholds, with the highest exceedance observed for chlorpyrifos and lambda-cyhalothrin at concentrations of up to 0.25 mg/kg. This research provides a comprehensive overview of pesticide residues prevalence in Romania’s fresh product supply while, at the same time, supporting consumer awareness initiatives and evidencing the critical demand for continuous monitoring and strengthened regulatory frameworks for food safety. Full article

The Apolipoprotein L1 (APOL1) innate immunity gene product represents the sole member of the APOL gene family in humans capable of secretion into circulation, thereby mediating the trypanolysis of T. brucei brucei. Gain-of-function variants of the APOL1 gene originated and spread among human population groups to extend APOL1’s protective capacity to include also serum-resistant subspecies, such as T. brucei gambiense (S342G known as APOL1-G1) and T. brucei rhodesiense (N388_Y389del known as APOL1-G2). The biochemical pathways underlying the lytic activity of these evolutionary favored mutations against bloodstream trypanosomes have been elucidated with remarkable precision. However, the intricate molecular mechanisms by which such variants confer an increased susceptibility to renal cellular injury and consequent kidney disease remain incompletely defined. In the absence of a consistent mechanistic explanation for differential kidney injury, we propose pursuing three interrelated avenues of investigation informed by prior epidemiological and mechanistic evidence linking them to APOL1’s cytotoxicity: (1) Molecular evolution of APOL1 haplotypes in human populations, (2) APOL1 splicing and consequent splice isoforms, (3) Interaction of APOL1 with other APOL gene family members, prioritizing APOL3. In the current study, we use reanalysis of population genetics datasets to resolve the haplotype contexts of all protein-altering APOL1 variants, uncovering previously unrecognized variant–haplotype couplings. We further characterize distinct cellular physiological properties among APOL1 splice isoforms, stressing the importance of isoform vB and what can be learned from isoform vC. Finally, a native interaction, and its interface, between APOL1 and APOL3 is reported, and shown to be differentially modulated by G1 and G2. We contend that continuing studies integrating these three interrelated domains will substantially advance mechanistic insights into APOL1 variant-driven renal injury, and leverage the findings to provide a more cohesive framework to guide future research. Full article