Viruses. 2024 Dec 5;16(12):1885. doi: 10.3390/v16121885.

ABSTRACT

Viromics studies are allowing us to understand not only the enormous diversity of the virosphere, but also the potential threat posed by the emerging viruses. Regarding the latter, the main concern lies in monitoring the presence of RNA viruses, but the zoonotic potential of some DNA viruses, on which we have focused in the present study, should also be highlighted. For this purpose, we analyzed 160 fecal samples from 14 species of small terrestrial mammals, 9 of them belonging to the order Rodentia. This allowed us to identify a total of 25 complete or near-complete genomes belonging to the families Papillomaviridae, Polyomaviridae, Adenoviridae, Circoviridae, and Genomoviridae, 18 of which could be considered new species or types. Our results provide a significant increase in the number of complete genomes of DNA viruses of European origin with zoonotic potential in databases, which are at present under-represented compared to RNA viruses. In addition, the characterization of whole genomes is of relevance for the further study of the evolutionary forces governing virus adaptation, such as recombination, which may play an important role in cross-species transmission.

PMID:39772193 | DOI:10.3390/v16121885

Vaccines (Basel). 2024 Dec 6;12(12):1377. doi: 10.3390/vaccines12121377.

ABSTRACT

Background/Objectives: Poxviruses are large DNA viruses that replicate in the host cytoplasm without a nuclear phase. As vaccine vectors, they can package and express large recombinant cassettes from different positions of their genomic core region. We present a comparison between wildtype modified vaccinia Ankara (MVA) and isolate CR19, which has significantly expanded inverted terminal repeats (ITRs). With this expansion, a site in wildtype MVA, called deletion site (DS) IV, has been duplicated at both ends of the genome and now occupies an almost central position in the newly formed ITRs. Methods: We inserted various reporter genes into this site and found that the ITRs can be used for transgene expression. However, ITRs are genomic structures that can rapidly adapt to selective pressure through transient duplication and contraction. To test the potential utility of insertions into viral telomers, we inserted a factor from the cellular innate immune system that interferes with viral replication as an example of a difficult transgene. Results: A site almost in the centre of the ITRs can be used for transgene expression, and both sides are mirrored into identical copies. The example of a challenging transgene, tetherin, proved to be surprisingly efficient in selecting candidate vectors against the large background of parental viruses. Conclusions: Insertion of transgenes into ITRs automatically doubles the gene doses. The functionalisation of viruses with tetherin may accelerate the identification and generation of recombinant vectors for personalised medicine and pandemic preparedness.

PMID:39772039 | DOI:10.3390/vaccines12121377

Polymers (Basel). 2024 Dec 21;16(24):3573. doi: 10.3390/polym16243573.

ABSTRACT

Polyurethane materials, widely used in indoor environments, occasionally exhibit unpleasant odors. An important source of polyurethane odorants is polyether polyols. Previous studies identified odorous 2-ethyldimethyl-1,3,6-trioxocanes in polyurethane materials and polyols but did not investigate the odor activity of the individual isomers. In the present work, an isomer mixture of the precursor dipropylene glycol was fractionated through preparative high-performance liquid chromatography. After the conversion to the corresponding trioxocanes, gas chromatography-olfactometry analyses revealed that just one positional isomer, namely 2-ethyl-4,7-dimethyl-1,3,6-trioxocane, was odor active. Moreover, we observed clear differences in the odor threshold concentrations among its stereoisomers. Only two out of eight isomers displayed an odor, both with an earthy smell and one being approximately 60 times more potent than the other. These insights contribute to a better understanding of polyurethane odor on a molecular level and provide a basis for effective odor control.

PMID:39771426 | DOI:10.3390/polym16243573

Plants (Basel). 2024 Dec 18;13(24):3536. doi: 10.3390/plants13243536.

ABSTRACT

Medicinal plants have long played a crucial role in healthcare systems, but limited genomic information on these species has impeded the integration of modern biological technologies into medicinal plant research. In this study, we selected nine common medicinal plants, each belonging to a different plant family, including Sarcandra glabra (Chloranthaceae), Nekemias grossedentata (Vitaceae), Uraria crinita (Fabaceae), Gynostemma pentaphyllum (Cucurbitaceae), Reynoutria japonica (Polygonaceae), Pseudostellaria heterophylla (Caryophyllaceae), Morinda officinalis (Rubiaceae), Vitex rotundifolia (Lamiaceae), and Gynura formosana (Asteraceae), to estimate their genome sizes and conduct preliminary genomic surveys. The estimated genome sizes by flow cytometry were 3.66 Gb, 0.65 Gb, 0.58 Gb, 1.02 Gb, 3.96 Gb, 2.99 Gb, 0.43 Gb, 0.78 Gb, and 7.27 Gb, respectively. The genome sizes of M. officinalis, R. japonica, and G. pentaphyllum have been previously reported. Comparative analyses suggest that variations in genome size may arise due to differences in measurement methods and sample sources. Therefore, employing multiple approaches to assess genome size is necessary to provide more reliable information for further genomic research. Based on the genome survey, species with considerable genome size variation or polyploidy, such as G. pentaphyllum, should undergo a ploidy analysis in conjunction with population genomics studies to elucidate the development of the diversified genome size. Additionally, a genome survey of U. crinita, a medicinal plant with a relatively small genome size (509.08 Mb) and of considerable interest in southern China, revealed a low heterozygosity rate (0.382%) and moderate repeat content (51.24%). Given the limited research costs, this species represents a suitable candidate for further genomic studies on Leguminous medicinal plants characteristic of southern China. This foundational genomic information will serve as a critical reference for the sustainable development and utilization of these medicinal plants.

PMID:39771235 | DOI:10.3390/plants13243536

Toxics. 2024 Dec 23;12(12):938. doi: 10.3390/toxics12120938.

ABSTRACT

This review delves into the impact of benzo(a)pyrene (B(a)P), which is a toxic and pervasive polycyclic aromatic hydrocarbon (PAH) and known carcinogen, on the human health risk from a gut microbiome perspective. We retrieved the relevant articles on each PAH and summarized the reporting to date, with a particular focus on benzo(a)pyrene, which has been reported to have a high risk of gut microbiome-related harm. B(a)P exposure can compromise the homeostasis of the gut microbiota, leading to dysbiosis, a state of microbial imbalance. The consequences of B(a)P-induced gut dysbiosis can be far-reaching, potentially contributing to inflammation, metabolic disorders, and an increased risk of various diseases. Additionally, due to the strong coupling between B(a)P and microparticles, the toxicity of B(a)P may be further compounded by its reaction with strong gut disruptors such as micro-/nanoplastics, which have recently become a serious environmental concern. This review summarizes current research on the impact of B(a)P on the gut microbiome, highlighting the intricate relationship between environmental exposure, gut health, and human disease. Further research is necessary to elucidate the underlying mechanisms and develop effective strategies to mitigate the adverse health effects of B(a)P exposure.

PMID:39771153 | DOI:10.3390/toxics12120938

Toxics. 2024 Nov 27;12(12):860. doi: 10.3390/toxics12120860.

ABSTRACT

Copper mining drives economic growth, with the global demand expected to reach 120 million metric tons annually by 2050. However, mining produces tailings containing heavy metals (HMs), which poses environmental risks. This study investigated the efficacy of phytoremediation (Phy) combined with electrokinetic treatment (EKT) to increase metal uptake in Carpobrotus aequilaterus grown in tailings from the Metropolitan Region of Chile. The plants were exposed to varying voltages and treatment durations. In the control (no EKT), the root metal contents were Fe (1008.41 mg/kg) > Cu (176.38 mg/kg) > Mn (103.73 mg/kg) > Zn (30.26 mg/kg), whereas in the shoots, the order was Mn (48.69 mg/kg) > Cu (21.14 mg/kg) > Zn (17.67 mg/kg) > Fe (27.32 mg/kg). The optimal EKT (15 V for 8 h) significantly increased metal uptake, with roots accumulating Fe (5997.24 mg kg-1) > Mn (672 mg kg-1) > Cu (547.68 mg kg-1) > Zn (90.99 mg kg-1), whereas shoots contained Fe (1717.95 mg kg-1) > Mn (930 mg kg-1) > Cu (219.47 mg kg-1) > Zn (58.48 mg kg-1). Although EKT enhanced plant growth and biomass, higher voltages stressed the plants. Longer treatments were more effective, suggesting that EK-Phy is a promising method for remediating metal-contaminated tailings.

PMID:39771075 | DOI:10.3390/toxics12120860

Microorganisms. 2024 Dec 2;12(12):2475. doi: 10.3390/microorganisms12122475.

ABSTRACT

Wastewater-based surveillance (WBS) is a proven tool for monitoring population-level infection events. Wastewater contains high concentrations of inhibitors, which contaminate the total nucleic acids (TNA) extracted from these samples. We found that TNA extracts from raw influent of Berlin wastewater treatment plants contained highly variable amounts of inhibitors that impaired molecular analyses like dPCR and next-generation sequencing (NGS). By using dilutions, we were able to detect inhibitory effects. To enhance WBS sensitivity and stability, we applied a combination of PCR inhibitor removal and TNA dilution (PIR+D). This approach led to a 26-fold increase in measured SARS-CoV-2 concentrations, practically reducing the detection limit. Additionally, we observed a substantial increase in the stability of the time series. We define suitable stability as a mean absolute error (MAE) below 0.1 log10 copies/L and a geometric mean relative absolute error (GMRAE) below 26%. Using PIR+D, the MAE could be reduced from 0.219 to 0.097 and the GMRAE from 65.5% to 26.0%, and even further in real-world WBS. Furthermore, PIR+D improved SARS-CoV-2 genome alignment and coverage in amplicon-based NGS for low to medium concentrations. In conclusion, we strongly recommend both the monitoring and removal of inhibitors from samples for WBS.

PMID:39770678 | DOI:10.3390/microorganisms12122475

Microorganisms. 2024 Nov 28;12(12):2449. doi: 10.3390/microorganisms12122449.

ABSTRACT

Arctic char is a top predator in Arctic waters and is threatened by mercury pollution in the context of changing climate. Gill microbiota is directly exposed to environmental xenobiotics and play a central role in immunity and fitness. Surprisingly, there is a lack of literature studying the effect of mercury on gill microbiota. To fill this knowledge gap, our primary goal was to measure to what extent gill exposure to mercury may alter gill microbiota activity in Arctic char. Specifically, we calculated the correlation between the taxonomic distribution of gill-associated bacterial symbiont activity and total mercury concentration in livers and muscles in wild populations of Arctic char in the Canadian Arctic. Our results showed that total mercury concentrations in tissues were higher in Ekaluktutiak (Nunavut) than in the other sites in Nunavik. Proteobacteria was the main phylum correlated to mercury concentration in both tissues, followed by Bacteroidetes and Cyanobacteria. In the most contaminated sites, Aeromonas and Pseudomonas (Proteobacteria) were predominant, while mercury concentration negatively correlated with Photobacterium (Proteobacteria) or Cerasicoccus (Verrucomicrobia). In summary, we found that mercury contamination correlates with active gill microbiota composition, with potential implications of strains in modulating mercury toxicity, making them interesting for future biomarker studies.

PMID:39770652 | DOI:10.3390/microorganisms12122449

Pharmaceuticals (Basel). 2024 Dec 22;17(12):1736. doi: 10.3390/ph17121736.

ABSTRACT

Background: At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because their analysis tends to be valuable for the extraction of novel biological knowledge. Methods: For this reason, we constructed a disease-protein-drug network, focusing on a category of rare protein-misfolding diseases, known as amyloidoses, and on other pathological conditions also associated with amyloid deposition. Apart from the amyloidogenic proteins that self-assemble into fibrils, we also included other co-deposited proteins found in amyloid deposits. Results: In this work, protein-protein, protein-drug, and disease-drug associations were collected to create a heterogenous network. Through disease-based and drug-based analyses, we highlighted commonalities between diseases and proposed an approved drug with prospects of repurposing. Conclusions: The identified disease associations and drug candidates are proposed for further study that will potentially help treat diseases associated with amyloid deposition.

PMID:39770578 | DOI:10.3390/ph17121736

Int J Mol Sci. 2024 Dec 18;25(24):13540. doi: 10.3390/ijms252413540.

ABSTRACT

Gene transfection is a fundamental technique in the fields of biological research and therapeutic innovation. Due to their biocompatibility and membrane-mimetic properties, lipid vectors serve as essential tools in transfection. The successful delivery of genetic material into the cytoplasm is contingent upon the fusion of the vector and cellular membranes, which enables hydrophilic polynucleic acids to traverse the hydrophobic barriers of two intervening membranes. This review examines the critical role of membrane fusion in lipofection efficiency, with a particular focus on the molecular mechanisms that govern lipoplex-membrane interactions. This analysis will examine the key challenges inherent to the fusion process, from achieving initial membrane proximity to facilitating final content release through membrane remodeling. In contrast to viral vectors, which utilize specialized fusion proteins, lipid vectors necessitate a strategic formulation and environmental optimization to enhance their fusogenicity. This review discusses recent advances in vector design and fusion-promoting strategies, emphasizing their potential to improve gene delivery yield. It highlights the importance of understanding lipoplex-membrane fusion mechanisms for developing next-generation delivery systems and emphasizes the need for continued fundamental research to advance lipid-mediated transfection technology.

PMID:39769303 | DOI:10.3390/ijms252413540

Int J Mol Sci. 2024 Dec 14;25(24):13424. doi: 10.3390/ijms252413424.

ABSTRACT

The predominant neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all of them share a combination of one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, and TAR DNA-binding protein 43. These toxic proteins share some common attributes, making them potentially universal and simultaneous targets for therapeutic intervention. First, they all form toxic aggregates prior to taking on their final forms as contributors to plaques, neurofibrillary tangles, Lewy bodies, and other protein deposits. Second, the primary enzyme that directs their aggregation is transglutaminase 2 (TGM2), a brain-localized enzyme involved in neurodegeneration. Third, TGM2 binds to calmodulin, a regulatory event that can increase the activity of this enzyme threefold. Fourth, the most common mixed pathology toxic biomarkers (Aβ, pTau, αSyn, nHtt) also bind calmodulin, which can affect their ability to aggregate. This review examines the potential therapeutic routes opened up by this knowledge. The end goal reveals multiple opportunities that are immediately available for universal therapeutic treatment of the most devastating neurodegenerative diseases facing humankind.

PMID:39769187 | DOI:10.3390/ijms252413424

Int J Mol Sci. 2024 Dec 14;25(24):13418. doi: 10.3390/ijms252413418.

ABSTRACT

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM. In this study, we analyzed WES data from 35 MM patients to identify potential mutational signatures and driver mutations correlated with clinical and cytogenetic characteristics. Our findings confirm the complex mutational spectrum and its impact on previously described ontogenetic and epigenetic pathways. They show TYW1 as a possible new potential driver gene and find no significant associations of mutational signatures with clinical findings. Further studies are needed to strengthen the role of mutational signatures in the clinical context of patients with MM to improve patient management.

PMID:39769182 | DOI:10.3390/ijms252413418

Diagnostics (Basel). 2024 Dec 18;14(24):2848. doi: 10.3390/diagnostics14242848.

ABSTRACT

BACKGROUND: This study investigated whether point-of-care platelet function measurements could predict favorable outcomes in patients with acute ischemic stroke (AIS). Antiplatelet agents, such as aspirin, are known to reduce the risk of recurrent stroke by 20-30%. However, identifying nonresponders to therapy remains a clinical challenge. The study aimed to assess the prognostic value of serial Platelet Function Analyzer (PFA)-100 measurements and hematological ratios in AIS patients.

METHODS: A prospective cohort study was conducted on 212 AIS patients in Taiwan. Platelet function was assessed at baseline, week 2, and week 4 using PFA-100. The primary outcome was functional recovery, defined by a modified Rankin Scale (mRS) score of 0-3, at 1-month and 1-year. Subgroup analyses compared outcomes between pre- and post-aspirin administrations. Statistical analyses examined the association between changes in platelet function and clinical outcomes.

RESULTS: Difference in collagen and epinephrine (CEPI) measurements between baseline and week 2 was associated with favorable mRS scores (p < 0.001). A difference in CEPI closure time greater than 99 seconds was most predictive of a favorable outcome with an adjusted odds ratio of 11.859 (95% CI 2.318-60.669) at 1-month follow-up. Subgroup analyses revealed predictive value in pre-aspirin measurements at 1-month follow-up (p = 0.007).

CONCLUSIONS: Serial PFA-100 measurements and hematological biomarkers, specifically changes in on-treatment CEPI closure times, may help predict favorable clinical outcome in AIS patients. These findings suggest that dynamic platelet function assessment could play a role in optimizing antiplatelet therapy in AIS management.

PMID:39767209 | DOI:10.3390/diagnostics14242848

Genes (Basel). 2024 Dec 15;15(12):1602. doi: 10.3390/genes15121602.

ABSTRACT

BACKGROUND/OBJECTIVES: Neural differentiation requires a multifaceted program to alter gene expression along the proliferation to the differentiation axis. While critical changes occur at the level of transcription, post-transcriptional mechanisms allow fine-tuning of protein output. We investigated the role of tRNAs in regulating gene expression during neural differentiation in Drosophila larval brains.

METHODS: We quantified tRNA abundance in neural progenitor-biased and neuron-biased brains using the hydrotRNA-seq method. These tRNA data were combined with cell type-specific mRNA decay measurements and transcriptome profiles in order to model how tRNA abundance affects mRNA stability and translation efficiency.

RESULTS: We found that (1) tRNA abundance is largely constant between neural progenitors and neurons but significant variation exists for 10 nuclear tRNA genes and 8 corresponding anticodon groups, (2) tRNA abundance correlates with codon-mediated mRNA decay in neuroblasts and neurons, but does not completely explain the different stabilizing or destabilizing effects of certain codons, and (3) changes in tRNA levels support a shift in translation optimization from a program supporting proliferation to a program supporting differentiation.

CONCLUSIONS: These findings reveal coordination between tRNA expression and codon usage in transcripts that regulate neural development.

PMID:39766869 | DOI:10.3390/genes15121602

Genes (Basel). 2024 Nov 27;15(12):1530. doi: 10.3390/genes15121530.

ABSTRACT

BACKGROUND: In the realm of system biology, it is a challenging endeavor to infer a gene regulatory network from time-series gene expression data. Numerous Boolean network inference techniques have emerged for reconstructing a gene regulatory network from a time-series gene expression dataset. However, most of these techniques pose scalability concerns given their capability to consider only two to three regulatory genes over a specific target gene.

METHODS: To overcome this limitation, a novel inference method, LBF-MI, has been proposed in this research. This two-phase method utilizes limited Boolean functions and multivariate mutual information to reconstruct a Boolean gene regulatory network from time-series gene expression data. Initially, Boolean functions are applied to determine the optimum solutions. In case of failure, multivariate mutual information is applied to obtain the optimum solutions.

RESULTS: This research conducted a performance-comparison experiment between LBF-MI and three other methods: mutual information-based Boolean network inference, context likelihood relatedness, and relevance network. When examined on artificial as well as real-time-series gene expression data, the outcomes exhibited that the proposed LBF-MI method outperformed mutual information-based Boolean network inference, context likelihood relatedness, and relevance network on artificial datasets, and two real Escherichia coli datasets (E. coli gene regulatory network, and SOS response of E. coli regulatory network).

CONCLUSIONS: LBF-MI's superior performance in gene regulatory network inference enables researchers to uncover the regulatory mechanisms and cellular behaviors of various organisms.

PMID:39766797 | DOI:10.3390/genes15121530

Antibiotics (Basel). 2024 Dec 2;13(12):1154. doi: 10.3390/antibiotics13121154.

ABSTRACT

Background: Klebsiella pneumoniae is an opportunistic pathogen that causes a wide range of infections worldwide. The emergence and spread of multidrug-resistant clones requires the implementation of novel therapeutics, and phages are a promising approach. Results: In this study, two Klebsiella phages, KpTDp1 and KpTDp2, were isolated from wastewater samples in Tunisia. These phages had a narrow host range and specifically targeted the hypervirulent K2 and K28 capsular types of K. pneumoniae. Both phages have double-stranded linear DNA genomes of 49,311 and 49,084 bp, respectively. Comparative genomic and phylogenetic analyses placed phage KpTDp2 in the genus Webervirus, while phage KpTDp1 showed some homology with members of the genus Jedunavirus, although its placement in a new undescribed genus may be reconsidered. The replication efficiency and lytic ability of these phages, combined with their high stability at temperatures up to 70 °C and pH values ranging from 3.5 to 8.2, highlight the potential of these phages as good candidates for the control of hypervirulent multidrug-resistant K. pneumoniae. Methods: Phage isolation, titration and multiplicity of infection were performed. The stability of KpTDp1 and KpTDp2 was tested at different pH and temperatures. Genomic characterization was done by genome sequencing, annotation and phylogenetic analysis. Conclusions: The ability of KpTDp1 and KpTDp2 to lyse one of the most virulent serotypes of K. pneumoniae, as well as the stability of their lytic activities to pH and temperature variations, make these phages promising candidates for antibacterial control.

PMID:39766544 | DOI:10.3390/antibiotics13121154

Brain Sci. 2024 Nov 25;14(12):1180. doi: 10.3390/brainsci14121180.

ABSTRACT

Accurate identification and functional annotation of splicing isoforms and non-coding RNAs (lncRNAs), alongside full-length protein-encoding transcripts, are critical for understanding gene (mis)regulation and metabolic reprogramming in Alzheimer's disease (AD). This study aims to provide a comprehensive and accurate transcriptome resource to improve existing AD transcript databases. Background/Objectives: Gene mis-regulation and metabolic reprogramming play a key role in AD, yet existing transcript databases lack accurate and comprehensive identification of splicing isoforms and lncRNAs. This study aims to generate a refined transcriptome dataset, expanding the understanding of AD onset and progression. Methods: Publicly available RNA-seq data from pre-AD and AD tissues were utilized. Advanced bioinformatics tools were applied to assemble and annotate full-length transcripts, including splicing isoforms and lncRNAs, with an emphasis on correcting errors and enhancing annotation accuracy. Results: A significantly improved transcriptome dataset was generated, which includes detailed annotations of splicing isoforms and lncRNAs. This dataset expands the scope of existing AD transcript databases and provides new insights into the molecular mechanisms underlying AD. The findings demonstrate that the refined dataset captures more relevant details about AD progression compared to publicly available data. Conclusions: The newly developed transcriptome resource and the associated analysis tools offer a valuable contribution to AD research, providing deeper insights into the disease's molecular mechanisms. This work supports future research into gene regulation and metabolic reprogramming in AD and serves as a foundation for exploring novel therapeutic targets.

PMID:39766379 | DOI:10.3390/brainsci14121180

Biomolecules. 2024 Dec 14;14(12):1599. doi: 10.3390/biom14121599.

ABSTRACT

Extracellular vesicles (EVs) are lipid bilayer nanoparticles released from all known cells and are involved in cell-to-cell communication via their molecular content. EVs have been found in all tissues and body fluids, carrying a variety of biomolecules, including DNA, RNA, proteins, metabolites, and lipids, offering insights into cellular and pathophysiological conditions. Despite the emergence of EVs and their molecular contents as important biological indicators, it remains difficult to explore EV-mediated biological processes due to their small size and heterogeneity and the technical challenges in characterizing their molecular content. EV-associated small RNAs, especially microRNAs, have been extensively studied. However, other less characterized RNAs, including protein-coding mRNAs, long noncoding RNAs, circular RNAs, and tRNAs, have also been found in EVs. Furthermore, the EV-associated proteins can be used to distinguish different types of EVs. The spectrum of EV-associated RNAs, as well as proteins, may be associated with different pathophysiological conditions. Therefore, the ability to comprehensively characterize EVs' molecular content is critical for understanding their biological function and potential applications in disease diagnosis. Here, we set out to provide an overview of EV-associated RNAs and proteins as well as approaches currently being used to characterize them.

PMID:39766306 | DOI:10.3390/biom14121599

Biomolecules. 2024 Nov 27;14(12):1513. doi: 10.3390/biom14121513.

ABSTRACT

Immune checkpoint inhibitors, such as anti-PD-1 antibodies, represent a significant advancement in cancer immunotherapy, but their efficacy varies notably between individuals, influenced by complex biological systems. Recent evidence suggests that sex-related biological differences play a pivotal role in modulating these responses. This study uses a systems biology approach to examine how sex-specific differences in the immune system contribute to variability in the response to treatment. Our model extends previous frameworks by incorporating sex-specific parameters that reflect observed immunological distinctions. The results from the simulation studies align with our clinical observations, showing that on average, males exhibit a more robust response to anti-PD-1 treatment compared to females. Additionally, this study explores the potential of combination therapy with recombinant IL-12, revealing sex-specific differences in treatment efficacy. These findings underscore the need for personalized immunotherapy strategies that consider individual immunological profiles, including sex, to optimize treatment outcomes.

PMID:39766221 | DOI:10.3390/biom14121513

Antioxidants (Basel). 2024 Dec 5;13(12):1485. doi: 10.3390/antiox13121485.

ABSTRACT

Elaeagnus latifolia (EL) is a wild fruit known for containing several health-promoting compounds. This study aimed to evaluate the effects of EL fruit extract on high-fat diet (HFD)-induced obesity and lipopolysaccharide (LPS)-activated macrophages. Mice fed an HFD and given EL fruit extract for 10 weeks exhibited significantly lower body weight, reduced lipid accumulation, diminished oxidative stress in adipocytes, and decreased macrophage infiltration compared to those not receiving the EL extract. Moreover, the EL fruit extract activated the transcription factors Pparg and Cebpa, initiating adipogenesis and modulating the expression of NF-κB/Nrf-2-induced target genes. This resulted in smaller adipocyte size, reduced inflammation, and less oxidative stress in HFD-fed mice. In vitro, the EL extract induced a shift in macrophage phenotype from M1 to M2, reduced IκBα/NF-κB phosphorylation, and effectively decreased energy production in macrophages by downregulating the expression of several proteins involved in glycolysis and the tricarboxylic acid cycle. This mechanistic study suggests that administering EL fruit extract could be an effective strategy for managing obesity and its associated pathologies.

PMID:39765814 | DOI:10.3390/antiox13121485