Bioorg Chem. 2025 Jan 3;155:108127. doi: 10.1016/j.bioorg.2025.108127. Online ahead of print.

ABSTRACT

Novel pH-sensitive polymeric photosensitizer carriers from the phthalocyanine (Pc) group were investigated as potential photodynamic therapy drugs for the treatment of breast cancer. Their high antiproliferative activity was confirmed by photocytotoxicity studies, which indicated their high efficacy and specificity toward the SK-BR-3 cell line. Importantly, the Pcs encapsulated in the polymeric nanoparticle (NP) carrier exhibited a much better penetration into the acidic environment of tumor cells than their free form. The investigated Pc4-NPs and TT1-NPs exhibited a high selectivity to healthy fibroblasts as well as non-toxicity without irradiation. This paper describes the detailed mechanism of action of the evaluated compounds by measuring reactive oxygen species (ROS), including singlet oxygen; imaging cellular localization; and analyzing key signaling pathway proteins. An additional advantage of the evaluated compounds is their ability to inhibit the Akt protein expression, including its phosphorylation, which the Western blot test confirmed. This is particularly important because breast cancers often overexpress the HER-2 receptor-related signaling proteins. Moreover, an analysis of proteins such as GLUT-1, HO-1, phospho-p42/44, and BID revealed the significant involvement of ROS in disrupting cellular homeostasis, thereby leading to the induction of oxidative stress and resulting in apoptotic cell death.

PMID:39798455 | DOI:10.1016/j.bioorg.2025.108127

Food Chem. 2024 Dec 29;471:142691. doi: 10.1016/j.foodchem.2024.142691. Online ahead of print.

ABSTRACT

Gluten-free products must not contain more than 20 mg/kg of gluten to be safe for consumption by celiac disease patients. Almost all analytical methods are calibrated to wheat, wheat gluten or gliadin, and there is no rye-specific reference material available. The aim of this study was to assess the effect of the harvest year on rye gluten composition and to generate distinct rye isolates to serve as calibration standards. Four different extraction procedures of a specific rye cultivar mixture were tested yielding prolamins (PROL), glutelins (GLUT), gluten (G) and acetonitrile/water-extractable proteins (AWEP). The isolates were characterized using different methods such as RP-HPLC, GP-HPLC, SDS-PAGE and LC-MS/MS. The isolates were evaluated in the R5 ELISA which resulted in the following response order: PROLiso > AWEPiso > Giso > GLUTiso. This paper represents a significant step towards improving gluten analysis, particularly in the context of rye-contaminated gluten-free products.

PMID:39798370 | DOI:10.1016/j.foodchem.2024.142691

Virology. 2025 Jan 7;603:110397. doi: 10.1016/j.virol.2025.110397. Online ahead of print.

ABSTRACT

The influenza A virus evades the host innate immune response to establish infection by inhibiting RIG-I activation through its nonstructural protein 1 (NS1). Here, we reported that receptor-transporting protein 4 (RTP4), an interferon-stimulated gene (ISG), targets NS1 to inhibit influenza A virus infection. Depletion of RTP4 significantly increased influenza A virus multiplication, while NS1-deficient viruses were unaffected. Mechanistically, RTP4 interacts with NS1 in an RNA-dependent manner and sequesters it from the TRIM25-RIG-I complex, thereby restoring TRIM25-mediated RIG-I K63-linked ubiquitination and subsequent activation of IRF3. Antiviral activity of RTP4 requires the evolutionarily conserved CXXC motifs and an H149 residue in the zinc finger domain, mutations of which disrupted RTP4-NS1 interaction and abrogated the ability of RTP4 to rescue RIG-I-mediated signaling. Collectively, our findings provided insights into the mechanism by which an ISG restricts influenza A virus replication by reactivating host antiviral signaling.

PMID:39798334 | DOI:10.1016/j.virol.2025.110397

Nucleic Acids Res. 2025 Jan 11;53(2):gkae1312. doi: 10.1093/nar/gkae1312.

ABSTRACT

The expansion of single-cell analytical techniques has empowered the exploration of diverse biological questions at the individual cells. Droplet-based single-cell RNA sequencing (scRNA-seq) methods have been particularly widely used due to their high-throughput capabilities and small reaction volumes. While commercial systems have contributed to the widespread adoption of droplet-based scRNA-seq, their relatively high cost limits the ability to profile large numbers of cells and samples. Moreover, as the scale of single-cell sequencing continues to expand, accommodating diverse workflows and cost-effective multi-biospecimen profiling becomes more critical. Herein, we present inDrops-2, an open-source scRNA-seq technology designed to profile live or preserved cells with a sensitivity matching that of state-of-the-art commercial systems but at a 6-fold lower cost. We demonstrate the flexibility of inDrops-2, by implementing two prominent scRNA-seq protocols, based on exponential and linear amplification of barcoded-complementary DNA, and provide useful insights into the advantages and disadvantages inherent to each approach. We applied inDrops-2 to simultaneously profile multiple human lung carcinoma samples that had been subjected to cell preservation, long-term storage and multiplexing to obtain a multiregional cellular profile of the tumor microenvironment. The scalability, sensitivity and cost efficiency make inDrops-2 stand out among other droplet-based scRNA-seq methods, ideal for large-scale studies on rare cell molecular signatures.

PMID:39797728 | DOI:10.1093/nar/gkae1312

J Fish Biol. 2025 Jan 11. doi: 10.1111/jfb.16056. Online ahead of print.

ABSTRACT

Animal growth is a fundamental component of population dynamics, which is closely tied to mortality, fecundity, and maturation. As a result, estimating growth often serves as the basis of population assessments. In fish, analysing growth typically involves fitting a growth model to age-at-length data derived from counting growth rings in calcified structures. Additionally, fish growth can be estimated using length-frequency data or data on changes in length derived from mark-recapture events. In our study of the European grayling (Thymallus thymallus L.) in the alpine region of Germany, we utilized all three types of datasets to develop the initial growth model. For the age-at-length data from scales, we applied the traditional von Bertalanffy growth function using both a Bayesian and a frequentist approach. Furthermore, we adopted the mark-recapture data along with the Fabens model for reparametrizing the von Bertalanffy growth model. The electronic length-frequency analysis (ELEFAN) was employed to examine the length-frequency data of the grayling, encompassing multiple sampling events from 2013 to 2022. Our findings indicated that the mark-recapture data, in conjunction with the Fabens model, yielded the most plausible values for both statistical approaches. When the von Bertalanffy growth function was used, the frequentist approach generated unreasonably high values, whereas the Bayesian version produced meaningful results when appropriate priors were applied, suggesting potential issues with the age-at-length data related to ageing. The ELEFAN approach produced the smallest yet reasonable growth parameters, contradicting other studies on the European grayling. The lower values may be attributed to the lack of larger fish in most of the sampling events, resulting in a relatively low asymptotic length and slow growth rate. As demonstrated in this case study on grayling from the River Inn, the use of growth characteristics may be a currently underestimated yet very useful indicator of target species assessment that can nicely complement other population health indicators.

PMID:39797550 | DOI:10.1111/jfb.16056

J Clin Med. 2025 Jan 6;14(1):288. doi: 10.3390/jcm14010288.

ABSTRACT

Objective: The clinical trial Effect of Modulated Auditory Stimulation on Interaural Auditory Perception (NCT0544189) aimed to determine whether an auditory intervention (AI)-"Bérard in 10"-can enhance the effect of standard therapies for people with anxiety and/or depression. Methods: Design: unblinded, randomized, controlled clinical trial.

LOCATION: Mejorada del Campo Health Centre, Madrid (Primary Care).

PARTICIPANTS: A total of 233 patients selected by systematic sampling and meeting the following selection criteria: age of majority, absence of severe acute pathology or chronic decompensated pathology. They were evaluated with the Goldberg and Hamilton tests and classified into the Emotional Well-Being group (EWB, n = 86) or the Anxiety and/or Depression group (AD, n = 147). Just half of each group received an AI.

INTERVENTION: Listening to classical music processed through a frequency modulator (Earducator) to attenuate abnormal frequencies, 30 min per session, two sessions a day for 5 days.

MAIN MEASUREMENTS: Hamilton Tests for Anxiety and Hamilton Test for Depression, at 3 and 6 months. Results: In the analysis by protocol, EWB with AI (n = 14) obtained lower scores in anxiety and depression at 3 and 6 months than EWB without AI (n = 36) (p < 0.05), the effects being large and moderate, respectively; AD with AI (n = 31) had lower scores on anxiety and depression at 3 months and anxiety at 6 months than AD without AI (n = 52) (p < 0.05), the effect being small. No damage reported. Conclusions: The AI "Bérard in 10" significantly prevents the onset of anxiety and depression and somewhat improves the effect of standard treatments in primary care.

PMID:39797370 | DOI:10.3390/jcm14010288

Cancers (Basel). 2024 Dec 25;17(1):19. doi: 10.3390/cancers17010019.

ABSTRACT

The treatment of cancers with immunotherapies has yielded significant milestones in recent years. Amongst these immunotherapeutic strategies, the FDA has approved several checkpoint inhibitors (CPIs), primarily Anti-Programmed Death-1 (PD-1) and Programmed Death Ligand-1/2 (PDL-1/2) monoclonal antibodies, in the treatment of various cancers unresponsive to immune therapeutics. Such treatments resulted in significant clinical responses and the prolongation of survival in a subset of patients. However, not all patients responded to CPIs, due to various mechanisms of immune resistance. One such mechanism is that, in addition to PD-1 expression on CD8 T cells, other inhibitory receptors exist, such as Lymphocyte Activation Gene 3 (LAG-3), T cell Immunoglobulin Mucin 3 (TIM3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT). These inhibitory receptors might be active in the presence of the above approved CPIs. Clearly, it is clinically challenging to block all such inhibitory receptors simultaneously using conventional antibodies. To circumvent this difficulty, we sought to target a potential transcription factor that may be involved in the molecular regulation of more than one inhibitory receptor. The transcription factor Yin Yang1 (YY1) was found to regulate the expression of PD-1, LAG-3, and TIM3. Therefore, we hypothesized that targeting YY1 in CD8 T cells should inhibit the expression of these receptors and, thus, prevent the inactivation of the anti-tumor CD8 T cells by these receptors, by corresponding ligands to tumor cells. This strategy should result in the prevention of immune evasion, leading to the inhibition of tumor growth. In addition, this strategy will be particularly effective in a subset of cancer patients who were unresponsive to approved CPIs. In this review, we discuss the regulation of LAG-3 by YY1 as proof of principle for the potential use of targeting YY1 as an alternative therapeutic approach to preventing the immune evasion of cancer. We present findings on the molecular regulations of both YY1 and LAG-3 expressions, the direct regulation of LAG-3 by YY1, the various approaches to targeting YY1 to evade immune evasion, and their clinical challenges. We also present bioinformatic analyses demonstrating the overexpression of LAG-3, YY1, and PD-L1 in various cancers, their associations with immune infiltrates, and the fact that when LAG-3 is hypermethylated in its promoter region it correlates with a better overall survival. Hence, targeting YY1 in CD8 T cells will result in restoring the anti-tumor immune response and tumor regression. Notably, in addition to the beneficial effects of targeting YY1 in CD8 T cells to inhibit the expression of inhibitory receptors, we also suggest targeting YY1 overexpressed in the tumor cells, which will also inhibit PD-L1 expression and other YY1-associated pro-tumorigenic activities.

PMID:39796650 | DOI:10.3390/cancers17010019

Int J Mol Sci. 2024 Dec 31;26(1):275. doi: 10.3390/ijms26010275.

ABSTRACT

Cancer occurrence rates exhibit diverse age-related patterns, and understanding them may shed new and important light on the drivers of cancer evolution. This study systematically analyzes the age-dependent occurrence rates of 23 carcinoma types, focusing on their age-dependent distribution patterns, the determinants of peak occurrence ages, and the significant difference between the two genders. According to the SEER reports, these cancer types have two types of age-dependent occurrence rate (ADOR) distributions, with most having a unimodal distribution and a few having a bimodal distribution. Our modeling analyses have revealed that (1) the first type can be naturally and simply explained using two age-dependent parameters: the total number of stem cell divisions in an organ from birth to the current age and the availability levels of bloodborne growth factors specifically needed by the cancer (sub)type, and (2) for the second type, the first peak is due to viral infection, while the second peak can be explained as in (1) for each cancer type. Further analyses indicate that (i) the iron level in an organ makes the difference between the male and female cancer occurrence rates, and (ii) the levels of sex hormones are the key determinants in the onset age of multiple cancer types. This analysis deepens our understanding of the dynamics of cancer evolution shared by diverse cancer types and provides new insights that are useful for cancer prevention and therapeutic strategies, thereby addressing critical gaps in the current paradigm of oncological research.

PMID:39796131 | DOI:10.3390/ijms26010275

Int J Mol Sci. 2024 Dec 30;26(1):248. doi: 10.3390/ijms26010248.

ABSTRACT

Sharka disease, caused by the plum pox virus (PPV), negatively impacts stone fruit production, resulting in economic losses. It has been demonstrated that grafting the almond (Prunus dulcis (Miller) D.A. Webb) variety 'Garrigues' into susceptible peach (Prunus persica (L.) Batsch) rootstocks can result in PPV resistance. The molecular circuits related to grafting in Prunus species, however, have not been fully investigated. In this study, susceptible peach rootstocks 'GF305' were either heterografted with 'Garrigues' almond or homografted with the same cultivar. Peach samples were collected at two stages of scion development, with ungrafted plants utilized as controls. Profiles of transcripts, small RNAs (sRNAs), and DNA methylation were obtained and analyzed on a genome-wide scale. Homografting and heterografting significantly altered the transcriptome and methylome of peach rootstocks, with these modifications being more pronounced during the early stages of scion development. The profiles of sRNAs were significantly more impacted when almonds were used as a scion as opposed to peaches, likely due to the transmission of PPV-unrelated viral sequences. Gene expression differences resulting from DNA methylation alterations are more thoroughly documented at the promoter sequences of genes than within their bodies. This study suggests that the 'Garrigues' almond variety triggers a complex defense response in the peach rootstock, potentially involving the interplay of epigenetic modifications and small RNA-mediated priming of antiviral defenses, which ultimately may contribute to PPV resistance.

PMID:39796109 | DOI:10.3390/ijms26010248

Int J Mol Sci. 2024 Dec 28;26(1):183. doi: 10.3390/ijms26010183.

ABSTRACT

Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context. It reveals their multifaceted impact on hallmark cancer processes, including sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis, resisting cell death, inducing angiogenesis, and enabling replicative immortality. SIRT1, for example, fosters chemoresistance and castration-resistant prostate cancer through metabolic reprogramming, immune modulation, androgen receptor signaling, and enhanced DNA repair. SIRT3 and SIRT4 suppress oncogenic pathways by regulating cancer metabolism, while SIRT2 and SIRT6 influence tumor aggressiveness and androgen receptor sensitivity, with SIRT6 promoting metastatic potential. Notably, SIRT5 oscillates between oncogenic and tumor-suppressive roles by regulating key metabolic enzymes; whereas, SIRT7 drives PCa proliferation and metabolic stress adaptation through its chromatin and nucleolar regulatory functions. Furthermore, we provide a comprehensive summary of the roles of individual sirtuins, highlighting their potential as biomarkers in PCa and exploring their therapeutic implications. By examining each of these specific mechanisms through which sirtuins impact PCa, this review underscores the potential of sirtuin modulation to address gaps in managing advanced PCa. Understanding sirtuins' regulatory effects could redefine therapeutic approaches, promoting precision strategies that enhance treatment efficacy and improve outcomes for patients with aggressive disease.

PMID:39796040 | DOI:10.3390/ijms26010183

Int J Mol Sci. 2024 Dec 28;26(1):172. doi: 10.3390/ijms26010172.

ABSTRACT

Heat stress transcription factors (HSFs) play a critical role in orchestrating cellular responses to elevated temperatures and various stress conditions. While extensively studied in model plants, the HSF gene family in Betula platyphylla remains unexplored, despite the availability of its sequenced genome. In this study, we employed bioinformatics approaches to identify 21 BpHSF genes within the Betula platyphylla genome, revealing their uneven distribution across chromosomes. These genes were categorized into three subfamilies: A, B, and C. Each was characterized by conserved protein motifs and gene structures, with notable divergence observed between subfamilies. Collinearity analysis suggested that segmental duplication events have driven the evolutionary expansion of the BpHSF gene family. Promoter region analysis identified an array of cis-acting elements linked to growth, development, hormonal regulation, and stress responses. Subcellular localization experiments confirmed the nuclear localization of BpHSFA2a, BpHSFB1a, and BpHSFC1a, consistent with in silico predictions. RNA-seq and RT-qPCR analyses revealed tissue-specific expression patterns of BpHSF genes and their dynamic responses to heat stress, with qPCR validation highlighting a significant upregulation of BpHSFA2a under high-temperature conditions. In summary, this study provided a comprehensive characterization of the HSF gene family in Betula platyphylla, laying a solid foundation for future functional studies. Particularly, BpHSFA2a emerges as a promising candidate gene for enhancing heat tolerance in Betula platyphylla, warranting further detailed investigation.

PMID:39796031 | DOI:10.3390/ijms26010172

Int J Mol Sci. 2024 Dec 28;26(1):163. doi: 10.3390/ijms26010163.

ABSTRACT

Over the last three decades, adult neurogenesis in mammals has been a central focus of neurobiological research, providing insights into brain plasticity and function. However, interest in this field has recently waned due to challenges in translating findings into regenerative applications and the ongoing debate about the persistence of this phenomenon in the adult human brain. Despite these hurdles, significant progress has been made in understanding how adult neurogenesis plays a critical role in the adaptation of brain circuits to environmental stimuli regulating key brain functions. This review focuses on the role of olfactory neurogenesis in the brain's response to social reproductive cues in rodents, highlighting its influence on animal behaviors critical for survival. We also address open questions and propose future directions to advance our understanding of the relationship between adult neurogenesis and reproductive function regulation.

PMID:39796023 | DOI:10.3390/ijms26010163

Int J Mol Sci. 2024 Dec 24;26(1):33. doi: 10.3390/ijms26010033.

ABSTRACT

DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks. Gepotidacin has been observed to sit on the twofold axis of the complex, midway between the two four-base-pair separated DNA-cleavage sites and has been observed to stabilize singe-stranded DNA breaks. Here, we use information from three crystal structures of complexes of Staphlococcus aureus DNA gyrase (one with a precursor of gepotidacin and one with the progenitor of zoliflodacin) to propose a simple single moving metal-ion-catalyzed DNA-cleavage mechanism. Our model explains why the catalytic tyrosine is in the tyrosinate (negatively charged) form for DNA cleavage. Movement of a single catalytic metal-ion (Mg2+ or Mn2+) guides water-mediated protonation and cleavage of the scissile phosphate, which is then accepted by the catalytic tyrosinate. Type IIA topoisomerases need to be able to rapidly cut the DNA when it becomes positively supercoiled (in front of replication forks and transcription bubbles) and we propose that the original purpose of the small Greek Key domain, common to all type IIA topoisomerases, was to allow access of the catalytic metal to the DNA-cleavage site. Although the proposed mechanism is consistent with published data, it is not proven and other mechanisms have been proposed. Finally, how such mechanisms can be experimentally distinguished is considered.

PMID:39795899 | DOI:10.3390/ijms26010033

Molecules. 2024 Dec 26;30(1):43. doi: 10.3390/molecules30010043.

ABSTRACT

Curcumin is among the most well-studied natural substances, known for its biological actions within the central nervous system, its antioxidant and anti-inflammatory properties, and human health benefits. However, challenges persist in effectively utilising curcumin, addressing its metabolism and passage through the blood-brain barrier (BBB) in therapies targeting cerebrovascular diseases. Current challenges in curcumin's applications revolve around its effects within neoplastic tissues alongside the development of intelligent formulations to enhance its bioavailability. Formulations have been discovered including curcumin's complexes with brain-derived phospholipids and proteins, or its liposomal encapsulation. These novel strategies aim to improve curcumin's bioavailability and stability, and its capability to cross the BBB, thereby potentially enhancing its efficacy in treating cerebrovascular diseases. In summary, this review provides a comprehensive overview of molecular pathways involved in interactions of curcumin and its metabolites, and brain vascular homeostasis. This review explores cellular and molecular current aspects, of curcumin-based effects with an emphasis on curcumin's metabolism and its impact on pathological conditions, such as neurodegenerative diseases, schizophrenia, and cerebral angiopathy. It also highlights the limitations posed by curcumin's poor bioavailability and discusses ongoing efforts to surpass these impediments to harness the full therapeutic potential of curcumin in neurological disorders.

PMID:39795101 | DOI:10.3390/molecules30010043

Microb Cell Fact. 2025 Jan 10;24(1):14. doi: 10.1186/s12934-024-02641-5.

ABSTRACT

Genome mining is a promising avenue for expanding the repertoire of microbial natural products, which are important for drug development. This approach involves predicting genetically encoded small molecules by examining bacterial genomes via accumulated knowledge of microbial biosynthesis. However, it is also important that the microbes produce the predicted molecule in practice. Here, we introduce an endophytic Streptomyces sp. N50, which was isolated from the medicinal plant Selaginella tamariscina. Upon sequencing its entire genome, 33 biosynthetic gene clusters (BGCs) were identified in a chromosome and a megaplasmid. Subsequent genome mining revealed that the new 15-deoxynaphthomycin could be produced due to the presence of an enoyl reductase domain, which is absent in the known BGC of naphthomycin, a type of ansamycin antibiotics. In addition, the engineered strain with the introduction of the global regulatory gene afsR2 into N50 successfully produced 15-deoxynaphthomycins. Furthermore, molecular network analysis via MS/MS selectively confirmed the presence of additional sulfur-containing 15-deoxynaphthomycin congeners. Eventually, six new 15-deoxynaphthomycins were isolated and elucidated from the engineered strain N50. This family of compounds is known to exhibit various biological activities. Also, the presence of quinone moieties in these compounds, which are known to activate NRF2, they were tested for their ability to activate NRF2. Among the new compounds, three (1, 5, and 6) activated the antioxidant NRF2-ARE signaling pathway. Treatment with these compounds significantly elevated NRF2 levels in HepG2 cells and further induced the expression of NRF2 target genes associated with the antioxidant response. This study suggests that the combination of genome mining, gene engineering and molecular networking is helpful for generating new small molecules as pharmaceutical candidates from microorganisms.

PMID:39794808 | DOI:10.1186/s12934-024-02641-5

BMC Genomics. 2025 Jan 10;26(1):28. doi: 10.1186/s12864-025-11210-y.

ABSTRACT

BACKGROUND: Sugarcane is a crucial crop for both sugar and bioethanol production. The nobilization breeding and utilization of wild germplasm have significantly enhanced its productivity. However, the pollen sterility in Saccharum officinarum restricts its role to being a female parent in crosses with Saccharum spontaneum during nobilization breeding, resulting in a narrow genetic basis for modern sugarcane cultivars. Mitochondria, often referred to as the intracellular "energy factories", provide energy for plant life activities, and are also implicated in cytoplasmic male sterility (CMS).

RESULTS: We performed mitochondrial genome assembly and structural analysis of two Saccharum founding species. We discovered that the proportions of repeat sequences are the primary factor contributing to the variations in mitochondrial genome structure and size between the two Saccharum species. Heterologous expression of the mitochondrial chimeric gene ORF113, which is highly expressed in male-sterile S. officinarum flowers, significantly inhibits growth and ATP synthesis in yeast cells, making it a key candidate CMS-related gene in sugarcane. Furthermore, we developed two co-dominant simple sequence repeat (SSR) markers based on the mitochondrial genome, which can effectively distinguish the cytoplasmic types of the two Saccharum species.

CONCLUSION: In this study, we identified structural variants and developed SSR molecular markers in the mitochondrial genomes of both S. officinarum and S. spontaneum. We also identified a novel mitochondrial chimeric ORF as a key candidate CMS-related gene. These findings offer valuable insights into variety identification, genetic resource development, and cross-breeding strategies in sugarcane.

PMID:39794692 | DOI:10.1186/s12864-025-11210-y

Commun Biol. 2025 Jan 10;8(1):38. doi: 10.1038/s42003-024-07444-3.

ABSTRACT

Prenatal maternal stress (PNMS) determines lifetime mental and physical health. Here, we show in rats that PNMS has consequences for placental function and fetal brain development across four generations (F0-F3). Using a systems biology approach, comprehensive DNA methylation (DNAm), miRNA, and mRNA profiling revealed a moderate impact of PNMS in the F1 generation, but drastic changes in F2 and F3 generations, suggesting compounding effects of PNMS with each successive generation. Both maternal and placental miRNA gene targets included de novo DNA methyltransferases, indicating robust PNMS-induced disruption in the complex epigenetic regulatory network between miRNAs and DNAm. Transgenerational programming mainly involved genes and biological pathways associated with neurological and psychiatric diseases which were linked to maternal-fetal crosstalk facilitated by the placenta. The highly correlated placenta-brain profiles support the use of placenta as a noninvasive biomarker resource to predict pathological changes in the neonatal brain. The transgenerational persistence of critical DNAm, miRNA and mRNA signatures may explain familial non-genetic disease risks.

PMID:39794497 | DOI:10.1038/s42003-024-07444-3

Cell Death Discov. 2025 Jan 10;11(1):2. doi: 10.1038/s41420-025-02286-2.

ABSTRACT

Oral cavity squamous cell carcinoma (OSCC) represents the most prevalent malignancy among head and neck squamous cell carcinomas (HNSCCs). Standard treatment modalities include surgical resection combined with radiation and chemotherapy. However, locoregional failure remains a critical issue affecting the prognosis of OSCC patients, largely due to tumor resistance against radiation or chemotherapy. In this study, we established a gene database related to OSCC recurrence and identified PSMA2 as a novel molecule influencing prognosis in OSCC patients. An independent Taiwanese cohort confirmed that elevated PSMA2 transcript levels were associated with poorer prognosis and contributed to the chemo- and radioresistance phenotype in OSCC. Furthermore, we confirmed that PSMA2 regulates cell cycle, mitochondrial dysfunction, and mitophagy, thereby contributing to carcinogenesis and resistance. Notably, mitophagy inducer exhibit antitumor effects in PSMA2-overexpressing OSCC xenograft mouse model. Collectively, our results provide a mechanistic understanding of the atypical function of PSMA2 in promoting OSCC recurrence.

PMID:39794329 | DOI:10.1038/s41420-025-02286-2

Trends Cancer. 2025 Jan 9:S2405-8033(24)00288-7. doi: 10.1016/j.trecan.2024.12.003. Online ahead of print.

ABSTRACT

Myeloid cells play a crucial dual role in cancer progression and response to therapy, promoting tumor growth, enabling immune suppression, and contributing to metastatic spread. The ability of these cells to modulate the immune system has made them attractive targets for therapeutic strategies aimed at shifting their function from tumor promotion to fostering antitumor immunity. Therapeutic approaches targeting myeloid cells focus on modifying their numbers, genetics, metabolism, and interactions within the tumor microenvironment. These strategies aim to reverse their suppressive functions and redirect them to support antitumor immune responses by inhibiting immunosuppressive pathways, targeting specific receptors, and promoting their differentiation into less immunosuppressive phenotypes. Here, we discuss recent approaches to clinically target tumor myeloid cells, focusing on reprogramming myeloid cells to promote antitumor immunity.

PMID:39794212 | DOI:10.1016/j.trecan.2024.12.003

Curr Biol. 2025 Jan 4:S0960-9822(24)01587-2. doi: 10.1016/j.cub.2024.11.046. Online ahead of print.

ABSTRACT

Anaphase is tightly controlled spatiotemporally to ensure proper separation of chromosomes.1,2,3 The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm.4,5,6,7 Yet, the relationship between spindle size and chromosome movement remains poorly understood. Here, we address this relationship during the cleavage divisions of the Drosophila blastoderm. We show that the speed of chromosome separation gradually decreases during the four nuclear divisions of the blastoderm. This reduction in speed is accompanied by a similar reduction in spindle length, ensuring that these two quantities are tightly linked. Using a combination of genetic and quantitative imaging approaches, we find that two processes contribute to controlling the speed at which chromosomes move in anaphase: the activity of molecular motors important for microtubule depolymerization and sliding and the cell cycle oscillator. Specifically, we found that the levels of multiple kinesin-like proteins important for microtubule depolymerization, as well as kinesin-5, contribute to setting the speed of chromosome separation. This observation is further supported by the scaling of poleward flux rate with the length of the spindle. Perturbations of the cell cycle oscillator using heterozygous mutants of mitotic kinases and phosphatases revealed that the duration of anaphase increases during the blastoderm cycles and is the major regulator of chromosome velocity. Thus, our work suggests a link between the biochemical rate of mitotic exit and the forces exerted by the spindle. Collectively, we propose that the cell cycle oscillator and spindle length set the speed of chromosome separation in anaphase.

PMID:39793565 | DOI:10.1016/j.cub.2024.11.046