Search Results (97,320)

The diverse hormonal treatments applied to hemp (Cannabis sativa L.) carry significant implications for cultivation, and yield optimization across a range of applications, including fiber, seed, oil production, and the enhancement of medicinal compounds. However, there is no evidence concerning the long-term consequences of hormonal treatment. To determine the connection between the effects of hormonal treatment and cannabinoid accumulation, hemp plants were treated with γ-aminobutyric acid (GABA), abscisic acid (ABA), and salicylic acid (SA) to investigate their effects on gene expression and cannabinoid content levels in female inflorescences at 3 days and 4 weeks after treatment. The treatments influenced the transcript levels of five key cannabinoid biosynthesis genes, with 1.0 mM GABA significantly increasing OAC, THCAS, and CBCAS transcripts within 48 to 72 h. Additionally, 1.0 mM GABA led to a significant increase in tetrahydrocannabinol content by day three and significant increases in total cannabidiol and cannabinoid by week four. In addition, both ABA and SA induced transient, dose-dependent increases or decreases in gene expressions, but cannabinoid accumulation at 4 weeks showed no significant changes compared to the control. These results provide valuable insights for hormonal application in cultivation and the development of traits that enhance cannabinoid production in cannabis cultivation, which could significantly contribute to optimizing industrial applications. Full article

Despite providing highly accurate results, the short reads generated by second generation sequencing have major limitations in mapping complex genomic regions. Longer reads can resolve these issues and additionally phase distant variants. The third generation sequencing platform ONT currently achieves the longest sequencing reads but falls short in sequencing accuracy. Additionally, deriving phased haplotypes from amplicon-based NGS data remains a complex and time-consuming task that requires extensive bioinformatic expertise. We constructed an integrative, open-access modular data-analysis framework that allows for automated processing of high-throughput sequencing data from both second (Illumina) and third generation (ONT) sequencing platforms, combining the strengths of both technologies. Variant information is automatically evaluated and color-coded for discrepancies. Haplotypes are listed by frequency. All parts of the framework can be used independently. The framework’s performance was validated using synthetic and tested with real-life data by analyzing partly homologous FUT1/2/3 sequencing data from 400 blood donors. Full article

Genome-editing technology has advanced significantly since the 2020 Nobel Prize in Chemistry was awarded for the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9). While CRISPR–Cas9 has become widely used in academic research, its social implementation has lagged due to unresolved patent disputes and slower progress in gene function analysis. To address this, new approaches bypassing direct gene function analysis are needed, with bioinformatics and next-generation sequencing (NGS) playing crucial roles. NGS is essential for sequencing the genome of target species, but challenges such as data quality, genome heterogeneity, ploidy, and small individual sizes persist. Despite these issues, advancements in sequencing technologies, like PacBio high-fidelity (HiFi) long reads and high-throughput chromosome conformation capture (Hi-C), have improved genome sequencing. Bioinformatics contributes to genome editing through off-target prediction and target gene selection, both of which require accurate genome sequence information. In this review, I will give updates on the development of genome editing and bioinformatics technologies with a focus on the rapid progress in genome sequencing. Full article

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is strongly associated with both environmental and genetic risk factors, but its genetic underpinnings remain partially known. While variants in interferon regulatory factor 6 (IRF6) are linked to NSCL ± P risk in populations from Asia and Europe, studies on the highly admixed Brazilian population are scarce and have produced ambiguous results. This study aimed to investigate the contribution of IRF6 variants to the risk of NSCL ± P. Five tag-single nucleotide polymorphisms (rs599021, rs2073485, rs2235375, rs7552506, and rs642961) were analyzed in a large multicenter cohort composed of 1006 patients with NSCL ± P and 942 healthy controls. Statistical analyses involved multiple logistic regression tests consideration the tri-hybrid genetic origin of the Brazilian population, under a Bonferroni p value correcting for multiple comparisons. The A allele (OR: 1.43, 95% CI: 1.22–1.67, p < 0.0001) and AA genotype (OR: 2.04, 95% CI: 1.46–2.86, p < 0.0001) frequencies of rs642961 were significantly associated with NSCL ± P risk. Stratified analyses indicated that the variant is associated with susceptibility to both nonsyndromic cleft lip only (NSCLO) and nonsyndromic cleft lip and palate (NSCLP). However, the association with NSCLO was primarily observed in patients with high African ancestry, whereas the association with NSCLP was predominantly seen in patients with high European ancestry. No significant associations were found for the other investigated variants. Our results support the notion that the IRF6 rs642961 variant represents a marker of susceptibility to NSCL ± P in the Brazilian population, and that genetic ancestry composition plays a central role in the association with the cleft type. Full article

To stimulate further research, this review summarizes studies linking liver fibrosis with the risk of abdominal aortic aneurysms (AAA). AAA is defined as a permanently weakened and dilated abdominal aorta, which develops due to inflammation of the tunica media, activation of the renin–angiotensin–aldosterone system, immune system activation, and coagulation disorders. Typically asymptomatic, AAA is often incidentally detected through imaging done for abdominal symptoms or as part of screening programs. AAA follows a variable course and has a mortality rate strongly dependent on age and sex. Risk factors for AAA include age, male sex, ethnicity, family history of AAA, lifestyle habits, arterial hypertension, dyslipidemia, and comorbid atherosclerotic cardiovascular disease. Conversely, individuals with type 2 diabetes, female sex, and certain ethnicities are at a reduced risk of AAA. Liver fibrosis, resulting from chronic liver diseases owing to varying etiologies, is increasingly recognized as a potential contributor to AAA development. Evidence increasingly indicates that metabolic dysfunction-associated steatotic liver disease (MASLD) and other chronic liver conditions may intensify inflammatory pathways shared with AAA, thereby potentially exacerbating AAA progression. This review specifically examines the epidemiology and risk factors associated with the link between AAA and liver fibrosis. It also highlights potential pathomechanisms, including systemic inflammation, oxidative stress, and extracellular matrix remodeling, which may contribute to both conditions. Although these findings underscore significant overlaps in risk profiles, additional research is needed to clarify whether type 2 diabetes, female sex, and certain ethnicities truly confer protection against AAA or if this association is influenced by other confounding variables. Ultimately, addressing these open questions will help guide targeted therapeutic interventions and the identification of novel biomarkers to predict disease progression. Full article

Approximately 70–80% of breast cancers are estrogen receptor-positive (ER+), with 65% of these cases also being progesterone receptor-positive (ER+PR+). In most cases of ER+ advanced breast cancer, endocrine therapy (ET) serves as the first-line treatment, utilizing various drugs that inhibit ER signaling. These include tamoxifen, a selective estrogen receptor modulator (SERM); fulvestrant, a selective estrogen receptor degrader (SERD); and aromatase inhibitors (AIs), which block estrogen synthesis. However, intrinsic or acquired hormone resistance eventually develops, leading to disease progression. The combination of ET with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) has been shown to significantly increase progression-free survival (PFS) and, in some cases, overall survival (OS). CDK4/6is works by arresting the cell cycle in the G1 phase, preventing DNA synthesis, and enhancing the efficacy of ET. This review highlights the key mechanisms of resistance to ET, whether used alone or in combination with biological agents, as well as emerging therapeutic strategies aimed at overcoming resistance. Addressing ET resistance remains a work in progress, and in the near future, better patient selection for different therapeutic approaches is expected through the identification of more precise biological and genetic markers. In particular, liquid biopsy may provide a real-time portrait of the disease, offering insights into mechanisms driving ET resistance and cancer progression. Full article

The Araliaceae family has significant economic and medicinal value. However, the phylogenetic relationships and the expression patterns of key genes of the active triterpenoid substance within this family are still unclear. In this study, we employed comparative transcriptomics to analyze the transcriptomes of 19 species from 11 genera of Araliaceae, aiming to elucidate the evolutionary history of the family and the expression patterns of key genes in the ginsenoside biosynthesis pathway. Our results divide Araliaceae into two subfamilies: Aralioideae and Hydrocotyloideae. Aralioideae is further classified into three groups: the Aralia–Panax group, the Polyscias–Pseudopanax group, and the Asian Palmate group. PhyloNet analysis reveals that the common ancestor of Panax ginseng, Panax quinquefolius, and Panax japonicus was an allopolyploid, likely resulting from hybridization between Panax notoginseng and Panax pseudoginseng. Additionally, all Aralioideae species underwent the pg-β event, which may be critical for ginsenoside biosynthesis. We discovered that Panax species exhibit distinct expression patterns of key enzyme genes (β-AS, DDS, CYP450, UGTs) compared to other Araliaceae species. These enzyme genes show independent evolutionary lineages in gene trees, suggesting unique functional adaptations that enable Panax species to efficiently synthesize ginsenosides. This study provides a theoretical foundation for the conservation and utilization of Araliaceae germplasm resources. Full article

Husk number (HN) trait is an important factor affecting maize kernel dehydration rate after the physiological maturity stage. In general, a reasonable reduction in HN is a key target sought for breeding maize varieties that are suitable for mechanized harvesting. In this study, the HN of a maize natural population panel containing 232 inbred lines was analyzed, and the results showed a broad-sense heritability of 0.89, along with a wide range of phenotypic variation. With the best linear unbiased prediction (BLUP) values across the three environments, a genome-wide association study (GWAS) was conducted using 995,106 single-nucleotide polymorphism (SNP) markers. A total of 16 SNPs significantly associated with HN were identified by the mixed linear model and general linear model using the TASSEL 5.0 software program. A local linkage disequilibrium (LD) study was performed to infer the candidate interval around the lead SNPs. A total of 19 functionally annotated genes were identified. The candidate genes were divided into multiple functional types, including transcriptional regulation, signal transduction, and metabolic and cellular transport. These results provide hints for the understanding of the genetic basis of the HN trait and for the breeding of maize varieties with fewer HN and faster dehydration rate. Full article

During embryonic development, zygotic genome activation (ZGA) is a critical event that determines the rational process and the fate of embryonic cells. The tricarboxylic acid cycle (TCA cycle) provides necessary reactants and energy for biological activities such as genome activation, chromatin opening, and epigenetic modifications during ZGA. Recent studies have shown that during ZGA, core enzymes associated with TCA briefly enter the nucleus and participate in initiating the ZGA process. However, the regulatory relationship between ZGA factors, such as Dux, Dppa2, and Dppa4, and the core enzymes of the TCA cycle remains unknown. In this study, we found that Dppa2 plays a key role in ZGA by directly determining the localization of TCA core enzymes, thereby affecting the early embryonic development. To further investigate the effect of Dppa2 on the localization of pyruvate dehydrogenase (PDH), we followed the establishment of an inducible Dppa2 transgenic mouse model. We found that the “chronoectopic” expression of Dppa2 prior to normal ZGA time could lead to the advanced nuclear localization of PDH. In summary, Dppa2 plays a key role in ZGA, directly determining the location of TCA core enzymes in early embryos. This study provides a theoretical basis for early embryonic development at the metabolic regulation level. Full article

Sidransky syndrome represents a distinct variant of Parkinson’s disease (PD) that is linked to pathogenic variants in the glucocerebrosidase (GBA1) gene. This disorder exhibits an earlier onset, a more severe course, and a higher dementia prevalence compared to idiopathic PD. While the pathogenesis remains debated between loss-of-function and gain-of-function mechanisms, targeted therapies are emerging. Pharmacological chaperones (PCs), like high-dose Ambroxol, aim to mitigate enzyme misfolding—a primary driver of this disorder—rather than addressing metabolic deficiencies seen in Gaucher disease. Despite failed trials of substrate reduction therapies, current clinical trials with Ambroxol and other PCs highlight promising avenues for disease modification. This commentary advocates for increased awareness of Sidransky syndrome to advance diagnostic strategies, promote genetic testing, and refine targeted treatments, with the potential to transform care for GBA1-related PD and prodromal stages of the disease. Full article

The essential SUP35 gene encodes yeast translation termination factor Sup35/eRF3. The N-terminal domain of Sup35 is also responsible for Sup35 prionization that leads to generation of the [PSI⁺] prion. Previously we isolated different types of sup35 mutations (missense and nonsense) and demonstrated that sup35 nonsense mutations (sup35-n) are incompatible with the [PSI⁺] prion, leading to lethality of sup35-n [PSI⁺] haploid cells. Here, we show that sup35 missense mutations (sup35-m) within conservative regions of the Sup35 C-domain result in lethality of [PSI⁺] cells because of weak activity of Sup35/eRF3 as a translation termination factor. Mutant Sup35 maintain their ability to be incorporated into pre-existing [PSI⁺] aggregates and to form amyloid aggregates in vitro, while sup35-m mutations do not influence the [PSI⁺] prion induction and stability. All these mutations (D363N, R372K, T378I) are located in the conservative GTPase region of Sup35, decreasing the GTPase activity of mutated proteins. We propose that such low activity of mutant Sup35 combined with aggregation of Sup35 constituting the [PSI⁺] prion is not sufficient to maintain the viability of yeast cells. Full article

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation. Full article

Microbiota have emerged as a promising tool for estimating the post-mortem interval (PMI) in forensic investigations. The role of oral and nasal microbiota in cadaver decomposition is crucial; however, their distribution across human cadavers at different PMIs remains underexplored. In this study, we collected 88 swab samples from the oral and nasal cavities of 10 healthy volunteers and 34 human cadavers. Using 16S rRNA gene sequencing, we conducted comprehensive analyses of the alpha diversity, beta diversity, and relative abundance distribution to characterize the microbial communities in both healthy individuals and cadavers at varying PMIs and under different freezing conditions. Random forest models identified Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, and Fusobacteriota as potential PMI-associated biomarkers at the phylum level for both the oral and nasal groups, along with genus-level biomarkers specific to each group. These biomarkers exhibited nonlinear changes over increasing PMI, with turning points observed on days 5, 12, and 22. The random forest inference models demonstrated that oral biomarkers at both the genus and phylum levels achieved the lowest mean absolute error (MAE) values in the training dataset (MAE = 2.16 days) and the testing dataset (MAE = 5.14 days). Additionally, freezing had minimal impact on the overall phylum-level microbial composition, although it did affect the relative abundance of certain phyla. At the genus level, significant differences in microbial biomarkers were observed between frozen and unfrozen cadavers, with the oral group showing greater stability compared to the nasal group. These findings suggest that the influence of freezing should be considered when using genus-level microbial data to estimate PMIs. Overall, our results highlight the potential of oral and nasal microbiota as robust tools for PMI estimation and emphasize the need for further research to refine predictive models and explore the environmental factors shaping microbial dynamics. Full article

Kidney injury molecule-1 (KIM-1) is a transmembrane protein that is significantly upregulated in renal cells following injury. It has considerable potential as a biomarker for diagnosing and monitoring renal cell carcinoma (RCC). This review examines KIM-1 expression across multiple biological sources—including tissue, blood, and urine—and highlights its strong association with RCC risk. Clinical studies have shown that KIM-1 levels decline within weeks after nephrectomy, underscoring its utility in assessing therapeutic response. Additionally, urinary KIM-1 levels correlate with histopathological outcomes following cisplatin treatment, supporting its role as a non-invasive marker for treatment effectiveness. Despite these promising findings, several challenges remain. These include variability in assay performance and the modulatory effects of the tumour microenvironment on KIM-1 expression. Overcoming these technical limitations is crucial for integrating KIM-1 into clinical workflows. Furthermore, its potential role in guiding combination therapies—such as tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and mTOR inhibitors—could enhance therapeutic precision while minimizing toxicity. Continued research is essential to validate these applications and facilitate the routine clinical use of KIM-1 in RCC management. Full article

Cannabidiol (CBD) and tetrahydrocurcumin (THC) have demonstrated anti-inflammatory activity as well as generating new lymph vessels. We present the formulations and evaluations of CBD and THC loaded in hydrogels for the treatment of lymphedema to promote angiogenesis of lymph vessels and an anti-inflammatory response. Six CBD-THC hydrogel formulations were prepared and evaluated. The hydrodynamic particle sizes were 302.0–545.1 nm and the zeta potentials were from −58.80 to −33.63 mV. The hydrogel pHs were 6.43–6.54. The hydrogel formulations were non-toxic for both CBD (<25 µg/mL) and THC (<12.5 µg/mL). It was observed that high-molecular-weight hyaluronic acid in hydrogel affected collagen production. Hydrogel formulations at 2 µg/mL of CBD and 1 µg/mL of THC induced human dermal lymphatic endothelial cell tube formation. CBD-THC hydrogel formulations showed a notable ability to induce angiogenesis, which suggested its potential effectiveness in promoting new lymphatic vessel formation. Moreover, CBD-THC hydrogels showed anti-inflammatory properties. Further research is needed to ensure these treatments effectively enhance lymphatic repair. Full article