Search Results (198)

Stress granule formation is a type of liquid–liquid phase separation in the cytoplasm, leading to RNA–protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of mammalian stress granules is the DEAD-box RNA helicase DDX3, which unwinds RNA in an ATP-dependent manner. DDX3 is involved in multiple steps of RNA metabolism, facilitating gene transcription, splicing, and nuclear export and regulating cytoplasmic translation. In this study, we investigate the role of the RNA helicase DDX3’s enzymatic activity in shaping the RNA content of ribonucleoprotein (RNP) condensates formed during arsenite-induced stress by inhibiting DDX3 activity with RK-33, a small molecule previously shown to be effective in cancer clinical studies. Using the human osteosarcoma U2OS cell line, we purified the RNP granule fraction and performed RNA sequencing to assess changes in the RNA pool. Our results reveal that RK-33 treatment alters the composition of non-coding RNAs within the RNP granule fraction. We observed a DDX3-dependent increase in circular RNA (circRNA) content and alterations in the granule-associated intronic RNAs, suggesting a novel role for DDX3 in regulating the cytoplasmic redistribution of non-coding RNAs. Full article

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

Medulloblastoma (MB) is the most common malignant brain tumor in children and typically arises in the cerebellum, likely due to disruptions in neuronal precursor development. The primary inhibitory neurotransmitter in the central nervous system (CNS), γ-aminobutyric acid (GABA), exerts its effects through GABA_A, GABA_B, and GABA_C receptors. GABA receptor activity regulates the development and function of cerebellar neurons, including glutamatergic cerebellar granule cells (CGCs). Beyond the nervous system, GABA is also a common metabolite in non-neuronal cell types. An increasing body of evidence indicates that GABA can influence cell proliferation, differentiation, and migration in several types of adult solid tumors, including brain cancers. GABA and GABA_A receptor agonists can impair the viability and survival of MB cells, primarily acting on GABA_A receptors containing the α5 subunit. A marked expression of the gene encoding the α5 subunit is found across all MB tumor molecular subgroups, particularly Group 3 MB, which has a poor prognosis. Importantly, high levels of the γ-aminobutyric acid type A receptor subunit α5 (GABRA5) gene are associated with shorter patient overall survival in Group 3 and Group 4 MB. In contrast, high γ-aminobutyric acid type A receptor subunit β1 (GABRB1) gene expression is related to longer survival in all MB subgroups. The GABAergic system may, therefore, regulate MB cell function and tumor progression and influence patient prognosis, and is worthy of further investigation as a biomarker and therapeutic target in MB. Full article

Stress granules (SG), dynamic cytoplasmic condensates formed via liquid-liquid phase separation (LLPS), serve as a critical hub for cellular stress adaptation and antiviral defense. By halting non-essential translation and sequestering viral RNA, SG restrict viral replication through multiple mechanisms, including PKR-eIF2α signaling, recruitment of antiviral proteins, and spatial isolation of viral components. However, viruses have evolved sophisticated strategies to subvert SG-mediated defenses, including proteolytic cleavage of SG nucleators, sequestration of core proteins into viral replication complexes, and modulation of stress-responsive pathways. This review highlights the dual roles of SG as both antiviral sentinels and targets of viral manipulation, emphasizing their interplay with innate immunity, autophagy, and apoptosis. Furthermore, viruses exploit SG heterogeneity and crosstalk with RNA granules like processing bodies (P-bodies, PB) to evade host defenses, while viral inclusion bodies (IBs) recruit SG components to create proviral microenvironments. Future research directions include elucidating spatiotemporal SG dynamics in vivo, dissecting compositional heterogeneity, and leveraging advanced technologies to unravel context-specific host-pathogen conflicts. This review about viruses and SG formation helps better understand the virus-host interaction and game process to develop new drug targets. Understanding these mechanisms not only advances virology but also informs innovative strategies to address immune escape mechanisms in viral infections. Full article

Background: Assisted reproductive technologies (ARTs) are essential in treating infertility but often face limited success due to low implantation and live birth rates. East Asian traditional medicine (EATM), including acupuncture and herbal medicine (HM), may enhance physiological responses during ART cycles. This study evaluated the effectiveness and safety of EATM in improving clinical pregnancy and live birth outcomes in women undergoing ART. Methods: This review, registered in PROSPERO (CRD42023411712), systematically searched 11 databases up to 31 March 2023. We included randomized controlled trials (RCTs) comparing EATM interventions to control groups. Data extraction and quality assessment were performed independently by two authors. Meta-analysis used the inverse-variance method in Stata 12.0. A total of 37 RCTs involving 10,776 women (aged 29–38) were analyzed. Studies addressed infertility causes including polycystic ovary syndrome, tubal blockage, diminished ovarian reserve, and unexplained infertility. Acupuncture therapies included body, electro-, laser, and auricular acupuncture. Herbal treatments were administered as powders, pills, granules, decoctions, and ointments based on traditional Chinese formulas. Results: EATM interventions were associated with significant improvements in clinical pregnancy and live birth rates. Acupuncture increased clinical pregnancy rates (CPR: RR 1.316, 95% CI 1.171–1.480) and live birth rates (LBR: RR 1.287, 95% CI 1.081–1.533). HM also enhanced CPRs (RR 1.184) and LBRs (RR 1.147). Subgroup analysis showed true acupuncture and HM were more effective than sham or placebo. No significant differences in adverse events were found. Conclusions: EATM, particularly acupuncture and HM, appears to be a safe and effective complementary therapy that can be used to improve ART outcomes. Future research should focus on developing standardized acupuncture and herbal protocols to optimize integration with ART. Full article

Background and Objectives: Total laparoscopic hysterectomy (TLH) is a commonly performed gynecological procedure. Vaginal cuff closure significantly impacts operative time and outcomes. This study evaluates the newly developed Anchorflow Suture (AFS) technique compared to conventional continuous suturing in terms of efficiency and safety. Materials and Methods: A multicenter retrospective cohort study was conducted at two tertiary referral hospitals involving 208 women who underwent TLH for benign indications. Women were divided into two groups based on vaginal cuff closure technique: AFS and continuous suturing. Demographic characteristics, surgical parameters, and postoperative outcomes were analyzed using appropriate statistical tests, with a significance level of p < 0.05. Results: No significant differences were found between groups in age, BMI (body mass index), gravida, parity, or menopausal status. Vaginal cuff closure time was significantly shorter with AFS (10.26 ± 2.3 min) compared to continuous suturing (13.36 ± 2.8 min, p < 0.001). Operative time was shorter in the AFS group, though not statistically significant (p = 0.15). Both techniques demonstrated similar safety profiles, with no cases of vaginal cuff dehiscence and comparable rates of granulation tissue formation, bleeding, and urinary incontinence. The AFS group showed a slightly lower incidence of postoperative bleeding (five cases vs. three cases). Conclusions: The AFS technique significantly reduces vaginal cuff closure time and demonstrates a comparable safety profile to continuous suturing. This method enhances surgical efficiency without increasing complications. Further prospective studies are needed to evaluate its long-term effects on pelvic floor integrity, sexual function, and surgeon proficiency. Full article

Cellular stressors have been demonstrated to exert a substantial influence on the functionality of organelles, thereby impacting cellular homeostasis and contributing to the development of disease pathogenesis. This review aims to examine the impact of diverse stressors, including environmental, chemical, biological, and physical factors, on critical organelles such as the cell membrane, mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, and membrane-less organelles. The intricate molecular mechanisms underlying cellular stress responses, encompassing oxidative stress, protein misfolding, and metabolic reprogramming, have the capacity to elicit adaptive responses or culminate in pathological conditions. The interplay between these stressors and organelle dysfunction has been implicated in a myriad of diseases, including neurodegenerative disorders, cancer, metabolic disorders, and immune-related pathologies. A comprehensive understanding of the mechanisms by which organelles respond to stress can offer valuable insights into the development of therapeutic strategies aimed at mitigating cellular damage. Full article

In order to obtain a highly nutritious extrudate, a combination of pseudocereals, vegetable protein, and banana flour, a fruit with high sensory acceptability, was used. The objective of the research was to produce a multi-component extrudate (ME) based on cañihua and quinoa with the addition of pea protein isolate and banana flour. The response variables evaluated were composition, expansion, hydration, colour, and hardness properties, as well as the microscopy and sensory characteristics of the flakes produced. These flakes were compared with three commercial extrudates, commercial quinoa-based extrudate (QE), commercial corn-based extrudate (CE), and commercial wheat-based extrudate (WE), which had similar characteristics. The ME showed a higher protein content compared to commercial extrudates (13.60%), and it had significant amounts of lipids, fibre, and ash. The expansion of the ME was like commercial quinoa but significantly lower than the CE and the WE in terms of expansion (p < 0.05). Regarding the absorption and solubility indices of the ME, these indicated that it had lower starch fragmentation compared to the commercial CE and WE. In addition, the instrumental hardness of the ME was higher than the commercial ones due to the complex nature of the product. Through scanning electron microscopy (SEM), it was observed that the ME showed some remaining extrusion-resistant starch granules from quinoa and cañihua with the presence of protein bodies. Finally, the flash profile described the ME as having a pronounced flavour, higher hardness, and lower sweetness, and the free sorting task allowed it to be differentiated from commercial extrudates based on its natural appearance and chocolate flavour. Full article

Castration is a common management practice among livestock producers, and animal welfare concerns exist following this procedure. The study’s aim was to compare the behavior, performance, and blood parameters between calves castrated with a lidocaine-infused castration band (Lidoband™; LLB) to a standard band with no pain relief. In this blinded, randomized controlled trial, 26 male beef–dairy cross calves were followed for 7 weeks post banding. There were no significant differences between treatment groups in regard to overall body weight, average daily gain (ADG), feed conversion (G:F), clinical illness scores, banding site scores, and approach tests. However, there were treatment differences in the weekly ADG and G:F (p < 0.05). There was a significant treatment by time interaction between the number of lying bouts and the average stand bout time (p < 0.05). There was also a significant treatment difference in the number of wound licks (p < 0.05). Overall, band castration presented acute and chronic pain, regardless of treatment. Performance, analyzed weekly, and behavioral patterns around the time of wound granulation (days 21–35 post castration) demonstrated positive outcomes for calves in the LLB group. Banding with an LLB proved to be beneficial in terms of both performance and behavioral aspects, implying greater animal welfare. Full article

Background/Objectives: Translation and the formation of membraneless organelles are linked mechanisms to promote cell stress surveillance. LncRNAs responsive to ethanol stress transcr_9136 of the SEY6210 strain and transcr_10027 of the BY4742 strain appear to act on tolerance to ethanol in these strains. Here, we investigate whether the ethanol responsiveness of transcr_9136 and transcr_10027 and their role in ethanol stress are associated with protein biogenesis and membraneless organelle assembly. Methods: SEY6210 transcr_9136∆ and BY4742 transcr_10027∆ and their wild-type counterparts were subjected to their maximum ethanol-tolerant stress. The expression of the transcr_9136, transcr_10027, ILT1, RRP1, 27S, 25S, TIR3, and FAA3 genes was accessed by qPCR. The level of DCP1a, PABP, and eIF4E proteins was evaluated by Western blotting. Bioinformatics analyses allowed us to check whether transcr_9136 may regulate the expression of RRP1 and predict the interaction between transcr_10027 and Tel1p. The cell death rate of SEY6210 strains under control and ethanol stress conditions was assessed by flow cytometry. Finally, we evaluated the total protein yield of all strains analyzed. Results: The results demonstrated that transcr_9136 of SEY6210 seems to control the expression of RRP1 and 27S rRNA and reduce the general translation. Furthermore, transcr_9136 seems to act on cell membrane integrity. Transcr_10027 of BY4742 appears to inhibit processing body formation and induce a general translation level. Conclusions: This is the first report on the effect of lncRNAs on yeast protein synthesis and new mechanisms of stress-responsive lncRNAs in yeast, with potential industrial applications such as ethanol production. Full article

Chronic liver diseases, such as those encountered with obesity, chronic/abusive alcohol consumption or viral infections, represent not only major public health concerns with limited therapeutic options but also important risk factors for the onset of hepatocellular carcinoma (HCC). Deciphering the molecular traits underlying these disorders is of high interest for designing new and effective treatments. The tristetraprolin (TTP) family members are of particular importance given their ability to control the expression of a wide range of genes involved in metabolism, inflammation and carcinogenesis at the post-transcriptional level. This regulation can occur within small cytoplasmic granules, namely, processing bodies (P-bodies), where the mRNA degradation occurs. Increasing evidence indicates that TTP family members and P-bodies are involved in the development of chronic liver diseases and cancers. In this review, we discuss the role of this regulatory mechanism in metabolic-dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), hepatic viral infections and HCC. Full article

Toxic cyanobacterial blooms are a growing environmental problem, persisting in freshwater bodies globally, and potentially hazardous to populations that rely on surface freshwater supplies. Nature-based solution units (NBSUs) are effective and sustainable approaches for water treatment, with sorption being an important process. The purpose of this study was to evaluate unmodified agro-based waste materials (rice husks, olive pulp pomace pellets (OP), cork granules) and the benchmark NBSU substrates (biochar, light expanded clay aggregate (LECA), and sand) for their microcystin-LR (MC-LR) and cylindrospermopsin (CYN) sorption potential. The kinetics and sorption mechanism of the two best sorbent materials were studied for future incorporation into NBSUs. Pre-screening of the sorbents showed highest sorption with biochar (>86% MC-LR and >98% CYN) and LECA (78% MC-LR and 80% CYN) and lower sorption with rice husk (<10%), cork (<10%), and sand (<26%). Leaching from OP made them unsuitable for further use. The sorption of both the cyanotoxins onto biochar was rapid (8 h), whereas onto LECA it was steadier (requiring 48 h for equilibrium). The pseudo-second-order kinetic model fit the sorption of both cyanotoxins onto biochar and LECA (R²: 0.94–0.99), suggesting that the sorption rate is limited by chemisorption. The sorption of MC-LR and CYN to biochar and LECA fit the Freundlich and D–R models better, suggesting multilayer sorption, high heterogeneity, and porosity in the sorbents (which was also confirmed by SEM/EDS). The sorption capacity was observed to be higher for biochar (K_f: MC-LR = 0.05, CYN = 0.16) than LECA (K_f: MC-LR = 0.02, CYN = 0.01). Full article

Numerous reports have indicated that the type 3 resistant starch (RS3) derived from Canna edulis can regulate lipid metabolism. However, it remains unclear whether the type 5 resistant starch (RS5) exhibits similar effects. In this study, RS5 was prepared from Canna edulis native starch and lauric acid through a hydrothermal method for the first time, and its nutritional intervention effects on hyperlipidemia in mice were investigated. The Canna edulis type 5 resistant starch (Ce-RS5) prepared using Canna edulis native starch and lauric acid exhibited a high compound index and resistant starch content, along with decreased swelling power and enhanced starch granule stability. The crystallinity of Ce-RS5 was decreased, and its crystal structure displayed a B+V pattern. Microscopically, the surface appeared rough with deepened grooves, and the granules were loose. Feeding mice with 1.5 g/kg and 3 g/kg of Ce-RS5 significantly reduced their body weight, positively regulated their blood lipid levels, and improved liver damage and fat accumulation. Additionally, Ce-RS5 promoted the abundance of beneficial gut bacteria, such as norank_f_Muribaculaceae, and inhibited the abundance of harmful bacteria like Colidextribacter. This study provides the first evidence of the hypolipidemic and weight loss effects of Ce-RS5 in hyperlipidemia mice. Full article

Despite being one of the most common infectious diseases, urinary tract infections (UTIs) still represent a challenge for clinicians to diagnose and treat, especially in the era of growing antibiotic resistance among uropathogenic bacteria. Recent studies investigating the pathophysiology of UTIs have discovered the prominent role of antimicrobial peptides in the urinary tract defense system. Cathelicidin is an evolutionary conserved antimicrobial peptide encoded by one single gene in humans. Except for being stored in neutrophil cytoplasmic granules, cathelicidin is produced by uroepithelial cells rapidly upon contact with a uropathogen, even before leukocytes invade the urinary tract. In addition to its bactericidal effect, cathelicidin acts as a chemoattractant for multiple immune cells and a potent inductor of numerous cytokine synthesis. Such a crucial role in the initial pathogenesis of a UTI makes cathelicidin a potential biomarker for an early UTI diagnosis. Indeed, multiple studies over the last two decades have proved the potential clinical utility of cathelicidin as a UTI diagnostic biomarker. Furthermore, since patients after the resolution of a UTI have been found to express a lower urinary cathelicidin level than healthy controls, decreased cathelicidin levels have been suggested as a risk factor for developing UTI recurrence. Therefore, measuring cathelicidin levels in urine might help in distinguishing patients with a higher risk for a recurrent UTI. Interestingly, except in UTIs, cathelicidin has also been evaluated in other urinary tract diseases and proposed as a biomarker for diagnosing severe vesicoureteral reflux (VUR) and for recognizing renal scar development in patients with VUR. Finally, a prominent role in UTI pathogenesis also makes cathelicidin an attractive therapeutic target for treating UTIs and, lately, different therapeutic agents up-regulating cathelicidin expression have been investigated in this matter. Therefore, the present review aims to summarize the current body of knowledge on the diagnostic, prognostic and therapeutic potential of cathelicidin in urinary tract diseases. For this purpose, three databases (Scopus, Medline and Web of Science) were extensively searched to cover all the published articles. This exhaustive review will update clinicians on the contemporary state of knowledge about the potential clinical utility of cathelicidin in urinary tract diseases and hopefully encourage further research, resulting in improvement in the current management of urinary tract diseases. Full article

Scrub bars are an innovative alternative to traditional liquid, semi-liquid, and oily body scrubs. Through the elimination of water from their formulas, they align with the current ‘waterless’ trend in the cosmetics market. The aims of this study were to create anhydrous formulations for body scrub bars and to assess their physical, chemical, and sensory characteristics depending on the type of exfoliant added. A total of five solid body scrub formulations were developed using different natural exfoliants: sugar, microcrystalline cellulose, ground coffee beans, corn granules, and sodium chloride. The shape and dimensions of the exfoliant particles were characterized by scanning electron microscopy (SEM). The formulations were subjected to texturometric tests. The final products underwent color assessment along with a consumer evaluation of sensory appeal. The test results showed that the body scrubs exhibiting the highest hardness and adhesive force were those containing exfoliants with small particles, either angular (sodium chloride) or subrounded (Coffea arabica seed powder) in shape. Conversely, the lowest hardness was determined for the product formulated with the addition of an exfoliant with well-rounded particles (microcrystalline cellulose). Among the exfoliants tested, microcrystalline cellulose proved to be the most suitable for body scrubs, demonstrating superior texture and exfoliating effectiveness. However, cosmetics containing ground coffee received the highest esthetic ratings. Coffee gave the product a natural color and an appealing scent, as judged by the testers. Full article