Search Results (49)

Background/Objectives: Tubulins (Tub) are central components of microtubules, but intraspecific variation and developmental expression of the Tub family in Gossypium barbadense remain poorly characterized. This study aimed to characterize the GbTub family using a pan-genome framework and identify candidates associated with fiber development and strength. Methods: A total of 50 GbTub genes were identified in the G. barbadense 3-79 reference genome, and their orthologous presence–absence patterns were subsequently assessed across 12 additional G. barbadense accessions. Phylogenetic, presence–absence variation (PAV), Ka/Ks, structural variation (SV), RNA-seq, RT-qPCR, co-expression, and GO enrichment analyses were integrated. Results: Among the 50 reference-defined GbTub genes, 43 were classified as core genes, 6 as near-core genes, and 1 as an accessory gene, and the encoded proteins were classified into α-, β-, and γ-tubulin clades. All genes showed Ka/Ks < 1. Twenty-three GbTub genes differed between the fiber-strength-contrasting accessions 5917 and PimaS-7, and representative expression trends were supported by RT-qPCR. Network analysis prioritized 10 GbTub candidates based on degree centrality. GbTub21 was the sole SV-associated GbTub gene displaying significant differential expression between accessions harboring versus lacking the corresponding SV. Non-Tub neighbors of the candidate hub genes were enriched for cytoskeletal, intracellular-transport, and plasma-membrane functions. Conclusions: The pan-genome analysis reveals strong conservation with limited intraspecific variation in the GbTub family. Co-expression profiles nominate candidates associated with fiber secondary-wall development, and their causal contribution to fiber strength awaits functional dissection. Full article

Tubulins are essential cytoskeletal components involved in plant cell division and expansion, yet their evolutionary dynamics across plant lineages and potential roles in horticultural seed/kernel development remain insufficiently understood. Here, we identified 2535 tubulin-related genes from 97 plant genomes and performed an integrated phylogenomic analysis. Phylogenetic and synteny network analyses resolved four ancient clades, including α-, β-,γ-tubulin and FtsZ, all of which were predominantly subjected to purifying selection. The α- and β-tubulin subfamilies exhibited lineage-specific expansion in angiosperms, particularly in eudicots, and these expansions were associated with ancient WGD and WGT events while retaining relatively conserved chromosomal contexts. By employing a pyramid-structured microsynteny framework across 12 Rosaceae genomes, we further traced the orthologous conservation and lineage-specific rearrangements of tubulin loci, with Prunus armeniaca as a reference. Spatiotemporal transcriptome profiling of Siberian apricot and kernel apricot revealed a group of tubulin genes highly expressed during key stages of kernel development, highlighting PaTUA1 as a priority candidate gene. Transient overexpression of PaTUA1 in wounded developing apricot kernels was associated with short-term increases in average phytohormone concentrations, including IAA, GA₃, BR, and cytokinins. Together, these results suggest that PaTUA1 represents a promising candidate gene associated with hormone-related responses during apricot kernel development, providing a basis for future functional validation rather than direct evidence of kernel-size determination. Full article

Background: The sperm centrosome is a key organelle composed of two centrioles surrounded by pericentriolar material and is essential for sperm aster formation and first mitotic spindle formation after sperm entry into the oocyte, thereby supporting early embryonic development. Methods: This systematic review evaluated 83 publications published between 1986 and 2026 to provide an updated overview of the human sperm centrosome, including its structural organization, protein composition, role in reproductive success, and association with embryonic abnormalities. Results: The available evidence indicates that centrosome-associated proteins such as centrin, γ-tubulin, and pericentrin are critical for spindle assembly, microtubule nucleation, and centriole duplication, and that alterations in their expression or localization are associated with poor sperm quality and reduced fertilization potential. Centrosomal dysfunction has also been linked to fertilization failure despite intracytoplasmic sperm injection, abnormal embryo cleavage, and possible embryonic aneuploidy. Although diagnostic approaches have improved, targeted treatments remain limited. Conclusions: These findings highlight the clinical relevance of sperm centrosomal integrity and support the need for further research into its diagnostic and therapeutic implications. Full article

Microtubule minus-end binding proteins (−TIPs) are critical regulators of microtubule dynamics and stability, whose dysfunctions are increasingly associated with tumorigenesis and cancer progression. This review systematically consolidates current research advances on the molecular characteristics, oncogenic mechanisms, and therapeutic potential of −TIPs in cancer. By integrating preclinical studies, multi-omics data, and clinical evidence, it was found that calmodulin-regulated spectrin-associated proteins (CAMSAPs) and abnormal spindle microtubule assembly (ASPM) primarily exhibit oncogenic properties, whereas CAMSAP3 acts as a tumor suppressor by negatively regulating tumor cell migration. Studies also demonstrate that pharmacological inhibition of the γ-tubulin ring complex (γ-TuRC) effectively attenuates the centrosomal hyper-clustering capacity of malignant cells, thereby suppressing invasive phenotypes. This result underscores the therapeutic value of targeting −TIPs. In summary, −TIPs play critical and complex roles in cancer progression and hold significant potential as prognostic biomarkers and therapeutic targets. Intervention strategies focusing on specific −TIPs, such as γ-TuRC, offer promising strategies for precision cancer therapy; however, the context-dependent functions of these proteins require further investigation to facilitate clinical translation. Full article

Parkinson’s disease (PD), the second most common neurodegenerative disease, is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta along with the aggregation of α-synuclein in Lewy bodies. Among the pathological mechanisms involved is the alteration of iron homeostasis, which promotes oxidative stress and neuronal damage. Despite therapeutic advances, today, no treatment is available to modify the course of the disease. In this study, we investigated for the first time the neuroprotective potential of bovine lactoferrin (bLf) in both its Native (Nat-) and Holo forms, using rotenone-treated N1E-115 cells to mimic PD phenotype. The results showed that the Nat-bLf was more effective than Holo-bLf in counteracting rotenone-induced cytotoxicity and neurite retraction, preserving neuronal morphology and promoting neuritogenesis, as evidenced by increased β3-Tubulin and Growth-Associated Protein-43 markers (GAP-43). Both forms of bLf preserved Tyrosine Hydroxylase (TH) levels, crucial for dopamine synthesis, reduced the DNA damage marker γ-H2Ax and prevented rotenone-induced downregulation of Divalent Metal Transporter-1 (DMT-1) and Ferroportin (Fpn), key proteins involved in iron uptake and release, thereby limiting intracellular iron accumulation. Notably, only Nat-bLf reduced the levels of α-synuclein and markers of oxidative damage. Conversely, Holo-bLf exhibited pro-oxidant effects and increased α-synuclein accumulation even in absence of rotenone. Overall, these results highlight the differential neuroprotective effects of both Nat- and Holo-form, resulting from their distinct iron saturation level and their ability to modulate protein expression, with the native form emerging as a promising candidate for therapeutic strategies to counteract PD-associated neurodegeneration. Full article

Ovarian cancer cells overexpress HDAC6, and selective HDAC6 inhibitors have been considered potential new drugs for ovarian cancer either alone or in combination with other anticancer agents. We screened 46 potential novel HDAC6 inhibitors in ES-2 ovarian cancer cells and showed that compound 25253 demonstrated the most potent anti-proliferative activity and effective synergy with paclitaxel, which was also validated in TOV21G ovarian cancer cells. The combination of 25253 and paclitaxel significantly induced subG1 and apoptotic cells, revealed by PI staining assay and Annexin V-FITC/PI double staining assay, respectively. Western blot analysis showed downregulation of Bcl-2 and Bcl-XL, and upregulation of Bax and Bak, indicating that apoptosis was mediated through the intrinsic pathway. The combination increased γ-H2AX and p-p53 protein levels, suggesting the induction of DNA damage. Furthermore, HDAC6 was downregulated and acetylated α-tubulin was profoundly increased. Compound 25253 enhanced the inhibitory effect of paclitaxel on cell migration and invasion, possibly due to the extensive accumulation of acetylated α-tubulin, which affected microtubule dynamics. Taken together, the combination of 25253 and paclitaxel synergistically inhibited the growth, migration, and invasion of ovarian cancer cells and induced apoptosis, providing supporting evidence that the combination of HDAC6 inhibitors and paclitaxel may be a promising treatment strategy for ovarian cancer. Full article

Background: Percutaneous electrolysis is an invasive physical therapy technique that is receiving attention. The objective of this article is to evaluate the biological and cellular effects of percutaneous electrolysis and its influence on tissue healing processes. Methods. The search strategy performed in PubMed, Cochrane Library, and Web of Sciences databases resulted in a total of 25 studies. Once inclusion and exclusion criteria were applied, seven studies were finally included in this systematic review. The biological effects of percutaneous electrolysis were evaluated and grouped into pro-inflammatory and anti-inflammatory effects, cell death, and extracellular matrix and tissue remodeling effects. Results. Percutaneous electrolysis generates a significant pro-inflammatory increase in the chronic tendon condition of IL1β-6-18-1α-1rn, NLRP3, and M1 polymorphonuclear cells and increased expression of COX2, TNFα, Cxcl10, and TGFβ1 during the first 7 days. This inflammation is regulated as of day 13. A significant increase in cell death markers, such as LDH, Yo-Pro, cytochrome C, and Smac/Diablo markers, was observed during the first 7 days. Finally, a significant increase in markers Mmp9, VEGF, VEGFR, PPAR-γ/tubulin, and COL-I was observed in the extracellular matrix and tissue remodeling, and a decrease in COL-III was observed during the first 7 days. In the acute inflammatory injury condition, an increase in anti-inflammatory markers, such as IL-10-13, CCL1, and IkB, and a significant decrease in pro-inflammatory cytokines, such as IL-6-1β, CCL3-4-5, CCR5-8, NFkB, and TNFα, were observed during the first 7 days. Finally, a significant increase in VEGF, VEGFR, and PPAR-γ/tubulin markers in the extracellular matrix and tissue remodeling was observed for this condition during the first 7 days. Conclusions. Percutaneous electrolysis generates a controlled local pro-inflammatory effect in chronic conditions and regulates inflammation in inflammatory injuries (during the first 7 days). Electrolysis has short-term effects (0–7 days post) of cell death and controlled extracellular matrix destruction. Additionally, it facilitates subsequent healing by improving extracellular matrix synthesis starting from 7 days after application. Full article

Background: Inflammation plays a critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction (AMI) inflammatory processes has not been established. IL-10 is a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. The objective was to explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. Methods: The predicted protein of colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with colchicine, cardiac fibrosis, and acute myocardial infarction were analyzed with DisGeNET and Open Target databases. Analysis and visualization of protein–protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl₂ was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analyzed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with colchicine. Assessments occurred at 24 h and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA and analyzed using a T-test. Results: Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notably activity values highlighting its probable role as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with the protein–protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators—IL-1β, IFN-γ, CCL2, TNF, and TGF-β1—during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl₂-induced 3T3 cell model show significantly elevated HIF-1α compared to controls (p < 0.0001). Colchicine use significantly increased IL-10 expression in CoCl₂-treated cells (p < 0.0001) and in AMI patients within five days (p < 0.05). Conclusions: Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing inflammation after AMI. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required. Full article

Rotenone (ROT), the most significant rotenoid, which has shown anticancer activity, has also been reported to be toxic to normal cells, inducing Parkinson’s disease (PD)-like neuronal loss with aggregation of α-synuclein (α-syn). To reduce the adverse effects of ROT, its derivative, rotenoisin A (ROA), is obtained by directly irradiating a ROT solution in methanol using γ-rays, which has been reported for potential anticancer properties. However, its PD-inducing effects have not yet been researched or reported. This study sought to compare the activities of ROA and ROT on the aggregation of α-syn, apoptosis, and autophagy in SH-SY5Y cells. ROA decreased cell survival less when compared with ROT on SH-SY5Y cells at 48 h in a dose-dependent manner. ROT (0.5 and 1 μM) and ROA (4 and 5 μM) decreased the expression of tyrosine hydroxylase. Western blot analysis of the Triton X-100 insoluble fraction revealed that both ROT and ROA significantly increased the levels of oligomeric, dimeric, and monomeric phosphorylated Serine129 α-syn and total monomeric α-syn. Moreover, both compounds decreased the proportion of neuronal nuclei, the neurofilament-heavy chain, and β3-tubulin. The phosphorylation of ERK and SAPK were reduced, whereas ROA did not act on Akt. Additionally, the increased Bax/Bcl-2 ratio further activated the downstream caspases cascade. ROT promoted the LC3BII/I ratio and p62 levels; however, different ROA doses resulted in different effects on autophagy while inducing PD-like impairments in SH-SY5Y cells. Full article

Deep sowing is an efficient strategy for maize to ensure the seedling emergence rate under adverse conditions such as drought or low temperatures. However, the genetic basis of deep-sowing tolerance-related traits in maize remains largely unknown. In this study, we performed a genome-wide association study on traits related to deep-sowing tolerance, including mesocotyl length (ML), coleoptile length (CL), plumule length (PL), shoot length (SL), and primary root length (PRL), using 255 maize inbred lines grown in three different environments. We identified 23, 6, 4, and 4 quantitative trait loci (QTLs) associated with ML, CL, PL, and SL, respectively. By analyzing candidate genes within these QTLs, we found a γ-tubulin-containing complex protein, ZmGCP2, which was significantly associated with ML, PL, and SL. Loss of function of ZmGCP2 resulted in decreased PL, possibly by affecting the cell elongation, thus affecting SL. Additionally, we identified superior haplotypes and allelic variations of ZmGCP2 with a longer PL and SL, which may be useful for breeding varieties with deep-sowing tolerance to improve maize cultivation. Full article

The widespread occurrence of breast cancer and its propensity to develop drug resistance highlight the need for a comprehensive understanding of the molecular mechanisms involved. This study investigates the intricate pathways associated with secondary resistance to taxol in triple-negative breast cancer (TNBC) cells, with a particular focus on the changes observed in the cytoplasmic actin isoforms. By studying a taxol-resistant TNBC cell line, we revealed a shift between actin isoforms towards γ-actin predominance, accompanied by increased motility and invasive properties. This was associated with altered tubulin isotype expression and reorganisation of the microtubule system. In addition, we have shown that taxol-resistant TNBC cells underwent epithelial-to-mesenchymal transition (EMT), as evidenced by Twist1-mediated downregulation of E-cadherin expression and increased nuclear translocation of β-catenin. The RNA profiling analysis revealed that taxol-resistant cells exhibited significantly increased positive regulation of cell migration, hormone response, cell–substrate adhesion, and actin filament-based processes compared with naïve TNBC cells. Notably, taxol-resistant cells exhibited a reduced proliferation rate, which was associated with an increased invasiveness in vitro and in vivo, revealing a complex interplay between proliferative and metastatic potential. This study suggests that prolonged exposure to taxol and acquisition of taxol resistance may lead to pro-metastatic changes in the TNBC cell line. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP⁺), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP⁺-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91^phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP⁺-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP⁺-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABA_A-α1), and γ-Aminobutyric acid type B (GABA_B). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD. Full article

Silkworm ovary-derived BmN4 cells rely on chromatin-induced spindle assembly to form microtubule-based square mitotic spindles that ensure accurate segregation of holocentric chromosomes during cell division. The chromosome passenger protein Aurora B regulates chromosomal condensation and segregation, spindle assembly checkpoint activation, and cytokinesis; however, its role in holocentric organisms needs further clarification. This study examined the architecture and dynamics of spindle microtubules during prophase and metaphase in BmN4 cells and those with siRNA-mediated BmAurora B knockdown using immunofluorescence labeling. Anti-α-tubulin and anti-γ-tubulin antibodies revealed faint γ-tubulin signals colocalized with α-tubulin in early prophase during nuclear membrane rupture, which intensified as prophase progressed. At this stage, bright regions of α-tubulin around and on the nuclear membrane surrounding the chromatin suggested the start of microtubules assembling in the microtubule-organizing centers (MTOCs). In metaphase, fewer but larger γ-tubulin foci were detected on both sides of the chromosomes. This resulted in a distinctive multipolar square spindle with holocentric chromosomes aligned at the metaphase plate. siRNA-mediated BmAurora B knockdown significantly reduced the γ-tubulin foci during prophase, impacting microtubule nucleation and spindle structure in metaphase. Spatiotemporal BmAurora B expression analysis provided new insights into the regulation of this mitotic kinase in silkworm larval gonads during gametogenesis. Our results suggest that BmAurora B is crucial for the formation of multipolar square spindles in holocentric insects, possibly through the activation of γ-tubulin ring complexes in multiple centrosome-like MTOCs. Full article

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target. Full article

Given its critical role in cell mitosis, the tubulin γ chain represents a viable chemotherapeutic target to solve the specificity issues associated with targeting α and β tubulin. Since γ tubulin is overexpressed in glioblastoma multiforme (GBM) and some breast lesions, the glaziovianin A derivative gatastatin, presented as a γ-tubulin-specific inhibitor, could yield a successful therapeutic strategy. The present work aims to identify the binding sites and modes of gatastatin and its derivatives through molecular-docking simulations. Computational binding free energy predictions were compared to experimental microscale thermophoresis assay results. The computational simulations did not reveal a strong preference toward γ tubulin, suggesting that further derivatization may be needed to increase its specificity. Full article