One of the most prevalent oral cancers, oral squamous cell carcinoma (OSCC), is distinguished by its rapid growth, invasiveness, and high metastatic potential. Green AgNPs are important because they can reduce systemic toxicity by inducing oxidative stress, cytotoxicity, and apoptosis in cancer cells. The goal of this study was to use saponins as natural stabilizers to create AgNPs, and the detrimental apoptotic effects on cancer cells were examined using high-content screening (HCS) assays such as TNI, CMP, and VCC.

Cervical cancer is the second leading cause of mortality in women globally, with its incidence increasing due to multidrug resistance (MDR) and adverse side effects associated with chemotherapeutic agents. Hence, this study was carried out to investigate the selective cytotoxicity and apoptotic induction potential of Buddleja polystachya leaf diethyl ether (BPL-DE) extract on cervical cancer HeLa cell lines.

The aim of the study was to determine how the chemotherapeutic alkylating agent dacarbazine, together with the application of the miR-204-5p mimic in vivo, affects the presence of disseminated melanoma cells in distant organs - the lungs and liver.

To elucidate how ALX Homeobox 4 (ALX4) modulates cisplatin sensitivity via DNA damage regulation in breast cancer (BC), this study explored the established role of mRNA-mediated DNA repair in driving chemoresistance.

Anthropogenic activities have increased cadmium (Cd) accumulation in agricultural soils, severely affecting crop productivity. This study investigated the role of melatonin (Mlt) and a Pseudomonas consortium (PGPR) in modulating secondary metabolism in Brassica juncea L. seedlings under Cd stress. Combined Mlt-PGPR treatment significantly reduced Cd accumulation and regulated the expression of genes involved in Cd transport and detoxification. Enhanced levels of osmolytes and organic acids were observed, along with upregulation of genes associated with osmoprotection and metal chelation. Antioxidant defense was experimentally assessed through enzymatic and non-enzymatic analyses, confirming improved redox homeostasis. FTIR spectroscopy supported treatment-induced biochemical alterations. Transcriptomic profiling revealed activation of melatonin biosynthesis genes and secondary metabolism-related pathways. A structural model of BjCand2, a putative melatonin receptor, and docking analysis suggested its involvement in signaling regulation. Overall, Mlt-PGPR application mitigates Cd toxicity through coordinated receptor-mediated signaling and metabolic reprogramming.

Overuse of chemical pesticides motivates green disease control strategy. Levan-derived oligosaccharides (LOS) are immune elicitors, but its structure information and underlying regulatory mechanisms remain unclear. In this study, LOS produced from sucrose using LevB1SacB fusion enzyme, was purified by CSR-1Na resin, and characterized by HPLC, ATR-FTIR and 1D/2D NMR. Foliar LOS spraying (0.5‰) enhanced barley resistance to Rhizoctonia solani and Pyrenophora graminea, reducing necrotic area by 60.5% and 22.4%, but had little effect on the hemibiotrophic pathogen Bipolaris sorokiniana of spot blotch. LOS itself did not inhibit fungal growth in vitro. LOS priming strengthened infection-triggered antioxidant and defense responses. RNA-seq analysis indicated pathogens but not LOS enhanced transcriptional reprogramming, with differential genes enriched in amino acid metabolism. Among transcriptome-guided candidates, HvAS1, an asparagine synthetase, was verified to participate in LOS-enhanced resistance: HvAS1 overexpression in Arabidopsis accumulated more asparagine and jasmonate after infection and reduced R. solani lesions by >50%, whereas virus-induced silencing in barley compromised resistance. Besides, foliar asparagine spraying also increased barley resistance to R. solani. Together, LOS acts as an efficient elicitor and reveals the link between amino acid metabolism and plant immunity.

Temozolomide (TMZ) resistance in glioblastoma (GBM) remains a critical barrier to treatment success, driven by O6-methylguanine-DNA methyltransferase (MGMT) overexpression, glioma stem cell (GSC) persistence, and redox adaptation.

Brassica species are major oilseed crops valued for their high seed oil content; however, salinity severely limits their growth, productivity, and oil quality. Since membrane stability and oil composition are primarily governed by fatty acid metabolism, this study focused on two key lipid biosynthesis genes, FAE1 (Fatty Acid Elongase 1) and FAD2 (Fatty Acid Desaturase 2), to elucidate their role under NaCl-induced stress. Understanding the regulatory and functional behavior of these genes under salinity is essential for developing salt-resilient Brassica cultivars capable of maintaining oil quality on saline soils. To establish a mechanistic foundation, gene and protein sequences of FAE1 and FAD2 were retrieved from publicly available genomic databases. Various bioinformatics analyses were conducted to identify conserved domains, structural integrity, phylogenetic relationships, and regulatory features, thereby verifying their functional relevance in fatty acid biosynthesis. Promoter regions were also examined for stress-responsive cis-acting elements, including dehydration-responsive elements (DRE) and ABA-responsive elements (ABRE), providing predictive evidence of transcriptional regulation under salt stress. Based on these computational predictions, controlled salt stress was imposed to experimentally evaluate gene responsiveness and physiological adaptation. Tissue-specific expression analysis revealed significant differential regulation of FAE1 and FAD2 under salt stress, with pronounced transcriptional modulation observed in developing siliques and leaves compared to roots. Salt stress caused a dose-dependent reduction in growth attributes and yield-related traits in both species. Two-way ANOVA revealed significant NaCl effects on yield parameters (F = 6.6-20, P < 0.05), with seed yield declining by approximately 25-35% at 200 mM NaCl, with comparatively higher yield stability in B. juncea than in B. napus under salinity. Seed quality analysis showed species-specific responses in oil and protein content, whereas most fatty acids, including erucic acid, remained relatively stable. Despite transcriptional modulation of both genes, the overall fatty acid profile exhibited limited variation, suggesting metabolic buffering within the lipid biosynthetic network. Together, this integrative approach links in silico predictions with experimental validation, establishing a continuum from gene structure and regulation to phenotypic performance and seed quality. These findings enhance our understanding of lipid metabolism-mediated salt stress adaptation and provide a foundation for breeding and genome-editing strategies aimed at improving oilseed stability in Brassica under saline conditions.

Twenty different amino acids are required for the human body for proper functioning as amino acids serve as building blocks for proteins. We screened different essential and non-essential amino acids for the ability to stimulate lysosomal biogenesis and, interestingly, found an essential amino acid L-leucine as the most potent one in stimulating lysosomal biogenesis in astrocytes. However, D-leucine remained weaker than L-leucine in terms of stimulation of lysosomal biogenesis. Accordingly, L-leucine increased autophagy in cultured brain cells and in vivo in the brain of 5XFAD mice, one of the animal models of Alzheimer's disease (AD). L-Leucine also stimulated the uptake and degradation of amyloid-β in astrocytes and reduced the plaque load and improved cognitive functions in 5XFAD mice. Although L-leucine was discovered about 200 years back, until now, no receptor has been identified for L-leucine. Here, we noticed that L-leucine binds to the ligand-binding domain of peroxisome proliferator-activated receptor α (PPARα) to activate this nuclear hormone receptor. Accordingly, L-leucine remained ineffective in increasing lysosomal biogenesis and autophagy in PPARα-/- brain cells. Lentiviral establishment of full-length PPARα, but not Y314D-PPARα, reinstated the autophagy-stimulating effect of L-leucine in PPARα-/- astrocytes, emphasizing the importance of leucine's interaction with the Y314 residue. Moreover, oral L-leucine decreased the plaque load and improved spatial learning and memory in 5XFAD mice, but not in 5XFADΔPPARα mice (5XFAD lacking PPARα), highlighting the involvement of PPARα in the neuroprotective effects of L-leucine. These results may be beneficial for AD patients.

This study investigated the effects of melatonin supplementation in the culture medium on the development, cellular dynamics and gene expression of bovine embryos produced in vitro under low (5%) or high (20%) oxygen tension. Zygotes were cultured without melatonin or with (10-9 M), and cleavage, blastocyst rates, blastomere number, apoptosis, mitochondrial activity, lipid accumulation, and expression of genes related to metabolism, oxidative stress and embryo quality were evaluated. Under high O₂ tension, melatonin increased blastocyst rate (39.8% vs. 34.0%), raised blastomere number, reduced apoptosis, and decreased lipid accumulation. It also upregulated SOD2, KRT8, IFN-τ, and PLAC8. Under low O₂ tension, melatonin increased cleavage rate and mitochondrial activity but did not affect blastocyst rate; only SOD2 was upregulated. Embryos cultured without melatonin under low O₂ showed higher IFN-τ and PLAC8 expression. In conclusion, melatonin improves embryo quality and viability mainly under high oxygen tension, acting as an antioxidant, gene modulator and apoptosis inhibitor. Its effects are more limited under low O2, likely because this environment is closer to physiological conditions and requires fewer responses to oxidative stress.

Cisplatin is a widely used chemotherapeutic agent; however, its therapeutic efficacy is often limited by severe cytotoxic side effects, particularly gastrointestinal toxicity, which manifests as intestinal mucositis. MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in both normal physiological and pathological processes by regulating gene expression. However, their role in cisplatin-induced gastrointestinal toxicity remains unclear. In this study, we investigated the regulatory effects of miRNAs on cisplatin-induced inflammation in intestinal epithelial cells (IEC-6). Our results demonstrate that cisplatin significantly decreases cell viability while inducing interleukin-6 (IL-6) expression in a dose-dependent manner. Moreover, we observed that cisplatin activates the phosphorylation of p38 and ERK but does not activate JNK in IEC-6 cells. Using specific inhibitors of p38 and ERK, we confirmed their roles in regulating IL-6 expression. Through analysis of the miRNA database, we identified several miRNAs that potentially target IL-6. Notably, rno-let-7f-5p and rno-let-7g-5p showed significant downregulation following cisplatin treatment. Transfection mimics and inhibitors of rno-let-7f-5p and rno-let-7g-5p further confirmed their regulatory role in IL-6 expression. Importantly, inhibition of the p38 and ERK pathways attenuated the cisplatin-induced reduction of rno-let-7f-5p and rno-let-7g-5p levels, suggesting a potential regulatory link between MAPK signaling and miRNA expression. In conclusion, our findings support a model in which cisplatin promotes inflammation in intestinal epithelial cells by activating the p38 and ERK pathways and is associated with the suppression of rno-let-7f-5p and rno-let-7g-5p. These findings provide mechanistic rationale that may inform future efforts to mitigate cisplatin-associated gastrointestinal toxicity.

Background/Aims: Globally, colorectal cancer ranks third in causing 900,000 deaths annually. Some patients undergoing chemotherapy develop resistance, leading to metastasis. We investigated CHGA and UCHL1 proteins correlate with lymph node metastasis (J Cell Mol Med. 2023;27:2004-2020). This study aimed to analyze the relationship of CHGA and UCHL1 with the epithelial-mesenchymal transition (EMT) and the Rho/ERK/NFκB signaling pathway in OXA-resistant CRC cells.

Osteosarcoma (OS) is an aggressive primary bone tumour with high metastatic potential. Current treatments including surgery and chemotherapy are limited by side effects and chemoresistance, underscoring the need for novel therapies. This study aimed to investigate the antitumor potential of resveratrol (RSV), a natural polyphenol, as a novel treatment for OS. The effects of RSV were evaluated in two osteosarcoma cell lines (SAOS-2 and U2-OS). A viability assay established 100 μM as the effective concentration, and hyperspectral imaging confirmed cellular uptake. Apoptosis was measured via caspase-3/7 activity and Annexin V/PI staining, while qRT-PCR assessed pro-apoptotic gene expression. Flow cytometry evaluated cell-cycle progression, and a wound-healing assay measured migration. Gene expression analyses (qRT-PCR) examined markers of cell adhesion, tumour progression and epithelial-mesenchymal transition. Finally, RSV's impact on the Wnt/β-catenin pathway was determined by quantifying nuclear β-catenin accumulation and the expression of its downstream oncogenic targets. RSV inhibited cell proliferation and induced apoptosis, increasing caspase-3/7 activity and modulating apoptotic gene expression. RSV also caused cell cycle arrest in S-phase. It reduced the cells' migration and altered the expression of cell adhesion and tumour progression genes, promoting a less invasive phenotype. Notably, RSV decreased nuclear β-catenin accumulation, downregulated oncogenic targets like c-Myc and MMPs, and upregulated E-cadherin while reducing vimentin levels, suggesting a reversal of epithelial-mesenchymal transition. These results suggest that RSV may offer a promising therapeutic approach for osteosarcoma, modulating key pathways involved in tumour progression, metastasis and chemoresistance. Further studies are required to assess its clinical applicability.

Systemic neoadjuvant chemotherapy, often combined with immunotherapy, is the standard of care for early-stage, non-breast cancer susceptibility gene (BRCA)-mutant triple negative breast cancer (TNBC). However, up to 70% of patients retain residual disease after treatment, which is linked to recurrence and mortality within 5 years. To define mechanisms of resistance, we performed single-cell RNA sequencing on orthotopic TNBC patient-derived xenografts during a cycle of treatment with doxorubicin and cyclophosphamide (AC). Clustering identified four tumor epithelial cell populations, with basal cells enriched in residual tumors. These basal cells up-regulated C15ORF48, a paralog of the mitochondrial cytochrome c oxidase associated subunit FA4 (NDUFA4), while exhibiting reciprocal down-regulation of NDUFA4. Functionally, C15ORF48 knockdown sensitized breast cancer cells to AC, increasing reactive oxygen species (ROS) and apoptosis. Thus, the up-regulation of C15ORF48 blunts ROS accumulation and induces resistance to chemotherapy in the basal cell subpopulations. Our findings identify C15ORF48 as a potential therapeutic target for overcoming AC resistance in TNBC.

Salt stress is a primary abiotic constraint that adversely affects the growth and development of tomato plants. Silicon, a beneficial element, has shown potential in mitigating various abiotic stresses. However, although numerous studies have been conducted in this field, the precise mechanism by which exogenous silicon mitigates salt stress in tomato seedlings remains to be fully elucidated. In this study, we analyzed the physiological responses and underlying molecular mechanisms in tomato seedlings under NaCl stress with or without silicon application. The results showed that salt stress severely inhibited seedling growth, as indicated by reductions in shoot and root fresh weight and plant height, while this damage was markedly alleviated by the application of exogenous silicon. Compared to the treatment with NaCl alone (Na), salt stress plus silicon treatment (Na + Si) improved plant growth, the leaf chlorophyll a content, the net photosynthetic rate (Pn), and the proline content and decreased the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) in tomato seedlings. Transcriptomic analysis showed that there were 435 differentially expressed genes (DEGs) (397 upregulated and 38 downregulated) between Na + Si and Na treatments. Further enrichment analysis showed that the upregulated DEGs in Na + Si treatment were enriched in response to salt stress, ethylene and abscisic acid biosynthesis process, lignin catabolic process, cell wall biogenesis and the MAPK signaling pathway. Additionally, exogenous silicon application (Na + Si) upregulated the expression of key families of transcription factors, notably the AP2/ERF, WRKY and NAC families. Taken together, our study preliminarily revealed candidate genes and metabolic pathways affected by exogenous silicon treatment, which may provide a strategy for improving the adaptation of tomato to salt stress.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the immunohistochemical images shown in Fig. 1A on p. 1377, the 'DNMT3A' and 'DNMT3B' images for the 'BN' row of data contained an overlapping section, such that date which were intended to show the results from differently performed experiments had apparently been derived from the same original source. In addition, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that the same data had been included for the Petri dish images in Fig. 3B on p. 1382 for the DMSO experiments with the T24 and EJ cell lines, albeit the EJ image had been rotated through 90°. The authors were contacted by the Editorial Office to offer an explanation for this apparent duplication of data within these figures; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 35: 1375‑1384, 2016; DOI: 10.3892/or.2015.4492].

Progesterone (P4) is believed to inhibit breast cancer growth, but its role in counteracting estrogen (E2)-driven progression remains unclear. This study aimed to investigate the inhibitory effect of P4 on E2-induced cell proliferation, migration, and invasion in Estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer cells by examining its regulatory role in the epithelial-mesenchymal transition (EMT).

MicroRNAs (miRNAs) are small, non-coding RNAs that play a key role in the development of chemoresistance in various cancer types, including colorectal cancer (CRC). In this study, we aimed to study the underlying mechanisms of miRNA in chemotherapy-resistant CRC.

Androgen receptor (AR) signaling is a central driver of prostate cancer progression, yet the metabolic and transcriptional mechanisms regulating AR expression remain incompletely characterized. This study investigated whether the immunoproteasome inhibitor ONX-0914 suppresses hormone-sensitive prostate cancer (HSPC) through metabolic modulation of AR and aimed to identify the transcriptional mediator involved.

Pheochromocytomas and Paragangliomas (PPGL) are rare neuroendocrine tumors with favorable prognosis, although a significant subset (20-25%) progress to metastasis, worsening patient prognosis. For metastatic cases, pharmacological interventions become essential, yet most tumors show poor response to treatment. While clinical trials are ongoing, there is no established treatment for metastatic PPGL. Like other neuroendocrine tumors, PPGL exhibit high membrane expression of somatostatin receptors, and despite Peptide Receptor Radionuclide Therapy, PRRT, strategies have successfully been implemented, trials with cold somatostatin analogs were abandoned prematurely due to inconsistent results. To investigate this issue and identify potential therapeutic tools, we widely profiled somatostatin receptors expression in PPGL and conducted a comprehensive functional screening on wild-type and SDHB knockdown PPGL cell lines of native and synthetic somatostatin analogs. Results revealed that pheochromocytomas and paragangliomas similarly display a predominant SSTR2 and SSTR1 expression regardless of molecular cluster. Treatment with somatostatin, cortistatin, octreotide or pasireotide did not exert clear antitumoral effects on model cell lines. Notably, the selective SST2 agonist BIM-23120 significantly reduced cell proliferation and induced apoptosis in an SST2-dependent manner, but only in SDHB knocked-down PPGL cells. Indeed, only SDHB KD cells showed stronger membrane-enriched SST2 and clear receptor internalization upon BIM-23120 treatment. Molecular analysis revealed a generalized dephosphorylation affecting key proliferation, growth and cell survival pathways in response to BIM-23120 (unlike when treating with octreotide). Altogether, our results provide novel information on the status of the somatostatin system in PPGL and identify new potential therapeutic tools selectively targeting somatostatin receptors on this refractory tumor.