IUBMB Life [JOURNAL]
Sun
200 papers
Ethical bioprospecting and microbial assessments for sustainable solutions to the AMR crisis.
Cartledge K, Short FL, Hall A … +3 more , Lambert K, McDonald MJ, Lithgow T
IUBMB Life · 2025 Jan · PMID 39718471 · Full text
Antimicrobial resistance (AMR) has been declared one of the top 10 global public health challenges of our age by the World Health Organization, and the World Bank describes AMR as a crisis affecting the finance, health,...
Antimicrobial resistance (AMR) has been declared one of the top 10 global public health challenges of our age by the World Health Organization, and the World Bank describes AMR as a crisis affecting the finance, health, and agriculture sectors and a major threat to the attainment of Sustainable Development Goals. But what is AMR? It is a phenotype that evolves in microbes exposed to antimicrobial molecules and causes dangerous infections. This suggests that scientists and healthcare workers should be on the frontline in the search for sustainable solutions to AMR. Yet AMR is also a societal problem to be understood by everyone. This review aims to explore the need to address the problem of AMR through a coherent, international strategy with buy-in from all sectors of society. As reviewed here, the sustainable solutions to AMR will be driven by better understanding of AMR biology but will require more than this alone to succeed. Some advances on the horizon, such as the use of bacteriophage (phage) to treat AMR infections. However, many of the new technologies and new therapeutics to address AMR require access to biodiversity, where the custodians of that biodiversity-and the traditional knowledge required to access it-are needed as key partners in the scientific, clinical, biotechnological, and international ventures that would treat the problem of AMR and ultimately prevent its further evolution. Many of these advances will be built on microbial assessments to understand the extent of AMR in our environments and bioprospecting to identify microbes that may have beneficial uses. Genuine partnerships for access to this biodiversity and sharing of benefits accrued require a consideration of ethical practice and behavior. Behavior change is needed across all sectors of culturally diverse societies so that rapid deployment of solutions can be implemented for maximum effect against the impacts of AMR.
Genomic features of lichen-associated black fungi.
Keller V, Calchera A, Otte J … +1 more , Schmitt I
IUBMB Life · 2025 Jan · PMID 39710945 · Full text
Lichens are mutualistic associations consisting of a primary fungal host, and one to few primary phototrophic symbiont(s), usually a green alga and/or a cyanobacterium. They form complex thallus structures, which provide...
Lichens are mutualistic associations consisting of a primary fungal host, and one to few primary phototrophic symbiont(s), usually a green alga and/or a cyanobacterium. They form complex thallus structures, which provide unique and stable habitats for many other microorganisms. Frequently isolated from lichens are the so-called black fungi, or black yeasts, which are mainly characterized by melanized cell walls and extremophilic lifestyles. It is presently unclear in which ways these fungi interact with other members of the lichen symbiosis. Genomic resources of lichen-associated black fungi are needed to better understand the physiological potential of these fungi and shed light on the complexity of the lichen consortium. Here, we present high-quality genomes of 14 black fungal lineages, isolated from lichens of the rock-dwelling genus Umbilicaria. Nine of the lineages belong to the Eurotiomycetes (Chaetothyriales), four to the Dothideomycetes, and one to the Arthoniomycetes, representing the first genome of a black fungus in this class. The PacBio-based assemblies are highly contiguous (5-42 contigs per genome, mean coverage of 79-502, N50 of 1.0-7.3 mega-base-pair (Mb), Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness generally ≥95.4%). Most contigs are flanked by a telomere sequence, suggesting we achieved near chromosome-level assemblies. Genome sizes range between 26 and 44 Mb. Transcriptome-based annotations yielded ~11,000-18,000 genes per genome. We analyzed genome content with respect to repetitive elements, biosynthetic genes, and effector genes. Each genome contained a polyketide synthase gene related to the dihydroxynaphthalene-melanin pathway. This research provides insights into genome content and metabolic potential of these relatively unknown, but frequently encountered lichen associates.
Human disease-causing missense genetic variants are enriched in the evolutionarily ancient domains of the cytosolic aminoacyl-tRNA synthetase proteins.
Turvey AK, Cavalcanti ARO
IUBMB Life · 2025 Jan · PMID 39710895 · Full text
All life depends on accurate and efficient protein synthesis. The aminoacyl-tRNA synthetases (aaRSs) are a family of proteins that play an essential role in protein translation, as they catalyze the esterification reacti...
All life depends on accurate and efficient protein synthesis. The aminoacyl-tRNA synthetases (aaRSs) are a family of proteins that play an essential role in protein translation, as they catalyze the esterification reaction that charges a transfer RNA (tRNA) with its cognate amino acid. However, new domains added to the aaRSs over the course of evolution in eukaryotes confer novel functions unrelated to protein translation. To date, damaging variants that affect aaRS-encoding genes have been linked to over 50 human diseases. In this study, we leverage the evolutionary history of the aaRS proteins to better understand the distribution of disease-causing missense variants in human cytosolic aaRSs. We hypothesized that disease-causing missense variants in human aaRSs were more likely to be located in the ancient domains of the aaRS, essential for the aminoacylation reaction, rather than in the evolutionarily more recent domains found in eukaryotes. We determined the locations of the modern and ancient domains in each aaRS protein found in humans. We then statistically assessed the positional conservation across each domain and examined the distribution of pathogenic and benign/unknown missense human genetic variants across these domains. We establish that pathogenic missense variants in the human aaRS proteins are enriched in the evolutionarily ancient domains while benign/unknown missense variants are enriched in the modern domains. In addition to defining the evolutionary history of human aaRS proteins through domain identification, we anticipate that this work will improve the ability to diagnose patients affected by damaging genetic variants in the aaRS protein family.
Integrated multi-omics and machine learning reveal a gefitinib resistance signature for prognosis and treatment response in lung adenocarcinoma.
Zhou D, Zheng Z, Li Y … +4 more , Zhang J, Lu X, Zheng H, Dai J
IUBMB Life · 2025 Jan · PMID 39612355 · Publisher ↗
Gefitinib resistance (GR) presents a significant challenge in treating lung adenocarcinoma (LUAD), highlighting the need for alternative therapies. This study explores the genetic basis of GR to improve prediction, preve...
Gefitinib resistance (GR) presents a significant challenge in treating lung adenocarcinoma (LUAD), highlighting the need for alternative therapies. This study explores the genetic basis of GR to improve prediction, prevention, and treatment strategies. We utilized public databases to obtain GR gene sets, single-cell data, and transcriptome data, applying univariate and multivariate regression analyses alongside machine learning to identify key genes and develop a predictive signature. The signature's performance was evaluated using survival analysis and time-dependent ROC curves on internal and external datasets. Enrichment and tumor immune microenvironment analyses were conducted to understand the mechanistic roles of the signature genes in GR. Our analysis identified a robust 22-gene signature with strong predictive performance across validation datasets. This signature was significantly associated with chromosomal processes, DNA replication, immune cell infiltration, and various immune scores based on enrichment and tumor microenvironment analyses. Importantly, the signature also showed potential in predicting the efficacy of immunotherapy in LUAD patients. Moreover, we identified alternative agents to gefitinib that could offer improved therapeutic outcomes for high-risk and low-risk patient groups, thereby guiding treatment strategies for gefitinib-resistant patients. In conclusion, the 22-gene signature not only predicts prognosis and immunotherapy efficacy in gefitinib-resistant LUAD patients but also provides novel insights into non-immunotherapy treatment options.
Role of the initiation factor 3 in the fidelity of initiator tRNA selection on ribosome.
Singh J, Varshney U
IUBMB Life · 2025 Jan · PMID 39578968 · Publisher ↗
Initiation factors play critical roles in fine-tuning translation initiation, which is the first and the rate-limiting step in protein synthesis. In bacteria, initiation factors, IF1, IF2 and IF3 work in concert to accur...
Initiation factors play critical roles in fine-tuning translation initiation, which is the first and the rate-limiting step in protein synthesis. In bacteria, initiation factors, IF1, IF2 and IF3 work in concert to accurately position the initiator tRNA (i-tRNA) in its formyl-aminoacyl form, and the mRNA start codon at the ribosomal P-site, setting the stage for accommodation of the aminoacyl-tRNA in response to the second codon, and formation of the first peptide bond. Among these, IF3 is particularly crucial in ensuring the fidelity of translation initiation as it is involved in the accuracy of the selection of i-tRNA and the start codon. The two-domains (N- and C-terminal) dumbbell shaped structure and dynamics of IF3 significantly influence its fidelity function. This review explores how the N- and C-terminal domains of IF3 communicate with each other and how their interaction with i-tRNA helps to maintain the fidelity of translation initiation.
YTHDF3 rs7464 A > G polymorphism increases Chinese neuroblastoma risk: A multiple-center case-control study.
Lin H, Chen Y, Chen L … +11 more , Zhang W, Zhu J, Zhang X, Yang Z, Zhang J, Cheng J, Li L, Zhou H, Li S, Zhuo Z, He J
IUBMB Life · 2025 Jan · PMID 39575986 · Publisher ↗
Neuroblastoma (NB), a rare childhood cancer originating in nerve tissue. YTHDF3, a member of the YTH domain protein family, is involved in RNA m6A modification and cancer progression. Polymorphisms in YTHDF3 may influenc...
Neuroblastoma (NB), a rare childhood cancer originating in nerve tissue. YTHDF3, a member of the YTH domain protein family, is involved in RNA m6A modification and cancer progression. Polymorphisms in YTHDF3 may influence its expression and biological function. Herein, this study estimated the association between YTHDF3 polymorphisms (rs2241753, rs2241754, and rs7464) and NB susceptibility in a multicenter study comprising 898 cases and 1734 controls. We genotyped YTHDF3 candidate polymorphisms by the TaqMan assay. Logistic regression analysis was applied to indicate the possible relationships between these polymorphisms and NB susceptibility, using odds ratios (ORs) and 95% confidence intervals (CIs). Logistic regression analysis revealed that the rs2241753 GA versus GG decreased NB risk (Adjusted OR = 0.84, 95% CI = 0.71-0.997, p = .047), while the rs7464 GG versus AA enhanced NB risk (Adjusted OR = 1.62, 95% CI = 1.20-2.18, p = .002). Additionally, rs7464 GG versus AA/AG showed a higher risk (Adjusted OR = 1.66, 95% CI = 1.24-2.22, p = .0006). Combination analysis showed that having 1-3 risk genotypes versus 0 was associated with increased NB risk (Adjusted OR = 1.28, 95%CI = 1.09-1.51, p = .003). The significance of rs7464 and the risk genotypes combination persisted across multiple subgroups, whereas rs2241754 was significant only in mediastinal NB. False-positive report probability (FPRP) confirmed the reliability of results. Notably, the interaction between rs7464 and rs2241754 may increase NB risk dramatically. Our study demonstrated that YTHDF3 rs7464 A > G significantly affected NB susceptibility, warranting validation in larger sample sizes.
KRT80 in hepatocellular carcinoma plays oncogenic role via epithelial-mesenchymal transition and PI3K/AKT pathway.
Hua R, Yan X, He J … +4 more , Wu N, Yu W, Yu P, Qin L
IUBMB Life · 2025 Jan · PMID 39569942 · Publisher ↗
Hepatocellular carcinoma (HCC), a globally prevalent form of cancer, is featured by aggressive growth and early metastasis. Elucidating the underlying mechanism and identifying the effective therapy are critical for adva...
Hepatocellular carcinoma (HCC), a globally prevalent form of cancer, is featured by aggressive growth and early metastasis. Elucidating the underlying mechanism and identifying the effective therapy are critical for advanced HCC patients. In the study, we detect that KRT80 was upregulated in HCC samples. HCC patients with higher KRT80 are associated with worse overall survival after surgery. Gain-of and loss-of function studies show that KRT80 enhanced HCC cells proliferation, migration, invasion, and angiogenesis, whereas its silencing abolishes the effects in vivo and in vitro. Mechanistic investigation shows that KRT80 may function as an independent prognostic risk factor and act as an oncogene by influencing EMT and modulating the PI3K/AKT signaling pathway. Together, these findings suggest that KRT80 may be a potential oncogene and a good indicator in predicting prognosis. Targeting KRT80 can offer new insights into the prevention and treatment of HCC.
Depletion of macrophages and osteoclast precursors mitigates iron overload-mediated bone loss.
Passin V, Ledesma-Colunga MG, Altamura S … +4 more , Muckenthaler MU, Baschant U, Hofbauer LC, Rauner M
IUBMB Life · 2025 Jan · PMID 39555707 · Full text
Iron is an essential element for physiological cellular processes, but is toxic in excess. Iron overload diseases are commonly associated with low bone mass. Increased bone resorption by osteoclasts as well as decreased...
Iron is an essential element for physiological cellular processes, but is toxic in excess. Iron overload diseases are commonly associated with low bone mass. Increased bone resorption by osteoclasts as well as decreased bone formation by osteoblasts have been implicated in bone loss under iron overload conditions. However, the exact contribution of individual cell types has not yet been formally tested. In this study, we aimed to investigate the role of osteoclast precursors in iron overload-induced bone loss. To that end, we used clodronate liposomes to deplete phagocytic cells (including macrophages and osteoclast precursors) in male C57BL/6J mice that were exposed to ferric derisomaltose. Bone microarchitecture and bone turnover were assessed after 4 weeks. The application of clodronate resulted in the efficient depletion of circulating myeloid-lineage cells by about 70%. Depletion of osteoclast precursors mitigated iron overload-induced trabecular bone loss at the lumbar vertebrae and distal femur. While clodronate treatment led to a profound inhibition of bone turnover in control mice, it significantly reduced osteoclast numbers in iron-treated mice without further impacting the bone formation rate or serum PINP levels. Our observations suggest that even though bone formation is markedly suppressed by iron overload, osteoclasts also play a key role in iron overload-induced bone loss and highlight them as potential therapeutic targets.
KGF secreted from HSCs activates PAK4/BMI1, promotes HCC stemness through PI3K/AKT pathway.
Li Q, Chen Q, Wang W … +3 more , Xie R, Li Z, Chen D
IUBMB Life · 2025 Jan · PMID 39544166 · Publisher ↗
In our present study, we investigated the interaction between HSCs and HCC, also explored the molecular mechanism. Clinical samples were collected from HCC and adjacent tissue with different degree of liver fibrosis. HCC...
In our present study, we investigated the interaction between HSCs and HCC, also explored the molecular mechanism. Clinical samples were collected from HCC and adjacent tissue with different degree of liver fibrosis. HCC cells were co-cultured with LX-2 cell by Transwell system or cultured with conditioned medium (CM), which was collected from LX-2. The tumor spheroid growth and colony formation analyses were performed to evaluate the cell stemness. Flow cytometry analysis was conducted on cell apoptosis after 5-Fu treatment. Co-immunoprecipitation assay confirmed the interaction between BMI1 and PAK4. Our results showed that BMI1 was highly expressed in HCC and was correlated with HCC liver fibrosis. Both co-cultured with LX-2 and cultured with CM promoted HCC stemness, also increased KGF level and BMI1 expression. KGF treatment had a similar effect with co-culture with LX-2 on HCC. BMI1 overexpression promoted HCC stemness and activated PI3K/AKT pathway, which was reversed by PI3K inhibition. PAK4 was activated by KGF, then phosphorylated S315 site and promoted protein stability of BMI1, therefore enhanced HCC stemness. BMI1 also had a promote effect on liver fibrosis. In summary, we found that KGF secreted by HSCs activated PAK4, which phosphorylated S315 and promoted protein stability of BMI1, and further promoted liver fibrosis and HCC stemness through the PI3K/AKT signaling pathway. Our present study deeply studied the interaction and mechanism between HSCs and HCC, which might provide a new insight for HCC therapy.
RETRACTION: Nutritional Flavonoids Modulate Estrogen Receptor α Signaling.
IUBMB Life · 2025 Jan · PMID 39509549 · Publisher ↗
F. Virgili , F. Acconcia , R. Ambra , A. Rinna , P. Totta , and M. Marino , "Nutritional Flavonoids Modulate Estrogen Receptor α Signaling," IUBMB Life 56, no. 3 (2004): 145-151, https://doi.org/10.1080/15216540410001685...
F. Virgili , F. Acconcia , R. Ambra , A. Rinna , P. Totta , and M. Marino , "Nutritional Flavonoids Modulate Estrogen Receptor α Signaling," IUBMB Life 56, no. 3 (2004): 145-151, https://doi.org/10.1080/15216540410001685083. The above article, published online on 3 January 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Efstathios S. Gonos; the International Union of Biochemistry and Molecular Biology; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, duplication of several Western Blot bands has been detected within Figure 2a. The relative raw data could no longer be accessed due to the considerable time elapsed since the article's publication. The corresponding author, Maria Marino, maintains that the concerns do not impact the overall results and conclusions of the study, and disagrees with the decision of retraction. However, the article is retracted as the editors have lost trust in the integrity of the data presented and consider the conclusions invalid.
Aminoacyl-tRNA synthetase defects in neurological diseases.
Zhang H, Ling J
IUBMB Life · 2025 Jan · PMID 39487674 · Full text
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes to support protein synthesis in all organisms. Recent studies, empowered by advancements in genome sequencing, have uncovered an increasing number of disease-causi...
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes to support protein synthesis in all organisms. Recent studies, empowered by advancements in genome sequencing, have uncovered an increasing number of disease-causing mutations in aaRSs. Monoallelic aaRS mutations typically lead to dominant peripheral neuropathies such as Charcot-Marie-Tooth (CMT) disease, whereas biallelic aaRS mutations often impair the central nervous system (CNS) and cause neurodevelopmental disorders. Here, we review recent progress in the disease onsets, molecular basis, and potential therapies for diseases caused by aaRS mutations, with a focus on biallelic mutations in cytoplasmic aaRSs.
Correction to "Astrakurkurone, a Sesquiterpenoid From Wild Edible Mushroom, Targets Liver Cancer Cells by Modulating Bcl-2 Family Proteins".
IUBMB Life · 2024 Dec · PMID 39472765 · Publisher ↗
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Coexisting bacterial aminoacyl-tRNA synthetase paralogs exhibit distinct phylogenetic backgrounds and functional compatibility with Escherichia coli.
Radecki AA, Fantasia-Davis A, Maldonado JS … +5 more , Mann JW, Sepulveda-Camacho S, Morosky P, Douglas J, Vargas-Rodriguez O
IUBMB Life · 2024 Dec · PMID 39417753 · Publisher ↗
Aminoacyl-tRNA synthetases (aaRSs) are universally essential enzymes that synthesize aminoacyl-tRNA substrates for protein synthesis. Although most organisms require a single aaRS gene for each proteinogenic amino acid t...
Aminoacyl-tRNA synthetases (aaRSs) are universally essential enzymes that synthesize aminoacyl-tRNA substrates for protein synthesis. Although most organisms require a single aaRS gene for each proteinogenic amino acid to translate their genetic information, numerous species encode multiple gene copies of an aaRS. Growing evidence indicates that organisms acquire extra aaRS genes to sustain or adapt to their unique lifestyle. However, predicting and defining the function of repeated aaRS genes remains challenging due to their potentially unique physiological role in the host organism and the inconsistent annotation of repeated aaRS genes in the literature. Here, we carried out comparative, phylogenetic, and functional studies to determine the activity of coexisting paralogs of tryptophanyl-, tyrosyl-, seryl-, and prolyl-tRNA synthetases encoded in several human pathogenic bacteria. Our analyses revealed that, with a few exceptions, repeated aaRSs involve paralogous genes with distinct phylogenetic backgrounds. Using a collection of Escherichia coli strains that enabled the facile characterization of aaRS activity in vivo, we found that, in almost all cases, one aaRS displayed transfer RNA (tRNA) aminoacylation activity, whereas the other was not compatible with E. coli. Together, this work illustrates the challenges of identifying, classifying, and predicting the function of aaRS paralogs and highlights the complexity of aaRS evolution. Moreover, these results provide new insights into the potential role of aaRS paralogs in the biology of several human pathogens and foundational knowledge for the investigation of the physiological role of repeated aaRS paralogs across bacteria.
Genetic variations in NER pathway gene polymorphisms and Wilms tumor risk: A six-center case-control study in East China.
Zhan X, Zhou H, Deng C … +9 more , Hua RX, Pan L, Zhang S, Lu H, He S, Wang Y, Ruan J, Zhou C, He J
IUBMB Life · 2024 Dec · PMID 39415460 · Publisher ↗
The nucleotide excision repair (NER) system is one of the main ways to protect organisms from DNA damage caused by endogenous and exogenous carcinogens. NER deficiency increases genome mutations, chromosomal aberrations,...
The nucleotide excision repair (NER) system is one of the main ways to protect organisms from DNA damage caused by endogenous and exogenous carcinogens. NER deficiency increases genome mutations, chromosomal aberrations, and cancer viability. However, the genetic association between Wilms tumor and NER pathway gene polymorphisms needs to be further validated. We assessed the associations between 19 NER gene polymorphisms and Wilms tumor susceptibility in 416 cases and 936 controls from East China via the TaqMan method. We found that xeroderma pigmentosum group D (XPD) rs238406 and rs13181 significantly decreased the risk of Wilms tumor [adjusted odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.46-0.75, p <.0001; adjusted OR = 0.63, 95% CI = 0.44-0.89, p = .009, respectively]. Furthermore, the rs751402 and rs2296147 polymorphisms in the xeroderma pigmentosum group G (XPG) gene were significantly correlated with an increased risk for Wilms tumor (adjusted OR = 1.47, 95% CI = 1.03-2.09, p = .034; adjusted OR = 2.14, 95% CI = 1.29-3.56, p = .003, respectively). Expression quantitative trait loci (eQTL) analysis revealed that these four polymorphisms may affect the expression of genes that are adjacent to XPD and XPG. Our study provides evidence that XPD and XPG gene polymorphisms are associated with Wilms tumor risk. Nonetheless, these findings should be confirmed in a larger sample size.
Characterization of a novel heterozygous variant in the histidyl-tRNA synthetase gene associated with Charcot-Marie-Tooth disease type 2W.
Wilhelm SDP, Moresco AA, Rivero AD … +2 more , Siu VM, Heinemann IU
IUBMB Life · 2024 Dec · PMID 39352000 · Full text
Heterozygous pathogenic variants in the histidyl-tRNA synthetase (HARS) gene are associated with Charcot-Marie-Tooth (CMT) type 2W disease, classified as an axonal peripheral neuropathy. To date, at least 60 variants cau...
Heterozygous pathogenic variants in the histidyl-tRNA synthetase (HARS) gene are associated with Charcot-Marie-Tooth (CMT) type 2W disease, classified as an axonal peripheral neuropathy. To date, at least 60 variants causing CMT symptoms have been identified in seven different aminoacyl-tRNA synthetases, with eight being found in the catalytic domain of HARS. The genetic data clearly show a causative role of aminoacyl-tRNA synthetases in CMT; however, the cellular mechanisms leading to pathology can vary widely and are unknown in the case of most identified variants. Here we describe a novel HARS variant, c.412T>C; p.Y138H, identified through a CMT gene panel in a patient with peripheral neuropathy. To determine the effect of p.Y138H we employed a humanized HARS yeast model and recombinant protein biochemistry, which identified a deficiency in protein dimerization and a growth defect which shows mild but significant improvement with histidine supplementation. This raises the potential for a clinical trial of histidine.
Adsorptive removal of naproxen onto nano magnesium oxide-modified castor wood biochar: Treatment of pharmaceutical wastewater via sequential Fenton's-adsorption process.
Bano A, Aziz MK, Ameen F … +8 more , Singh K, Prasad B, Nandan, Dave H, Ravi R, Manjhi J, Kumari M, Prasad KS
IUBMB Life · 2024 Dec · PMID 39283051 · Publisher ↗
This current investigation explored the thermal conversion process of castor wood into biochar, which was subsequently harnessed for removing naproxen from pharmaceutical industrial effluent via adsorption. Surface compo...
This current investigation explored the thermal conversion process of castor wood into biochar, which was subsequently harnessed for removing naproxen from pharmaceutical industrial effluent via adsorption. Surface composition analyses conducted through scanning electron microscopy-energy dispersive X-ray, laser-induced breakdown spectroscopy, and Fourier-transform infrared studies unveiled the presence of nano MgO particles within the adsorbent material. Employing optimization techniques such as response surface methodology facilitated a refined approach to batch study. The optimized conditions for batch naproxen sodium (NPX) adsorption on nano-MgO-modified biochar were identified as pH 4, 1.5 g/L adsorbent dosage, and a 120-min contact time maintaining a constant NPX concentration of 10 mg/L. The adsorption capacity was calculated to be 123.34 mg/g for a nano-magnesium oxide-modified castor wood biochar (modified biochar) and 99.874 mg/g for pristine castor wood biochar (pristine biochar). Fenton's reagents comprising 15 mM of FeSO (7HO) and 25 mM of HO have been scrutinized under conditions of pH 3.0, a reaction time of 30 min, a temperature of 30°C, and stirring at 120 rpm, followed by batch adsorption treatment. The COD, NH-N, NO , PO , and NPX removal percentages was found to be 90%, 87%, 79%, 80%, and 90%, respectively. Thus nano MgO-modified biochar holds promise of treatment of pharmaceutical effluent.
Pyrimidine-triazole-tethered tert-butyl-piperazine-carboxylate suppresses breast cancer by targeting estrogen receptor signaling and β-catenin activation.
Yuan J, Yang L, Li Z … +14 more , Zhang H, Wang Q, Wang B, Chinnathambi A, Govindasamy C, Basappa S, Nagaraja O, Madegowda M, Beeraka NM, Nikolenko VN, Wang M, Wang G, Rangappa KS, Basappa B
IUBMB Life · 2024 Dec · PMID 39275910 · Publisher ↗
Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical out...
Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical outcomes. Many breast cancer patients present with tumors that are positive for estrogen receptors (ERs), highlighting the importance of targeting the ER pathway in this particular subtype. Although selective estrogen receptor modulators (SERMs) are commonly used, their side effects and resistance issues necessitate the development of new ER-targeting agents. In this study, we report that a newly synthesized compound, TTP-5, a hybrid of pyrimidine, triazole, and tert-butyl-piperazine-carboxylate, effectively binds to estrogen receptor alpha (ERα) and suppresses breast cancer cell growth. We assessed the impact of TTP-5 on cell proliferation using MTT and colony formation assays and evaluated its effect on cell motility through wound healing and invasion assays. We further explored the mechanism of action of this novel compound by detecting protein expression changes using Western blotting. Molecular docking was used to confirm the interaction of TTP-5 with ERα. The results indicated that TTP-5 significantly reduced the proliferation of MCF-7 cells by blocking the ERα signaling pathway. Conversely, although it did not influence the growth of MDA-MB-231 cells, TTP-5 hindered their motility by modulating the expression of proteins associated with epithelial-mesenchymal transition (EMT), possibly via the Wnt/β-catenin pathway.
Investigation through naphtho[2,3-a]pyrene on mutated EGFR mediated autophagy in NSCLC: Cellular model system unleashing therapeutic potential.
Samarth N, Gulhane P, Singh S
IUBMB Life · 2024 Dec · PMID 39275879 · Publisher ↗
Mutant epidermal growth factor receptor (EGFR) signaling has emerged as a key cause of carcinogenesis and therapy resistance in non-small cell lung cancer (NSCLC), which continues to pose a serious threat to world health...
Mutant epidermal growth factor receptor (EGFR) signaling has emerged as a key cause of carcinogenesis and therapy resistance in non-small cell lung cancer (NSCLC), which continues to pose a serious threat to world health. In this study, we aimed to elucidate the complex molecular pathways of EGFR-mediated autophagy signaling in NSCLC. We identified naphtho[2,3-a]pyrene, an anthraquinolone derivative, to be a promising investigational drug that targets EGFR-mediated autophagy using a cellular model system. By utilizing systems biology, we developed a computational model that explained the signaling of EGFR-mediated autophagy and identified critical crosstalk sites that could be inhibited therapeutically. As a lead compound, naphtho[2,3-a]pyrene was confirmed by molecular docking experiments. It was found to be cytotoxic to NSCLC cells, impact migration, induce apoptosis, and arrest cell cycle, both on its own and when combined with standard drugs. The anticancer efficacy of naphtho[2,3-a]pyrene was validated in vivo on CDX nude mice. It showed synergistic activity against NSCLC when coupled with gefitinib, chloroquine, and radiation. Altogether, our study highlights naphtho[2,3-a]pyrene's therapeutic promise in NSCLC by focusing on EGFR-mediated autophagy and providing a new strategy to fight drug resistance and tumor survival.
CircSLC4A7 in resistant-cells-derived exosomes promotes docetaxel resistance via the miR-1205/MAPT axis in prostate cancer.
Lin A, Li J, He W
IUBMB Life · 2024 Dec · PMID 39266461 · Publisher ↗
Prostate cancer (PCa) is a high-mortality cancer. Docetaxel (DCT) combined with second-generation anti-androgens is considered the golden standard therapy for PCa, whose application is limited for DCT resistance (DR). Th...
Prostate cancer (PCa) is a high-mortality cancer. Docetaxel (DCT) combined with second-generation anti-androgens is considered the golden standard therapy for PCa, whose application is limited for DCT resistance (DR). Therefore, exploring the mechanism of DR is of great importance. In this study, PCa cell lines of PC3 and DU145 were employed, and DR cells were constructed by treatment with graded DCT. CircSLC4A7, miR-1205, and microtubule-associated protein tau (MAPT) transfections were established. Cell counting kit-8 assay was performed to evaluate the cell activity and IC of DCT. After being treated with DCT, DR was assessed by colony formation assay, flow cytometry analysis, and terminal transferase-mediated UTP nick end-labeling assay. Real-time quantitative PCR and western blotting analysis evaluated the expression levels of genes. The dual-luciferase reporter gene assay verified the miR-1205 binding sites with circSLC4A7 and MAPT. An animal experiment was performed to assess the tumor growth influenced by circSLC4A7. After conducting DR cells and isolated exosomes, we found that not only co-culture with DR cells but also treatment with DR cells' exosomes would promote the DR of normal cells. Moreover, circSLC4A7 was highly expressed in DR cells and their exosomes. CircSLC4A7 overexpression enhanced DR, represented as raised IC50 of DCT, increased colony formation, and decreased cell apoptosis after DCT treatment, while circSLC4A7 knockdown had the opposite effect. MiR-1205 was confirmed as a circSLC4A7-sponged miRNA and miR-1205 inhibitor reversed the effect of sh-circSLC4A7. MAPT was further identified as a target of miR-1205 and had a similar effect with circSLC4A7. The effect of circSLC4A7 on DR was also confirmed by xenograft experiments. Collectively, circSLC4A7 in resistant-cells-derived exosomes promotes DCT resistance of PCa via miR-1205/MAPT axis, which may provide a new treatment strategy for DR of PCa.
SNHG14 promotes triple-negative breast cancer cell proliferation, invasion, and chemoresistance by regulating the ERK/MAPK signaling pathway.
Wang B, Xing AY, Li GX … +2 more , Liu L, Xing C
IUBMB Life · 2024 Dec · PMID 39266460 · Publisher ↗
The functional role and molecular mechanisms of small-nucleolar RNA host gene 14 (SNHG14) in triple-negative breast cancer (TNBC) progression remain unclear. The expression levels of SNHG14 in breast cancer samples and c...
The functional role and molecular mechanisms of small-nucleolar RNA host gene 14 (SNHG14) in triple-negative breast cancer (TNBC) progression remain unclear. The expression levels of SNHG14 in breast cancer samples and cell lines were determined using real-time quantitative polymerase chain reaction. Cell proliferation, migration, and invasion abilities were detected using MTS and transwell assays. By RNA sequencing, differentially expressed genes were identified between the SNHG14 siRNA and the negative control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to predict the targets and pathways regulated by SNHG14. pRAF, pMEK, and pERK expression were measured by western blot. The xenograft model was constructed to access the biological function of SNHG14 in vivo. A minimal patient-derived xenograft model was established to evaluate the sensitivity to chemotherapy drugs. Our data indicated that SNHG14 expression was increased in TNBC tissues and cell lines. SNHG14 knockdown attenuated the proliferation, migration, and invasion abilities of TNBC cells both in vivo and in vitro. High SNHG14 expression was associated with lymph node metastasis and a high Ki67 index. The targets of SNHG14 were mainly enriched in the MAPK signaling pathway. pRAF, pMEK, and pERK expression were downregulated after being transfected with SNHG14 siRNA. Compared with the negative control group, the expression of CACNA1I, DUSP8, FGF17, FGFR4, FOS, PDGFRB, and DDIT3 was increased, and the expression of MKNK1 was decreased in the SNHG14 siRNA group. Minimal patient-derived xenograft model demonstrated that knockdown of SNHG14 enhanced the sensitivity to Docetaxel in vivo. Compared with the DMSO group, the proliferation of Docetaxel-resistant MDA-MB-231 cells was decreased in Dabrafenib, PD184352, and FR180204 treatment groups. SNHG14 knockdown inhibits TNBC progression by regulating the ERK/MAPK signaling pathway, which provides evidence for SNHG14 as a potential target for TNBC therapy.
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