Reverse Transcriptase Research Articles

A virus-like particle assembly system for probing the HIV-1 Gag-Pol dimerization domain: supporting evidence for reverse transcriptase involvement in protease activation by influencing Gag-Pol/Gag-Pol interaction.

HIV-1 protease (PR) activation for mediating virus particle processing is essential for virus infectivity. As part of our attempt to determine whether Gag-Pol dimerization triggers PR activation, we found that RT point mutations that impair RT heterodimer stability and virus particle processing markedly reduced VLP assembly efficiencies in a p6gag-containing Gag-Pol expression vector (designated Gagp6-Pol). Further, these unstable RT point mutations markedly inhibited the facilitating effect of an RT dimerization enhancer on Gagp6-Pol VLP assembly. Our data support the proposal that RT/RT interaction contributes to PR activation by promoting Gag-Pol/Gag-Pol interaction, thus suggesting that targeting Gag-Pol dimerization may serve as an alternative HIV/AIDS treatment strategy. A Gag-Pol VLP assembly assay might be usable for probing the potential impacts of Gag-Pol dimerization on PR activation.

Effect of N1-methyladenosine in the quantification of RNA.

The reverse transcription (RT) of RNA to cDNA is a key step for the quantification of nucleic acid molecules in numerous basic research and medical diagnosis. Although multiple sources of errors have been considered, little is known about the impact of RNA modifications on the validity of genes of interest for quantitative RT-PCR. Here, we evaluated the influence of RNA modifications of N1-methyladenosine (m1A) on the validity of the RT step by quantifying two RNAs with commercial reverse transcriptase and RNA sample from HEK-293T cells or in vitro transcription. Our findings prove that RNA modification of m1A is a source of RT variability as it acts as an arrest signal of RT at its position, in turn affecting the corresponding RNA quantification.

Potential Unnecessity of Bismuth in Standard Triple Therapy for Clarithromycin-Susceptible Helicobacter pylori Infection

Objectives: The standard first-line treatment for <i>Helicobacter pylori</i> infection typically involves proton pump inhibitors, amoxicillin, and clarithromycin (PAC), yet the eradication success rates are not entirely satisfactory. Recognizing bismuth’s antibacterial properties and its potential to enhance antibiotic efficacy, this study compared the eradication success rates of a 7-day course of PAC with bismuth (PACB) versus PAC alone in patients with clarithromycin-susceptible <i>H. pylori</i> infections.Methods: We conducted a retrospective review at Eunpyeong St. Mary’s Hospital involving 499 patients with confirmed clarithromycin-susceptible <i>H. pylori</i> infection. These patients were treated either with PACB or PAC for 7 days. Clarithromycin resistance-associated point mutations were evaluated using reverse transcriptase polymerase chain reaction. Successful eradication was confirmed by a negative <sup>13</sup>C-urea breath test.Results: Of the patients, 261 received PACB therapy, and 238 received PAC therapy. The intention-to-treat analysis showed eradication success rates of 82.8% (216/261) for PACB and 89.1% (212/238) for PAC (<i>p</i>=0.093). The per-protocol analysis revealed eradication rates of 85.3% (215/252) for PACB and 90.5% (210/232) for PAC (<i>p</i>=0.081). The incidence of adverse effects was similar between the two groups, with 41.3% (104/252) in the PACB group and 34.1% (79/232) in the PAC group (<i>p</i>=0.102).Conclusions: Adding bismuth to the standard 7-day PAC regimen did not significantly increase eradication rates in patients with clarithromycin-susceptible <i>H. pylori</i> infections compared to PAC alone.

Identification of a novel small-molecule inhibitor of the HIV-1 reverse transcriptase activity with a non-nucleoside mode of action

BackgroundHuman immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome, which is a major global health problem. Although combination antiretroviral therapy (cART) successfully expands the lifespan of HIV-1-infected patients, long-term cART often increases drug resistance and adverse effects. Therefore, efforts are ongoing to develop novel anti-HIV-1 drugs.MethodsThe anti-HIV-1 activities of compounds were investigated using TZM-bl reporter cell line, A3.01 T cell line, and peripheral blood mononuclear cells infected with several HIV-1 strains, including wild type and drug-resistance associated mutants. Next-generation sequencing analysis and in silico molecular docking studies were employed to determine the mode of action of the compound.ResultsWe identified a small-molecule inhibitor consisting of a thiadiazole core appended to two pyrazoles (BPPT), which exerted a highly potent inhibitory effect on HIV-1 infectivity, with a half-maximal effective concentration (EC50) of 60 nM, without causing cytotoxicity. In experiments with various HIV-1 strains and cell types, the potency of BPPT was found to be comparable to that of commercial antiretroviral agents (azidothymidine, nevirapine, and others). Further analysis of the mode of action demonstrated that BPPT is a novel type of HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). Analysis of viruses harboring drug-resistance-associated mutations showed that BPPT was potent against G190A (C or S) mutations in reverse transcriptase (RTase), exhibiting high-level resistance to other NNRTIs. Next-generation sequencing analysis of long-term treatment with BPPT displayed an RTase mutation profile different from that in the case of established NNRTIs. Given these data, in silico molecular docking studies demonstrated the molecular mechanism underlying the BPPT-mediated inhibition of RTase.ConclusionOur data suggest that BPPT is a novel small-molecule inhibitor of HIV-1 RTase and could serve as a promising chemical scaffold to complement or replace conventional treatments, particularly for overcoming resistance associated with the G190 mutation.

An Intervertebral Disc (IVD) Regeneration Model Using Human Nucleus Pulposus Cells (iHNPCs) and Annulus Fibrosus Cells (iHAFCs).

Intervertebral disc (IVD) degeneration (IVDD), primarily caused by nucleus pulposus (NP) dehydration, leads to low back pain. While current treatments focus on symptom management or surgical intervention, tissue engineering using IVD-derived cells, biofactors, and scaffolds offers a promising regenerative approach. Here, human NP cells (NPCs) and annulus fibrosus cells (AFCs) are immortalized with human telomerase reverse transcriptase (hTERT), generating immortalized NPCs (iHNPCs) and AFCs (iHAFCs). These cells express NP and AF-specific markers, are reversible via FLP recombinase, and are non-tumorigenic. iHAFCs exhibit osteogenic potential, while iHNPCs show chondrogenic differentiation. A 3D-printed citrate-based scaffold was employed to develop an IVD regeneration model, with BMP9-stimulated iHAFCs in the peripheral region and BMP2-stimulated iHNPCs in the central region. Histological analysis revealed bone formation in the iHAFC region and cartilage formation in the iHNPC region, mimicking the natural IVD structure. Additionally, an ex vivo spine fusion model demonstrated robust bone formation in iHAFC-treated segments. These findings highlight the potential of iHAFCs and iHNPCs as valuable tools for IVD tissue engineering and regeneration.

An Amazing 30-Year Journey around the DABO Family: A Medicinal Chemistry Lesson on a Versatile Class of Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors.

Since the emergence of AIDS, the non-nucleoside HIV-1 RT inhibitors (NNRTIs) have attracted the attention of scientists and clinicians due to their high potency and specificity combined with low toxicity. 3,4-Dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs) are a family of NNRTIs described since 1992, and the best members among S-, NH-, and N,N-DABOs showed high anti-HIV-1 potency in both cellular and enzymatic assays. During 30 years of research, the central 4-(3H)-pyrimidinone nucleus has been decorated with 2,6-dihaloaryl or cyclohexyl groups at the methylene at C6, alkyl- or (arylalkyl/aroylalkyl)thio/amino chains at C2, and hydrogen or a small alkyl group at C5. The further introduction of small (i.e., methoxy) groups at the C6 α-benzylic position furnished potency at the sub-nanomolar level against wild-type HIV-1 and at the nanomolar level against HIV-1 mutant strains. Importantly, some compounds of the DABO family exhibited preventative microbicidal activity, valuable in clinical settings where oral adherence rates are low.

Repurposing Efavirenz, the HIV Antiretroviral Drug for Chikungunya Virus Infection.

Chikungunya virus (CHIKV) has frequently recurred in recent decades, causing outbreaks worldwide in tropical and subtropical regions. The re-emergence of CHIKV poses a substantial risk to human health, as no efficacious drugs are currently available to curb new outbreaks. Here, the anti-CHIKV activity of efavirenz was investigated by in vitro cell culture-based antiviral assays in different relevant cell lines. Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of acquired immunodeficiency syndrome (AIDS), and it has good oral bioavailability, long half-life, and affordable low cost. This study demonstrated dose-dependent robust anti-CHIKV activity of efavirenz at low micromolar concentration in two different cell lines with 50% effective concentration (EC50) of 1.1 to 1.3 μM. Interestingly, efavirenz also inhibited the replication of Sindbis virus (SINV) at a low micromolar range indicating potential broad anti-alphavirus activity. Time of addition assay, direct transfection of virus replicon RNA, and minus-sense-specific reverse transcription polymerase chain reaction (RT-PCR) elucidated that efavirenz hinders the viral replication at an early stage after the virus entry by inhibiting the viral RNA synthesis. Further, the binding affinity of efavirenz toward purified capsid protein (CP) was observed, suggesting that CP could be one of the antiviral targets for efavirenz in addition to viral or host proteins involved in viral RNA replication. Finally, the in vivo efficacy of efavirenz was assessed in a murine model and a decrease in CHIKV viral load was observed. In summary, the present study underscores the potential of repurposing efavirenz for antiviral therapy against CHIKV to curb future viral outbreaks.

Non-canonical HIV drug resistance mutations: need to close existing gaps.

An increasing number of people living with HIV (PLHIV) are failing treatment without HIV drug resistance in the drug target region. While sub-optimal adherence is likely the cause of treatment failure in many PLHIV, resistance emerging at non-canonical (HIV drug resistance mutations occurring outside the drug target site) drug target site sites is also plausible. Non-canonical drug resistance mechanisms have been identified for integrase strand transfer inhibitors (INSTIs), protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and NRTIs. Overall, they may act by i) restoring viral fitness caused by mutations in the drug target sites, ii) enhance resistance when occurring with mutations at the drug target sites iii) independently cause resistance even in the absence of drug resistant mutations (DRMs) at the drug target site iv) prime the emergence of resistant variants with DRMs at drug target sites. However, the clinical relevance of non-canonical resistance mechanism beyond in vitro and small in vivo studies is still needed and could include the assessment of such mechanisms in clinical trials and implementation studies. This information would be vital in guiding effective management of PLHIV with viral non-suppression despite good adherence as well as informing public health surveillance strategies.

Pharmacokinetics of islatravir in participants with moderate hepatic impairment.

Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1 infection. People living with HIV are at risk of liver disease. ISL is metabolized by adenosine deaminase (ADA), which is expressed in the liver; thus, ISL pharmacokinetics (PK) may be affected by hepatic impairment. This study evaluated the effect of moderate hepatic impairment on ISL PK. This nonrandomized, open-label, phase 1 study (MK-8591-030) evaluated the effects of a single oral dose of ISL 60 mg in HIV-seronegative adults with moderate hepatic insufficiency (n = 6) and matched healthy adult participants (n = 6). Blood samples for plasma ISL and 4'-ethynyl-2-fluoro-2'deoxyinosine (M4) and peripheral blood mononuclear cell (PBMC) ISL-triphosphate (ISL-TP) were collected at multiple time points through 672 h, and safety was monitored throughout. Modest decreases in maximum measured concentration (Cmax) and area under the concentration-time curve (AUC) of plasma ISL and AUC of PBMC ISL-TP were observed in participants with moderate hepatic impairment versus matched healthy participants, while ISL-TP Cmax was relatively unchanged. In contrast, plasma M4 was modestly increased in the moderate hepatic impairment group, suggesting that hepatic impairment may result in increased metabolism of ISL to M4 via ADA. The clinical relevance of the overall modest changes in M4, ISL, and ISL-TP levels with moderate hepatic impairment will be contextualized once exposure response data from ongoing clinical studies are available to elucidate the thresholds for clinical efficiency. A single oral dose of ISL 60 mg was generally well tolerated in both groups.CLINICAL TRIALSThis study is registered with Clinicaltrials.gov as NCT04515641.

Evolutionary Studies on the Coxsackievirus A-24 Variants Causing Acute Hemorrhagic Conjunctivitis with Emphasis on the Recent Outbreak of 2023 in India

Acute Hemorrhagic Conjunctivitis (AHC) is primarily caused by viral infections, with Coxsackievirus A-24v (CV-A24v) being a significant culprit. Enteroviruses, including CV-A24v, are responsible for global AHC outbreaks. Over time, CV-A24v has evolved, and genotype IV (GIV) has become the dominant strain. This study focused on examining the genetic features and evolutionary trends of CV-A24v responsible for the recent AHC outbreak of 2023 in India. Researchers isolated viral strains from ocular swabs and confirmed the presence of CV-A24v using reverse transcriptase quantitative PCR (RT-qPCR) and whole-genome sequencing. Genomic comparisons between isolates of 2023 and those from a previous outbreak in 2009 were conducted. Phylogenetic analysis revealed that the 2023 isolates formed a distinct cluster within GIV-5 and were related to recent strains from China and Pakistan. The older Indian isolates from 2009 grouped with GIV-3. New subclades, GIV-6 and GIV-7, were also identified in this study, indicating the diversification of CV-A24. Molecular clock and phylogeographic analysis traced the virus’s circulation back to the 1960s, with the common ancestor likely to have originated in Singapore in 1968. The 2023 Indian strains probably originated from Thailand around 2014, with subsequent spread to China and Pakistan. This study concluded that the 2023 outbreak was caused by a genetically distinct CV-A24v strain with nine mutations, underlining the virus’s ongoing evolution and adaptations and offering valuable insights for future outbreak control.

Cellular pharmacology of tenofovir alafenamide and emtricitabine in neutrophils and platelets in people with and without HIV.

Previous studies have primarily focused on nucleos(t)ide reverse transcriptase inhibitor pharmacology in peripheral blood mononuclear cells (PBMCs) and erythrocytes via dried blood spots (DBS), but not other major blood cells. Our objectives were to describe and compare the concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in DBS, PBMCs, neutrophils, and platelets in people with HIV (PWH) and people without HIV (PWOH). DBS, PBMCs, neutrophils, and platelets were isolated from whole blood drawn from PWH and PWOH receiving tenofovir alafenamide and emtricitabine. TFV-DP and FTC-TP concentrations were quantified using LC-MS/MS in each cell type. Linear regression models controlled for time on drug, adherence, and time since last dose, where applicable, to determine geometric mean percent differences (95% confidence interval) by HIV status and estimated half-lives. Data were available in 13 PWH (96% male) and 30 PWOH (53% male). Compared with PWOH, TFV-DP in DBS was 48.9% (15.6%, 91.9%) higher and FTC-TP in platelets was 36.3% (4.5%, 77.7%) higher; TFV-DP in platelets also trended higher [43.5% (-3.24%, 113%)]. No other cell types significantly differed by HIV status. TFV-DP and FTC-TP demonstrated the longest half-lives in neutrophils, followed by PBMCs and then platelets. After normalizing to cell volume, both drugs accumulated from greatest to least in PBMCs, neutrophils, platelets, and erythrocytes across both PWH and PWOH. Our findings highlight differential drug disposition across cell types that also vary by serostatus in DBS and platelets. The mechanisms and implications of these findings require additional research.

Acute HIV-1 Infection: Paradigm and Singularity

Acute HIV-1 infection (AHI) is a transient period where the virus causes evident damage to the immune system, including an extensive apoptosis of CD4+ T cells associated with a high level of activation and a major cytokine storm to fight the invading virus. HIV infection establishes persistence by integrating the viral genome into host cell DNA in both replicating and non-replicating forms, effectively hiding from immune surveillance within infected lymphocytes as cellular reservoirs. The measurement of total HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) is a reliable reflection of this reservoir. Initiating treatments during AHI with nucleoside reverse transcriptase inhibitors (NRTIs) and/or integrase strand transfer inhibitors (INSTIs) is essential to alter the dynamics of the global reservoir expansion, and to reduce the establishment of long-lived cellular and tissue reservoirs, while preserving and enhancing specific and non-specific immune responses. Furthermore, some of the patients treated at the AHI stage may become post-treatment controllers and should be informative regarding the mechanism of viral control, so patients treated during AHI are undoubtedly the best candidates to test innovative remission strategies toward a functional cure that could play a pivotal role in long-term HIV control. AHI is characterized by high levels of viral replication, with a significant increase in the risk of HIV transmission. Detecting AHI and initiating early treatment following diagnosis provides a window of opportunity to control the epidemic, particularly in high-risk populations.

Utility of [18F]fluciclovine PET/MRI for identifying the optimal biopsy target region, helping to avoid underdiagnosis in patients with glioblastoma: illustrative case.

Glioblastoma (GBM) is known for its significant intratumoral heterogeneity, making biopsies susceptible to underdiagnosis if samples are taken from less malignant regions. [18F]Fluciclovine, a novel PET tracer, has demonstrated high accumulation in glioma tissue, with minimal uptake in normal brain tissue. A 50-year-old woman presented with sensory aphasia. MRI revealed a FLAIR lesion extending from the left parietal to the medial temporal lobe. [18F]Fluciclovine PET/MRI identified two areas of increased uptake, both FLAIR negative. Stereotactic biopsy was used to obtain samples from PET-positive (PET+) and FLAIR-positive (FLAIR+) lesions. Pathological analysis of the PET+ lesion revealed densely proliferating tumor cells with irregularly enlarged nuclei, while the FLAIR+ lesion exhibited sparsely proliferating cells. Molecular analysis showed that both lesions were IDH wildtype with MGMT promoter hypomethylation. Sanger sequencing identified a telomerase reverse transcriptase promoter -124 C>T mutation in the PET+ lesion but not in the FLAIR+ lesion. The integrated diagnosis, based primarily on the PET+ lesion, was GBM, IDH wildtype. This case highlights the importance of [18F]fluciclovine PET/MRI in identifying high-cell-density regions, minimizing the risk of underdiagnosis in GBM. Further studies are necessary to evaluate its prognostic value in GBM management. https://thejns.org/doi/10.3171/CASE24677.

High-Yield and Quantitative Purification Method for HIV Which Minimizes Forces Applied to Virions Utilized to Investigate Maturation of HIV-1 via Cryo-Electron Tomography

HIV is a lentivirus characterized by its cone shaped mature core. Visualization and structural examination of HIV requires the purification of virions to high concentrations. The yield and integrity of these virions are crucial for ensuring a uniform representation of all viral particles in subsequent analyses. In this study, we present a method for the purification of HIV virions which minimizes the forces applied to virions while maximizing the efficiency of collection. This method, which relies on virion sedimentation simulations, allows us to capture between 1000 and 5000 HIV virions released from individual HEK293 cells after transfection with the NL4.3 HIV backbone. We utilized this approach to investigate HIV core formation from several constructs: pNL4-3(RT:D185A&D186A) with an inactive reverse transcriptase, NL4.3(IN: V165A&R166A) with a type-II integrase mutation, and NL4.3(Ψ: Δ(105–278)&Δ(301–332)) featuring an edited Ψ packaging signal. Notably, virions from NL4.3(Ψ: Δ(105–278)&Δ(301–332)) displayed a mixed population, comprising immature virions, empty cores, and cores with detectable internal density. Conversely, virions derived from NL4.3(IN: V165A&R166A) exhibited a type II integrase mutant phenotype characterized by empty cores and RNP density localized around the cores, consistent with previous studies. In contrast, virions released from pNL4-3(RT:D185A&D186A) displayed mature cores containing detectable RNP density. We suggest that the sedimentation simulations developed in this study can facilitate the characterization of enveloped viruses.

P53-mediated regulation of LINE1 retrotransposon-derived R-loops.

p53-mediated regulation of LINE1 retrotransposon-derived R-loops.

The role of SFRP1 in human dermal papilla cell growth and its potential molecular mechanisms as a target in regenerative therapy.

The role of SFRP1 in human dermal papilla cell growth and its potential molecular mechanisms as a target in regenerative therapy.

An Efficient Suppression of EGFR and B-Raf mRNA Overexpression in the Lung of Benzo[a]pyrene-induced mice by Cationic Lipo-ATRA Nanoformulation.

The molecular drug all-trans retinoic acid (ATRA) acts on cancer cells via different molecular pathways, but its poor bioavailability in cancer cells limits its potency. Recently few patents have been published for the development of liposome-based drug for enhanced action. This study was, therefore, carried out to analyse the oncogene expressions in the lung tissue of benzo[ a]pyrene (B[a]P)-induced mice and compare between free ATRA and cationic liposome nanoformulation (lipo-ATRA) treatments. This study was designed to analyse the changes in the expression levels of epidermal growth factor receptor (EGFR) and B-Raf in the lung tissues of B[a]P-induced mice during the cancer development stage itself and to find the suppressive effect of free ATRA and lipo-ATRA. Lung cancer was induced in mice by oral ingestion of 50mg/kg body weight B[a]P weekly twice for four consecutive weeks. Then, the mice were treated with free and lipo-ATRA (0.60 mg/kg) for 30 days via i.v injection. The EGFR and B-Raf gene expressions were analyzed in lung cells by reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative polymerase chain reaction (qPCR). The RT-PCR gene band density and the relative quantity (RQ) values from qPCR revealed both EGFR and B-Raf genes to be significantly overexpressed in B[a]P control mice while having very low or no expression in normal mice. This indicates that they function as oncogenes in B[a]P-induced lung carcinogenesis. The lipo-ATRA treatment has shown a highly significant increase in RQ values for both EGFR and BRaf when compared to the free ATRA treatment. The study results have revealed the cationic lipo-ATRA treatment to have enhanced the bioavailability of ATRA in lung tissue due to its significant suppression action on EGFR-mediated oncogenes' expressions. Furthermore, the EGFR and BRaf could be the molecular targets of ATRA action in lung carcinogenesis.

Corrigendum to “Exploration of carboxamide hybrid indolyl aryl sulfones as antiretroviral agents by HIV-1 reverse transcriptase inhibition and antioxidant effects: Synthesis, biochemical screening and computational analysis” [Journal of Molecular Structure 1319 (2025) 139483

Corrigendum to “Exploration of carboxamide hybrid indolyl aryl sulfones as antiretroviral agents by HIV-1 reverse transcriptase inhibition and antioxidant effects: Synthesis, biochemical screening and computational analysis” [Journal of Molecular Structure 1319 (2025) 139483

Detecting IDH and TERTp mutations in diffuse gliomas using 1H-MRS with attention deep-shallow networks.

Detecting IDH and TERTp mutations in diffuse gliomas using 1H-MRS with attention deep-shallow networks.

Knockdown of VDAC1 Promotes Ferroptosis in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin's lymphoma (NHL). Ferroptosis is a novel form of cell death involved in multiple tumor development. However, the relationship between ferroptosis-related genes and DLBCL has not been extensively studied. The GSE95290 dataset was downloaded from the Gene Expression Omnibus (GEO) database and merged with genes associated with ferroptosis to screen differentially expressed genes (DEGs). Hub genes were identified by constructing a protein-protein interaction (PPI) network. The messenger RNA (mRNA) expressions of hub genes were subsequently detected in vitro using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The impact of voltage dependent anion channel 1 (VDAC1) on the proliferation, apoptosis, and ferroptosis of DLBCL was evaluated using Cell Counting Kit-8, flow cytometry, and relevant ferroptosis assays, respectively. Six highly expressed hub genes were identified, all of which could be used as diagnostic biomarkers for DLBCL. In vitro studies revealed that suppressing VDAC1 expression inhibited DLBCL cell proliferation and promoted apoptosis. Furthermore, knockdown of VDAC1 promoted ferroptosis in DLBCL cells and xenograft tumor models, resulting in elevated levels of malondialdehyde (MDA) and iron and increased protein levels of Acyl-CoA synthetase long-chain family 4 (ACSL4) and cyclooxygenase-2 (COX2). Conversely, glutathione (GSH) and superoxide dismutase (SOD) levels were reduced, accompanied by decreased protein levels of glutathione peroxidase 4 (GPX4) and ferritin heavy chain1 (FTH1). VDAC1 knockdown induces ferroptosis in DLBCL, which provides new insights into the pathogenic mechanisms of DLBCL.