Reactive Oxygen Species Modulator 1 Research Articles

Activation of Nuclear Factor Erythroid 2-Related Factor 2 Antagonizes the Reactive Oxygen Species Modulator 1-Induced Oxidative Stress in Nucleus Pulposus Cells

This study investigates the role of Reactive Oxygen Species Modulator 1 (ROMO1) in oxidative stress within nucleus pulposus (NP) cells and its potential regulation by Nuclear factor erythroid 2-related factor 2 (Nrf2). Intervertebral disc samples from patients were collected, and ROMO1, Nrf2, collagen I/II levels were analyzed to establish their potential connection. Human NP cells were cultured and exposed to H2O2 to induce oxidative stress. To elucidate ROMO1’s impact on NP cell metabolism, NP cells were transfected with ROMO1. Concurrently, Nrf2 activators and inhibitors were used to modulate Nrf2 expression during culturing. Oxidative stress was assessed through CAT and SOD1 gene expression analysis and measurement of cellular reactive oxygen species (ROS) production. NP cell status was determined by evaluating cell viability and collagen I/II expression. Results indicated elevated ROMO1 expression in severe intervertebral disc degeneration (IDD) and after H2O2 treatment. ROMO1 overexpression increased ROS production, suppressed CAT, SOD, and collagen II expression, while elevating collagen I and negatively affecting cell viability. However, Nrf2 activation effectively suppressed ROMO1 expression and protected NP cells from oxidative stress induced by H2O2 or ROMO1. In conclusion, ROMO1 exacerbates oxidative stress and contributes to NP cell degeneration, a process mitigated by Nrf2 activation.

EXPLORING THE ROLE OF sFRP-4, TFF-3, NF-кB AND ROMO1 LEVELS IN COLORECTAL CANCER: IMPLICATIONS FOR PATHOPHYSIOLOGY AND DISEASE PROGRESSION

Objective: Colorectal cancer (CRC) is a significant global health concern with high morbidity and mortality rates. Early detection and accurate diagnostic tools are critical for managing the clinical course. This research explores the molecular landscape of CRC, aiming to provide valuable insights beyond traditional diagnostic approaches. The main aim of this study was to investigate the potential contribution of specific biomarkers, such as secreted frizzled associated protein-4 (sFRP-4), trefoil factor-3 (TFF-3), nuclear factor-kappa-B (NF-κB) and reactive oxygen species modulator-1 (Romo1), to understanding the pathophysiology and determining the progression of CRC.
 Methods: This study analyzed plasma levels of sFRP-4, TFF-3, NF-κB and Romo1 in a cohort of patients with CRC (n=50) and age- and gender-matched control group (n=40), utilizing ELISA. The diagnostic performance of these biomarkers was assessed through Receiver Operating Characteristic (ROC) analysis.
 Results: Our research revealed a significant increase in the levels of NF-κB, TFF-3 and Romo1 in patients with a diagnosis of CRC. Furthermore, these parameters were found to maintain elevated levels in patients with tumors larger than 4 cm as opposed to those with smaller tumors. Patients with metastases also had elevated levels of the three parameters compared with patients without metastases. The ROC analysis revealed that NF-κB showed the most promise as a parameter for distinguishing patients from control subjects, whereas TFF-3 displayed the most potential in identifying tumor size and the presence of metastasis.
 Conclusion: This research contributes valuable insights into understanding the pathophysiology and progression of CRC. The potential roles of NF-κB, TFF-3, and Romo1 as biomarkers, as revealed in our study, offer a promising avenue for early detection and improved management of CRC. Further validation and prospective studies are necessary to clarify the roles of these biomarkers in the pathophysiological mechanism of CRC and to establish their clinical utility.

TRAF2 inhibits senescence in hepatocellular carcinoma cells via regulating the ROMO1/ NAD+/SIRT3/SOD2 axis

The suppression of tumor proliferation via cellular senescence has emerged as a promising approach for anti-tumor therapy. Tumor necrosis factor receptor-associated factor 2 (TRAF2), an adaptor protein involved in the NF-κB signaling pathway and reactive oxygen species (ROS) production, has been implicated in hepatocellular carcinoma (HCC) proliferation. However, little is currently known about whether TRAF2 promotes HCC development by inhibiting cellular senescence. Replicative senescence model and IR-induced mouse model demonstrated that TRAF2 expression was decrease in senescence cells or liver tissues. Depletion of TRAF2 could inhibit proliferation and arrest the cell cycle via activating p53/p21WAF1 and p16INK4a/pRb signaling pathways in HCC cells and eventually lead to cellular senescence. Mechanistically, TRAF2 deficiency increased the expression of mitochondrial protein reactive oxygen species modulator 1 (ROMO1) and subsequently activated the NAD+/SIRT3/SOD2 pathway to promote the production of ROS and cause mitochondrial dysfunction, which eventually contributed to DNA damage response (DDR). Our findings demonstrate that TRAF2 deficiency inhibits the proliferation of HCC by promoting senescence. Therefore, targeting TRAF2 through various approaches holds therapeutic potential for treating HCC.

Metal-organic framework-encapsulated dihydroartemisinin nanoparticles induces apoptotic cell death in ovarian cancer by blocking ROMO1-mediated ROS production

Dihydroartemisinin (DHA), a natural product derived from the herbal medicine Artemisia annua, is recently used as a novel anti-cancer agent. However, some intrinsic disadvantages limit its potential for clinical management of cancer patients, such as poor water solubility and low bioavailability. Nowadays, the nanoscale drug delivery system emerges as a hopeful platform for improve the anti-cancer treatment. Accordingly, a metal-organic framework (MOF) based on zeolitic imidazolate framework-8 was designed and synthesized to carry DHA in the core (ZIF-DHA). Contrast with free DHA, these prepared ZIF-DHA nanoparticles (NPs) displayed preferable anti-tumor therapeutic activity in several ovarian cancer cells accompanied with suppressed production of cellular reactive oxygen species (ROS) and induced apoptotic cell death. 4D-FastDIA-based mass spectrometry technology indicated that down-regulated reactive oxygen species modulator 1 (ROMO1) might be regarded as potential therapeutic targets for ZIF-DHA NPs. Overexpression of ROMO1 in ovarian cancer cells significantly reversed the cellular ROS-generation induced by ZIF-DHA, as well as the pro-apoptosis effects. Taken together, our study elucidated and highlighted the potential of zeolitic imidazolate framework-8-based MOF to improve the activity of DHA to treat ovarian cancer. Our findings suggested that these prepared ZIF-DHA NPs could be an attractive therapeutic strategy for ovarian cancer.

Targeting PKLR/MYCN/ROMO1 signaling suppresses neuroendocrine differentiation of castration-resistant prostate cancer

Conventional treatment of prostate cancer (PCa) uses androgen-deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to an AR-negative phenotype with neuroendocrine (NE) histologic features, which are associated with metabolic disturbances and poor prognoses. However, the metabolic pathways that regulate NE differentiation (NED) in PCa remain unclear. Herein, we show a regulatory mechanism in NED-associated metabolism dysfunction induced by ADT, whereby overexpression of pyruvate kinase L/R (PKLR) mediates oxidative stress through upregulation of reactive oxygen species modulator 1 (ROMO1), thereby promoting NED and aggressiveness. ADT mediates the nuclear translocation of PKLR, which binds to the MYCN/MAX complex to upregulate ROMO1 and NE-related genes, leading to altered mitochondrial function and NED of PCa. Targeting nuclear PKLR/MYCN using bromodomain and extra-terminal motif (BET) inhibitors has the potential to reduce PKLR/MYCN-driven NED. Abundant ROMO1 in serum samples may provide prognostic information in patients with ADT. Our results suggest that ADT resistance leads to upregulation of PKLR/MYCN/ROMO1 signaling, which may drive metabolic reprogramming and NED in PCa. We further show that increased abundance of serum ROMO1 may be associated with the development of NE-like PCa.

The Association of Oxidative Stress and Reactive Oxygen Species Modulator 1 (ROMO1) with Infertility: A Mini Review.

Infertility is one of the disorders that worries many couples around the world, although novel and molecular methods can be used to cure this disease in different stages. One of the factors that causes infertility in men and women is the increased oxidative stress within the cells, which can lead to damage in zygote formation. ROMO1 is one of the most important proteins in the production of reactive oxygen species. This protein can enhance oxidative stress in the cells and body through cellular pathways, such as TNF-α and NF-κB routes, which will eventually lead to many diseases, especially infertility. We engage several international databases by using keywords; ROMO1, Infertility, and Reactive Oxygen Species, and gained a great quantity of information about ROMO1, Infertility, and Oxidative Stress. Although not proven, it is hypothesized that ROMO1 might elevate oxidative stress by activating NF-κB pathway in the cells, furthermore, TNF-α can arouse ROMO1 that can end up with apoptosis and cell death, which consequently can have a lot of disturbing effects on the body, especially the reproductive system. To sum up, revealing the exact cellular and molecular mechanisms of ROMO1-dependent TNF-α and NF-κB pathways in the pathogenesis of infertility might find interesting therapeutic and management strategies for this disorder.

The Association of COVID-19 and Reactive Oxygen Species Modulator 1 (ROMO1) with Oxidative Stress.

There is no denying that the massive spread of COVID-19 around the world has worried everyone. The virus can cause mild to severe symptoms in various organs, especially the lungs. The virus affects oxidative stress in the cells. Reactive Oxygen Species modulator 1 (ROMO1) is one of the most important mitochondrial proteins that plays a critical regulatory role in the production of Reactive Oxygen Species (ROS). According to the studies, COVID-19 can promote oxidative stress through some important pathways, for instance, TNF-α and NF-κB routes. Furthermore, ROMO1 is closely related to these pathways and its dysfunction may affect these routes, then promote oxidative stress, and ultimately cause tissue damage, especially in the lungs. Another factor to consider is that the TNF-α and NF-κB pathways are associated with ROMO1, COVID-19, and oxidative stress. To summarize, it is hypothesized that COVID-19 may increase oxidative stress by affecting ROMO1. Understanding the exact molecular mechanisms of ROMO1 in the pathogenesis of COVID-19 can pave the way to find better therapeutic strategies.

Effects of dietary arachidonic acid on growth, immunity and intestinal microbiota of Litopenaeus vannamei under microcystin-LR stress

The harmful effects of microcystin-LR (MC-LR) stress are unavoidable in shrimp culture. Arachidonic acid (AA) is a fatty acid that regulates immune responses in aquatic animals. In this study, we investigated the effects of dietary AA on growth, immunity and intestinal microbiota of Litopenaeus vannamei under MC-LR stress. The shrimp were fed a control diet (non-supplemented with AA) or a AA diet (supplemented with 8.0 g/kg AA) for 56 days, followed by an acute MC-LR stress for 72 h. The results showed that dietary AA improved the growth and feed utilization of the shrimp. Microcystin-LR exposure increased the mRNA expressions of reactive oxygen species modulator 1 (ROMO1), glutathione peroxidase (GPx), caspase-3 (Casp-3), NADPH-cytochrome P450 reductase (NCPR) and sulfotransferase (SULT), but decreased that of catalase (CAT) and cytochrome C (Cytc). Dietary AA supplementation reversed the expressions of ROMO1, CAT, GPx and NCPR to the control level, but still maintained the higher levels of Cytc, Casp-3 and SULT than the control and MC-LR stress groups. Dietary AA could not effectively reverse the changes of intestinal microbial diversity, but it could improve intestinal microbial composition variation induced by MC-LR stress. Specially, dietary AA increased the relative abundances of beneficial bacteria Bacteroides and Lactobacillus, and reversed the changes of pathogenic bacteria Vibrio and Photobacterium induced by MC-LR stress to the control level. The changes of intestinal bacteria were correlated with immune gene expression. These results revealed that dietary AA had a positive effect on L. vannamei resistance to MC-LR stress by modulating immune response and intestinal microbial composition.

Predictors of low ovarian reserve in cART-treated women living with HIV.

Ovarian dysfunction and lower circulating anti-Müllerian hormone (AMH) feature women living with HIV (WLWH). Because treated human immunodeficiency virus (HIV) infection is characterized by a pro-inflammatory/oxidative phenotype resulting in residual comorbidity, we sought to investigate possible associations between plasma AMH and markers of inflammation, immune activation/senescence/exhaustion, oxidative stress as well as comorbidities in a cohort of combined anti-retroviral therapy (cART)-treated WLWH versus age-matched HIV-uninfected, healthy women.Eighty WLWH on effective cART aged 25 to 50 years and 66 age-matched healthy women were enrolled. We measured: plasma AMH, IL-6, reactive oxygen species modulator 1 (ROMO1) (ELISA); plasma tumor necrosis factor α, IL-10, soluble vascular cell adhesion molecule 1, osteopontin (Luminex); CD4/CD8 activation (CD38/CD69), apoptosis (CD95), exhaustion (PD1), maturation (CD45RA/CD45R0/CD127/CCR7), recent thymic emigrants (CD31/CD103) (flow cytometry). Mann Whitney and chi-squared tests were used. Univariate and multivariate logistic regression analyses were used to assess factors associated with low AMH (≤1 ng/mL).Compared to healthy women, WLWH were more frequently non-Caucasian, drug/alcohol abusers, with history of late menarche, lower hormonal contraceptive use, with higher gravidity and lower parity. WLWH showed significantly lower AMH (P = .004) as well as higher ROMO1 (P = .0003) and tumor necrosis factor α (P < .0001). The multivariate analyses revealed ROMO1 (adjusted odds ratio [AOR]: 1.42, P = .03) and HIV infection (AOR: 8.1, P = .0001) as independently associated with low AMH. The logistic regression model with both HIV status and ROMO1 (a marker of oxidative stress) confirmed HIV as the only predictor of low AMH (AOR: 17, P = .0003).Despite effective cART, WLWH showed lower AMH compared to age-matched peers, indicating pre-mature ovarian ageing. Both HIV and oxidative stress are independently associated with low AMH, emphasizing the impact of HIV-associated oxidative stress on reproductive aging.

Gold nanoparticles synergize with bacterial lipopolysaccharide to enhance class A scavenger receptor dependent particle uptake in neutrophils and augment neutrophil extracellular traps formation

Gold nanoparticles (AuNPs) are extensively utilized in biomedical fields. However, their potential interaction with host cells has not been comprehensively elucidated. In this study, we demonstrated a size-dependent effect of AuNPs to synergize with bacterial lipopolysaccharide (LPS) in promoting neutrophil extracellular traps (NETs) release in human peripheral neutrophils. Mechanistically, LPS was more efficient to contact with 10 nm AuNPs and promote their uptake in neutrophils compared to 40 and 100 nm AuNPs, leading to a synergistic upregulation of class A scavenger receptor (SRA) which mediated AuNPs uptake and triggered activation of extracellular regulated protein kinase (ERK) and p38. Blocking SRA or inhibiting ERK and p38 activation remarkably abrogated the effect of AuNPs and LPS to induce NETs formation. Further experiments demonstrated that AuNPs and LPS augmented the production of cytosolic reactive oxygen species (ROS) in p38 and ERK dependent manner, through upregulating and activating NADPH oxidase 2 (NOX2). Accordingly, scavenging of ROS or inhibiting the NOX2 dampened NETs release induced by combined AuNPs and LPS treatment. AuNPs and LPS also synergized to upregulate reactive oxygen species modulator 1 (ROMO1) via activating ERK, thereby increasing mitochondrial ROS generation and promoting the release of NETs. In summary, we provide new evidences about the synergy of AuNPs and LPS to augment cellular responses in neutrophils, which implicates the need to consider the amplifying effect by pathogenic stimuli when utilizing nanomaterials in infectious or inflammatory conditions.

The C allele of the reactive oxygen species modulator 1 (ROMO1) polymorphism rs6060566 is a biomarker predicting coronary artery stenosis in Slovenian subjects with type 2 diabetes mellitus

BackgroundWe aimed to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator 1 (ROMO1) gene in the development of myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).MethodsA total of 1072 subjects with T2DM were enrolled in this cross-sectional case–control study: 335 subjects with MI and 737 subjects without clinical signs of coronary artery disease (CAD). The genetic analysis of the rs6060566 polymorphism was performed in all subjects. To assess the degree of coronary artery obstruction, a subpopulation of 128 subjects with T2DM underwent coronary computed tomography angiography. Next, endarterectomy samples were obtained during myocardial revascularization from diffusely diseased coronary arteries in 40 cases, which were analysed for ROMO1 expression according to their genotype.ResultsThere were no statistically significant associations between different genotypes or alleles of the rs6060566 polymorphism and MI in subjects with T2DM. The carriers of the C allele of the ROMO1 rs6060566 had a threefold increased likelihood of having 50–75% coronary artery stenosis (Adjusted OR = 3.27, 95% CI 1.16–9.20). Subjects with two affected coronary arteries had a 3.72 fold higher prevalence of MI (OR = 3.72, 95% CI 1.27–10.84). With CAD in LMCA or LAD, MI prevalence was about 3.5-fold higher (p = 0.07 for LMCA and p = 0.01 for LAD). Furthermore, the carriers of the rs6060566 C allele showed higher number of positive cells for ROMO1 expression in endarterectomy samples of coronary arteries.ConclusionsAccording to our study, the rs6060566 polymorphism of the ROMO1 gene is not a risk factor for MI in Caucasians with T2DM. However, we found that subjects carrying the C allele were at a 3.27-fold increased risk of developing severe CAD compared with those who had non-obstructive CAD. Moreover, C allele carriers showed a statistically higher number of cells positive for ROMO1 compared with T allele carriers in coronary endarterectomy samples.

TUG1 long non-coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis.

Hepatocellular carcinoma (HCC) is a prevalent and highly aggressive cancer. Long non‐coding RNAs (lncRNAs) are recognized as potential molecular targets for HCC and are currently under increased research focus. Here, we investigate the regulatory processes underlying the axis of the lncRNA taurine upregulated gene 1 (TUG1), Upstream Transcription Factor 1 (USF1), and reactive oxygen species modulator 1 (ROMO1) in the propagation and metastasis of HCC cells. Distribution of lncRNA TUG1 was found to be prominent in HCC cell cytoplasm and nuclei. LncRNA TUG1 conscripted the USF1 transcription factor to enhance the promoter function of ROMO1. Enlisting the USF1 transcription factor to increase ROMO1 expression following upregulation of TUG1 lncRNA enhanced HCC Huh7 cell proliferation, motility, and metastasis. Rapid tumor proliferation in nude mice provided in vivo verification. The importance of the lncRNA TUG1/USF1/ROMO1 complex as a target for HCC therapy is a key result of this investigation which is exemplified by its role in regulating the proliferation, motility, and metastasis of HCC cells.

Romo1 Inhibition Induces TRAIL-Mediated Apoptosis in Colorectal Cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to behave as an attractive anti-cancer agent in various cancers. Despite its promise TRAIL has limitations such as short half-life and rapid development of resistance. In this regard, approaches to sensitizers of TRAIL that can overcome the limitations of TRAIL are necessary. However, the molecular targets and mechanisms underlying sensitization to TRAIL-induced apoptosis are not fully understood. Here, we propose that reactive oxygen species modulator-1 (Romo1) as an attractive sensitizer of TRAIL. Romo1 is a mitochondrial inner membrane channel protein that controls reactive oxygen species (ROS) production, and its expression is highly upregulated in various cancers, including colorectal cancer. In the present study, we demonstrated that Romo1 inhibition significantly increased TRAIL-induced apoptosis of colorectal cancer cells, but not of normal colon cells. The combined effect of TRAIL and Romo1 inhibition was correlated with the activation of mitochondrial apoptosis pathways. Romo1 silencing elevated the protein levels of BCL-2-associated X protein (Bax) by downregulating the ubiquitin proteasome system (UPS). Romo1 inhibition downregulated the interaction between Bax and Parkin. Furthermore, Romo1 knockdown triggered the mitochondrial dysfunction and ROS generation. We validated the effect of combination in tumor xenograft model in vivo. In conclusion, our study demonstrates that Romo1 inhibition induces TRAIL-mediated apoptosis by identifying the novel mechanism associated with the Bax/Parkin interaction. We suggest that targeting of Romo1 is essential for the treatment of colorectal cancer and may be a new therapeutic approach in the future and contribute to the drug discovery.

Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer.

Reactive Oxygen Species Modulator 1 (ROMO1) plays a pivotal role in the regulation of mitochondrial structure integrity, and the production of reactive oxygen species (ROS). Increased ROMO1 expression was reported in various cancer cell lines; however, the possible association between ROMO1 expression and bladder cancer was not well studied. The present study aimed to investigate the rate of ROMO1 expression and the correlation of oxidative stress with the development of bladder cancer. In this study, a total of 35 cancerous and healthy adjacent tissues were examined using quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the gene expression of ROMO1. Also, we evaluated the serum level of ROMO1 and Total Antioxidant Capacity (TAC), as well as Total Oxidant Status (TOS) in patients with bladder cancer along with age- and sex-matched healthy individuals. The ROMO1 gene was significantly higher in cancerous tissues than that of adjacent healthy tissues. Also, the serum levels of ROMO1, TAC, TOS, and Oxidative Stress Index (OSI) were increased in patients with bladder cancer compared with healthy subjects. It can be concluded that the overexpression of the ROMO1 gene is associated with advanced grades of bladder cancer as well as an increase in oxidative stress conditions. Our findings also suggest that the serum level of ROMO1 might be a promising tumor marker for bladder cancer.

BMAL1 Modulates Epidermal Healing in a Process Involving the Antioxidative Defense Mechanism.

The circadian rhythm regulates the physiology and behavior of living organisms in a time-dependent manner. Clock genes have distinct roles including the control over gene expression mediated by the transcriptional activators CLOCK and BMAL1, and the suppression of gene expression mediated by the transcriptional repressors PER1/2 and CRY1/2. The balance between gene expression and repression is key to the maintenance of tissue homeostasis that is disrupted in the event of an injury. In the skin, a compromised epithelial barrier triggers a cascade of events that culminate in the mobilization of epithelial cells and stem cells. Recruited epithelial cells migrate towards the wound and reestablish the protective epithelial layer of the skin. Although we have recently demonstrated the involvement of BMAL and the PI3K signaling in wound healing, the role of the circadian clock genes in tissue repair remains poorly understood. Here, we sought to understand the role of BMAL1 on skin healing in response to injury. We found that genetic depletion of BMAL1 resulted in delayed healing of the skin as compared to wild-type control mice. Furthermore, we found that loss of Bmal1 was associated with the accumulation of Reactive Oxygen Species Modulator 1 (ROMO1), a protein responsible for inducing the production of intracellular reactive oxygen species (ROS). The slow healing was associated with ROS and superoxide dismutase (SOD) production, and pharmacological inhibition of the oxidative stress signaling (ROS/SOD) led to cellular proliferation, upregulation of Sirtuin 1 (SIRT1), and rescued the skin healing phenotype of Bmal1−/− mice. Overall, our study points to BMAL1 as a key player in tissue regeneration and as a critical regulator of ROMO1 and oxidative stress in the skin.

Overexpression of ROMO1 and OMA1 are Potentially Biomarkers and Predict Unfavorable Prognosis in Gastric Cancer.

One of the worst types of cancers is gastric cancer and no specific tumor marker is found in relation to it. Reactive oxygen species modulator 1 (ROMO1) and the overlapping with the M-AAA protease 1 homolog (OMA1) proteins are the most important mitochondrial membrane proteins, which are involved in modulating reactive oxygen species (ROS) production and the regulation of mitochondrial structure dynamics. If these proteins do not function properly, oxidative stress increases in the cell, and this can initiate the cancer or worsen the condition. In this study, ROMO1 and OMA1 gene expressions in 40 fresh frozen gastric cancer tissue and healthy adjacent tissues were evaluated by real-time PCR, and some of the important parameters related to oxidative stress such as TAC, TOS, MDA, and TTG in the serum of cancer patients compared to healthy people were measured by spectrophotometric and fluorometric techniques. We observed that ROMO1 and OMA1 gene expressions in gastric cancer tissues increased compared to that in healthy adjacent tissues. In addition, oxidative stress parameters including TOS, OSI, and MDA in the serum of cancer patients have increased significantly and the parameters including TAC and TTG have decreased. The results in our study represented that ROMO1 and OMA1 gene expressions in gastric cancer tissue have increased compared to that in healthy adjacent tissues, and oxidative stress levels have also increased significantly in relation to these proteins; therefore, these two proteins may be considered as an important cause of gastric cancer, and even introduced as tumor markers.

Reactive Oxygen Species Modulator 1 As An Adverse Prognostic Marker In Stage III Non-Small Cell Lung Cancer Treated With Radiotherapy: A Retrospective Pilot Study.

PurposeReactive oxygen species modulator 1 (ROMO1) is a novel protein regulating intracellular reactive oxygen species production. Although increased ROMO1 expression has been associated with poor clinical outcomes in several human malignancies, the clinical implication of this protein in a radiotherapy setting has never been explored. The aim of this study was to investigate whether ROMO1 expression is associated with survival in lung cancer patients who received radiotherapy.MethodsROMO1 protein expression was evaluated immunohistochemically using histologic score (H-score) in 49 tumor tissues from stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We performed survival analyses according to various clinicopathological parameters including ROMO1 expression.ResultsROMO1 expression was not associated with any clinicopathological parameter of age, sex, smoking status, stage, or histological subtype. Multivariate analyses showed that high ROMO1 expression was independently associated with worse progression-free survival (hazard ratio [HR] = 1.87, 95% confidence interval [CI]: 1.02–4.23) and with worse overall survival (HR = 2.79, 95% CI:1.13–6.87). In addition, high ROMO1 expression was independently associated with shorter time to loco-regional recurrence (HR=2.71, 95% CI:1.04–6.28) but was not associated with time to distant metastasis.ConclusionROMO1 overexpression was associated with early loco-regional recurrence and poor survival outcomes in stage III NSCLC treated with definitive radiotherapy. Our exploratory results provide a basis for further large-scale studies to validate whether ROMO1 could be a prognostic marker in this setting.

20(S)-Ginsenoside Rg3-loaded electrospun membranes to prevent postoperative peritoneal adhesion.

Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG-b-PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG-b-PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG-b-PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.

Stimulation of the class-A scavenger receptor induces neutrophil extracellular traps (NETs) by ERK dependent NOX2 and ROMO1 activation

Neutrophil extracellular traps (NETs) play a critical role in host antimicrobial response whereas they are also implicated in the pathogenesis of inflammatory and autoimmunediseases. Generation of reactiveoxygen species (ROS) is key to NETs formation. A variety of stimulatory ligands have been found to enhance ROS production and thus trigger NETs. However, the mechanisms that connect receptor stimuli with ROS production and NETs formation remain unclear. In this study, we described a new mechanism of NETs generation in neutrophils triggered by stimulation of the class A scavenger receptor (SRA), a major subtype of scavenger receptors in response to various stimuli during infection and inflammatory disorders. By using polyinosinic acid (Poly I), a ribonucleotide ligand of SRA, we demonstrated that SRA stimulation lead to selective ERK phosphorylation, which upregulated cytosol ROS levels and induced canonical NETs formation by activating NADPH oxidase 2 (NOX2). Interestingly, our results showed that mitochondrial ROS (mtROS) production was also enhanced by the SRA dependent ERK activation through upregulation and activation of reactive oxygen species modulator 1(ROMO1), a mitochondrial membrane protein and a key mediator of mtROS. Moreover, inhibition of the SRA elicited ROMO1 activation dampened NETs release upon SRA stimulation. Overall, our study describes a new insight into the NETs release triggered by membrane SRA stimulation and mediated by ERK dependent NOX2 and ROMO1 activation.

Reactive Oxygen Species Modulator 1 (ROMO1), a New Potential Target for Cancer Diagnosis and Treatment.

Today, the incidence of cancer in the world is rising, and it is expected that in the next several decades, the number of people suffering from cancer or (the cancer rate) will double. Cancer is defined as the excessive and uncontrolled growth of cells; of course (in simple terms), cancer is considered to be a set of other diseases that ultimately causes normal cells to be transformed into neoplastic cells. One of the most important causes of the onset and exacerbation of cancer is excessive oxidative stress. One of the most important proteins in the inner membrane of mitochondria is Reactive Oxygen Species (ROS) Modulator 1 (ROMO1) that interferes with the production of ROS, and with increasing the rate of this protein, oxidative stress will increase, which ultimately leads to some diseases, especially cancer. In this overview, we use some global databases to provide information about ROMO1 cellular signaling pathways, their related proteins and molecules, and some of the diseases associated with the mitochondrial protein, especially cancer.