Levels Of Oxygen Free Radicals Research Articles

The surface protein GroEl of lactic acid bacteria mediates its modulation of the intestinal barrier in Penaeus vannamei

The molecular chaperone GroEL, commonly found in various bacterial species, exhibits heightened expression levels in response to high temperatures and increased levels of oxygen free radicals. Limited literature currently exists on the probiotic role of GroEL in invertebrates. This study sought to explore how the surface protein GroEL from Lactobacillus plantarum Ep-M17 impacts the intestinal barrier function of Penaeus vannamei. Through pull-down and immunofluorescence assays, the interaction between GroEL and Act1 in the gastrointestinal tract of P. vannamei was confirmed. Results from bacterial binding assays demonstrated that rGroEL can bind to pathogens like Vibrio parahaemolyticus E1 (V. p-E1). In vitro experiments revealed that the administration of rGroEL significantly decreased the levels of inflammatory cytokines induced by pathogens while preserving the integrity of tight junctions between intestinal epithelial cells and reducing bacteria-induced apoptosis. Additionally, rGroEL notably lessened the intestinal loading of V. p-E1 in P. vannamei, downregulated immune-related gene expression, and upregulated BCL/BAX expression in the intestines following V. p-E1 challenge. Mechanistic investigations further showed that rGroEL treatment effectively suppressed the expression and phosphorylation of proteins involved in the NF-κB and PI3K-AKT-mTOR signalling pathways in the intestines of bacteria-infected P. vannamei. Furthermore, GroEL reinforces protection against bacterial infections by enhancing the phagocytic and anti-apoptotic capabilities of P. vannamei hemocytes. These results suggest that GroEL may impede the interaction between pathogens and the intestinal mucosa through its competitive binding characteristics, ultimately reducing bacterial infections.

Hesperetin ameliorates spinal cord injury in rats through suppressing apoptosis, oxidative stress and inflammatory response

Spinal cord injury (SCI), a fatal condition, is characterized by progressive tissue degradation and extreme functional deficits with limited treatment options. Hesperetin, a natural flavonoid with potent antioxidant, antiapoptotic and anti-inflammatory properties, has yet to be systematically investigated for its therapeutic effects on neurological damage in rat models of SCI. In this study, rats were given oral hesperetin once daily for 28 days, and their locomotion and histopathological changes were assessed. The findings demonstrated that hesperetin alleviates neurological damage caused by SCI. The observed behavioral improvement could be due to an increase in the survival rate of neurons and oligodendrocytes. This improvement further boosted the ability to repair tissue and form myelin after SCI, ultimately resulting in better neurological outcomes. Furthermore, the present study revealed that hesperetin possesses potent antioxidant capabilities in the context of SCI, reducing the levels of harmful oxygen free radicals and increasing the activity of antioxidant enzymes. Additionally, hesperetin markedly inhibited injury-induced apoptosis, as assessed by caspase-3 immunofluorescence staining and the expression level of caspase-3, indicating the ability of hesperetin to prevent cell death after SCI. Finally, after SCI, hesperetin treatment effectively reduced the expression of inflammatory factors, including IL-1β, TNFα, and NF-kB, demonstrating the anti-inflammatory effect of hesperetin. Together, our results suggest that hesperetin should be considered a valuable therapeutic aid following SCI, as its positive effects on the nervous system, including antioxidant, anti-inflammatory and antiapoptotic effects, may be crucial mechanisms through which hesperetin exerts neuroprotective effects against SCI.

Correlation between interleukin 17 (IL-17) levels and malondialdehyde (MDA) levels in patients with chronic suppurative otitis media

Background: Otitis media is one of the most common causes of fever in the pediatric population. CSOM or also called chronic otitis media is an ear disease condition where a chronic infection is found in the middle ear without an intact tympanic membrane. Oxygen free radical levels and deficiency of antioxidant defense complexes may be involved in the pathogenesis of chronic suppurative otitis media. The IL-17 pathway plays an important role in the pathogenesis of otitis media by increasing ROS including MDA levels. Purpose: To analyze the levels of interleukin 17 (IL-17) and malondialdehyde (MDA) in chronic suppurative otitis media patients. Method: Analytical observational research with a cross sectional approach was conducted in December 2022 at RSUD Dr. Moewardi, the research sample was a patient with chronic suppurative otitis media without active phase cholesteatoma. Sampling used consecutive sampling, namely a non-random sampling method, so that a sample size of 40 participants was obtained, divided into two groups, namely the CSOM group and the healthy group. The data analysis used is univariate and bivariate analysis using parametric tests, namely the product moment correlation test and if it is not normally distributed (p-value <0.05) then use the Spearman rank correlation test. Results: The mean IL-17 level in the CSOM group was 78.76 ± 28.01 and the healthy group was 47.68 ± 21.75 with p = 0.000 < 0.05. The mean MDA value in the CSOM group was 138.37 ± 123.96 and in the healthy group was 55.84 ± 47.37 with a p value = 0.008 < 0.05. Because the p value is <0.05 for the IL-7 and MDA variables, there is a significant difference between CSOM and the group of healthy people. The product moment correlation test obtained a correlation coefficient value of 0.623 with a p value = 0.000. Because the p value is <0.05, there is a significant positive relationship between IL-17 levels and MDA in the blood of chronic suppurative otitis media (CSOM) patients. Conclusion: There is a significant positive relationship between IL-17 levels and MDA in the blood of chronic suppurative otitis media (CSOM) patients.

Comparison of the Clinical Efficacy of Arthroscopic Surgery and Extracorporeal Shock Wave Therapy in the Treatment of Knee Osteoarthritis

This paper aims to explore the clinical efficacy of arthroscopic surgery and extracorporeal shock wave therapy in patients with knee osteoarthritis. The research period was from February 2022 to January 2023. A total of 79 patients with knee osteoarthritis were included and divided into the study group (n = 40) and the control group (n = 39) by lottery method using computer software. The patients in the control group were treated with arthroscopic surgery, and the patients in the study group were treated with extracorporeal shock wave therapy. The Lysholm score, visual analogue scale (VAS) score, Western Ontario and McMaster University Osteoarthritis (WOMAC) score, superoxide dismutase (SOD) level, and malondialdehyde (MDA) level were compared between the two groups. After treatment, the Lysholm score of the study group was higher than that of the control group, and the VAS score and WOMAC score were lower than those of the control group (P < 0.05). While the MDA level of the study group was lower than that of the control group, and the SOD level was higher than that of the control group (P < 0.05). Extracorporeal shock wave therapy for patients with knee osteoarthritis can restore joint function, relieve pain, and effectively regulate the level of oxygen free radicals.

Imatinib-Functionalized Galactose Hydrogels Loaded with Nanohydroxyapatite as a Drug Delivery System for Osteosarcoma: In Vitro Studies.

This study reports an impact of structure (XRPD, FT-IR) and surface morphology (SEM-EDS) of imatinib-functionalized galactose hydrogels, loaded and unloaded with nHAp, on osteosarcoma cell (Saos-2 and U-2OS) viability, levels of free oxygen radicals, and nitric oxide, levels of BCL-2, p53, and caspase 3 and 9, as well as glycoprotein-P activity. It was investigated how the rough surface of the crystalline hydroxyapatite-modified hydrogel affected amorphous imatinib (IM) release. The imatinib drug effect on cell cultures has been demonstrated in different forms of administration-directly to the culture or the hydrogels. Administration of IM and hydrogel composites could be expected to reduce the risk of multidrug resistance development by inhibiting Pgp.

A novel oxidative-stress related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a primary malignant tumour of tubular epithelial origin and is most common in the urinary tract. Growing evidence suggests that oxidative stress (OS), generates high levels of reactive oxygen species (ROS) and free radicals, and plays a critical role in cancer in humans. However, the predictive value of OS-related long non-coding RNAs (lncRNAs) in ccRCC remains unclear. We constructed a predictive signature of survival based on OS-related lncRNAs that were obtained from The Cancer Genome Atlas (TCGA–KIRC), to predict the prognosis of patients with ccRCC. The signature comprised seven lncRNAs: SPART-AS1, AL162586.1, LINC00944, LINC01550, HOXB-AS4, LINC02027, and DOCK9-DT. OS-related signature of lncRNAs had diagnostic efficiency higher than that of clinicopathological variables, with an area of 0.794 under the receiver operating characteristic curve. Additionally, the nomogram based on risk scores and clinicopathological variables (age, gender, grade, stage, M-stage, and N-stage) showed strong predictive performance. Patients with high-risk were found to be more sensitive to the therapeutic drugs ABT.888, AICAR, MS.275, sunitinib, AZD.2281, and GDC.0449. Our constructed the predictive signature can independently predict the prognosis of patients with ccRCC; however, the underlying mechanism needs further investigation.

FREE RADICALS AND DIABETES MELLITUS

Oxidative stress or free radicals has been found in many studies to participate in progression of diabetes mellitus which plays an important role during diabetes, including impairment of insulin action and increase in complicated incidence. This review was based on the detection of roles of free radicals in the progression of diabetes mellitus thru using different sites like PubMed, Medline, Scopus etc. Endothelial cells also contain high amounts of aldo-keto reductase, and are thus prone to increased polyol pathway activation. Moreover, a large body of evidence supports hypothesis that hyperglycaemia or diabetes leads to vascular diacylglycerol accumulation and subsequent PKC activation, causing a variety of cardiovascular defects. Increase in the levels of oxygen and nitrogen free radicals (ROS/RNS) has been linked with lipid peroxidation, non-enzymatic glycation of proteins and oxidation of glucose which contributes toward diabetes mellitus and its complications. Most of the studies have shown relationship between oxidative stress and diabetes along with their complications related to heart, liver kidney and eye. Thus, oxidative stress seems to be more worrying in metabolic disorders specially NIDDM. It concludes that metabolic oxidation is the strongest factor behind insulin dependent and non-insulin dependent diabetes mellitus.

The Protective Effect of Berberine Against Memory Impairment Induced by Intrahippocampal Injection of Aluminium Chloride in Rats

Background and Objectives: Aluminum is a component of environmental pollutants, which causes neurotoxicity. Berberine is in the group of plant-derived alkaloids such as barberry and its beneficial therapeutic properties in various diseases have been proven. The aim of the present study was to investigate the protective effect of berberine on aluminum-induced neurotoxicity. Methods: In this experimental study, 32 male Wistar rats were randomly divided into 4 groups: sham, berberine-receiving sham, lesions-seeing and berberine-receiving lesions. To induce neurotoxicity, a solution of aluminum chloride (AlCl3) dissolved in distilled water was injected at 5 µL at a dose of 0.37 mg/kg to the left of the dorsal hippocampus. The treated rats received 100 mg/kg of berberine daily from one hour before surgery to one week after surgery and orally. In the fourth week, all groups were tested for behavioral learning and memory using the shuttle box. At the end, malondialdehyde, protein, ROS levels and acetylcholinesterase activity were measured. The results were analyzed using one-way ANOVA test and Tukey test. Results: In the treated AlCl3 group compared to the AlCl3 group, the initial delay was not significantly different but the delay during transit was significantly increased. MDA and ROS levels and acetylcholinesterase activity showed a significant decrease. Conclusion: The results of this study showed that although treatment with berberine in the lesion group by aluminum chloride did not cause a significant difference in learning in rats, but it significantly improved memory, significantly reduced malondialdehyde, significantly reduced oxygen free radical levels and significantly reduced activity. Acetylcholinesterase and it can be said that berberine with antioxidant properties improved memory and neuroprotection against neurotoxicity caused by aluminum chloride.

S2643 Rare Gastrointestinal Bleeding in a Patient With Severe Plasmodium Falciparum Malaria

Introduction: Malaria clinically presents as a systemic febrile illness; the most severe form is caused by Plasmodium Falciparum. In addition to hematologic manifestations such as severe anemia, thrombocytopenia, and coagulopathy, malaria patients uncommonly experience gastrointestinal complications such as GI bleeds, splenic rupture and subacute intestinal obstruction. We report a severe case of P. falciparum malaria complicated by a GI bleed. Case Description/Methods: A 66-year-old male with recent travel to Nigeria and a medical history of hypertension was brought to the ER with altered mental status, abdominal pain and a 25lb weight loss in the last month. In the ED he spiked a fever to 102F, prompting a thorough infectious workup. An LP was remarkable for many RBCs, glucose 81 and protein 47. CSF was negative for meningitis/encephalitis; he did not have EBV, CMV or HIV. Blood and fungal cultures were negative. Due to his recent travel history, our patient had a 5-thin and 2-thick malarial smear which showed P. falciparum malaria ring forms. He was started on cefepime, vancomycin, metronidazole, atovaquone/proguanil. Over the next 12-hours, the patient rapidly deteriorated with a large coffee ground emesis, a hemoglobin drop from 12.1 to 8.6, and a thrombocytopenia from 135 to 15. Hemolysis labs were positive: haptoglobin < 30, LDH 607, reticulocyte 14.6%, fibrinogen 112. Upper endoscopy showed Grade-C esophagitis, an oozing duodenal ulcer and hematin all throughout the stomach wall. Abdominal ultrasound and CT showed no acute intra-abdominal pathologies. With new ongoing hematemesis and melena, he went into progressive septic vs hemorrhagic shock and required vasopressors and stress-dose steroids. Discussion: The hematologic manifestations often seen in malaria rarely lead to massive GI bleeds. Our patient did not use NSAIDS, he was not tested for H. Pylori, and despite the stress of his acute severe illness, he had no other risk factors for duodenal ulceration. High levels of free oxygen radicals and tumor necrosis factor may have played a role in the etiology of his peptic ulcer formation. Malarial hemolysis results from the release of cytokines, macrophage recruitment, causing a cytokine storm and activation of endothelial adhesion molecule type 1, E-selectin, enhancing cytoadherence of parasitized cells, mediating lactic acidemia, shock, gut mucosal damage and increased permeability. Despite aggressive measures, our patient ultimately developed shock and died.

Impact of NMDA receptor activation on DNA damage in PC12 neuron-like cell cultures in the presence of β-amyloid peptides

ObjectiveThis study aimed to investigate the effect of low nanomolar concentrations of Aβ1–40 and Aβ25–35 on DNA double-strand breaks following NMDA activation of cells.Materials and methodsAfter incubating the differentiated PC12 cells with Aβ25−35, Aβ1−40 or Aβ1−42 for 24 h, the culture was washed and stimulated for 15 min with NMDA. Then, tests were performed at four-time intervals from stimulation to assess the viability of the culture, the level of oxygen free radicals, and the γH2AX and pATM kinase. NMDAR1 expression was also evaluated by performing immunocytochemical staining.ResultsIt was found that amyloid peptides in nanomolar concentrations reduce double-stranded DNA breaks after NMDA neuron activation. A slight antioxidant effect was also demonstrated when measured 120 min after NMDA cell activation.ConclusionThe NMDA stimulation of PC12 cells led to a rapid increase in the number of double-stranded DNA breaks in the cells and is assumed to be the initial step in IEG activation and LTP induction. The effect of Aβ on the reduction of double-strand breaks after NMDA cell stimulation indicates that at concentrations similar to physiological amyloid peptides, it may reduce the mobilization of the neuronal response to stimuli, leading to inhibition of LTP induction and decreasing synaptic plasticity in the early stages of Alzheimer’s disease.

A study on the correlation between pain frequency and severity and vitamin B12 levels in episodic and chronic migraine.

It is believed that vitamin B12 deficiency and hyperhomocysteinemia cause endothelial cell damage by increasing the levels of free oxygen radicals, which may, in turn, be related to the onset of migraine episodes. The objective of our study was to ascertain a correlation between vitamin B12 levels and migraine attack frequency and pain severity. 127 patients with migraine and 45 healthy controls who presented to Okmeydanı Training and Research Hospital were included in the study. The migraine attack frequency and the duration and severity of pain in migraineurs were recorded. Pain severity was evaluated using a visual analogue scale (VAS). Vitamin B12 levels below 300 ng/L were considered low. The vitamin B12 levels in migraineurs were found to be significantly lower than those in the control group (227.30 ± 104.72 ng/L vs 278.44 ± 149.83 ng/L; p = 0.047). The vitamin B12 levels of patients with chronic migraine (CM) were found to be lower than those in patients with less frequent migraine attacks (197.50 ± 69.16 ng/L vs 278.56 ± 147.91 ng/L; p = 0.019). The ratio of vitamin B12 levels of 300 ng/L and above in patients with CM was lower than that of patients with episodic migraine (p < 0.05). Along with attack frequency and pain severity assessment, it is important that migraine follow-ups should include regular measurement of vitamin B12 levels. We found lower vitamin B12 values in the CM group.

Long-term effects of orchiopexy and orchiectomy on the testes of rats with testicular torsion

Ischemia/reperfusion injury occurs after testicular torsion, levels of free oxygen radicals and inflammatory cytokines are increased in both the torsional and contralateral testis, leading to testicular injury. The present study investigated whether orchiopexy or orchiectomy after testicular torsion was superior in terms of fertility potential in the long term. Following 720°, 4h left testicular torsion, orchiectomy or orchiopexy was performed on 84 rats, which were then sacrificed and evaluated for testicular function at day 1, at 3 months and 6 months (n=14 per group). An additional 14 rats were in the control group. Follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were significantly lower in the orchiopexy group than the orchiectomy and control groups after 3 months. However, there were no significant differences in hormone parameters among the three groups after 6 months. The hormone levels, Johnsen score, seminiferous tubule diameter, and inducible nitric oxide synthase (iNOS) expression at 3 and 6 months were not significantly different between the orchiectomy group and controls. Histopathological analyses at 3 and 6 months indicated significant decreases in Johnsen score and seminiferous tubule diameter in the ipsilateral testis in the orchiopexy group. At 3 months, the level of iNOS expression in the contralateral testis was significantly lower in the orchiopexy group than in other groups. At 6 months, however, it was not significantly different between the orchiopexy and control groups. There were no significant differences in iNOS expression at 3 or 6 months in the orchiectomy group compared to controls. The ipsilateral testis in the orchiopexy group began to atrophy at 3 months, and the degree of atrophy became more evident at 6 months. The level of iNOS expression was low in the bilateral testis at 3 months in the orchiopexy group, and sperm in the contralateral testis were not yet functionally healthy. The level of iNOS expression in the ipsilateral testis decreased further at 6 months in the orchiopexy group, while that in the contralateral testis returned to the normal level. Testicular functions were restored faster after orchiectomy compared to orchiopexy following testicular torsion. However, follow-up of the rats for 6 months demonstrated that orchiopexy or orchiectomy procedures conducted on the testicular torsion had no effect on future fertility potential after 4h of torsion.

Retinitis Pigmentosa (RP): The Role of Oxidative Stress in the Degenerative Process Progression.

Purpose: Retinitis Pigmentosa is a term that includes a group of inherited bilateral and progressive retinal degenerations, with the involvement of rod photoreceptors, which frequently leads to blindness; oxidative stress may be involved in the degeneration progression as proposed by several recent studies. The goal of this study is to evaluate whether circulating free radicals taken from capillary blood are related to one of the most important features of Retinitis pigmentosa that can affect frequently patients: cystoid macular oedema (CME). Materials: A total of 186 patients with Retinitis Pigmentosa (range: 25–69 years) were enrolled; all patients completed an ophthalmologic examination and SD-OCT at baseline and were divided into three subgroups according to the SD-OCT features. ROS blood levels were determined using FORT with monitoring of free oxygen radicals. Results: Test levels of free oxygen radicals were significantly increased, almost twice, in RP patients showing cystoid macular oedema and significantly increased compared to the control group. (p < 0.001). Discussion: Our findings suggest that oxidative stress may speed cone photoreceptors’ morphological damage (CMT); because long lasting oxidative stress in the RP may cause oxidative damage, with animal models of RP suggesting this is a micromolecular mechanism of photoreceptors’ (cone) death, it can be similar to cone damage in human RP eyes. The limitations of this paper are the relatively small sample, the horizontal design of the study, and the lack of data about the levels of ROS in the vitreous body.

Zinc Deficiency Induces Inflammation and Apoptosis via Oxidative Stress in the Kidneys of Mice.

Zinc (Zn) is an essential element that regulates not only cellular immunity but also antioxidant and anti-inflammatory agents. The present study investigated the effect of Zn deficiency on renal cell apoptosis and its mechanism. A Zn-deficient kidney model in mice was created by a Zn-deficient diet. Mice were fed diets with different Zn levels for 41days as follows: normal-Zn group (NG, 34mg Zn/kg), low-Zn group (LG, 2mg Zn/kg), and high-Zn group (HG, 100mg Zn/kg). H&E staining showed that inflammatory cells and many erythrocytes exuded in the renal tissue space of the low-Zn group, and TUNEL staining indicated massive death of kidney cells in the low-Zn group. In the low-Zn group, the levels of oxygen free radicals (ROS) were significantly increased, the antioxidants were significantly decreased, and the total antioxidant capacity was decreased. Moreover, RT-qPCR and ELISA results showed that inflammatory factors (TNF-α, IL-1β, and IL-6) were significantly increased in the low-Zn group. In addition, the levels of p-IκBα, p-NF-κB p65, p-ERK, p-JNK, and p-p38 were significantly increased in the low-Zn group, indicating that zinc deficiency activates NF-κB and MAPK signalling as well as increases its expression. RT-qPCR analysis of apoptosis-related genes, including Bcl-2 Bax, Caspa8, Caspa6, and Caspa3, demonstrated that the expression levels of proapoptotic genes in mouse kidneys were significantly increased. Importantly, the in vitro results were consistent with the in vivo results. Together, these data suggested that zinc deficiency induces renal oxidative stress to activate NF-κB and MAPK signalling, thereby inducing renal cell apoptosis.

Analysis of Short-Term and Stable DNA Damage in Patients with Differentiated Thyroid Cancer Treated with 131I in Hypothyroidism or with Recombinant Human Thyroid-Stimulating Hormone for Remnant Ablation.

It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of 131I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. Methods: We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before 131I therapy and 1 wk and 3 mo after 131I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. Results: We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. Conclusion: An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of 131I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.

Downregulation of CHCHD2 may Contribute to Parkinson's Disease by Reducing Expression of NFE2L2 and RQCD1.

Parkinson's disease (PD) is associated with coiled-coil-helix-coiled-coilhelix domain containing 2 (CHCHD2) downregulation, which has been linked to reduced cyclocytase activity and increased levels of oxygen free radicals, leading to mitochondrial fragmentation and apoptosis. Little is known about how CHCHD2 normally functions in the cell and, therefore, how its downregulation may contribute to PD. This study aimed to identify such target genes using chromatin immunoprecipitation sequencing from SH-SY5Y human neuroblastoma cells treated with neurotoxin 1-methyl-4- phenylpyridinium (MPP+) as a PD model. In this study, we established a MPP+ -related SH-SY5Y cell model and evaluated the effects of CHCHD2 overexpression on cell proliferation and apoptosis. At the same time, we used high-throughput chromatin immunoprecipitation sequencing to identify its downstream target gene in SH-SY5Y cells. In addition, we verified the possible downstream target genes and discussed their mechanisms. The expression level of α-synuclein increased in SH-SY5Y cells treated with MPP+, while the protein expression level of CHCHD2 decreased significantly, especially after 24 h of treatment. Chip-IP results showed that CHCHD2 might regulate potential target genes such as HDX, ACP1, RAVER2, C1orf229, RN7SL130, GNPTG, erythroid 2 Like 2 (NFE2L2), required for cell differentiation 1 homologue (RQCD1), solute carrier family 5 member 7 (SLA5A7), and NAcetyltransferase 8 Like (NAT8L). NFE2L2 and RQCD1 were validated as targets using PCR and western blotting of immunoprecipitates, and these two genes together with SLA5A7 and NAT8L were upregulated in SH-SY5Y cells overexpressing CHCHD2. Downregulation of CHCHD2 may contribute to PD by leading to inadequate expression of NFE2L2 and RQCD1 as well as, potentially, SLA5A7 and NAT8L. Our results suggest that CHCHD2 plays a protective role by maintaining mitochondrial homeostasis and promoting proliferation in neurons. In this study, the changes of CHCHD2 and downstream target genes such as NFE2L2/RQCD1 may have potential application prospects in the future. These findings provide leads to explore PD pathogenesis and potential treatments.

Where are we with the use of N-acetylcysteine as a preventive and adjuvant treatment for COVID-19?

As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.

The neuroprotective role of morroniside against spinal cord injury in female rats

Spinal cord injury (SCI) is a disabling condition that often leads to permanent neurological deficits without an effective treatment. Reactive oxygen species (ROS) produced during oxidative stress play a vital role in the pathogenesis following SCI. The antioxidant morroniside is the main active component of the Chinese medicine Cornus officinalis. In recent years, it has been reported that morroniside has therapeutic effects on damage to multiple organs mediated by oxidative damage, but the effect of morroniside on SCI has not been reported. The purpose of this study was therefore to assess the therapeutic effect of morroniside on SCI, and to identify its underlying mechanism by direct intragastric administration immediately after SCI. Our study showed that morroniside treatment improved the functional recovery of rats following SCI. This behavioral improvement was associated with the higher survival in neurons and oligodendrocytes following SCI, which increased the capacity of injured spinal cord (SC) to form myelin and repair tissue, eventually contributing to improved neurological outcome. Furthermore, our study found that oxygen free radicals increased and antioxidant enzyme activity decreased in the injured SC. Interestingly, morroniside treatment decreased oxygen free radical levels and increased antioxidant enzyme activities. Together, our results suggested that morroniside may be an effective treatment for improving outcomes following SCI, and that its antioxidant activity may be one of the mechanisms by which morroniside exerts neuroprotective effects on SCI.

Nanohydroxyapatite as a Biomaterial for Peripheral Nerve Regeneration after Mechanical Damage-In Vitro Study.

Hydroxyapatite has been used in medicine for many years as a biomaterial or a cover for other biomaterials in orthopedics and dentistry. This study characterized the physicochemical properties (structure, particle size and morphology, surface properties) of Li+- and Li+/Eu3+-doped nanohydroxyapatite obtained using the wet chemistry method. The potential regenerative properties against neurite damage in cultures of neuron-like cells (SH-SY5Y and PC12 after differentiation) were also studied. The effect of nanohydroxyapatite (nHAp) on the induction of repair processes in cell cultures was assessed in tests of metabolic activity, the level of free oxygen radicals and nitric oxide, and the average length of neurites. The study showed that nanohydroxyapatite influences the increase in mitochondrial activity, which is correlated with the increase in the length of neurites. It has been shown that the doping of nanohydroxyapatite with Eu3+ ions enhances the antioxidant properties of the tested nanohydroxyapatite. These basic studies indicate its potential application in the treatment of neurite damage. These studies should be continued in primary neuronal cultures and then with in vivo models.

The COVID-19 Mortality Puzzle: A Single Explanation for Why Men, Elders, People of Color, and Hypertensives are Dying from Coronavirus

Oxidative stress, particularly through excess endogenous NADPH-oxidase production of oxygen free-radicals, is proposed here as the single unifying framework for explaining the seemingly puzzling range of risk factors for severe coronavirus (SARS-CoV-2) infection including aging, male gender, African-American race, cardiovascular disease, obesity, and diabetes. Evidence is presented that death rate as a function of age better resembles the near-exponential rise seen in cancer, where oxidative stress is high, rather than the historical W or U-shaped functions of pandemic or seasonal flu. In addition, consideration of more than 10,000 CDC and Montgomery County, PA publicly available cases suggested a deviation from an exponential rise in the oldest-old, consistent with lower oxidative stress levels reported in that group. Gender analyses unexpectedly found male-to-female risk of mortality to be an inverted U-shaped function peaking at nearly 2.5 times from age 30 to 50 and may reverse to half the female risk at the oldest ages, providing a good fit to known oxidative stress gender differences across the lifespan. Race data were consistent with higher mortality from COVID-19 and higher oxidative stress levels in African Americans. It is argued pre-existing conditions that increase risk all share high oxidative stress levels while, intriguingly, the possibly protective Inflammatory Bowel Disease and Lupus have low levels of NADPH oxidase-derived oxygen free radicals. It is further argued that oxidative stress is not simply a useful construct but its ability to explain differences in coronavirus severity stems from the known unique adaptations in bats, where the virus co-evolved, to accommodate flight which generates large amounts of oxygen free radicals. Finally, strategies for prevention and treatment that follow from the theory are briefly covered including N-acetyl cysteine in older men to restore glutathione levels to more youthful values and especially exciting, pursuing the inhibition of NADPH oxidases not only with well-known melatonin but also with less known compounds such as the naturally occurring apocynin, which is also inexpensive and readily available.