Indirect bilirubin impairs invasion of osteosarcoma cells via inhibiting the PI3K/AKT/MMP-2 signaling pathway by suppressing intracellular ROS.

Background: Osteosarcoma is most prevalently found primary malignant bone tumors, with primary metastatic patients accounting for approximately 25% of all osteosarcoma patients, yet their 5-year OS remains below 30%. Bilirubin plays a key role in oxidative stress-associated events, including malignancies, making the regulation of its serum levels a potential anti-tumor strategy. Herein, we investigated the association of osteosarcoma prognosis with serum levels of TBIL, IBIL and DBIL, and further explored the mechanisms by which bilirubin affects tumor invasion and migration. Methods: ROC curve was plotted to assess survival conditions based on the determined optimal cut-off values and the AUC. Then, Kaplan-Meier curves, along with Cox proportional hazards model, was applied for survival analysis. Inhibitory function of IBIL on the malignant properties of osteosarcoma cells was examined using the qRT-PCR, transwell assays, western blotting, and flow cytometry. Results: We found that, versus osteosarcoma patients with pre-operative higher IBIL (>8.9 µmol/L), those with low IBIL (≤8.9 µmol/L) had shorter OS and PFS. As indicated by the Cox proportional hazards model, pre-operative IBIL functioned as an independent prognostic factor for OS and PFS in total and gender-stratified osteosarcoma patients (P < 0.05 for all). In vitro experiments further confirmed that IBIL inhibits PI3K/AKT phosphorylation and downregulates MMP-2 expression via reducing intracellular ROS, thereby decreasing the invasion of osteosarcoma cells. Conclusions: IBIL may serve as an independent prognostic predictor for osteosarcoma patients. IBIL impairs invasion of osteosarcoma cells through repressing the PI3K/AKT/MMP-2 pathway by suppressing intracellular ROS, thus inhibiting its metastatic potential.

Evaluation of testicular torsion management in Ogbomoso, South-Western Nigeria and surgical detorsion-augmented treatment with phytochemical fractions of Corchorus olitorius leaf in experimental rats.

Background: There is need to investigate whether phytochemicals along with surgical detorsion could serve as better managements options in TT patients rather than surgical detorsion (SD) alone. Methods: The descriptive cross-sectional part of this study is questionnaire-based addressing sociodemographic characteristics of participants and their experience in management of TT. In the experimental part, male rats (n = 32) were grouped into: sham, Ischemia-reperfusion injury (IRI), dichloromethane (DCM) and ethanol fraction (100 mg/kg) of CO. Evaluation of tissue GPx, total thiol, SOD, MDA and H2O2 was done. Serum estimations of nitrite, TNF-α and IL-6, MPO, sperm motility, count and viability was also carried out. Tissue expression of bax and caspase 3 was assessed. Results: 68.9 % respondents agreed that SD alone is non-effective in the management of TT while 83.6 % reported a need to augment surgery with medications. Oxidative stress markers like H2O2, MDA and nitrite increased by IRI were decreased in post-treatment groups, along with a significant increase in the tissue level of GSH, GST, SOD, GPx, and total thiol. Inflammatory mediators were elevated in IRI while post-treatment rats showed significant decrease. IRI decreased sperm count significantly this was reversed by post-treatment. Bax and caspase 3 was increased in IRI rats and post-treatment with CO fractions reduced them. Conclusions: Quantitative cross-sectional study has revealed through experience of clinicians that surgical detorsion alone is not effective in managing TT. Augmented treatment with CO leaf fractions suppressed testicular IRI through inhibition of pro-apoptotic proteins expression, oxidative stress and inflammation.

Pathogenesis of Alcohol-Associated Liver Disease.

Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy alcohol consumption causes structural damage and/or disrupts normal organ function in virtually every tissue of the body, the liver sustains the greatest damage. This is primarily because the liver is the first to see alcohol absorbed from the gastrointestinal tract via the portal circulation and second, because the liver is the principal site of ethanol metabolism. Alcohol-induced damage remains one of the most prevalent disorders of the liver and a leading cause of death or transplantation from liver disease. Despite extensive research on the pathophysiology of this disease, there are still no targeted therapies available. Given the multifactorial mechanisms for alcohol-associated liver disease pathogenesis, it is conceivable that a multitherapeutic regimen is needed to treat different stages in the spectrum of this disease.

Trabecular Meshwork Mitochondrial Function and Oxidative Stress: Clues to Racial Disparities of Glaucoma.

Purpose: To identify racial differences of oxidative damage and stress and mitochondrial function in human trabecular meshwork (TM). Design: Experimental study. Participants: One hundred seventy-three eyes of 173 patients undergoing intraocular surgery provided aqueous humor (AH) for analysis. Trabecular meshwork tissues from eye bank donors were used as healthy controls for primary cell culture. Methods: Enzyme-linked immunosorbent assay methods were used to measure 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative damage marker, in AH comparing Black and White Americans. Human TM primary cultured cells from Black and White donors were used for adenosine triphosphate (ATP) measurement under high and low oxygen culture conditions. Complex I activity was measured in mitochondrial fractions isolated from cultured TM cells. Mitochondrial quantification was performed by translocase of outer mitochondrial membrane 20 (TOMM20) Western blot. Intracellular reactive oxygen species (ROS) production was measured in live TM cells. Main Outcome Measures: Oxidative damage in AH, ATP production, complex I activity, mitochondrial quantification, and intracellular ROS in cultured TM cells stratified by racial background. Results: Aqueous humor samples (75 Black, 98 White) displayed significantly higher 8-OHdG levels (P = 0.024) in Black compared with White patients with severe stage glaucoma. Using cultured healthy donor TM cells, ATP production was higher in Black than White TM cells (P = 0.002) in low oxygen culture conditions. Complex I activity was not statistically different in Black compared with White TM cells, but TOMM20 expression was higher in Black versus White cells (P = 0.001). In response to hydrogen peroxide challenge, ROS production was significantly higher in Black compared to White TM cells (P = 0.004). Conclusions: Significantly higher 8-OHdG levels in AH of Black compared with White patients with severe glaucoma indicated that oxidative damage may be a risk factor in glaucoma pathogenesis or the result of distinct pathologic features in the Black population. To identify potential origins or causes of this damage, our data showed that healthy Black cultured TM cells have higher ATP and ROS levels, with increased quantity of mitochondria, compared with White TM cells. These findings indicate that mitochondrial alterations and increased oxidative stress may influence racial disparities of glaucoma.

ELO2 Participates in the Regulation of Osmotic Stress Response by Modulating Nitric Oxide Accumulation in Arabidopsis.

The ELO family is involved in synthesizing very-long-chain fatty acids (VLCFAs) and VLCFAs play a crucial role in plant development, protein transport, and disease resistance, but the physiological function of the plant ELO family is largely unknown. Further, while nitric oxide synthase (NOS)-like activity acts in various plant environmental responses by modulating nitric oxide (NO) accumulation, how the NOS-like activity is regulated in such different stress responses remains misty. Here, we report that the yeast mutant Δelo3 is defective in H2O2-triggered cell apoptosis with decreased NOS-like activity and NO accumulation, while its Arabidopsis homologous gene ELO2 (ELO HOMOLOG 2) could complement such defects in Δelo3. The expression of this gene is enhanced and required in plant osmotic stress response because the T-DNA insertion mutant elo2 is more sensitive to the stress than wild-type plants, and ELO2 expression could rescue the sensitivity phenotype of elo2. In addition, osmotic stress-promoted NOS-like activity and NO accumulation are significantly repressed in elo2, while exogenous application of NO donors can rescue this sensitivity of elo2 in terms of germination rate, fresh weight, chlorophyll content, and ion leakage. Furthermore, stress-responsive gene expression, proline accumulation, and catalase activity are also repressed in elo2 compared with the wild type under osmotic stress. In conclusion, our study identifies ELO2 as a pivotal factor involved in plant osmotic stress response and reveals its role in regulating NOS-like activity and NO accumulation.

Subacute toxic effects of silver nanoparticles oral administration and withdrawal on the structure and function of adult Albino Rats' hepatic tissue.

Products containing Silver nanoparticles (Ag NPs) are becoming vastly used in our daily life. The widespread increased introduction of Ag NPs in many aspects of life has raised researchers' concerns regarding their safety and toxicity for biological and environmental life in the past few years. The current study aimed to explore the subsequent effects of Ag NPs withdrawal, following short-term oral administration. Eighteen rats were assigned randomly into three groups (control group "1" and AG NPs treated groups "2" and "3"; 6 animals each). The control group received normal food and tap water while groups 2 & 3 received 0.5 ml of a solution containing 25 ppm Ag NPs for 14 days. Group 2 rats were sacrificed on day 14 whereas group 3 was left for another 14 days of particle cessation followed by euthanasia on day 28. Functional assessment was done by liver enzyme assays, hydrogen peroxide activity, hepatic Bdnf expression, and P53 immunoreactivity. Hepatic tissue structural assessment was done via hematoxylin and eosin, periodic acid-Schiff as well as Masson's trichrome stains. The results revealed a significant elevation of Hydrogen peroxide in group 2 only compared to the control group. Hepatic Bdnf and liver enzymes were both insignificantly affected. Structural abnormalities and enhanced apoptosis in hepatic tissue were found 14 days after ceasing the nanoparticles. In conclusion: Structural and functional insults following Ag NPs oral administration continues after particle withdrawal, and interestingly they do not necessitate apparent reflection on liver enzyme assays.

DNP and ATP regulate the pulp breakdown development in Phomopsis longanae Chi-infected longan fruit through modulating the ROS metabolism.

Compared with the P. longanae-infected longan, the DNP-treated P. longanae-infected fruit represented a higher pulp breakdown index, a higher O2 -. production rate, and a higher MDA content, but the lower activities of APX, SOD and CAT, the lower transcript levels of DlAPX6, DlSOD1, DlSOD2, DlSOD3 and DlCAT1, the lower values of AsA, GSH, flavonoid and total phenolics, a lower scavenging ability of DPPH radical, and a lower value of reducing power. Whereas, the ATP-treated P. longanae-infected samples showed the contrary results. The above findings indicated that the DNP-promoted the pulp breakdown in P. longanae-infected longan was because DNP weakened the capacity of scavenging ROS, raised the O2 -. level, and accelerated the membrane lipids peroxidation. However, the ATP-suppressed the pulp breakdown in P. longanae-infected longan was because ATP improved the capacity of scavenging ROS, reduced the O2 -. level, and reduced the membrane lipids peroxidation.

Arabica coffee and olive oils mitigate malathion-induced nephrotoxicity in rat: In silico, immunohistochemical and biochemical evaluation.

Malathion (MAL) is an organophosphate insecticide that disrupts the body's antioxidant system; it is one of the earliest organophosphate insecticides extensively used as dust, emulsion, and vapor control a wide variety of insect pests under different conditions. This experimentation aims to evaluate the influence of Arabica coffee oil and olive oil on MAL-induced nephrotoxicity in male rat. 6 sets bearing the same number of animals were applied to this experiment. Each set comprised 10 rats. The first set of rats was used as the control group; rats in the second set were exposed to MAL measured at 100 mg/kg body weight for 7 weeks. Animals in the third and fourth set were treated with 400 mg/kg body weight of Arabica coffee oil and olive oil, and 100 mg/kg body weight of MAL. The fifth, together with the sixth set, were fed with a similar proportion of Arabica coffee oil and olive oil as administered to the third set of rats. After the experimental duration, rats of group 2 showed severe biochemical alterations, including significant increases of creatinine, uric acids, and urea nitrogen (BUN), resulting in marked decreases in serum albumin values and total protein (TP). Severe histopathological and immunohistochemical alterations of kidney tissues were observed in exposed MAL-intoxicated rats. Administration of these oils reduced the detected biochemical, histopathological modifications caused by MAL intoxication. Two active ingredients in Arabica coffee oil (oleic acid) and olive oil (hydroxytyrosol) showed good cyclooxygenase-2 (COX 2) interaction. Moreover, oleic acid from coffee oil and olive oil exhibited impressive association with xanthine oxidase (XO). The current finding showed that coffee oil and olive oil could be appraised as possible and a likely deterrence component against nephrotoxicity brought about by MAL.

Phomopsis longanae Chi causing the pulp breakdown of fresh longan fruit through affecting reactive oxygen species metabolism.

Phomopsis longanae Chi is a crucial pathogen causing fruit spoilage in postharvest fresh longan. The influence of P. longanae invasion with a suspension containing 1 × 104 P. longanae spores per mL on the breakdown occurrence and ROS metabolism in pulp of longan cv. Fuyan during storage at 28 °C was explicated. Compared to control group, more severe development of pulp breakdown (PB), higher PB index, O2 -. generation rate, H2O2 and MDA content, but lower SOD, APX and CAT activities, GSH, AsA, flavonoid and total phenolics amounts, ability of scavenging DPPH radical, and reducing power were displayed in the pulp of P. longanae-infected fruit during days 0-5. In this context, P. longanae induced breakdown of longan pulp by reducing the scavenging ability of ROS and increasing the cumulation of ROS, thereby enhancing the structural collapse and lipid peroxidation of cell membrane, which were responsible for the PB of harvested longans.

Comparative study of the antioxidant activity of the essential oils of five plants against the H2O2 induced stress in Saccharomyces cerevisiae.

The purpose of this work was to investigate the protective effect of five essential oils (EOs); Rosmarinus officinalis, Thymus vulgaris, Origanum compactum Benth., Eucalyptus globulus Labill. and Ocimum basilicum L.; against oxidative stress induced by hydrogen peroxide in Saccharomyces cerevisiae. The chemical composition of the EOs was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The in vitro antioxidant activity was evaluated and the protective effect of EOs was investigated. Yeast cells were pretreated with different concentrations of EOs (6.25-25 µg/ml) for an hour then incubated with H2O2 (2 mM) for an additional hour. Cell viability, antioxidants (Catalase, Superoxide dismutase and Glutathione reductase) and metabolic (Succinate dehydrogenase) enzymes, as well as the level of lipid peroxidation (LPO) and protein carbonyl content (PCO) were evaluated. The chemical composition of EOs has shown the difference qualitatively and quantitatively. Indeed, O. compactum mainly contained Carvacrol, O. basilicum was mainly composed of Linalool, T. vulgaris was rich in thymol, R. officinalis had high α-Pinene amount and for E. globulus, eucalyptol was the major compound. The EOs of basil, oregano and thyme were found to possess the highest amount of total phenolic compounds. Moreover, they have shown the best protective effect on yeast cells against oxidative stress induced by H2O2. In addition, in a dose dependent manner of EOs in yeast medium, treated cells had lower levels of LPO, lower antioxidant and metabolic enzymes activity than cells exposed to H2O2 only. The cell viability was also improved. It seems that the studied EOs are efficient natural antioxidants, which can be exploited to protect against damages and serious diseases related to oxidative stress.

Antiviral effect of mouthwashes against SARS-COV-2: A systematic review.

OBJECTIVE: This systematic review aimed to evaluate the antiviral effect of mouthwashes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIAL AND METHODS: An electronic search was performed on PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ProQuest, and Google Scholar, and was complemented by a manual search. Both clinical and in vitro studies that focused on the antiviral effect of mouthwashes against SARS-CoV-2 were included. Risk of bias assessment was performed only on the clinical studies using the RoB-2 and ROBINS-I tools. RESULTS: A total of 907 records were found; after initial selection by title and abstract, 33 full-text articles were selected to be evaluated for eligibility. Finally, a total of 27 studies were included for the qualitative synthesis, including 16 in vitro studies and 11 clinical trials. Antiviral effects were evaluated separately for the in vitro and clinical studies. In vitro studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, essential oils, cetylpyridinium chloride, and other compounds; in vivo studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, essential oils, chlorine dioxide, ß-cyclodextrin-citrox, and sorbitol with xylitol. Povidone-iodine, cetylpyridinium chloride, and essential oils were effective in vitro, while hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, ß-cyclodextrin-citrox, and sorbitol with xylitol were effective in vivo. Unclear or high risk of bias was found for almost all clinical studies, and only one study presented with a low risk of bias. No further quantitative analysis was performed. CONCLUSION: Although povidone-iodine, cetylpyridinium chloride, and essential oils may be an alternative to reduce the viral load in vitro and in vivo, more studies are needed to determine the real antiviral effect of these different mouthwashes against SARS-CoV-2.This work was not funded. The protocol was registered in PROSPERO (identification number: CRD42021236134).

Is hydrogen peroxide an effective mouthwash for reducing the viral load of SARS-CoV-2 in dental clinics?

BACKGROUND: Previous studies have demonstrated that SARS-CoV-2 is mainly transmitted by inhalation of aerosols and can remain viable in the air for hours. Viruses can spread in dental settings and put professionals and patients at high risk of infection due to proximity and aerosol-generating procedures, and poor air ventilation. OBJECTIVES: The aim of this study was to investigate the effects of a 1% hydrogen peroxide (H2O2) mouth rinse on reducing the intraoral SARS-CoV-2 load. METHODS: Portable air cleaners with HEPA filters exposed for 3 months were analysed to test for virus presence in a waiting room (where patients wore a face mask but did not undergo mouth rinsing) and three treatment rooms (where patients wore no mask but carried out mouth rinsing). As CO2 is co-exhaled with aerosols containing SARS-CoV-2 by COVID-19 infected people, we also measured CO2 as a proxy of infection risk indoors. Specific primer and probe RT-PCR were applied to detect viral genomes of the SARS-CoV-2 virus in the filters. Specifically, we amplified the nucleocapsid gene (Nuclv) of SARS-CoV-2. RESULTS: CO2 levels ranged from 860 to 907 ppm, thus indicating low ventilation and the risk of COVID-19 transmission. However, we only found viral load in filters from the waiting room and not from the treatment rooms. The results revealed the efficiency of 1-minute mouth rinsing with 1% H2O2 since patients rinsed their mouths immediately after removing their mask in the treatment rooms. CONCLUSIONS: Our findings suggest that dental clinics would be safer and more COVID-19 free by implementing mouth rinsing 1 min with 1% H2O2 immediately after the patients arrive at the clinic.

Thiol antioxidants protect human lens epithelial (HLE B-3) cells against tert-butyl hydroperoxide-induced oxidative damage and cytotoxicity.

Oxidative damage to lens epithelial cells plays an important role in the development of age-related cataract, and the health of the lens has important implications for overall ocular health. As a result, there is a need for effective therapeutic agents that prevent oxidative damage to the lens. Thiol antioxidants such as tiopronin or N-(2-mercaptopropionyl)glycine (MPG), N-acetylcysteine amide (NACA), N-acetylcysteine (NAC), and exogenous glutathione (GSH) may be promising candidates for this purpose, but their ability to protect lens epithelial cells is not well understood. The effectiveness of these compounds was compared by exposing human lens epithelial cells (HLE B-3) to the chemical oxidant tert-butyl hydroperoxide (tBHP) and treating the cells with each of the antioxidant compounds. MTT cell viability, apoptosis, reactive oxygen species (ROS), and levels of intracellular GSH, the most important antioxidant in the lens, were measured after treatment. All four compounds provided some degree of protection against tBHP-induced oxidative stress and cytotoxicity. Cells treated with NACA exhibited the highest viability after exposure to tBHP, as well as decreased ROS and increased intracellular GSH. Exogenous GSH also preserved viability and increased intracellular GSH levels. MPG scavenged significant amounts of ROS, and NAC increased intracellular GSH levels. Our results suggest that both scavenging ROS and increasing GSH may be necessary for effective protection of lens epithelial cells. Further, the compounds tested may be useful for the development of therapeutic strategies that aim to prevent oxidative damage to the lens.

A hybrid oxygen-generating wound dressing based on chitosan thermosensitive hydrogel and decellularized amniotic membrane.

Amniotic membrane (AM) has been utilized as a wound dressing extensively. Given the importance of oxygen in wound healing, here we have reported the fabrication and characterization of an oxygen-generating wound dressing based on AM. This construct was composed of H2O2-loaded polylactic acid (PLA) microparticles embedded within a chitosan/ß-glycerophosphate (ß-GP) thermosensitive hydrogel covered with a layer of decellularized human-AM. The microparticles had a diameter of 4.48 ± 1.8 µm, an encapsulation efficiency of 44.172 ± 4.49%, and generated oxygen for at least 7 days. The hybrid construct was formed at 32.4 ± 2 °C, had a porous structure (84.69 ± 8.34%) with a pore size of 46.72 ± 26.21 µm. The hydrogel/dAM extract was non-toxic after 7 days based on our MTT results, and the final composite supported cell growth and adhesion. This sample had the most negligible blood cell adhesion with less than 5% hemolysis. Our results indicate the proposed structure's desirable biological, chemical, and physical properties as an active wound dressing.

Functional resveratrol-biodegradable manganese doped silica nanoparticles for the spinal cord injury treatment.

Spinal cord injury (SCI) causes secondary injury, accompanied by pathological changes such as oxidative stress, inflammation and neuronal apoptosis. This leads to permanent disabilities such as paralysis and loss of movement or sensation. Due to the ineffectiveness of drugs passing through the blood spinal cord barrier (BSCB), there is currently no effective treatment for SCI. The aim of this experiment was to design plasma complex component functionalized manganese-doped silica nanoparticles (PMMSN) with a redox response as a targeted drug carrier for resveratrol (RES), which effectively transports insoluble drugs to cross the BSCB. RES was adsorbed into PMMSN with a particle size of approximately 110 â€‹nm by the adsorption method, and the drug loading reached 32.61 â€‹± â€‹3.38%. The RES release results for the loaded sample (PMMSN-RES) showed that the PMMSN-RES exhibited a release slowly effect. In vitro and vivo experiments demonstrated that PMMSN-RES decreased reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reduced the expression of inflammatory (TNF-α, IL-1ß and IL-6) and apoptotic cytokines (cleaved caspase-3) in spinal cord tissue after SCI. In summary, PMMSN-RES may be a potential pharmaceutical preparation for the treatment of SCI by reducing neuronal apoptosis and inhibiting inflammation caused by reducing oxidative stress to promote the recovery of mouse motor function.

Curcumin Reduced H2O2- and G2385R-LRRK2-Induced Neurodegeneration.

Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are the most frequent genetic factors contributing to Parkinson's disease (PD). G2385R-LRRK2 increases the risk for PD susceptibility in the Chinese population. However, the pathological role of G2385R-LRRK2 is not clear. In this study, we investigate the roles of G2385R-LRRK2 in neurodegeneration underlying PD pathogenesis using cell biology and pharmacology approaches. We demonstrated that expression of G2385R-LRRK2-induced neurotoxicity in human neuroblastoma SH-SY5Y and mouse primary neurons. G2385R-LRRK2 increased mitochondrial ROS, activates caspase-3/7, and increased PARP cleavage, resulting in neurotoxicity. Treatment with curcumin (an antioxidant) significantly protected against G2385R-LRRK2-induced neurodegeneration by reducing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage. We also found that the cellular environmental stressor, H2O2 significantly promotes both WT-LRRK2- and G2385R-LRRK2-induced neurotoxicity by increasing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage, while curcumin attenuated this combined neurotoxicity. These findings not only provide a novel understanding of G2385R roles in neurodegeneration and environment interaction but also provide a pharmacological approach for intervention for G2385R-LRRK2-linked PD.

Naringin prevents cyclophosphamide-induced erythrocytotoxicity in rats by abrogating oxidative stress.

Earlier reports have shown that Cyclophosphamide (CYCP), an anti-malignant drug, elicited cytotoxicity; and that naringin has several beneficial potentials against oxidative stress and dyslipidaemias. We investigated the influence of naringin on free radical scavenging, cellular integrity, cellular ATP, antioxidants, oxidative stress, and lipid profiles in the CYCP-induced erythrocytotoxicity rat model. Rats were pretreated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) naringin before single CYCP (200 mg/kg, i.p.) administration. Afterwards, the rats were sacrificed. Naringin concentrations required for 50 % scavenging hydrogen peroxide and nitric oxide radical were 0.27 mg/mL and 0.28 mg/mL, respectively. Naringin pretreatment significantly (p < 0.05) protected erythrocytes plasma membrane architecture and integrity by abolishing CYCP-induced decrease in the activity of erythrocyte LDH (a marker of ATP). Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-induced decreases in the erythrocytes glutathione levels, activities of glutathione-S-transferase, catalase, glutathione peroxidase, and glutathione reductase; attenuated CYCP-mediated increases in erythrocytes levels of malondialdehyde, nitric oxide, and major lipids (cholesterol, triacylglycerol, phospholipids, and non-esterified fatty acids). Taken together, different acute pretreatment doses of naringin might avert CYCP-mediated erythrocytes dysfunctions via its antioxidant, free-radical scavenging, and anti-dyslipidaemia properties.

Effects of neoadjuvant therapies on genetic regulation of targeted pathways in ER+ primary ductal breast carcinoma: A meta-analysis of microarray datasets.

Breast cancer arises as a result of multiple interactions between environmental and genetic factors. Conventionally, breast cancer is treated based on histopathological and clinical features. DNA technologies like the human genome microarray are now partially integrated into clinical practice and are used for developing new "personalized medicines" and "pharmacogenetics" for improving the efficiency and safety of cancer medications. We investigated the effects of four established therapies-for ER+ ductal breast cancer-on the differential gene expression. The therapies included single agent tamoxifen, two-agent docetaxel and capecitabine, or combined three-agents CAF (cyclophosphamide, doxorubicin, and fluorouracil) and CMF (cyclophosphamide, methotrexate, and fluorouracil). Genevestigator 8.1.0 was used to compare five datasets from patients with infiltrating ductal carcinoma, untreated or treated with selected drugs, to those from the healthy control. We identified 74 differentially expressed genes involved in three pathways, i.e., apoptosis (extrinsic and intrinsic), oxidative signaling, and PI3K/Akt signaling. The treatments affected the expression of apoptotic genes (TNFRSF10B [TRAIL], FAS, CASP3/6/7/8, PMAIP1 [NOXA], BNIP3L, BNIP3, BCL2A1, and BCL2), the oxidative stress-related genes (NOX4, XDH, MAOA, GSR, GPX3, and SOD3), and the PI3K/Akt pathway gene (ERBB2 [HER2]). Breast cancer treatments are complex with varying drug responses and efficacy among patients. This necessitates identifying novel biomarkers for predicting the drug response, using available data and new technologies. GSR, NOX4, CASP3, and ERBB2 are potential biomarkers for predicting the treatment response in primary ER+ ductal breast carcinoma.

Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.

Amelioration of diethylnitrosamine (DEN) induced renal oxidative stress and inflammation by Carissa carandas embedded silver nanoparticles in rodents.

INTRODUCTION: Inflammation and oxidative stress are the main factors ascribed with interruption in the process of renal tissue impairment. The toxicity of different types of nitrosamine is well recognized in animals and humans. Administration of the smallest quantities of diethylnitrosamine or dimethylnitrosamine either orally or parenterally results into renal damage. Therapeutic effects of phytofabricated silver nanoparticles of Carissa carandas aqueous extract has been scrutinised in current study for the assessment of renal cancer activity in animal model. METHODOLOGY: Phytofabricated silver nanoparticles were characterized by using different instrumentation. Nephroprotective activity of silver nanoparticles at different doses was evaluated against N-diethylnitrosamine (200 mg/kg b.w., intraperitoneal) in animal model. Serum and renal homogenate were taken to evaluate the renal toxicity markers, oxidative stress, and antioxidant parameter, proinflammatory cytokines and histopathological study. RESULT: Significant outcomes of silver nanoparticles in dose dependent manner down regulated the elevated serum marker, tumour marker enzymes and histopathology observation of repaired tissue assured the renal cancer activity in animals. In addition, profile of enzymatic and non-enzymatic antioxidant, proinflammatory cytokines and tumour promotion marker also favours the anticancer property of silver nanoparticles. CONCLUSION: The data of current study reveals silver nanoparticles ameliorates renal oxidative stress and carcinogenesis which was induced by N-diethylnitrosamine and accredited to antioxidant and anticancer activities of phytofabricated nanoparticles by biological approach.