Exploring serum amino acid signatures as potential biomarkers in Hashimoto's thyroiditis patients.

Hashimoto's thyroiditis (HT) is an autoimmune disease caused by the immune system attacking healthy tissues. However, the exact pathogenesis of HT remains unclear. Metabolomic analysis was performed to obtain information about the possible pathogenic mechanisms and diagnostic biomarkers of HT. The amino acid profile was analyzed using an LC-MS/MS method using serum samples obtained from 30 patients diagnosed with ultrasonographic imaging and laboratory markers (thyroid stimulating hormone) free thyroxine and thyroid peroxidase) and 30 healthy individuals. There were statistically significant changes in 27 amino acids out of 32 amino acids analyzed (p < 0.05). Based on the receiver operating characteristic curve analysis, the six amino acid (1-methylhistidine, cystine, norvaline, histidine, glutamic acid and leucine) biomarkers showed high sensitivity, specificity (area under the curve > 0.98), positive likelihood ratio and low negative likelihood ratio. Also, according to pathway analysis, degradation of phenylalanine, tyrosine and tryptophan biosynthesis was the highest metabolic pathway according to the impact value (p < 0.001 and impact value = 1.0). We provide serum amino acid profiles of patients with Hashimoto's thyroiditis and identify five potential biomarkers for early diagnosis by clinicians.

A mixed-apoptotic effect of Jurinea mesopotamica extract on prostate cancer cells: a promising source for natural chemotherapeutics.

This research investigates the potential use of Jurinea mesopotamica Hand.-Mazz. (Asteraceae) in cancer treatment. In this study, a plant extract was prepared using all parts of J. mesopotamica, and its effect on the proliferation of cancer and normal cells was tested using the MTT method. It was found to have a selective cytotoxic effect on prostate cancer cells, with the lowest IC50 (half-maximal inhibitory concentration) of 10µg/mL found in the butanol extract (JMBE). The extract suppressed the proliferation of prostate cancer cells (67 %), disrupted organelle integrity (49 %), increased reactive oxidative stress (66 %), and triggered cell death (51 %). In addition, apoptotic gene expressions and protein levels increased, and the profile of amino acids related to energy metabolism was elevated. Based on LC-MS/MS results, the plant contained higher levels of flavonoids, including isoquercitrin, cosmosiin, astragalin, nicotiflorin, luteolin, and apigenin. These results suggest that J. mesopotamica has a selective effect on prostate cancer due to its high flavonoid content and might be a promising natural alternative for cancer treatment.

UHPLC-MS/MS analysis, cytotoxic, enzyme inhibition, and antioxidant properties of Lantana camara L. extracts obtained by conventional and nonconventional methods.

Lantana camara is widely known as a garden plant, but its use for various medicinal purposes is widespread in traditional medicine. In the frame of this study, L. camara was subjected to several different extraction techniques, including supercritical carbon dioxide extraction, accelerated solvent extraction (ASE), homogenizer-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, maceration, and Soxhlet extraction. The investigation encompasses the analysis of the chemical composition alongside assessments of biological activities, such as antioxidant and enzyme-inhibition potential and cytotoxicity of the obtained extracts. The obtained results showed that the extract obtained by accelerated-solvent extraction was the richest in the content of total phenols and of individual compounds. Of the 17 components identified in total, hispidulin was detected in the highest concentration (5.43-475.97 mg/kg). In the antioxidant assays, the extracts obtained by accelerated-solvent and microwave extraction possessed the highest level of antioxidant and antiradical protection. All obtained extracts showed enzyme-inhibitory action on amylase, glucosidase, tyrosinase, and cholinesterase, showing a high potential for application against diseases induced by excessive activity of these enzymes. Cytotoxic analysis was performed on normal and tumor cells, whereby the obtained IC50 values were in the range of 7.685-79.26 µg/mL, showing the high cytotoxicity of the obtained extracts. Using Z score analysis, ASE resulted in an optimal combination of tested quality characteristics of the L. camara extracts.

Chemical composition and biological activities of Cucurbita okeechobeensis extracts from its aerial parts, seeds, and fruit shells.

The Cucurbita genus has been widely used in traditional medicinal systems across different countries. In this study, we aimed to investigate the chemical composition, antioxidant properties, enzyme inhibitory, and cytotoxic effects of methanol and aqueous extracts obtained from the aerial parts, seeds, and fruit shells of Cucurbita okeechobeensis. Antioxidant properties were assessed using various chemical methods, including radical quenching (DPPH and ABTS), reducing power (CUPRAC and FRAP), metal chelation, and phosphomolybdenum assays. The extracts' enzyme inhibitory effects were tested against cholinesterase, amylase, glucosidase, and tyrosinase, whereas different cancer cell lines were used for the cytotoxicity study. The chemical composition, evaluated by HPLC-ESI-MSn, showed that the most abundant compounds were flavonoids (mainly quercetin glycosides) followed by phenolic acids (mostly caffeic acid derivatives). The aerial parts displayed stronger antioxidant ability than the seed and fruit shells, in agreement with the highest content in phytochemicals. In addition, the methanol extracts presented the highest bioactivity and content in phytochemicals; among them, the extract of the aerial part exhibited significant cytotoxic effects on cancer cell lines and induced apoptosis. Overall, our results suggest that C. okeechobeensis is a valuable source of bioactive compounds for the pharmaceutical and nutraceutical industries.

Influence of extraction solvents on the chemical constituents and biological activities of Astragalus aduncus from Turkey flora: In vitro and in silico insights.

The n-hexane, ethyl acetate, ethanol, ethanol/water (70% ethanol), and water extracts of Astragalus aduncus aerial parts were investigated for their antioxidant potential, enzyme inhibition activity (anti-acetylcholinesterase [AChE], anti-butyrylcholinesterase [BChE], antityrosinase, antiamylase, and antiglucosidase) and antiproliferative effect (against colon adenocarcinoma cell line [HT-29], gastric cancer cell line [HGC-27], prostate carcinoma cell line [DU-145], breast adenocarcinoma cell line [MDA-MB-231], and cervix adenocarcinoma cell line [HeLa]). In addition, the phytochemical profile of the extracts was evaluated using validated spectrophotometric and high-pressure liquid chromatography-electrospray ionization/tandem mass spectroscopy methods. Generally, the 70% ethanol extract demonstrated the strongest antioxidant properties, and it was the richest source of total phenolic constituents. Our findings indicated that the ethyl acetate extract was the most potent BChE inhibitor (11.44 mg galantamine equivalents [GALAE]/g) followed by the ethanol extract (8.51 mg GALAE/g), while the ethanol extract was the most promising AChE inhibitor (3.42 mg GALAE/g) followed by the ethanol/water extract (3.17 mg GALAE/g). Excellent tyrosinase inhibitory activity (66.25 mg kojic acid equivalent/g) was observed in ethanol/water extracts of the aerial part of A. aduncus. Тhese results showed that the most cytotoxic effects were exhibited by the ethyl acetate extract against HGC-27 cells (IC50: 36.76 µg/mL), the ethanol extract against HT-29 cells (IC50: 30.79 µg/mL), and the water extract against DU-145 cells (IC50: 37.01 µg/mL). A strong correlation was observed between the highest total flavonoid content and the highest content of individual compounds in the ethanol extract, including rutin, hyperoside, isoquercitrin, delphinidin-3,5-diglucoside (delphinidin-3,5-O-diglucoside), and kaempferol-3-glucoside (kaempferol-3-O-glucoside). In the present study, the A. aduncus plant was considered a new source of antioxidants, enzyme inhibitors, and anticancer agents and could be used as a future health-benefit natural product.

Combining chemical profiles and biological abilities of different extracts from Tanacetum nitens (Boiss. & Noë) Grierson using network pharmacology.

Tanacetum nitens (Boiss. & Noë) Grierson is an aromatic perennial herb used in Turkish traditional medicine to treat headache, fever, and skin diseases. This study aimed to investigate the chemical composition, antioxidant, enzyme inhibition, and cytotoxic properties of T. nitens aerial parts. Organic solvent extracts were prepared by sequential maceration in hexane, dichloromethane, ethyl acetate, and methanol while aqueous extracts were obtained by maceration or infusion. Nuclear magnetic resonance (NMR) and LC-DAD-MS analysis allowed the identification and quantification of different phytoconstituents including parthenolide, tanacetol B, tatridin B, quinic acid derivatives, ß-sitosterol, and glycoside derivatives of quercetin and luteolin. The type and amount of these phytochemicals recovered by each solvent were variable and significant enough to impact the biological activities of the plant. Methanolic and aqueous extracts displayed the highest scavenging and ions-reducing properties while the dichloromethane and ethyl acetate extracts exerted the best total antioxidant activity and metal chelating power. Results of enzyme inhibition activity showed that the hexane, ethyl acetate, and dichloromethane extracts had comparable anti-acetylcholinesterase activity and the latter extract revealed the highest anti-butyrylcholinesterase activity. The best α-amylase and α-glucosidase inhibition activities were obtained from the hexane extract. The dichloromethane and ethyl acetate extracts exhibited the highest cytotoxic effect against the prostate carcinoma DU-145 cells. In conclusion, these findings indicated that T. nitens can be a promising source of biomolecules with potential therapeutic applications.

UHPLC-ESI-QTOF-MS metabolite profiles of different extracts from Pelargonium endlicherianum parts and their biological properties based on network pharmacological approaches.

In the present study, we aimed to investigate the chemical profiles and biological activities of different extracts (ethyl acetate, dichloromethane, ethanol, and water) of Pelargonium endlicherianum parts (aerial parts and roots). Free radical scavenging, reducing power, phosphomolybdenum, and metal chelating were assayed for antioxidant properties. To detect enzyme inhibitory properties, cholinesterase, amylase, glucosidase, and tyrosinase were chosen as target enzymes. The ethanol extract of the aerial parts contained higher amounts of total bioactive compounds (120.53 mg GAE/g-24.46 mg RE/g). The ethanol and water extracts of these parts were tentatively characterized by UHPLC-ESI-QTOF-MS and 95 compounds were annotated. In addition, the highest acetylcholiesterase (3.74 mg GALAE/g) and butyrylcholinesterase (3.92 mg GALAE/g) abilities were observed by the ethanol extract of roots. The water extract from aerial parts exhibited the most pronounced inhibitory effects on multiple cancer cell lines, especially A549 (IC50: 23.2 µg/mL) and HT-29 (IC50: 27.43 µg/mL) cells. Using network pharmacology, P. endlicherianum compounds were studied against cancer, revealing well-connected targets such as epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase (PI3K), AKT, receptor tyrosine-protein kinase erbB-2, and growth factor receptor bound protein 2 (GRB2) with significant impact on cancer-related pathways. The results could open a new path from natural treasure to functional applications with P. endlicherianum and highlight a new study on other uninvestigated Pelargonium species.

Effects of membrane content, feed phase, and stripping phase for palladium solution extraction by using a polymer inclusion membrane.

Palladium is now frequently utilized in fuel cells, electroplating, electronics, and catalysis. Due to their rarity and high cost, precious metal recovery has taken on a significant role. The extraction method frequently utilized in polymer inclusion membranes (PIMs) is both efficient and simple since it has been demonstrated that precious metal adsorption on the membrane significantly controls the mechanism of chemical adsorption. In this study, polyvinyl chloride (PVC) as a polymer, A336 as a plasticizer, and trioctylamine (TOA) as a carrier were used to produce a PIM by evaporation. After the production of PIMs, palladium extract was studied. The stripping phase, palladium concentration in the feed phase, and components of the membrane were changed to determine the optimum condition with better extraction ability. When 0.5 M of HCl was used, higher kinetic parameter results and higher than 85% extraction efficiency were achieved compared to other concen- trations. When the EDX results were examined, 3.3% palladium was retained on the membrane surface. When the palladium concentration was selected at 2.5 ppm, higher kinetic parameters were observed, and the extraction efficiency was over 90%. The best membrane was the PIM containing 40% PVC-40% A336-20% TOA.

Establishing a link between the chemical composition and biological activities of Gladiolus italicus Mill. from the Turkish flora utilizing in vitro, in silico and network pharmacological methodologies.

OBJECTIVES: Five solvent extracts (n-hexane, ethyl acetate, ethanol, ethanol/water (70%), and water) of Gladiolus italicus Mill. from Turkey were evaluated for chemical and biological properties. METHODS: Antioxidant activities, inhibitory properties against key enzymes involved in the etiology of chronic diseases were tested, as well as cytotoxic effects on different cell lines. Chemical characterization was also carried out to determine the most abundant compounds of each extract. RESULTS: The highest total phenolic content (TPC) was observed in the water extract while highest TFC in ethanol/water extract. The most abundant compounds in the extracts were hyperoside (69041.06 mg kg-1), isoquercitrin (46239.49 mg kg-1), delphindin-3,5-diglucoside (42043.81 mg kg-1), myricetin (21486.61 mg kg-1), and kaempferol-3-glucoside (21199.76 mg kg-1). Molecular dynamic (MD) simulations confirmed the structural stability and dynamic conformational integrity of these complexes over a period of 100 ns. In network pharmacology, A total of 657 unique target genes were screened: 52 associated with programmed cell death-1 (PD-1), 85 with vascular endothelial growth factor receptor-2 (VEGFR2), and 130 with fibroblast growth factor receptor-2 (FGFR2), identifying crucial gene interactions for these proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, revealing significant interactions and pathways such as the advanced glycation end products (AGE) and their receptors (RAGE) signaling pathway in diabetic complications and T- helper 17 (Th17) cell differentiation, among others. This elucidation of complex networks involving key genes like AKT Serine/Threonine Kinase 1 (AKT1), MYC proto-oncogene (MYC), tumor protein 53 (TP53), Interleukin 6 (IL6), and tumor necrosis factor (TNF) provides a promising foundation for the development of targeted therapies in the treatment of non-communicable diseases. CONCLUSION: These results show that G. italicus could be a natural source of potent antioxidants and enzyme inhibitors which need to be further explored for the development of biopharmaceuticals.

Serum ADAMTS-9 Level in Newborn Babies with Congenital Heart Disease.

OBJECTIVE: A Disintegrin and Metalloproteinase with Thrombospondin-9 (ADAMTS-9), one of the ADAMTS enzymes, is expressed in all fetal tissues, unlike other ADAMTS enzymes, and is thus thought to play a role in fetal development. In this context, the objective of this study is to investigate the relationship between ADAMTS-9 activity and the development of congenital heart diseases (CHD) with a view to using ADAMTS-9 level as a biomarker for CHDs. STUDY DESIGN: Newborns diagnosed with CHD and healthy newborns were included in the study as the CHD and control groups, respectively. Gestational age, maternal age, and mode of delivery information pertaining to the mothers and Apgar score and birthweight information pertaining to the newborns were recorded. Blood samples were taken from all newborns to determine their ADAMTS-9 levels in the first 24 hours of life. RESULTS: Fifty-eight newborns with CHD and 46 healthy newborns were included in the study. Median ADAMTS-9 levels were 46.57 (interquartile range [IQR]: 33.31 [min: 26.92, max: 124.25]) and 23.36 (IQR: 5.48 [min: 11.7, max: 37.71]) ng/mL in the CHD and control groups, respectively. ADAMTS-9 levels in the CHD group were statistically significantly higher than in the control group (p = 0.000). ADAMTS-9 levels of the CHD and control groups were analyzed by the receiver operating characteristics curve. The area under the curve value for ADAMTS-9 levels of >27.86 ng/mL as the cut-off value for predicting the development of CHD in newborns was 0.836 (95% confidence interval [CI]: 0.753-0.900, p = 0.0001). ADAMTS-9 levels of >27.86 ng/mL were determined to predict the development of CHD in newborns with a sensitivity of 77.78% (95% CI: 65.5-87.38) and a specificity of 84.78% (95% CI: 71.1-93.60). CONCLUSION: In conclusion, it was found that the serum ADAMTS-9 levels were significantly higher in newborns with CHD than in healthy newborns. In parallel, ADAMTS-9 levels above a certain cut-off value were associated with CHD. KEY POINTS: · ADAMTS-9 is expressed in fetal tissues.. · Its level increases in congenital heart diseases.. · It can be used as a biochemical marker in diagnosis..

LC-MS/MS and GC-MS profiling, antioxidant, enzyme inhibition, and antiproliferative activities of Thymus leucostomus H ausskn. & V elen. extracts.

The chemical composition as well as antioxidant, antiproliferative, and enzyme inhibition activities of extracts from aerial parts of Thymus leucostomus H ausskn. & V elen. obtained with hexane, methanol, and water were evaluated. Results showed that the methanol extract had significantly (p < 0.05) the highest total phenolic content (TPC; 107.80 mg GAE/g) and total flavonoids content (TFC; 25.21 mg RE/g) followed by the aqueous extract (102.72 mg GAE/g and 20.88 mg RE/g, respectively). LC-MS/MS-guided profiling of the three extracts revealed that rosmarinic acid (34.8%), hesperetin (42.9%), and linoleic acid (18%) were the dominant compounds in the methanol, aqueous and hexane extracts, respectively. GC-MS analysis of the hexane extract showed that É£-sitosterol (29.9%) was the major constituent. The methanol extract displayed significantly (p < 0.05) the highest Cu++ , Fe+++ , and Mo(VI) ions scavenging and reducing properties while the aqueous extract exerted significantly (p < 0.05) the highest metal chelating power (42.51 mg EDTAE/g). Both the hexane and methanol extracts effectively inhibited the acetylcholinesterase enzyme (2.63 and 2.65 mg GALAE/g, respectively) while the former extract exerted significantly (p < 0.05) the highest butyrylcholinesterase (2.32 mg GALAE/g), tyrosinase (19.73 mg KAE/g), and amylase (1.16 mmol ACAE/g) inhibition capacity. The aqueous extract exhibited the best glucosidase inhibition property (0.49 mmol ACAE/g). The methanol and hexane extracts exerted a higher cytotoxic effect on HT-29 (IC50 : 8.12 µg/mL) and HeLa (IC50 = 8.08 µg/mL) cells, respectively. In conclusion, these results provide valuable insight into the potential use of T. leucostomus bioactive extracts in different pharmaceutical applications.

Modification of reinforced hollow fiber membranes with WO3 nanosheets for treatment of textile wastewater by membrane bioreactor.

In this study, performance of braid reinforced hollow fiber membrane containing polyvinylidene fluoride (PVDF) embedded with tungsten trioxide (WO3) nanosheets in a membrane bioreactor (MBR) was examined for textile wastewater treatment. The WO3 nanosheets was synthesized and blended at different concentrations (0.1-0.02 wt%) in casting solutions of the membranes. The WO3 nanosheets characterized using various tests such as XRD, FTIR, SEM, EDS, dot-mapping, and TEM. Furthermore, the effects of the increased WO3 nanosheets into the PVDF matrix on the membrane morphology, hydrophilicity, permeability, antifouling, and COD and color removal efficiency was investigated. The addition of 0.1 wt% of the nanosheets reduces the water contact angle from 69.3° to 62.5° while increasing overall porosity from 37.5 to 43.2%. COD and color removal for PVDF/0.10 wt% WO3 membrane was between 86-89% and 72-76%, respectively. While the TMP of modified WO3 membranes did not significantly increase due to antimicrobial properties of the WO3 nanosheets, the TMP of the pure PVDF membrane increase, indicating considerable cake layer fouling. The results of this study showed that modification of PVDF braid reinforced hollow fiber membrane using WO3 nanosheets is promising membrane for MBR systems.

Coupling high-rate activated sludge process with aerobic granular sludge process for sustainable municipal wastewater treatment.

Achieving a neutral/positive energy balance without compromising discharge standards is one of the main goals of wastewater treatment plants (WWTPs) in terms of sustainability. Aerobic granular sludge (AGS) technology promises high treatment performance with low energy and footprint requirement. In this study, high-rate activated sludge (HRAS) process was coupled to AGS process as an energy-efficient pre-treatment option in order to increase energy recovery from municipal wastewater and decrease the particulate matter load of AGS process. Three different feeding strategies were applied throughout the study. AGS system was fed with raw municipal wastewater, with the effluent of HRAS process, and with the mixture of the effluent of HRAS process and raw municipal wastewater at Stage 1, Stage 2 and Stage 3, respectively. Total suspended solids (TSS), chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), and total phosphorus (TP) concentrations in the effluent were less than 10 mg/L, 60 mg/L, 0.4 mg/L, and 1.3 mg/L respectively at all stages. Fluctuations were observed in the denitrification performance due to changes in the influent COD/total nitrogen (TN) ratio. This study showed that coupling HRAS process with AGS process by feeding the AGS process with the mixture of HRAS process effluent and raw municipal wastewater could be an appropriate option for both increasing the energy recovery potential of WWTPs and enabling high effluent quality.

Pilot scale nanofiltration membrane fabrication containing ionic co-monomers and halloysite nanotubes for textile dye filtration.

Wastewater from the textile industry contains high concentrations of pollutants, so the wastewater must be treated before it is discharged. In addition, the reuse of treated wastewater should be considered from an environmental point of view, as large volumes of wastewater are produced. Since textile wastewater mainly contains dyestuffs, it must be treated effectively using environmentally friendly technologies. Membrane processes are widely used in textile wastewater treatment as they have distinct advantages over conventional wastewater treatment methods. This study reports the pilot-scale manufacturing and characterization of three different NF membranes. Three different types of membranes were fabricated. The fabricated membranes were compared through characterization by surface properties, chemical structure and morphology. Membranes were tested for pure water flux. Then the synthetic wastewater (SWW) was tested for flux and rejection. Lastly, the textile wastewater was tested. The textile wastewater flux of pure piperazine (PIP), 60% S-DADPS and 0.04% halloysite nanotubes (HNTs) were 22.42, 79.58 and 40.06 L m-2 h-1. It has been proven that the 60% s-DADPS membrane provides up to four times improvement in wastewater flux and simultaneously. In addition, NF membranes produced using HNT and sDADPS on a pilot scale have brought innovation to the literature with the good results obtained.

What is the impact of inflammasome mechanisms on male infertility?

BACKGROUND: Mechanisms to explain inflammation in male infertility of unknown cause are still being investigated. The inflammasome is a key regulator of innate immunity in the inflammatory response to infections. Our study aims to investigate the effects of varicocele on infertility, its relationship with antioxidant and inflammasome mechanisms, and how it could be guided in azoospermic or nonazoospermic patients. METHODS: A cross-sectional cohort study was conducted at the department of urology in our university hospital. Eightyeight randomly selected men aged 20-45 admitted to our hospital because of infertility between September 2019 and July 2020 were included in the study. Patients were divided into four equal groups according to their clinical status, those with/without azoospermia and with/without varicocele. Blood and semen samples were taken from the patients. NOD-like receptor pyrin domain-containing 3 (NLRP3) and interleukin-1 beta (IL1ß) and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were measured in serum and semen, and the groups were compared statistically. RESULTS: Serum and semen NLRP3, IL1ß, TAS, TOS, and OSI values of the patients with varicocele or azoospermia were significantlyhigher than those without either varicocele or azoospermia (p < 0.05). The oxidative stress markers TAS, TOS, and OSI values were significantly higher in the other groups than those without azoospermia and varicocele (p < 0.05). DISCUSSION: Inflammasome mechanisms, such as NLRP3 and IL1-ß molecules, may provide additional benefit in evaluating the need and benefit of surgical or medical treatment in infertility with and without vascular pathology and with and without azoospermia.

miR-320a promotes p53-dependent apoptosis of prostate cancer cells by negatively regulating TP73-AS1 invitro.

TP73 antisense RNA 1 (TP73-AS1) is an oncogenic long non-coding RNA that is activated in several types of cancers. It has been shown that the activity of TP73-AS1 is controlled by several miRNAs, but post-transcriptional mechanisms that regulate TP73-AS1 activity in prostate cancer remain highly elusive. Accordingly, in the present study, we aimed to determine the miRNAs that are involved in the regulation of TP73-AS1 in prostate cancer and to show the effects of these molecules on the malignant proliferation of prostate cancer cells. Remarkably, colony formation and cell migration were suppressed while cell cycle arrest and apoptosis were induced in prostate cancer cells overexpressing miR-200a and miR-320a. miR-200a and miR-320a were found to be upregulated in TP73-AS1 suppressed prostate cancer cells. Also, TP73-AS1 was shown to be downregulated following miR-200a and miR-320a overexpression. However, overexpression of miR-320a had no significant effect on the expression of TP73. Further analysis revealed that miR-320a induces p53-dependent apoptosis. Consequently, our findings indicate that miR-320a induces p53-dependent apoptosis by negatively regulating TP73-AS1 long non-coding RNA.

Oxidative stress and decreased Nrf2 level in pediatric patients with COVID-19.

The aim of this study was to investigate the change in nuclear factor erythroid 2-related factor (Nrf2), which plays a critical role in cytoprotection against oxidative stress, in pediatric patients with coronavirus disease 2019 (COVID-19) infection positivity, and to evaluate the relationship between Nrf2 and oxidative balance. The study included 40 children with confirmed COVID-19 infection and 35 healthy children. The groups were compared in respect of Nrf2, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), in addition to clinical findings of fever, cough, shortness of breath, contact history, and demographic data of age and gender. The mean Nrf2 values and TAS levels were determined to be statistically significantly low (p < 0.001) and the TOS level and OSI were statistically significantly high in the children with COVID-19 compared to the control group. A significant positive correlation was determined between Nrf2 and TAS (p < 0.01); as the Nrf2 value increased, so the TAS value increased. A significant negative correlation was determined between Nrf2 and TOS and OSI (p < 0.01); as the Nrf2 value increased, there was determined to be a significant decrease in the TOS and OSI values. COVID-19 infection in pediatric patients causes a decrease in the Nrf2 level. By causing a decrease in the TAS level and an increase in the TOS and OSI levels, the decrease in Nrf2 may explain the tissue damage which can be caused by COVID-19.

Glucocorticoids in a Neonatal Hyperoxic Lung Injury Model: Pulmonary and Neurotoxic effects.

BACKGROUND: We aimed to compare the effect of dexamethasone (Dex), hydrocortisone (Hc), and methylprednisolone (Mpz) at equivalent doses on somatic growth, lung healing, and neurotoxicity in a hyperoxic rat model. We hypothesized that Mpz and Hc would be superior to Dex with less neurotoxicity by exerting similar therapeutic efficacy on the injured lung. METHODS: Neonatal rats were randomized to control, bronchopulmonary dysplasia (BPD), Dex, Hc, and Mpz groups. All drugs were administered daily following day 15 over 7 days. Histopathological and immunohistochemical analyses of the lung and brain were performed on day 22. RESULTS: All types had much the same impact on lung repair. Oxidative markers in the lung were similar in the steroid groups. While nuclear factor erythroid 2-related factor and heat-shock protein 70 dropped following steroid treatment, no difference was noted in other biochemical markers in the brain between the study groups. Apoptotic activity and neuron loss in the parietal cortex and hippocampus were noted utmost in Dex, but alike in other BPD groups. CONCLUSIONS: Mpz does not appear to be superior to Dex or Hc in terms of pulmonary outcomes and oxidative damage in the brain, but safer than Dex regarding apoptotic neuron loss. IMPACT: This is the first study that compared the pulmonary efficacy and neurotoxic effects of Dex, Hc, and Mpz simultaneously in an established BPD model. This study adds to the literature on the importance of possible antioxidant and protective effects of glucocorticoid therapy in an oxidative stress-exposed brain. Mpz ended up with no more additional neuron loss or apoptosis risk by having interchangeable effects with others for the treatment of established BPD. Mpz and Hc seem safe as a rescue therapy in terms of adverse outcomes for established BPD in which lung and brain tissue is already impaired.

Silencing of TP73-AS1 impairs prostate cancer cell proliferation and induces apoptosis via regulation of TP73.

BACKGROUND: Prostate cancer is a malignant disease that severely affects the health and comfort of the male population. The long non-coding RNA TP73-AS1 has been shown to be involved in the malignant transformation of various human cancers. However, whether TP73-AS1 contributes to prostate cancer progression has not been reported yet. Accordingly, here we aimed to report the role of TP73-AS1 in the development and progression of prostate cancer and determine its relationship with TP73. METHODS AND RESULTS: TP73-AS1-specific siRNA oligo duplexes were used to silence TP73-AS1 in DU-145 and PC-3 cells. Results indicated that TP73-AS1 was upregulated whereas TP73 was downregulated in prostate cancer cells compared to normal prostate cells and there was a negative correlation between them. Besides, loss of function experiments of TP73-AS1 in prostate cancer cells strongly induced cellular apoptosis, interfered with the cell cycle progression, and modulated related pro- and anti-apoptotic gene expression. Colony formation and migration capacities of TP73-AS1-silenced prostate cancer cells were also found to be dramatically reduced. CONCLUSIONS: Our findings provide novel evidence that suggests a chief regulatory role for the TP73-TP73-AS1 axis in prostate cancer development and progression, suggesting that the TP73/TP73-AS1 axis can be a promising diagnostic and therapeutic target for prostate cancer.

Cedrus libani tar prompts reactive oxygen species toxicity and DNA damage in colon cancer cells.

BACKGROUND: Many chemotherapeutic drugs used in cancer treatment have anticancer properties by inducing reactive oxygen species (ROS). However, the same effect occurs in normal cells, limiting the availability of these drugs. Therefore, studies on the detection of new herbal anticancer agents that have selective effects on cancer cells are of great importance. The aim of this study is to investigate the metabolite profile of Cedrus libani tar and its mechanism of anticancer effect on colon cancer cells. METHODS AND RESULTS: Effect of cedar tar on cells (12 cancers and 5 normal cell lines) viability was determined by MTT, apoptosis induction was determined by Annexin-V, ROS and MMP determined by flow cytometry assay. Cleaved caspase-8, 9 and Ɣ-H2AX expression determined by western blot. Apoptotic and antioxidant genes expression level determined by qPCR. Metabolite profiling was performed with LC-MS/MS and GC-MS. Cedar tar showed the highest cytotoxic effect among cancer cells in colon cancer (HCT-116, IC50: 30.4 µg/mL) and its toxic effect on normal cells (HUVEC, IC50: 74.07 µg/mL) was less than cancer cell. Cedar tar increases ROS production in colon cancer cells. The metabolite profile of the cedar tar contains high amounts of metabolites such as fatty acids mainly (Duprezianene, Himachalene and Chamigrene), phenolic compounds (mostly Coumarin, p-coumaric acid, Vanillic acid and tr-Ferulic acid etc.) and organic acids (mainly 3-oh propanoic acid, 2-oh butyric acid and 3-oh isovaleric acid etc.). CONCLUSION: As a result, it has been found that cedar tar has the potential to be used in the treatment of colon cancer.