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Cerebral organoids, self-organizing structures with increased cellular diversity and longevity, have addressed shortcomings in mimicking human brain complexity and architecture. However, imaging intact organoids poses challenges due to size, cellular density, and light-scattering properties. Traditional one-photon microscopy faces limitations in resolution and contrast, especially for deep regions. Here, we first discuss the fundamentals of multiphoton microscopy (MPM) as a promising alternative, leveraging non-linear fluorophore excitation and longer wavelengths for improved imaging of live cerebral organoids. Then, we review recent applications of MPM in studying morphogenesis and differentiation, emphasizing its potential for overcoming limitations associated with other imaging techniques. Furthermore, our paper underscores the crucial role of cerebral organoids in providing insights into human-specific neurodevelopmental processes and neurological disorders, addressing the scarcity of human brain tissue for translational neuroscience. Ultimately, we envision using multimodal multiphoton microscopy for longitudinal imaging of intact cerebral organoids, propelling advancements in our understanding of neurodevelopment and related disorders.

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1β (TGF-1β) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1β levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ. [ABSTRACT FROM AUTHOR]

An overdose of acetaminophen (APAP) produces centrilobular hepatocellular necrosis. We aimed to investigate the hepatoprotective effects of N-acetylcysteine (NAC) only and hyperbaric oxygen (O2) treatment (HBOT) combined with NAC, and their anti-inflammatory properties in liver tissue. In the current study, a total of 32 male Sprague Dawley rats were divided into 4 groups: sham, APAP, NAC, and NAC + HBOT. In the APAP, NAC, and NAC + HBOT groups, liver injury was induced by oral administration of 1 g/kg APAP. The NAC group received 100 mg/kg NAC per day. NAC + HBOT group received intraperitoneal injection of 100 mg/kg/day NAC and were given HBOT at 2.8 ATA pressure with 100% O2 inhalation for 90 min every 12 h for 5 days. Rats in the sham group received distilled water only by gastric tube. All animals were killed on day 6 after APAP or distilled water administration. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic neopterin, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) levels were measured. There was a significant increase in serum AST and ALT activities in the APAP group compared with the sham group (in both p = 0.001). NAC and NAC + HBOT groups had significant decreases in hepatic neopterin, TNF-α, and IL-6 levels compared with the APAP group. APAP administration caused extensive hepatic necrosis. NAC and NAC + HBO treatments significantly reduced APAP-induced liver injury. Our results showed that the liver damage in APAP toxicity was attenuated by NAC and NAC + HBO treatments. NAC + HBOT exhibit hepatoprotective activity against APAP-induced liver injury in rats. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mud, which contains organic and mineral ingredients, is used for the treatment of several degenerative diseases. It has been proposed that beneficial effects of mud are not only related to its local thermal effects, but also to its chemical components. Unlike hydrophilic components, the lipophilic components of the mud extract have not been described precisely thus far. Thus, we aimed to determine the lipophilic components of the different mud species. METHODS: Three different mud species (e.g., krenogen, tone, and fango) were analyzed by using gas chromatography-mass spectrometry (GC-MS). RESULTS: There were organic substances with fatty-acid structures found in the structure of mud. Torf mud species contain the most compounds. The compounds of three mud species differ from each other. CONCLUSIONS: The chemical structure of mud does not only contain hydrophilic organic substances, such as humic, fulmic, and ulmic acids, but also low-molecular-weighted organic substances composed of fatty acids in the majority. Moreover, it would not be appropriate to explain mud with a single term, since it has different chemical structures and a new classification of the mud species is required. [ABSTRACT FROM AUTHOR]

Abstract Re-expansion pulmonary edema (RPE) is an acute, rare and potentially lethal complication [1,2]. Its beginning is sudden and dramatic. The mechanism is not yet fully understood [1]. Some authors suggest that it may occur after rapid re-inflation of a collapsed lung [1]. It was reported by other authors that it may relate to surfactant depletion or may result from hypoxic capillary damage, leading to increased capillary permeability [1,3]. In RPE, unilateral lung injury is initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils [1]. These toxic oxygen products are the results of re-oxygenation of a collapsed lung. Treatment of re-expansion pulmonary edema is basically preventive [4].

Turkish White Cheese is a brined (or pickled) cheese with a salty, acidic flavor and a soft or semi-hard texture. It is the most produced and consumed type of cheese in Turkey. The purpose of this study was to determine the non-starter lactic acid bacteria and yeast microbiota of traditionally produced Turkish White Cheese and analyze the chemical properties and the aroma profile of the cheese. The results of the study identified 27 distinct strains belonging to 14 the non-starter lactic acid bacteria species and 49 different strains belonging to 11 yeast species. Lactobacillus plantarum was found to be the dominant species among the lactic acid bacteria, while Candida zeylanoides was the dominant yeast species in the White Cheese samples. In addition, Kluyveromyces lactis and Debaryomyces hansenii were prominent yeast species in cheese samples. Turkish White Cheese samples had different aromatic properties. The study is highly significant as it anaylzed both non-starter lactic acid bacteria and yeast microbiota of traditionally produced Turkish White Cheese through molecular methods. It also determined and analyzed a number of chemical and aromatic properties of White Cheese., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

This study aimed to compare the antimicrobial effectiveness of ethanolic extract of propolis (EEP) to chlorhexidine gluconate (CHX) on planktonic Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lactobacillus salivarius subsp. salivarius, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Staphylococcus aureus, Enterococcus faecalis, Actinomyces israelii, Candida albicans, and their single-species biofilms by agar dilution and broth microdilution test methods. Both agents inhibited the growth of all planktonic species. On the other hand, CHX exhibited lower minimum bactericidal concentrations than EEP against biofilms of A. actinomycetemcomitans, S. aureus, and E. faecalis whereas EEP yielded a better result against Lactobacilli and P. intermedia. The bactericidal and fungicidal concentrations of both agents were found to be equal against biofilms of Streptecocci, P. gingivalis, A. israelii, and C. albicans. The results of this study revealed that propolis was more effective in inhibiting Gram-positive bacteria than the Gram-negative bacteria in their planktonic state and it was suggested that EEP could be as effective as CHX on oral microorganisms in their biofilm state.

Hyperinsulinism, one of the most important causes of hypoglycaemia, can be congenital or acquired. Rarely, drug toxicity can be a reason for hyperinsulinism. In the context of Munchausen syndrome by proxy (MSP), toxicity usually occurs in children due to drug administration by a parent or caregiver. A 7-year-old girl was referred to our department due to a hyperglycaemic period and hypoglycaemic episodes. On admission, gliclazide was initiated due to her hyperglycaemia, which we attributed to maturity onset diabetes of the young. However, during follow-up, hypoglycaemic levels were detected. Despite cessation of gliclazide, hypoglycaemic seizures occurred. Even with the medications administered, hypoglycaemia could not be prevented. During follow-up, the mother's affect, characterized by anxiety and interest in her daughter's medical care, appeared discordant with the situation. Due to our suspicion of MSP, we discovered toxic levels of gliclazide in the blood and urine samples which had been sent to the toxicology laboratory to search for hypoglycaemic agents. The patient was isolated, and all medications were stopped. After isolation, her hypoglycaemia disappeared, and she became hyperglycaemic (250 mg/dl). Physicians should consider the possibility of MSP in hyperinsulinaemic patients with discordant laboratory results and clinical symptoms, even if the child's parents display great concern., (© 2016 S. Karger AG, Basel.)

Besides its effect regarding addiction, ethanol also damages the central nervous system when it is used at high doses for a long time. The increase in the activity of Rho/Rho kinase pathway leads to central nervous system pathologies such as cerebral injury and epileptogenesis. The aim of this study was to investigate the contribution of Rho/Rho Kinase pathway to the degenerative and addictive effects of ethanol. For this purpose, we determined the Rho-kinase activity in striatum and hippocampus of rat brain. Wistar rats were treated with ethanol in a special liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to the rats in the control group during the study. At the end of the 21 day ethanol exposure, one group was kept on taking ethanol and another group was withdrawn from ethanol. The rats were decapitated and their brains were taken out. Striatum and hippocampus were isolated. Phospho-moesin protein levels were measured in striatum and hippocampus homogenates using by Western blot analysis. The Rho-kinase (ROCK) activity in the striatum was found to be significantly decreased in ethanol exposed rats. In the hippocampus, there was a significant increase in the ROCK activity in the ethanol group. Our results indicated that ethanol caused some significant changes in Rho/Rho Kinase pathway in rat brain (Fig. 2, Ref. 25).

Paraquat (PQ) overdose can cause acute lung injury and death. Ozone therapy (OT) was previously demonstrated to alleviate inflammation and necrosis in various pathologies. We therefore hypothesized that OT has ameliorative and preventive effects on PQ-induced lung damage due to anti-inflammatory and antioxidants properties. Sprague-Dawley rats (n = 24) were separated into three groups: sham, PQ, and PQ+OT groups. 15 mg/kg PQ was administered intraperitoneally in PQ and PQ+OT groups to induce experimental lung injury. One hour after PQ treatment, PQ+OT group was administered a single dose of ozone-oxygen mixture (1 mg/kg/day) by intraperitoneal route for four consecutive days. The animals were sacrificed on fifth day after PQ administration. Blood samples and lung tissues were collected to evaluate the inflammatory processes, antioxidant defense and pulmonary damage. Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, total TGF-β1 levels, and histological injury scores in PQ+OT group were significantly lower than PQ group (P<0.05, PQ vs. PQ+OT). Total antioxidant capacity in PQ+OT group was significantly higher than PQ group (P < 0.05, PQ+OT vs. PQ). These findings suggest that outcome in PQ-induced lung injury may be improved by using OT as an adjuvant therapy., (© 2014 by the Society for Experimental Biology and Medicine.)

Aim: To establish age- and sex-specific reference intervals for essential amino acids in a healthy Turkish pediatric population., Materials and Methods: A total of 945 clinically healthy children (531 boys and 414 girls, ranging in age from birth to 14 years) were enrolled. Plasma and urine amino acids' concentrations were measured by high-performance liquid chromatography., Results: Concentrations of essential amino acids in plasma were higher in girls than in boys in the age groups of 0-1 months and 7-14 years; however, there was no difference in the other age groups. Concentrations of essential amino acids in urine were higher in girls than in boys in the age group of 0-1 months; however, there was no difference in the other age groups. Our results demonstrated the sex-related differences in concentrations ofleucine, isoleucine, valine, phenylalanine, lysine, and histidine in plasma, which increased with age in boys but not in girls. The concentrations of leucine, tryptophan, methionine, and lysine in urine declined with age in girls but not in boys, which were sex-related differences, too., Conclusion: We defined essential amino acids' reference intervals in a Turkish pediatric population.

Objectives: Mustard is highly toxic to the lung. Its toxic effects are associated with inflammatory cell accumulation and increased pro-inflammatory cytokines as well as reactive oxygen and nitrogen species. In this study, we aimed to investigate the efficiency of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced lung toxicity., Methods: Thirty-six male rats were randomly divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Control group was given saline only via transdermal route. Other groups were exposured to a single dose of MEC (3.5 mg/kg) via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC., Results: MEC injection resulted in alveolar epithelial injury, hemorrhage, inflammation, edema and interalveolar septal thickening in the lung tissues. The tissue TNF-α, IL-1β, and nitrate/nitrite (NOx) levels were found significantly different for all groups (p<0.001). TNF-α and IL-1β levels increased significantly with MEC exposure, and MEL and SMT ameliorated these increases in lung tissues. MEC also elevated NOx levels in lung tissue. Melatonin showed meaningful protection against lung injury. But protection of SMT was weaker., Conclusion: Inflammation plays an important role in the MEC induced lung toxicity as well as oxidative and nitrosative stress. Melatonin has also anti-inflammatory properties similar to SMT, as well as anti-oxidant properties. But melatonin treatment was found more efficient than SMT treatment., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Introduction: Acetaminophen (APAP) is an analgesic and antipyretic agent. In overdoses, it is associated with nephrotoxicity. We examined the potential protective effects of N-acetylcysteine (NAC) and NAC + ozone therapy (OT) combination against APAP-induced nephrotoxicity., Materials and Methods: Thirty-two male Sprague-Dawley rats were divided into four groups: sham, control (APAP), NAC, and NAC + OT. In the APAP, NAC, and NAC + OT groups, kidney injury was induced by oral administration of 1 g/kg APAP. The NAC group received NAC (100 mg/kg/day). NAC + OT group received NAC (100 mg/kg/day) and ozone/oxygen mixture (0.7 mg/kg/day) intraperitoneally for 5 days immediately after APAP administration. All animals were killed at 5 days after APAP administration. Renal tissues and blood samples were obtained for biochemical and histopathological analyses. Neopterin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 levels were measured in sera. Malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activities were determined in renal homogenates., Results: NAC and NAC + OT significantly decreased MDA and TNF-α levels and increased IL-10 levels and GPx activities. Serum neopterin and IL-6 levels were not different among all groups. APAP administration caused tubular necrosis in the kidney. The degrees of renal necrosis of the APAP group were higher than the other groups. Renal injury in rats treated with combination of NAC and OT were found to be significantly less than the other groups., Conclusions: Our results showed that NAC and OT prevented renal injury in rats and reduced inflammation. These findings suggest that combination of NAC and OT might improve renal damages because of both oxidative stress and inflammation.

Objectives: Acetaminophen (APAP) overdose may cause acute liver injury. Ozone therapy (OT) is shown to reduce inflammation and necrosis in several entities. Thus, we have designed this study to evaluate the efficacy of OT in a rat model of APAP-induced liver injury., Methods: Twenty-seven Sprague-Dawley rats were divided into three groups: sham, APAP and APAP+OT groups. In the APAP and the APAP+OT groups, liver injury was induced by oral administration of 1 g/kg APAP. The APAP+OT group received a single dose ozone/oxygen mixture (0.7 mg/kg) intraperitoneally 1h after APAP administration. All animals were killed at 24 hour after APAP administration. Blood samples and liver tissues were harvested to determine liver injury and oxidative stress parameters. Liver tissues and blood samples were obtained for biochemical and histopathological analyses., Results: APAP administration caused necrosis in the liver after 24h. The degrees of liver necrosis of the APAP group were higher than the other groups (in both p<0.05, respectively). In the APAP+OT group, liver antioxidant enzymes activities were significantly higher than the APAP group (p<0.05), but were lower than the sham group (p<0.05). In the sham group, serum neopterin, a marker of cell-mediated immunity, concentrations (4.8±1.2 nmol/L) were lower than the APAP (14.7±1.4 nmol/L) and APAP+OT groups (7.5±2.4 nmol/L) (in both p<0.05, respectively)., Conclusion: Our results showed that OT prevented liver necrosis in rats and reduced neopterin levels. These findings suggest that the use of OT as an adjuvant therapy which might improve the outcome in APAP induced liver injury., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity., Materials and Methods: A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC., Results: The tissue TNF-α, IL-1β, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-α and IL-1β levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue., Conclusions: Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have anti-inflammatory properties, as well as anti-oxidant properties., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples., Materials and Methods: We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients., Results: System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes., Conclusion: This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney., Materials and Methods: Forty male Sprague-Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations., Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups., Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.

Objectives: The purpose of this study is to determine the reference of plasma total homocysteine levels from a Turkish population and to investigate the relationship of plasma total homocysteine levels with sex and age groups., Design and Methods: Plasma total homocysteine levels were measured in 2257 Turkish individuals (1381 men and 876 women) aged 1-90 years. Plasma total homocysteine concentrations were determined using high performance liquid chromatography with fluorescence detector., Results: The mean plasma total homocysteine level was significantly higher in men (mean, 10.6 micromol/L) than in women (mean, 8.7 micromol/L), P < 0.001. The mean plasma total homocysteine levels for the 1-10, 11-20, 21-30, and 31-40, 41-50, 51-60, and 61-70, 71-80, 81-90 age groups, were 6.5, 9.6, 10.1, and 10.4, 10.5, 10.9, and 11.3, 12.7, 14.6 miromol/L in men and 7.1, 7.6, 7.5, and 7.8, 8.7, 9.4, and 10.3, 11.2, 13.3 micromol/L in women, respectively., Conclusions: These data indicate the significance of sex- and age-associated differences of plasma total homocysteine levels in Turkish subjects. Plasma total homocysteine levels were increasing with age and men were found to have higher levels than women, as is found in other populations.

Re-expansion pulmonary edema (RPE) is an acute, rare and potentially lethal complication. Its beginning is sudden and dramatic. The mechanism is not yet fully understood. Some authors suggest that it may occur after rapid re-inflation of a collapsed lung. It was reported by other authors that it may relate to surfactant depletion or may result from hypoxic capillary damage, leading to increased capillary permeability. In RPE, unilateral lung injury is initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils. These toxic oxygen products are the results of re-oxygenation of a collapsed lung. Treatment of re-expansion pulmonary edema is basically preventive.