Molecular insights into the antioxidative and anti-inflammatory effects of P-coumaric acid against bisphenol A-induced testicular injury: In vivo and in silico studies.

This study investigated the protective effects of p-coumaric acid (PCA) against bisphenol A (BPA)-induced testicular toxicity in male rats. The rats were divided into control, BPA, BPA+PCA50, BPA+PCA100, and PCA100 groups. Following a 14-day treatment period, various analyses were conducted on epididymal sperm quality and testicular tissues. PCA exhibited dose-dependent cytoprotective, antioxidant, and anti-inflammatory effects, ameliorating the decline in sperm quality induced by BPA. The treatment elevated antioxidant enzyme activities (SOD, GPx, CAT) and restored redox homeostasis by increasing cellular glutathione (GSH) and reducing malondialdehyde (MDA) levels. PCA also mitigated BPA-induced proinflammatory responses while reinstating anti-inflammatory IL-10 levels. Apoptotic parameters (p53 and p38-MAPK) were normalized by PCA in BPA-treated testicular tissue. Immunohistochemical and immunofluorescent analyses confirmed the cytoprotective and anti-inflammatory effects of PCA, evidenced by the upregulation of HO-1, Bcl-2, and Nrf-2 and the downregulation of the proapoptotic gene Bax in BPA-induced testicular intoxication. PCA corrected the disturbance in male reproductive hormone levels and reinstated testosterone biosynthetic capacity after BPA-induced testicular insult. In silico analyses suggested PCA's potential modulation of the oxidative stress KEAP1/NRF2/ARE pathway, affirming BPA's inhibitory impact on P450scc. This study elucidates BPA's molecular disruption of testosterone biosynthesis and highlights PCA's therapeutic potential in mitigating BPA's adverse effects on testicular function, showcasing its cytoprotective, anti-inflammatory, and hormone-regulating properties. The integrated in vivo and in silico approach offers a comprehensive understanding of complex mechanisms, paving the way for future research in reproductive health and toxicology, and underscores the importance of employing BPA-free plastic wares in semen handling.

The effect of case-based mobile virtual patient application on students' academic achievement in clinical reasoning skills.

This mixed-method study aims to determine the effect of the use of mobile virtual patient application with narrated case-based virtual patients as an assistive technology on students' clinical reasoning skills. It makes a notable contribution by exploring the impact of mobile virtual patient applications on healthcare students' clinical skills and their preparation for real-world patient care. In addition, the accuracy of the analysis results regarding the effect on student achievement was analyzed with a second dataset tool, and thus, aiming to increase reliability by verifying the same research question with a different quantitative analysis technique. In the qualitative part of the study, students' views on the implementation were collected through an open-ended questionnaire and the data were subjected to content analysis. An achievement test was also developed to determine the development of students' clinical reasoning skills, which revealed that each of the learning environments had different outcomes regarding students' achievement and that supporting the traditional environment with the mobile virtual patient application yielded better results for increasing students' achievement. Students' opinions about the mobile virtual patient application and the process also support the increase in academic achievement aimed at measuring clinical reasoning skills. The content analysis showed that the students, who generally reported multiple positive factors related to the application, thought that the stories and cases presented created a perception of reality, and they especially highlighted the contribution of the application to learning the story organization. Based on all these results, it can be said that the application supports clinical reasoning, provides practical experience, improves academic achievement, and contributes positively to motivation.

Effect of fentanyl and remifentanil on neuron damage and oxidative stress during induction neurotoxicity.

Opioids can be used for medical and non-medical purposes. Chronic pain such as cancer, as well as the frequent use of such drugs in places such as operating rooms and intensive care units, and in non-medical areas like drug abuse the effects and side effects of these drugs need to be examined in more detail. For this purpose, the effects of fentanyl and remifentanil drugs on neuroinflammation, oxidative stress and cholinesterase metabolism were investigated. Neuron cells (CRL-10742) were used for the evaluation of the toxicity of fentanyl and remifentanil. MTT, PON1 activity and total thiol levels for its effect on oxidative stress, AChE and BChE activities for its effect on the cholinergic system, and TNF, IL-8 and IL-10 gene levels for its neuroinflammation effect were determined. The highest neurotoxic dose of fentanyl and remifentanil was determined as 10 µg/mL. It was observed that the rate of neuron cells in this dose has decreased by up to 61.80% and 56.89%, respectively. The IL-8 gene expression level in both opioids was down-regulated while IL 10 gene level was up-regulated in a dose-dependent manner compared to the control. In our results, the TNF gene expression level differs between the two opioids. In the fentanyl group, it was seen to be up-regulated in a dose-dependent manner compared to the control. Fentanyl and remifentanil showed an inhibitory effect against PON1, while remifentanil showed an increase in total thiol levels. PON1, BChE and total thiol activities showed similarity with MTT.

Analyzing the impact of synthetic and natural steroids: a study of cytochrome P450 metabolism, morphological alterations through metabolomics, and histopathological Examination.

This study focuses on the comparative metabolic profiling and effects of two steroid types: natural and synthetic, specifically 17α-methyl testosterone (17α-MT) at varying concentrations (1.5, 2, and 3 mg/kg) in rainbow trout (Oncorhynchus mykiss). Over a 75-day feeding trial, growth metrics, such as feed efficiency, daily specific growth, live weight gain, total weight gain, and survival rate were systematically monitored every 15 days. At the end of the feeding trial, histopathology, immunohistochemistry, and metabolome analyses were performed in the high-concentration groups (3 mg/kg natural and 3 mg/kg synthetic), in which the lowest survival rate was determined. Key findings reveal that the type of hormone significantly influences growth parameters. While some natural steroids enhanced certain growth aspects, synthetic variants often yielded better results. The metabolomic analysis highlighted significant shifts in the metabolism of tryptophan, purine, folate, primary bile acids, phosphonates, phosphinates, and xenobiotics via cytochrome P450 pathways. Histopathologically, the natural hormone groups showed similar testicular, hepatic, muscular, gill, cerebral, renal, and intestinal tissue structures to the control, with minor DNA damage and apoptosis observed through immunohistochemistry. Conversely, the synthetic hormone groups exhibited moderate DNA damage and mild degenerative and necrotic changes in histopathology.

Activity of zinc oxide and zinc borate nanoparticles against resistant bacteria in an experimental lung cancer model.

BACKGROUND: Recent research indicates a prevalence of typical lung infections, such as pneumonia, in lung cancer patients. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii stand out as antibiotic-resistant pathogens. Given this, there is a growing interest in alternative therapeutic avenues. Boron and zinc derivatives exhibit antimicrobial, antiviral, and antifungal properties. OBJECTIVES: This research aimed to establish the effectiveness of ZnO and ZB NPs in combating bacterial infections in lung cancer cell lines. METHODS: Initially, this study determined the minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of zinc oxide nanoparticles (ZnO NPs) and zinc borate (ZB) on chosen benchmark strains. Subsequent steps involved gauging treatment success through a lung cancer-bacteria combined culture and immunohistochemical analysis. RESULTS: The inhibitory impact of ZnO NPs on bacteria was charted as follows: 0.97 µg/mL for K. pneumoniae 700603, 1.95 µg/mL for P. aeruginosa 27853, and 7.81 µg/mL for Acinetobacter baumannii 19,606. In comparison, the antibacterial influence of zinc borate was measured as 7.81 µg/mL for Klebsiella pneumoniae 700603 and 500 µg/mL for both P. aeruginosa 27853 and A.baumannii 19606. After 24 h, the cytotoxicity of ZnO NPs and ZB was analyzed using the MTT technique. The lowest cell viability was marked in the 500 µg/mL ZB NPs group, with a viability rate of 48.83% (P < 0.001). However, marked deviations appeared at ZB concentrations of 61.5 µg/mL (P < 0.05) and ZnO NPs at 125 µg/mL. CONCLUSION: A synergistic microbial inhibitory effect was observed when ZnO NP and ZB were combined against the bacteria under investigation.

Mitigation of Acute Hepatotoxicity Induced by Cadmium Through Morin: Modulation of Oxidative and Pro-apoptotic Endoplasmic Reticulum Stress and Inflammatory Responses in Rats.

Cadmium (Cd) is a toxic heavy metal with significant environmental health hazards. It enters the body through various routes with tissue accumulation. The relatively longer half-life with slow body clearance significantly results in hepatotoxicity during its liver detoxification. Therefore, researchers are exploring the potential use of herbal-derived phytocomponents to mitigate their toxicity. Here, we investigated, for the first time, the possible ameliorative effect of the phytochemical Morin (3,5,7,29,49-pentahydroxyflavone) against acute Cd-induced hepatotoxicity while resolving its underlying cellular mechanisms in a rat animal model. The study involved 50 adult male Sprague-Dawley rats weighing 200-250 g. The animals were divided into five equal groups: control, Cd, Morin100 + Cd, Morin200 + Cd, and Morin200. The 2nd, 3rd, and 4th groups were intraperitoneally treated with Cd (6.5 mg/kg), while the 3rd, 4th, and 5th groups were orally treated with Morin (100 and 200 mg/kg) for 5 consecutive days. On the 6th day, hepatic function (serum ALT, AST, ALP, LDH enzyme activities, and total bilirubin level) testing, transcriptome analysis, and immunohistochemistry were performed to elucidate the ameliorative effect of Morin on hepatotoxicity. In addition to restoring liver function and tissue injury, Morin alleviated Cd-induced hepatic oxidative/endoplasmic reticulum stress in a dose-dependent manner, as revealed by upregulating the expression of antioxidants (SOD, GSH, Gpx, CAT, and Nrf2) and decreasing the expression of ER stress markers. The expression of the proinflammatory mediators (TNF-α, IL-1-ß, and IL-6) was also downregulated while improving the anti-inflammatory (IL-10 and IL-4) expression levels. Morin further slowed the apoptotic cascades by deregulating the expression of pro-apoptotic Bax and Caspase 12 markers concomitant with an increase in anti-apoptotic Blc2 mRNA expression. Furthermore, Morin restored Cd-induced tissue damage and markedly suppressed the cytoplasmic expression of JNK and p-PERK immunostained proteins. This study demonstrated the dose-dependent antioxidant hepatoprotective effect of Morin against acute hepatic Cd intoxication. This effect is likely linked with the modulation of upstream p-GRP78/PERK/ATF6 pro-apoptotic oxidative/ER stress and the downstream JNK/BAX/caspase 12 apoptotic signaling pathways.

Boron Compound-Based Treatments Against Multidrug-Resistant Bacterial Infections in Lung Cancer In Vitro Model.

Multidrug-resistant bacteria is one of the most important public health problems. Increasing rates of antibacterial resistance also affect the outcomes of medical approaches. Cancer treatment because of immune system deficiency (chemotherapy or steroids usage) commonly can cause infection. Lung cancer is the dominant cause of cancer-related deaths, and infection is the most common cause of death among those patients. In this study, it was aimed to determine the antimicrobial, antibiofilm, and anticancer activity of boron compounds. A549 lung cancer cell line was infected with Acinetobacter baumannii (ATCC 19606), Klebsiella pneumoniae (ATCC 700603), and Pseudomonas aeruginosa (ATCC 27853). In order to determine the fractional inhibitory concentration (FIC) index, antibiotics and boron compound concentrations prepared according to the minimum inhibitory concentration (MIC) values were determined by the checkerboard method. In our study results, the antibiofilm activity was an average of 46% in A. baumannii+boron compounds, 45% in P. aeruginosa+boron compounds, and 43% in K. pneumoniae. Cell culture analysis results show a decrease in viability and antioxidant capacity and an increase in total oxidant status after adding boron compounds to the culture. Immunofluorescence results show a correlation with MTT, and boron compounds increased 8-OHdG expression in comparison to antibiotic administration. In conclusion, boron compounds have promising effects on bacteria, especially in resistant bacteria spp.

Selenium reduces acrylamide-induced testicular toxicity in rats by regulating HSD17B1, StAR, and CYP17A1 expression, oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.

This study investigated the effects of Selenium (Se) on testis toxicity induced by Acrylamide (ACR) in rats. In our study, 50 male adult rats were used, and the rats were divided into five groups; control, ACR, Se0.5 + ACR, Se1 + ACR, and Se1. Se and ACR treatments were applied for 10 days. On the 11th day of the experimental study, intracardiac blood samples from the rats were taken under anesthesia and euthanized. Sperm motility and morphology were evaluated. Dihydrotestosterone, FSH, and LH levels in sera were analyzed with commercial ELISA kits. MDA, GSH, TNF-α, IL-6, and IL-1ß levels and SOD, GPx, and CAT, activities were measured to detect the level of oxidative stress and inflammation in rat testis tissues. Expression analysis of HSD17B1, StAR, CYP17A1, MAPk14, and P-53 as target mRNA levels were performed with Real Time-PCR System technology for each cDNA sample synthesized from rat testis RNA. Testicular tissues were evaluated by histopathological, immunohistochemical, and immunofluorescent examinations. Serum dihydrotestosterone and FSH levels decreased significantly in the ACR group compared to the control group, while LH levels increased and a high dose of Se prevented these changes caused by ACR. A high dose of Se prevented these changes caused by ACR. ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.

Effect of Upfront Docetaxel in De Novo Metastatic Castration-Sensitive Prostate Cancer Patients with Gleason Grade Group 5.

OBJECTIVE: To investigate whether adding docetaxel chemotherapy to androgen deprivation therapy is effective regarding progression-free and overall survival in patients with de novo metastatic castration-sensitive prostate cancer patients with Gleason Grade Group 5 (Gleason scores 9 and 10). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology at Manisa Celal Bayar University, Izmir Ege University, Bitlis Tatvan Public Hospital, Izmir Bozyaka Education and Research Hospital, and Izmir Kent Hospital, from March 2015 to May 2020. METHODOLOGY: Patients with de novo metastatic castration-sensitive and histopathologically confirmed GGG 5 prostate cancer were evaluated retrospectively. The patients were divided into two groups. The first group included patients who were given androgen deprivation therapy alone (ADT-only group), and the second group consisted of patients who were given ADT plus docetaxel (chemohormonal group). The two groups were compared in terms of overall survival and progression-free survival till cut-off limit. RESULTS: A total of 194 patients with metastatic castration-sensitive and GGG 5 prostate cancer were analysed retrospectively. The chemohormonal group comprised of 72 patients, and the ADT-only group included 122 patients. Median progression-free survival was 15.7 months in the chemohormonal group and 14.8 months in the ADT-only group (p = 0.97). The median overall survival was 37.5 months in the chemohormonal group and 37.8 months in the ADT-only group (p = 0.93). CONCLUSION: The addition of docetaxel chemotherapy in patients with metastatic castration-sensitive and GGG 5 prostate cancer did not result in a statistically significant difference in terms of overall survival and progression-free survival. Docetaxel may be ineffective in this group of patients. KEY WORDS: Prostate cancer, Castration-sensitive, Gleason grade group 5, Docetaxel, Androgen deprivation therapy (ADT), Overall survival.

Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo.

Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.

The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats.

Objectives: Cadmium (CD) causes widespread and severe toxic effects on various tissues. Studies have shown that apoptosis, inflammation, and endoplasmic reticulum stress play a role in organ damage caused by CD. Phenolic compounds with strong antioxidant effects are found in various fruits and vegetables. One of these compounds is Gallic acid (GA), which is found both free and hydrolyzable in grapes, pomegranate, tea, hops, and oak bark. Result of various studies show that GA has active antioxidant, anti-inflammatory, and anti-apoptotic properties. In our study, we investigated the mechanism of the protective effect of GA on CD-induced hepatotoxicity in rats. Materials and Methods: In this study, 50 adult male Sprague Dawley rats weighing approximately 200-250 g were used and the rats were divided into 5 groups: Control, CD, GA50+CD, GA100+CD, and GA100. The rats were treated with GA (50 and 100 mg/kg body weight), and Cd (6.5 mg/kg) was administrated to the rats for 5 consecutive days. The liver enzymes, TB levels in serum samples, oxidative stress, inflammation, ER stresses, apoptosis marker, histopathology, 8-OHDG, and caspase-3 positivity were analyzed. Results: CD administration significantly increased liver enzyme levels (AST, ALT, ALP, and LDH), MDA, IL-1-ß, IFN-γ, TNF-α, IL-10, IL-6, GRP78, CHOP, ATF6, p -IRE1, sXBP, Bax mRNA expression, Caspase 3, and 8-OHdG expression (P<0.05). These values were found to be significantly lower in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). CD administration significantly decreased the expression levels of TB, IL-4, SOD, GSH, CAT, GPX, and Bcl-2 mRNA (P<0.05). These values were found to be significantly higher in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). Conclusion: The results of the present study indicated that GA prevented Cd-induced hepatic oxidative stress, inflammation, ER stress, apoptosis, and tissue damage in rats.

ADAMTS-13 and HMGB1-induced oxidative stress in Taenia multiceps-infected animals.

This study investigated the cytotoxic effects of oxidative stress (OS), high mobility group box 1 (HMGB1), ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs), and neuropathology associated with coenurus cerebralis (Taenia multiceps). ADAMTS-13, HMGB1, glutathione reductase (GR), copper/zinc superoxide dismutase (Cu/Zn SOD), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression levels were studied. The study found that ADAMTS-13 (P < 0.005), HMGB1 (P < 0.005), GR (P < 0.005), Cu/Zn SOD (P < 0.005), and 8-OHdG (P < 0.005) levels were significantly higher in T. multiceps (c. cerebralis)-infected animals compared to healthy control animals. This study's most important finding was that HMGB1 up-regulation in neurons, endothelial cells, and glial cells can directly cause brain parenchymal destruction and that HMGB1-mediated oxidative stress plays a crucial role in the neuropathogenesis of coenurosis. The results also showed that increased levels of ADAMTS-13 may play a pivotal role in regulating and protecting the blood-brain barrier integrity and neuroprotection. These findings also suggest that ADAMTS-13 and HMGB1 compete in the prevention or formation of microthrombi, which was regarded as a remarkable finding. ADAMTS-13 and HMGB1 are valuable biomarkers for disease risk assessment, estimating host neuropathy following T. multiceps (c. cerebralis) exposure, and providing a new therapeutic target. This is the first study to show that HMGB1 and ADAMTS-13 are expressed in reactive cells and are associated with neuroimmunopathology in coenurosis.

Immunohistochemical investigation of parainfluenza 3 virus in sheep pneumonia.

The aim of this study was to determine the prevalence of parainfluenza 3 (PI3) virus antigen through histopathological and immunohistochemical (IHC) methods in sheep lung samples collected from Erzurum province, Türkiye. Between August and November 2017, 1462 sheep were dissected in the slaughterhouse and their lungs were examined macroscopically. In total, 100 of the lung samples with pneumonia were selected. Routine histopathological and IHC analyses of the collected lung tissues with pneumonia were performed. Pneumonia observed through macroscopical and histopathological examinations of the lung samples was classified as purulent-catarrhal bronchopneumonia (14.00%), fibrinous bronchopneumonia (23.00%), interstitial pneumonia (69.00%), granulomatous pneumonia (7.00%), verminous pneumonia (19.00%) and pulmonary adenomatosis (6.00%). Two or three types of pneumonia were observed in many of the same cases. The PI3 virus antigen positivity rate in the IHC analysis of sheep lung samples was 19.00%. In the IHC tracing, positivities were found mostly in the alveolar macrophages and cytoplasm of bronchial, bronchiolar and alveolar epithelial cells. As a result, the prevalence of PI3 virus in sheep in Erzurum province, Türkiye, was determined to be 19.00% using KLN BVB IHC method.

Mitigation potential of zingerone and rutin on toxicity mechanisms of nickel to zebrafish based on morphological, DNA damage and apoptosis outcome analysis.

Although nickel (Ni) is an important cofactor for various enzymes in biological systems, it can cause serious problems when insufficient or excessive in an organism. Therefore, it is very important to investigate Ni in biological systems, especially in cells with its related pathogenic mechanism. This study was carried out to demonstrate the effects of zingerone (ZO) and rutin (RN) administration against nickel chloride (NiCl2) toxicity on neurobehavioral performance and brain oxidative status in zebrafish (Danio rerio) embryos/larvae on histological perspective. The experimental design of the study, which included twenty groups of fish, each containing 10 embryos, was prepared as semi-static and the trial continued for 96 hpf. In the obtained findings, it was determined that ZO and RN had a mitigating effect in this toxicity table where Ni caused oxidative stress in zebrafish larvae, induced DNA damage and apoptosis. A similar picture is valid for malformation processes as well as survival and hatching rates. These results showed that nickel is toxic to developing embryos via acting different mechanisms. In conclusion, we observed that ZO and RN have a greater effect on physiology, DNA damage and apoptosis than gross morphology, with a significant ameliorative effect.

Second-Line Chemotherapy in Gastric Cancer: a Retrospective Study.

Second-line chemotherapy is recommended for patients who have disease progression after first-line chemotherapy and have a good performance status. The aim of our study is thus to determine which chemotherapy regimen is more appropriate for second-line gastric cancer treatment. Patients were included if they met the following inclusion criteria: metastatic gastric adenocarcinoma pathology; no previous treatment for local gastric cancer (surgery, chemotherapy, or radiotherapy); received first-line chemotherapy for metastatic gastric cancer and had the disease progress afterward; had adequate organ functions for second-line chemotherapy; had an Eastern Cooperative Oncology Group (ECOG) score 0-2; and were HER-2 negative. The patients were examined in three groups according to the second-line chemotherapy regimen they received. These three groups were compared in terms of overall and progression-free survival. The three groups were statistically similar in overall survival, which was the primary endpoint of the study; the median overall survival was 5 months in the FOLFIRI group (n = 79), 6.5 months in the platinum-based group (n = 55), and 5.6 months in the taxane-based group (n = 40) (p = 0.554). There was no statistical difference between the groups' progression-free survival either; the median progression-free survival time was 3.43 months in the FOLFIRI group, 4 months in the platinum-based group, and 2.77 months in the taxane-based group (p = 0.546). There was no statistically significant difference between the three irinotecan-based, platinum-based, and taxane-based treatments. According to our study's results, the chemotherapy given in second-line treatment should be decided on an individual basis according to toxicity and cost.

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries.

According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1ß levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.

Global warming and nanoplastic toxicity; small temperature increases can make gill and liver toxicity more dramatic, which affects fillet quality caused by polystyrene nanoplastics in the adult zebrafish model.

Increasing nanoplastics (NPs) pollution may lead to unknown environmental risks when considered together with climate change, which has the potential to become an increasingly important environmental issue in the coming decades. In this context, the present study aimed to evaluate the stressor modelling of polystyrene nanoplastic (PS-NPs) combined with temperature increase in zebrafish. For this purpose, changes in gill, liver and muscle tissues of zebrafish exposed to PS-NPs (25 ppm) and/or different temperatures (28, 29 and 30 °C) for 96 h under static conditions were evaluated. The results obtained emphasize that exposure to PS-NPs stressors under controlled conditions with temperature increase induces DNA damage through stress-induced responses accompanied by degeneration, necrosis and hyperaemia in zebrafish liver and adhesion of lamellae, desquamation and inflammation in lamellar epithelium in gills. Metabolomic analyses also supported changes indicating protein and lipid oxidation, especially PS-NPs-mediated. These findings will contribute to the literature as key data on the effects of PS-NPs presence on protein/lipid oxidation and fillet quality in muscle tissues.

Investigation of left ventricular changes according to valve type in patients with surgical replacement due to isolated aortic stenosis.

OBJECTIVE: The aim of this study was to investigate postoperative left ventricular changes [left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), patient-prosthesis mismatch (PPM), pulmonary artery pressure (PAP), gradients, and ejection fraction (EF)] according to the valve type used in patients undergoing aortic valve replacement (AVR) due to isolated aortic stenosis. METHODS: A total of 199 patients with isolated AVR due to aortic stenosis between 2010 and 2020 was retrospectively investigated. Four groups were identified according to the valve type used (mechanical, bovine pericardium, porcine and sutureless). Pre-operative and first year postoperative transthoracic echocardiography findings for the patients were compared. RESULTS: Mean age was 64.4 ± 13.0 years, while the gender distribution was 41.7% women and 58.3% men. Of the valves used in patients, 39.2% were mechanical, 18.1% were porcine, 8.5% were bovine pericardial and 34.2% were sutureless valves. Analysis independent of the valve groups observed LVEDD, LVESD, maximum gradient, mean gradient, PAP, LVM and LVMI values reduced significantly postoperatively (p < 0.001). EF was observed to increase by 2.1% (p = 0.008). Comparisons of the four valve groups revealed that LVEDD, LVESD, maximum gradient, mean gradient, LVM and LVMI significantly decreased in all groups. EF significantly increased only in the sutureless valve group (p = 0.006). Analysis of PPM groups showed that LVESD, maximum gradient, mean gradient, PAP, LVM and LVMI were significantly reduced in all groups. In the normal PPM group, there was an improvement in EF, which was significantly different to the other groups (p = 0.001), while in the severe PPM group, EF appeared to be reduced ( p = 0.19).

The anxiolytic and circadian regulatory effect of agarwood water extract and its effects on the next generation; zebrafish modelling.

Anxiety is one of the most common psychiatric symptoms worldwide. Studies show that there is an increase of >25 % in the prevalence of anxiety with the onset of the COVID-19 pandemic process. Due to the various side effects of drugs used in the treatment of anxiety, interest in natural therapeutic alternatives has increased. Agarwood is a plant used as a natural therapeutic due to its sedative effect as well as many effects such as antioxidant and antibacterial. Although there are many studies with agarwood, comprehensive behavioral studies, including the next generation, are limited. In present study, zebrafish fed with diets containing 10-100 ppm water extract of Agarwood (AWE) for 3 and 8 weeks were exposed to predator stress using Oscar fish in order to test the potential anxiolytic effect of AWE. At the end of the period, zebrafish exposed to predator stress were subjected to anxiety and circadian tests. Histopathological evaluation and immunofluorescent analyzes of BDNF and 5HT4-R proteins were performed in the brains of zebrafish. The effects on the next generation were examined by taking offspring from zebrafish. According to the results, it was observed that AWE had a healing effect on anxiety-like behaviors and on the disrupted circadian rhythm triggered by the predatory stress it applied, especially in the 8 weeks 100 ppm group. Interestingly, it was also found to be effective in offspring of zebrafish fed diets with AWE.

Pseudomonas aeruginosa Keratitis in Rats: Study of the Effect of Topical 5% Hesperidin Practice on Healing.

OBJECTIVE: The aim of this study is to investigate the effect of topical 5% hesperidin application on healing. MATERIALS AND METHODS: After 48 rats were randomized and divided into 7 groups, on the first day, an epithelial defect was created in the center of the cornea with the help of microkeratome under intraperitoneal ketamine+xylazine and topical 5% proparacaine anesthesia for the groups to be infected with keratitis according to the groups mentioned below. An amount of 0.05 mL of the solution containing 108 colony-forming units/ mL Pseudomonas aeruginosa (PA-ATC27853) will be taken and inoculated per rat. At the end of the 3 days incubation period, rats with keratitis will be added to the groups, and active substances and antibiotics will be given topically together with other groups for 10 days. At the end of the study, the ocular tissues of the rats will be removed and examined histopathologically. RESULTS: A clinically significant reduction in inflammation was detected in the groups using hesperidin. No transforming growth factor-ß1 staining was detected in the group in which keratitis+hesperidin was treated topically. In the group in which hesperidin toxicity was examined, mild inflammation and thickening of the corneal stroma layer were observed, and it was evaluated as a negative transforming growth factor-ß1 expression in the lacrimal gland tissue. Corneal epithelial damage was minimal in the keratitis group, and the toxicity group was treated with only hesperidin when compared to the other groups. CONCLUSION: Topical hesperidin drops may be an important therapeutic factor in tissue healing and in the fight against inflammation in the treatment of keratitis.