Vitamins Can Increase Antibiotic Effects Against Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii in an In Vitro Infection Model.

METHODS:  The study delves into the antimicrobial properties of vitamins P, K, and E against A. baumannii and P. aeruginosa, employing the minimum inhibitory concentration method and scrutinizing biofilm formation within the A549 cell culture. RESULTS:  The combined application of vitamins and antibiotics exhibited a statistically significant effect on both the minimal inhibitory concentration values and biofilm formation (P < .05). Within the realm of fat-soluble vitamins, vitamins K and E, when integrated with antibiotics, revealed varying degrees of influence, with vitamin K displaying the most substantial fractional inhibitory concentration value. Vitamin E, on the other hand, demonstrated a comparatively weaker fractional inhibitory concentration than the other constituents. Nevertheless, it exhibited robust optical density and a pronounced capacity to inhibit biofilm formation. Moreover, among the vitamin groups, it is evident that vitamin E surpasses the efficacy of others (antibacterials affecting K < P

Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats.

Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.

Comparison of Beating-Heart Technique Versus Aortic Cross-Clamping in Tricuspid Valve Surgery.

OBJECTIVE: Tricuspid valve surgery can be performed on a beating heart or on an arrested heart. We aimed to compare the outcomes of tricuspid valve surgery using these two different approaches. METHODS: Between January 2015 and February 2020, 204 patients who underwent tricuspid valve surgery along with concomitant cardiac surgical procedures were included in the study. Techniques of cross-clamping and beating-heart tricuspid surgery were applied to 103 and 101 patients, respectively. Concomitant valvular and/or coronary interventions were performed under cross clamping in both groups. Results from the preoperative period, immediate postoperative period, and six-month postoperative interval were compared between the groups. RESULTS: There were no differences in demographic characteristics or preoperative grades of tricuspid valve regurgitation between the groups. Duration of mechanical ventilation, and stays in the intensive care unit and hospital were significantly shorter in patients operated on using the beating-heart technique. Additionally, re-exploration surgery and mortality rates were significantly lower in the beating-heart group. Postoperative six-month echocardiography findings related to tricuspid valve regurgitation, maximum and minimum gradients of the tricuspid valve, and pulmonary arterial pressure were also lower in the beating-heart group. CONCLUSION: Beating-heart tricuspid valve surgery may be preferable to the cross-clamping technique to avoid clamp-induced ischemia, which can lead to worsened postoperative outcomes.

Effect of boramidic acid modified carbon nanotubes on neurological, morphological and physiological responses of zebrafish (Danio rerio) embryos and larvae.

This study aimed to determine the potential toxicological effects of carbon nanotubes (CNTs), their modifications with ethylenediamine (ED) and boric acid (BA) on aquatic organisms. Specifically, the research focused on the morphological, physiological, and histopathological-immuno-histochemical responses in zebrafish (Danio rerio) embryos and larvae, via applying different concentrations of CNTs, CNT-ED, and CNT-ED-BA (Control, 5, 10, and 20 mg/L). The results indicated that 20 mg/L CNT nanoparticles were toxic to zebrafish larvae, with mortality rates increasing with CNT and CNT-ED concentrations, reaching 36.7 % at the highest CNT concentration. The highest dose caused considerable degeneration, necrosis, DNA damage, and apoptosis, as evidenced by histopathological and immunohistochemical tests. In contrast, despite their high concentration, CNT-ED-BA nanoparticles exhibited low toxicity. Behavioral studies revealed that CNT and CNT-ED nanoparticles had a more significant impact on sensory-motor functions compared to CNT-ED-BA nanoparticles. These findings suggest that modifying the nanosurface with boric acid, resulting in boramidic acid, can reduce the toxicity induced by CNT and CNT-ED.

Antidiabetic Effect of Fig Seed Oil in Rats with Diabetes Induced by Streptozotocin.

The anti-diabetic effect of Ficus carica (Fig) seed oil was investigated. 4 groups with 6 rats in each group were used in the experiment as control, diabetes (45 mg/kg streptozotocin), fig seed oil (FSO) (6 mL/ kg/day/rat by gavage) and diabetes+FSO groups. Glucose, urea, creatinine, ALT, AST, GSH, AOPP and MDA analyses were done. Pancreatic tissues were examined histopathologically. When fig seed oil was given to the diabetic group, the blood glucose level decreased. In the diabetes+FSO group, serum urea, creatinine, AOPP, MDA levels and ALT and AST activities decreased statistically significantly compared to the diabetes group, while GSH levels increased significantly, histopathological, immunohistochemical, and immunofluorescent improvements were observed. It has been shown for the first time that FSO has positive effects on blood glucose level and pancreatic health. It can be said that the protective effect of fig seed oil on tissues may be due to its antioxidant activity.

Surgical and Histopathological Results in Carotid Body Tumors.

OBJECTIVE: The possible relationships between the histopathological findings of carotid body tumors and age, gender, tumor diameter, and Shamblin classification were investigated. In addition, preoperative embolization status, development of neurological complications, need for vascular reconstruction, hemoglobin change, and discharge time were examined and the effects of these variables on each other were analyzed. METHODS: Between 2008 and 2022, 46 cases who underwent carotid body tumor excision were examined retrospectively. The cases were followed for an average of 81 months postoperatively. Histopathological materials were reexamined and the effect of categorical variables was analyzed. RESULTS: Mean tumor diameter was 3.55 ± 1.26 cm, mean discharge time was 3.91 ± 2.37 days, and mean hemoglobin change was 1.86 ± 1.25. Neurological complications developed in 13% of cases. The amount of hemoglobin change was significantly (p = 0.003) higher in those who developed neurological complications, whereas the tumor diameter and discharge time were found to be insignificantly higher. Surgical complications requiring vascular repair occurred in 10.8% of cases. Tumor diameter (p = 0.017) and hemoglobin change (p = 0.046) were significantly higher in these patients. There were significant correlations between higher Shamblin classification and tumor diameter, discharge time, postoperative hemoglobin value, and number of surgical and neurological complications. No significant difference was found between Ki-67, capsular invasion, mitosis, pleomorphism, prominent nucleoli, mean island diameter, and tendency of islands to merge with categorical variables. CONCLUSION: As the tumor diameter increases, the operation becomes more difficult and the postoperative complication rate increases. We think that subadventitial and capsular removal of the tumor is effective in preventing recurrence. To reach a histopathological conclusion, a larger series of studies including tumors with high Ki-67 and mitosis rates, large size, and one or more of the criteria for necrosis are needed.

Morinda citrifolia protective effects on paclitaxel-induced testis parenchyma toxicity: An experimental study.

The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-ß (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.

Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases.

BACKGROUND: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate. METHODS: Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations. FINDINGS: Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals. INTERPRETATION: Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients.

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.

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.

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.

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.

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.