Üstündağ, Hilal; Doğanay, Songül; Kalındemirtaş, Ferdane Danışman; Demir, Özlem; Huyut, Mehmet Tahir; Kurt, Nezahat; Özgeriş, Fatma Betül; Akbaba, Özge

Aim: To investigate the combined therapeutic potential of melatonin and ascorbic acid in mitigating sepsis-induced heart and kidney injury in male rats and assess the combination therapy's effects on inflammation, cellular damage, oxidative stress, and vascular function-related markers. Materials and methods: Cecal ligation and puncture (CLP) induced sepsis in male rats, which were divided into five groups: Sham, CLP, MEL (melatonin), ASA (ascorbic acid), and MEL+ASA (melatonin and ascorbic acid). Rats were treated, and heart and kidney tissues were collected for biochemical and histopathological analyses. Inflammatory markers (presepsin, procalcitonin, NF-κB, IL-1β, IL-6, TNF-α), cellular damage marker (8-OHDG), oxidative status, nitric oxide (NO), vascular endothelial growth factor (VEGF), and sirtuin 1 (SIRT1) levels were assessed. Key findings: Melatonin and ascorbic acid treatment reduced inflammatory and cellular damage markers compared to the CLP group. Combined treatment improved NO, VEGF levels, and increased SIRT1 expression, suggesting a synergistic effect in mitigating sepsis-induced inflammation, cellular damage, and oxidative stress. Histopathological analyses supported these findings, revealing reduced heart and kidney injury in the MEL+ASA group. Significance: Our study highlights potential benefits of combining melatonin and ascorbic acid as a therapeutic strategy for alleviating sepsis-induced heart and kidney injury. The synergistic effects of these agents may provide stronger protection against inflammation, oxidative stress, and tissue damage, opening new avenues for future research and clinical applications in sepsis management.

Türkan, Fikret; Huyut, Zübeyir; Huyut, Mehmet Tahir; Calimli, Mehmet Harbi

The authors regret that some of the terms and methods applied in the statistical analysis (Section 2.5) section of the original article were misspelled. The detailed and understandable form of the statistical methods applied is given below. These statements will clear the confusion of readers in terms of biostatistics. These textual corrections do not affect the interpretation of the data or the conclusions drawn. The authors apologize to the journal and readers for these unintentional errors. Firstly, authors would like to replace Section 2.5 (statistical analysis) with the following text. “The assumption of normality regarding the distribution of enzyme activity data (GR and GSTs) by groups and time was analyzed with the Shapiro-Wilk test. The homogeneity of the population variances of the enzyme levels in the groups was examined by Levene test. Since the parametric test assumptions were met, the mean and standard deviation were used for the descriptive statistical values of the distribution of the parameters used in this study according to groups and time. Two-way mixed ANOVA model was used for the differences in the activity data of enzymes (GR and GSTs) according to groups and time. While the one-way ANOVA analysis was used to compare the enzyme levels measured at similar hours between the groups, the repeated ANOVA analysis was used for the variation of the difference between repeated measurement levels of enzymes in any group over time (1st hour, 3rd hour, 5th hour and 7th hour). The Bonferroni post-hoc test was then used for multiple comparisons between groups. Post-hoc test results are shown with letters in the tables and with symbols in the graphics. IBM SPSS Statistics for Windows 25.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analysis and p < 0.05 was considered statistically significant.” Secondly, authors want to use the word “statistically significant” instead of “meaningful values” in the description of Figs. 2, 3, 4, 5, 6, 7.

Kalın, Şeyda Nur; Altay, Ahmet; Budak, Harun

Aims: It was aimed to investigate the thioredoxin reductase 1 (TrxR1)-targeted anticancer effect of vulpinic (VA) and lecanoric (LA) acids, which are lichen secondary metabolites, on breast cancer MCF-7 and MDA-MB-453 cell lines, and to compare the effectiveness of this potential effect against commercial chemotherapeutic drugs carboplatin and docetaxel. Main methods: The anticancer effects of both lichen metabolites were evaluated by XTT, flow cytometry analysis, cell scratch, and transwell migration assays. Apoptotic results were also confirmed by qPCR and western blot. Changes in TrxR1 were investigated in gene and protein expressions and enzyme activity levels. Key findings: VA suppressed the proliferation of MCF-7 and MDA-MB-453 cells in a dose- and time-dependent manner, and the IC50 values were calculated as 22.92 μg/ml and 95.65 μg/ml, respectively. As for LA, it did not have a considerable antiproliferative effect on both cell lines. VA had stronger cytotoxicity than both chemotherapeutic drug in MCF-7 cells and showed antiproliferative activity closer to carboplatin in MDA-MB-453 cells. qPCR, western blot, and flow cytometry analysis results revealed that VA did not induce apoptosis in both cell lines. In contrast, VA caused cell cycle arrest, significantly. Migration assay results showed that VA suppressed migration in both cells. VA induced the gene expression of TrxR1 while inhibiting its protein expression and enzymatic activity in both cell lines. Significance: The findings reveal that vulpinic acid may be a novel inhibitor candidate on TrxR1 and could be considered a potential chemotherapeutic agent for breast cancer treatment, especially in MCF-7 cells.

Kalayci, Mehmet; Kocdor, Mehmet Ali; Kuloglu, Tuncay; Sahin, İbrahim; Sarac, Mehmet; Aksoy, Aziz; Yardim, Meltem; Dalkilic, Semih; Gursu, Onur; Aydin, Suna

Aims The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. Materials and methods The animals were divided into 13 groups, with 4 animals in each. Gastric ulcers was induced in the animals of 12 groups with one untreated group being left as the control (Group I - control; given normal saline (NS)). The other groups were: Group II (ulcer + NS); Group III (5 mg/kg sildenafil citrate, low dose); Group IV (10 mg/kg sildenafil citrate, high dose); Group V (0.6 mg/kg heparin, low dose); Group VI (6 mg/kg heparin, high dose); Group VII (20 nmol/kg des-acyl ghrelin); Group VIII (40 nmol/kg des-acyl ghrelin); Group IX (4 nmol/kg acyl ghrelin); Group X (8 nmol/kg acly ghrelin); Group XI (20 pmol/kg Nesfatin-1); Group XII (15 nmol/kg Obestatin) and Group XIII (5 nmol/kg Neuropeptide Y). Gastric neuropeptide expression was measured using an immunohistochemical method, and the amount in circulation was detected using ELISA. To compare with no treatment, the controls and other treatment groups, we recorded loss of the surface epithelium of the stomach, erosion, bleeding and inflammatory cell infiltration in the upper halves of the gastric glands. Key findings The muscularis and the layers beneath it were, however, apparently normal. The gastric mucosa healed with little or no inflammation when sildenafil citrate, low dose heparin, ghrelin, NUCB2/Nesfatin-1, obestatin, Neuropeptide Y were administered. Significance Overall the data indicate that low dose heparin, and especially sildenafil citrate and neuropeptides, can be used clinically as an alternative approach in the treatment of the gastric ulcer.

Ucuncu, Yilmaz; Celik, Nuray; Ozturk, Cengiz; Turkoglu, Murat; Cetin, Nihal; Kockara, Nizamettin; Sener, Ebru; Dundar, Cihat; Arslan, Aynur; Dogan, Hasan

Abstract Aims This study investigates the effect of a new combination of glucosamine hydrochloride, chondroitin sulfate, methylsulfonylmethane, Harpagophytum procumbens root extract (standardized to 3% harpagoside) and bromelain extract (GCMHB) on formalin-induced damage to cartilage tissue in the rat knee joint and evaluates this combination in comparison with another combination of glucosamine hydrochloride, chondroitin sulfate and methylsulfonylmethane (GKM). Materials and methods Animals in the control group were injected with formalin into the knee joint (FCG). Animals in the GCMHB-500 group were given 500 mg/kg GCMHB + formalin, and those in the GKM-500 group were given 500 mg/kg GKM + formalin. Finally, a healthy group (HG) was also used. GCMHB and GKM were administered to rats orally once a day for 30 days. At the end of this period, the rats were sacrificed and the levels of MDA, NO, 8-OH/Gua, and tGSH in the knee joint tissue were measured. Analysis of IL-1β and TNF-α gene expression was done and the tissue was evaluated histopathologically. Key findings MDA, NO and 8-OH/Gua levels and IL-1β and TNF-α gene expression were significantly lower in the GCMHB-500 group compared to the FCG group, whereas tGSH was significantly higher in the GCMHB-500 group than in the FCG group. No significant difference was found for the IL-1β, TNF-α and oxidant/antioxidant parameters between the GKM and FCG groups. The histopathological analysis showed that GCMHB could prevent damage to the cartilage joint, whereas GKM could not. Significance GCMHB may be used clinically by comparing with GKM in the treatment of osteoarthritis.