Mehmet Gül

This study aimed to investigate the potential protective effects of Omega‐3 (ω−3) against damage to pancreatic tissue in rats with experimentally induced diabetes using streptozotocin. Twenty‐eight male Wistar Albino rats were divided into four groups: Control, Diabetes Mellitus (DM), ω−3, and DM + ω−3, with seven rats in each group. STZ was injected intraperitoneally (i.p.) into the DM group, and blood glucose levels were measured on the fourth day after injection. Rats with blood glucose levels of ≥ 200 mg/dL were diagnosed with DM. The ω−3 group received 500 mg/kg of ω−3. After the 42‐day experiment, pancreatic tissue and blood samples were collected from the rats. The DM group showed increased levels of malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), tumor necrosis factor α (TNF‐α), interleukin‐6 (IL‐6), glucose, LDL, triglycerides, caspase‐3 immunoreactivity, and histopathological abnormalities in pancreatic tissue. At the same time, there were decreases in superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS), HDL, and insulin levels. Blood, biochemical, histopathological, and immunohistochemical parameters negatively impacted by ω−3 administration have improved. This study demonstrated that in STZ‐induced DM rats, DM increased oxidative capacity and led to oxidative stress, inflammation, apoptosis, and tissue damage. It was found that ω−3 has strong antioxidant, pro‐apoptotic, anti‐inflammatory, and protective effects.

Background/Objectives: The aim of this study was to compare the biochemical, histological, immunohistochemical and ultrastructural hepatic phenotypes associated with carbohydrate-, fat- and protein-enriched diets initiated during post-weaning growth. Methods: Forty 21-day-old male Wistar albino rats were divided into four groups: a control group and three experimental groups (carbohydrate, protein, and fat). The respective diets were fed for 13 weeks. Hepatic oxidant–antioxidant parameters, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histopathological scores; interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) immunoreactivity and transmission electron microscopy (TEM) findings were evaluated. Results: The carbohydrate group showed higher thiobarbituric acid-reactive substances (TBARS), total oxidant status (TOS) and oxidative stress index (OSI), together with lower reduced glutathione (GSH) and total antioxidant status (TAS). Histology showed hydropic change, vacuolization and inflammatory cell infiltration, while TEM showed mitochondrial swelling, loss of cristae and nuclear alterations. The fat group showed prominent vacuolization, TEM-observed lipid droplets, inflammatory cell infiltration and TNF-α immunoreactivity. Most findings in the protein group were closer to control values. Thus, the carbohydrate-enriched diet was associated with the most pronounced redox and ultrastructural injury profile, whereas the fat-enriched diet was associated with a morphological and inflammatory injury profile compatible with lipid accumulation. Conclusions: These findings identify distinct hepatic phenotypes associated with the dietary formulations administered during post-weaning growth. The carbohydrate- and fat-enriched formulations were associated with more pronounced biochemical and morphological changes; inference is made at the level of the complete dietary formulation.

Sepsis-associated renal injury involves oxidative, inflammatory, and microvascular disturbances. This study evaluated renal changes associated with molsidomine pretreatment in cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Forty Wistar rats were randomly allocated to Sham (n = 8), molsidomine (MOL; n = 8), CLP (n = 12), or MOL+CLP (n = 12) groups. Molsidomine (10 mg/kg/day) was administered orally for 14 days before surgery. Four animals in each septic group died before 24 h, leaving eight survivors per group. The primary outcome was total renal histopathological damage score; secondary outcomes included renal biochemical and immunohistochemical markers and serum renal indices. The total histopathological score differed across groups (overall p < 0.001) and was lower in surviving MOL+CLP than CLP animals (2.22 ± 0.97 vs. 5.38 ± 1.06). All four injury components were numerically lower, but adjusted pairwise differences were significant only for glomerular capillary collapse and renal tubular injury. Compared with CLP, MOL+CLP showed lower renal malondialdehyde (106.41 ± 9.03 vs. 136.45 ± 20.27 nmol/g), higher superoxide dismutase and glutathione peroxidase activities, and lower VEGF and P-selectin immunoreactivity. Renal nitric oxide, other redox and inflammatory markers, and serum creatinine, blood urea nitrogen, and urea did not differ significantly between septic groups after multiplicity adjustment. Among survivors, molsidomine pretreatment was associated with less pronounced renal structural injury and tissue-level abnormalities, without significant differences in conventional serum renal indices. Its effects when initiated after sepsis onset remain unknown. Further studies should evaluate post-sepsis dosing, antimicrobial and supportive care, and longer-term renal functional outcomes.

Sepsis-associated renal injury involves interacting oxidative, inflammatory, and microvascular mechanisms. Molsidomine, a nitric oxide donor, may modulate these pathways. We investigated whether molsidomine pretreatment attenuates renal injury in cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Forty male Wistar albino rats were randomized to Sham, molsidomine (MOL), CLP, or MOL+CLP groups. Molsidomine (10 mg/kg/day) was administered orally for 14 days before surgery. At 24 h, renal biochemical, histopathological, and immunohistochemical outcomes were assessed. Seven septic animals died before the endpoint, resulting in outcome-specific numbers of evaluable animals. The primary outcome was total renal histopathological damage score. The total renal histopathological damage score was lower in MOL+CLP than CLP animals [median (IQR), 2 (1–3) vs. 5.5 (5–6); overall p < 0.001], with reductions across all four histopathological components. Renal MDA was lower in MOL+CLP than CLP animals (106.41 ± 9.03 vs. 136.45 ± 20.27 nmol/g), whereas SOD (36.23 ± 4.19 vs. 24.12 ± 2.23 U/g) and GPx (99.43 ± 26.38 vs. 61.54 ± 9.10 U/mg) activities were higher. VEGF and P-selectin H-scores were also markedly lower in MOL+CLP than CLP animals. Conversely, renal NO, GSH, TOS, OSI, and TNF-α and serum creatinine, BUN, and urea did not differ significantly between the two septic groups. Molsidomine pretreatment attenuated renal structural injury, selected redox abnormalities, and VEGF/P-selectin immunoreactivity in experimental polymicrobial sepsis. This renoprotective phenotype was not accompanied by uniform biochemical or renal functional improvement. These proof-of-concept findings warrant evaluation using post-sepsis treatment protocols and longer-term renal outcomes.

The present study was designed to evaluate the structural and biochemical efficacy of Omega-3 fatty acids in preventing renal injury in streptozotocin (STZ)-induced diabetic kidney injury and to correlate systemic oxidative stress parameters with histological and ultrastructural parameters. Twenty-eight male Wistar Albino rats were randomly divided into four groups (n = 7) as follows: Control, Omega-3 (500 mg/kg, orally), Diabetes Mellitus (DM; 50 mg/kg STZ, i.p.), and DM+Omega-3 (STZ, followed by 500 mg/kg Omega-3 for 42 days). Biochemical analysis of renal function (blood urea nitrogen (BUN) and creatinine) and oxidative status (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) was measured by ELISA. Histopathological scoring and Caspase-3 staining were performed by Hematoxylin and Eosin (H&E) and immunohistochemically, respectively. Transmission Electron Microscopy (TEM) was used to examine the renal tissues. Our results showed that the DM group presented with severe hyperglycemia, uremia, and a significant oxidative shift, as evidenced by increased MDA/TOS levels and depleted antioxidant defenses. Light microscopy showed extensive glomerular damage, tubular degeneration and inflammatory infiltration in the kidneys of diabetic rats. Immunohistochemical analysis revealed strong Caspase-3 expression in the tubular and glomerular compartments. TEM showed severe podocyte effacement and damage to the glomerular basement membrane (GBM). Notably, Omega-3 supplementation significantly reversed renal dysfunction, restored the pro-oxidant/antioxidant balance and reduced histopathological injury scores. Moreover, Omega-3 treatment efficiently blocked Caspase-3-mediated apoptotic signaling and preserved the ultrastructural integrity of the glomerular filtration barrier (GFB) and tubular mitochondria. Our results demonstrate the potent nephroprotective effects of Omega-3 fatty acids in reducing oxidative stress, preventing programmed cell death and maintaining the stability of the renal parenchyma’s microarchitecture. These findings suggest that Omega-3 fatty acids could be an effective adjuvant therapeutic agent for the management of diabetic nephropathy.

Ovine pulmonary adenocarcinoma is a contagious pulmonary neoplasm of sheep associated with exogenous Jaagsiekte sheep retrovirus. This retrospective descriptive case series characterized seven suspected ovine pulmonary adenocarcinoma cases using histopathology, immunohistochemistry, and semi-nested polymerase chain reaction on archived formalin-fixed, paraffin-embedded lung tissues. Fresh pulmonary tissue from two cases was also examined by transmission electron microscopy. Histopathological findings were compatible with ovine pulmonary adenocarcinoma in all cases and consisted of well- differentiated bronchioloalveolar epithelial proliferations arranged in papillary and acinar/tubular patterns. Cytoplasmic immunoreactivity for the jaagsiekte sheep retrovirus envelope protein was detected in neoplastic epithelial cells and in non-neoplastic type II pneumocytes. Immunolabelling was also observed in alveolar macrophages and lymphocytes in some cases; this finding was interpreted cautiously because it may reflect uptake of viral antigen rather than productive infection. Nuclear thyroid transcription factor-1 immunolabelling in neoplastic cells supported pulmonary epithelial differentiation. Semi- nested polymerase chain reaction provided molecular support by amplifying the expected 133 bp jaagsiekte sheep retrovirus -specific product in clearly positive samples, although band intensity varied among lanes. Transmission electron microscopy demonstrated lamellar body-like structures, cytoplasmic vacuolation, vesiculation, and membranous-lamellar degeneration in alveolar epithelial cells, but clearly identifiable viral particles were not demonstrated. Therefore, the findings should be interpreted as descriptive evidence supporting jaagsiekte sheep retrovirus -associated ovine pulmonary adenocarcinoma, rather than as proof of productive jaagsiekte sheep retrovirus infection or as a diagnostic-performance study. Larger prospective studies incorporating viral ribonucleic acid detection, sequencing, or direct virion demonstration are required.

Background/Objectives: Bile duct ligation (BDL), characterized by marked inflammation and fibrosis, effectively mimics many clinical conditions and is a valuable tool for investigating biliary regeneration. Our objective was to clarify the therapeutic benefits of adipose-derived stem cell (ADSC) treatment and signaling pathways mediating regenerative processes in a rat model of BDL. Methods: The BDL model was performed on Sprague–Dawley rats, and ADSC was administered intrasplenically at a dose of 10⁶ cells per animal. Liver function tests, gene and protein expression analyses, histological evaluation, and immunohistochemistry staining were performed to assess liver function, signaling pathways, inflammation, and fibrosis. Results: ADSC treatment returned liver function to sham levels. ADSC upregulated the Hes1 gene and protein expression in the early and late term. Inflammation, fibrosis, and total damage scores were decreased following ADSC treatment compared with the control. Immunohistochemistry staining revealed higher CD90, CD44, and CD29 stem cell marker expression in the ADSC treatment group. Conclusions: ADSC administration reduced fibrosis and biliary damage and restored liver function, potentially in a manner mediated by upregulated Hes1 expression, supporting its promise in biliary regeneration.

Background: This study introduces an experimental model of a large, full-thickness skin defect and evaluates how adipose-derived stem cells characterized by high self-renewal and differentiation capacity affect both wound healing and the wound microenvironment when delivered using two different local application methods. Materials and Methods: In this preclinical study, we established an excisional full-thickness skin defect model involving approximately 30% of the total body surface area (TBSA). Five experimental groups were formed, each containing equal numbers of male and female rats: (1) subdermal ADSC injection (ADSC-I) (n = 8), (2) application of an acellular dermal matrix (ADM) seeded with ADSCs (n = 8) (ADSC-ADM), (3) ADM alone (n = 8), (4) subdermal saline injection (n = 8) (SS-I), and (5) an untreated skin-defect sham group (n = 8). Wound healing and wound microenvironment parameters were assessed at regular intervals using macroscopic and microscopic evaluations, as well as various quantitative measurements. The study was terminated when complete wound closure was achieved in all animals of at least one experimental group. Results: The most favorable healing outcomes were observed in the two ADSC-treated groups. More favorable microenvironmental conditions in the stem cell groups were detected from day 14 onward. Complete closure of the dermal defects occurred by day 32 in the ADSC-I group, whereas none of the other groups achieved full wound closure within the study period. Conclusions: Local application of adipose-derived stem cells may accelerate wound healing by favorably modulating the wound microenvironment.

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This study investigated the effect of denosumab on new bone formation, both alone and in combination with different graft materials. To this end, four defects were created in the skulls of 20 New Zealand rabbits. One defect was left empty, while the other three were treated with autograft, xenograft, and calcium phosphate (BCP) grafts. The animals were divided into an experimental group (n=10), which received 10 mg/kg of denosumab subcutaneously once a month for 2 months, and a control group (n=10), which was administered the same dose of physiological saline. After 8 weeks, the animals were sacrificed, and their bone tissue samples were analyzed histomorphometrically. The percentage of bone volume (PBV) was calculated by dividing the area of mature bone tissue by the total tissue area. The PBV in empty defects treated with denosumab was significantly higher than in the control group (p < 0.05). Moreover, the combination of denosumab and autograft resulted in a significant increase in new bone formation (NBF) (p < 0.05), thus demonstrating the positive effect of denosumab on bone formation. However, further research with larger experimental groups would be needed to determine the practicality, dosage, and duration of this treatment before clinical application.