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OBJECTIVE: Cancer is the second most common non-communicable disease group in the world and its frequency is increasing. In parallel, side effects of drugs used in cancer treatment are frequently encountered. Doxorubicin (DOX) is one of the most effective multi-purpose anticancer drugs. However, its use is significantly limited due to the risk of cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors are a group of antidiabetic drugs that have been shown to reduce cardiovascular events. Our aim is to examine the preventive effect of dapagliflozin on DOX-induced cardiac damage. SUBJECTS AND METHODS: We used 30 albino rats. 20 of 30 rats were administered doxorubicin for cardiomyopathy model. The rats in the DOX arm were divided into two groups: those given penicillin and placebo. After the rats were terminated, tissues were prepared for histopathological and immunohistochemical examination. TNF-α, pro-BNP, troponin T and plasma FGF-21 levels were also measured in plasma. RESULTS: The mean concentrations of cTnT and pro-BNP in the plasma of the DOX treated rats demonstrated a significantly higher value compared to the control group. Treatment with dapagliflozin caused a significant reduction in plasma cTnT, pro-BNP and TNF-a levels concentrations compared to the DOX control group (p < 0.001). The group of rats treated with dapagliflozin was effective in significantly decreasing the FGF-21 concentration and the percentage of fibronectin immunoexpression compared to the DOX control group (p < 0.0001). CONCLUSIONS: This study revealed, for the first time, that dapagliflozin can improve DOX-induced cardiac dysfunction and pathological changes in non-diabetic rats. This result has shown that dapaglifozin, may be promising in terms of preventing cardiac damage that may develop in cancer treatment. [ABSTRACT FROM AUTHOR]

A new coronavirus pandemic as known as the COVID-19 impacted on every aspect of daily life. The priority of the states in the second quarter of 2020 was to protect their citizens from COVID-19 outbreak due to uncontrolled spread. The study was undertaken at a time when all the world is still struggling to take the COVID-19 outbreak under control. The states took precautions to control the virus such as restriction on travelling and curfews for every citizen or age specifically. This research is focused on the COVID-19 measures adopted by the Turkish government and their effect on the case study megaprojects' finance at operational phases. Based on these, this research provides a new set of data to the existing body of literature on megaprojects with 'uncertainty and finance relation' through the COVID-19's impact. The research methodology is based on a mixed method and multiple-case study approach with two mega projects in Istanbul, Turkey (Eurasia Tunnel and Yavuz Sultan Selim Bridge) which was financed with the Build-Operate-Transfer (BOT) method. The data consists of a detailed primary source documents and secondary data. The data is collected through the official statement of public administrations, ministries, and statistic offices. This research uncovers how the COVID-19 precautions between March 11 to May 31 in Turkey affected the megaprojects' finances at their operational phases with an exogenous factor, COVID-19 and decrease the guaranteed incomes up to 94%. [ABSTRACT FROM AUTHOR]

Pentraxin-3 (PTX3) plays an important role in the primary inflammatory response. We aim to evaluate PTX3 as a diagnostic marker of ovarian torsion in an experimental rat model. In this study, 16 female Sprague Dawley albino mature rats were randomly allocated to Group 1 (control, sham operated) and Group 2 (experimental ovarian torsion model). A torsion model was set up using atraumatic vascular clips just above and below the right ovary for a 3-h ischaemia. Blood samples were collected before and three hours after ovarian torsion. Three hours after ovarian torsion, right ovary was surgically removed for histopathological examination in both groups. There was no significant difference in preoperative PTX3 level in both groups (1.05 ± 0.20 ng/mL vs 1.09 ± 0.28 ng/mL, p > 0.05). Three hours after the operation, mean plasma level of PTX3 was significantly higher in ovarian torsion group than the control group (2.13 ± 0.49 ng/mL vs 1.07 ± 0.22 ng/mL, p = 0.001). Also, the mean total histopathological score was significantly increased in the torsion group. PTX3 can be used in clinical practice as a useful marker for early diagnosis of ovarian torsion. [ABSTRACT FROM AUTHOR]

In this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3′,5-triiodo-l-thyronine (50 µg/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell–cell interactions, and pluripotency capacity. [ABSTRACT FROM PUBLISHER]

The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Student's t-test, analysis of variance (ANOVA) and the Mann-Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms. [ABSTRACT FROM AUTHOR]

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern closely linked to metabolic disorders, including obesity, insulin resistance, and dyslipidemia. Emerging evidence suggests that the gut-liver axis plays a critical role in the pathogenesis of NAFLD, with recent research highlighting the influence of gut microbiota, including fungal species such as Saccharomyces boulardii ( S. boulardii ). This study aimed to evaluate the effects of S. boulardii on lipid metabolism and oxidative stress in a rat model of fructose-induced NAFLD. Materials and Methods: Thirty Wistar rats were divided into three groups: a control group, a fatty liver group induced by 35% fructose supplementation, and a treatment group receiving S. boulardii (100 mg/kg/day) after fructose induction. Results: Biochemical analyses revealed that the treatment group exhibited significantly lower plasma levels of malondialdehyde (MDA), alanine aminotransferase (ALT), total triglycerides, and cholesterol compared to the untreated fatty liver group ( p < 0.05). Furthermore, liver tissue analysis showed a marked reduction in lipid accumulation and fatty infiltration in the treatment group, with no visible lipid vacuoles in hepatocytes. The expression of aquaporin-8 (AQP8) and sirtuin-1 (SIRT1), key markers associated with hepatocyte function and lipid metabolism, was significantly higher in the S. boulardii group compared to the fatty liver group ( p < 0.001). Conclusions: These findings indicate that S. boulardii supplementation mitigates the metabolic and oxidative stress-related alterations associated with fructose-induced NAFLD. In conclusion, our study suggests that S. boulardii exerts protective effects on the liver by reducing lipid accumulation and oxidative stress, highlighting its potential as a therapeutic intervention for NAFLD.

The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

The neuroprotective effects of choline chloride, an essential nutrient, a precursor for the acetylcholine and synthesis of membrane phospholipids, have been associated with neurological and neurodegenerative diseases. Its contribution to autism spectrum disorder, a neurodevelopmental disorder, remains unknown. Thus, we aimed to evaluate the effects of choline chloride on social behaviours, and histopathological and biochemical changes in a rat autism model. The autism model was induced by administration of 100 μg/kg lipopolysaccharide (LPS) on the 10th day of gestation. Choline chloride treatment (100 mg/kg/day) was commenced on PN5 and maintained until PN50. Social deficits were assessed by three-chamber sociability, open field, and passive avoidance learning tests. Tumour necrosis factor alpha (TNF-α), interleukin-2 (IL) and IL-17, nerve growth factor (NGF), and glutamate decarboxylase 67 (GAD67) levels were measured to assess neuroinflammatory responses. In addition, the number of hippocampal and cerebellar neurons and glial fibrillary acidic protein (GFAP) expression were evaluated. Social novelty and passive avoidance learning tests revealed significant differences in choline chloride-treated male rats compared with saline-treated groups. TNF-α, IL-2, and IL-17 were significantly decreased after choline chloride treatment in both males and females. NGF and GAD67 levels were unchanged in females, while there were significant differences in males. Histologically, significant changes in terms of gliosis were detected in hippocampal CA1 and CA3 regions and cerebellum in choline chloride-treated groups. The presence of ameliorative effects of choline chloride treatment on social behaviour and neuroinflammation through neuroinflammatory, neurotrophic, and neurotransmission pathways in a sex-dependent rat model of LPS-induced autism was demonstrated., (© 2024 International Society for Developmental Neuroscience.)

Background: This study investigates the effects of hydroxychloroquine (HCQ) on a sepsis-induced acute respiratory distress syndrome (ARDS) model in rats, initiated by a fecal intraperitoneal injection procedure (FIP)., Methods: Three groups were established: control (n=8), FIP + saline (n=7), and FIP + HCQ (20 mg/kg/day) (n=9). Blood samples were collected for arterial blood gas and biochemical analyses, and bilateral pneumonectomy was performed for histopathologic examination., Results: In the FIP + saline group, PaO2 decreased and PaCO2 increased, whereas these levels normalized in the FIP + HCQ group compared to the control (p<0.001 and p<0.05, respectively). Histopathological scores for alveolar congestion, perivascular/interstitial edema, hemorrhage in alveolar tissue, leukocyte infiltration or aggregation in air spaces/vascular walls, and alveolar wall/hyaline membrane thickness increased in the FIP + saline group compared to the control group (p<0.01). These scores decreased in the FIP + HCQ group compared to the FIP + saline group (p<0.01). HCQ reversed the sepsis-induced increase in malondialdehyde, tumor necrosis factor-alpha, interleukin-6, and lactic acid., Conclusion: HCQ may be an effective and safe option to mitigate the severe progression of ARDS.

Introduction: Sepsis-induced acute kidney injury (AKI) remains a major challenge in intensive care, contributing significantly to morbidity and mortality. Tibolone, known for its neuroprotective and hormonal properties, has not been explored for its potential in AKI management. This study investigates the protective effects of Tibolone and its underlying mechanisms involving Sirtuin-1 (SIRT1) and Yes-Associated Protein (YAP) in a rat sepsis model., Materials and Methods: Thirty-six female Wistar albino rats underwent cecal ligation and puncture (CLP) to induce sepsis. They were randomly assigned to control, CLP+Saline, and CLP+Tibolone groups. Tibolone was administered intraperitoneally. Biomarkers, including Sirtuin (SIRT1), Yes-associated protein (YAP), Tumor necrosis factor (TNF-α), High mobility group box 1 (HMGB1), malondialdehyde (MDA), creatinine, and urea, were assessed. Histopathological examination evaluated renal damage., Results: Tibolone administration significantly reduced plasma TNF-α, HMGB1, MDA, creatinine, and urea levels compared to the CLP+Saline group. Moreover, Tibolone elevated SIRT1 and YAP levels in kidney tissues. Histopathological examination demonstrated a significant decrease in tubular epithelial necrosis, luminal debris, dilatation, hemorrhage, and interstitial inflammation in Tibolone-treated rats., Conclusion: This study unveils the protective role of Tibolone against sepsis-induced AKI in rats. The improvements in inflammatory and oxidative biomarkers and histological evidence suggest Tibolone's potential as a therapeutic intervention in sepsis-associated kidney injury. The upregulation of SIRT1 and YAP indicates their involvement in Tibolone's renoprotective mechanisms. Further investigations are warranted to explore Tibolone's translational potential in human sepsis-induced AKI., Competing Interests: The authors report no conflicts of interest in this work.

The COVID-19 pandemic catalyzed the swift development and distribution of mRNA vaccines, including BNT162b2, to address the disease. Concerns have arisen about the potential neurodevelopmental implications of these vaccines, especially in susceptible groups such as pregnant women and their offspring. This study aimed to investigate the gene expression of WNT, brain-derived neurotrophic factor (BDNF) levels, specific cytokines, m-TOR expression, neuropathology, and autism-related neurobehavioral outcomes in a rat model. Pregnant rats received the COVID-19 mRNA BNT162b2 vaccine during gestation. Subsequent evaluations on male and female offspring included autism-like behaviors, neuronal counts, and motor performance. Molecular techniques were applied to quantify WNT and m-TOR gene expressions, BDNF levels, and specific cytokines in brain tissue samples. The findings were then contextualized within the extant literature to identify potential mechanisms. Our findings reveal that the mRNA BNT162b2 vaccine significantly alters WNT gene expression and BDNF levels in both male and female rats, suggesting a profound impact on key neurodevelopmental pathways. Notably, male rats exhibited pronounced autism-like behaviors, characterized by a marked reduction in social interaction and repetitive patterns of behavior. Furthermore, there was a substantial decrease in neuronal counts in critical brain regions, indicating potential neurodegeneration or altered neurodevelopment. Male rats also demonstrated impaired motor performance, evidenced by reduced coordination and agility. Our research provides insights into the effects of the COVID-19 mRNA BNT162b2 vaccine on WNT gene expression, BDNF levels, and certain neurodevelopmental markers in a rat model. More extensive studies are needed to confirm these observations in humans and to explore the exact mechanisms. A comprehensive understanding of the risks and rewards of COVID-19 vaccination, especially during pregnancy, remains essential., (© 2024. The Author(s).)

Objective: Estrogen (E2) plays a significant role in postmenopausal osteoporosis, and its deficiency is related to chronic low-grade inflammation. Intravenous immunoglobulin (IVIG) is composed of immunoglobulins derived from the plasma of healthy donors. Numerous anti-inflammatory pathways are responsible for IVIG's anti-inflammatory action The aim of this study is to investigate the effects of IVIG on experimental-induced osteoporosis., Materials and Methods: Forty adult female Wistar rats were included in the study. Thirty rats underwent bilateral dorsal ovariectomy. Rats were grouped as Group 1 (n = 10, ovariectomy and saline); Group 2 (n = 10, ovariectomy and E2); Group 3 (n = 10, ovariectomy and IVIG), and Control group (n = 10, no oophorectomy). Histopathological examination of bone tissue, and biochemical analysis for beta-catenin, plasma Tumor Necrosis Factor-α, IL-6, receptor activator of nuclear-κB ligand (RANKL), and osteoprotegerin (OPG) levels were made., Results: The IVIG group had increased trabecular number, area, and thickness with increased bone mineral density as well as decreased trabecular separation compared with the saline group. IVIG group had lower serum RANKL and higher serum OPG levels when compared with the saline group. The bone marrow beta-catenin level was significantly higher in the control and ovariectomy + IVIG groups., Conclusion: IVIG has beneficial effects on experimentally induced osteoporosis with a possible action on inflammation and RANKL-β-catenin pathway.

Background: Ischemia-reperfusion injury presents a substantial concern in various medical scenarios, notably in reconstructive surgery involving tissue flaps. Despite reports on the protective benefits of Propionyl-l-carnitine against ischemia-reperfusion injury, a thorough assessment of its efficacy in epigastric island flap models is currently lacking., Methods: Sixteen male Sprague-Dawley rats underwent epigastric island flap surgery and were divided into two groups: a Propionyl-l-carnitine group that received intraperitoneal Propionyl-l-carnitine prior to ischemia induction and a sham group that received saline treatment. A comprehensive evaluation was performed including macroscopic, biochemical and histological assessments encompassing measurements of flap survival areas, lipid peroxidation (malondialdehyde), glutathione, myeloperoxidase, nitric oxide and peripheral neutrophil counts., Results: The Propionyl-l-carnitine group demonstrated significantly increased flap survival areas when compared to the sham group. Administration of Propionyl-l-carnitine led to reduced malondialdehyde levels and elevated glutathione levels indicating a reduction in oxidative stress. Furthermore, the Propionyl-l-carnitine group exhibited lower myeloperoxidase levels, higher nitric oxide levels and reduced peripheral neutrophil counts, suggesting a decrease in the inflammatory response. Histopathological analysis revealed decreased levels of inflammation, necrosis, polymorphonuclear leukocyte infiltration and edema in the Propionyl-l-carnitine group. Additionally, vascularity was enhanced in the Propionyl-l-carnitine group., Conclusion: This study provides compelling evidence that Propionyl-l-carnitine administration effectively mitigates the deleterious effects of ischemia-reperfusion injury in epigastric island flaps. This is substantiated by the improved flap survival, diminished oxidative stress and inflammation, as well as the enhanced vascularity observed. Propionyl-l-carnitine emerges as a promising therapeutic intervention to enhance tissue flap survival in reconstructive surgery, warranting further exploration through larger-scale investigations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Low back pain is a common health issue, and such pains are often associated with muscle tightness. Understanding the link between lower back pain and tight lower extremity muscles is essential for effective pain management and enhanced quality of life., Objective: The objective of this study was to investigate the relationship between lower extremity muscle tightness and pain and disability in individuals with non-specific low back pain (NSLBP)., Methods: A total of 52 individuals with NSLBP were enrolled in this cross-sectional study. Lower extremity muscle tightness was assessed using various clinical tests, including the Active Knee Extension Test, Active Straight Leg Raise, Ober Test, and Modified Thomas Test. Pain intensity and disability were evaluated using the Visual Analog Scale and the Oswestry Disability Index, respectively. Statistical analyses were conducted to assess the correlation between muscle tightness, pain, and disability., Results: The study found weak to moderate negative correlations between lower extremity muscle tightness and both pain intensity and disability in individuals with NSLBP (r: -0.287 to -0.526, p < 0.05). Dominant and non-dominant extremities exhibited differences in muscle flexibility, with the dominant extremity showing greater flexibility (p < 0.05)., Conclusions: In individuals with NSLBP, lower extremity muscle tightness is closely related to pain severity and disability. These findings suggest that lower extremity muscle tightness plays a significant role in the severity of low back pain and disabilities. Additionally, the observed flexibility difference between dominant and non-dominant extremities warrants further investigation for more personalized treatment approaches.

Parkinson's disease (PD) is the second most common and progressive neurodegenerative disease. This experimental study was designed to investigate the neuroprotective effects of dexpanthenol on antioxidant and anti-inflammatory processes in a rotenone-induced Parkinson's disease model in rats. Twenty-one male rats were randomly divided into 2 groups. The rotenone group (n = 14) was administered rotenone by intrastriatal injection, and the vehicle group (n = 7) was administered DMSO with the same application route. All animals underwent rotational movement testing with apomorphine injection 10 days later. Those with Parkinson's disease model were randomly divided into 2 groups. While 1 ml/kg of saline was applied to the saline group (n = 7), 500 mg/kg was administered to the dexpanthenol group intraperitoneally for 28 days. After 28 days, all rats were euthanized and brain tissue was removed. While striatal areas were evaluated immunohistochemically, brain MDA, TNF-α, and HVA levels were measured to evaluate their anti-oxidative and anti-inflammatory effects. In the dexpanthenol group, the total count (p < 0.001) and intensity (p < 0.001) of dopaminergic neurons in the striatal areas increased compared to the saline group. It was revealed that MDA (nmol/g) (p < 0.001) and TNF-α (pg/g) (p < 0.001) levels decreased in the dexpanthenol group, while HVA (ng/mg) levels increased (p < 0.01). This study suggests that dexpanthenol may have a neuroprotective effect by reducing neuronal loss, oxidative damage, and neuroinflammation in the striatum in rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Unilateral osteoarthritis (OA) affects single knees and presents a unique scenario where individuals experience varying degrees of symptoms between their affected and unaffected knees., Objective: This study aims to investigate differences in muscle tightness between symptomatic and asymptomatic knees in individuals with unilateral knee OA while exploring the interplay among pain, functionality, and muscle tightness., Methods: In this cross-sectional study, thirty knee OA patients underwent assessments for hamstring (Active Knee Extension, Straight Leg Raise), iliotibial band (Ober Test), and quadriceps tightness (Modified Thomas Test). Pain intensity was measured using the Visual Analog Scale (VAS), and functional limitations were evaluated via the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)., Results: A negative correlation was observed between participants' pain and AKE (p= 0.004, r=-0.515), ASLR (p= 0.27, r=-0.403), Ober (p= 0.010, r=-0.461) values. However, no significant correlation was found with the Modified Thomas value (p= 0.204, r=-0.239). There was also a negative correlation between participants' WOMAC scores and AKE (p= 0.019, r=-0.427), OBER (p= 0.004, r=-0.510), and Modified Thomas (p= 0.022, r=-0.416) values, while ASLR (p= 0.286, r=-0.202) values showed no significant correlation. Comparisons between AKE, Ober, and Modified Thomas values showed higher values in asymptomatic extremities (AKE: p= 0.025, Ober: p= 0.021, Modified Thomas: p= 0.030)., Conclusion: This study emphasizes the significance of muscle tightness in the symptomatic extremities of individuals with unilateral knee OA. The results indicate that increased muscle tightness makes pain worse and limits movement. It's crucial for healthcare providers treating OA to focus on improving muscle flexibility, reducing pain, and enhancing overall function.