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This study aimed to prepare, characterize and assess the antioxidant activity of yellow bedstraw extracts (YBEs), focusing on identifying extracts with high antioxidant capacity. The selected extract was loaded into an oral liquid formulation and further investigated for its therapeutic potential in reducing blood pressure and associated complications in spontaneously hypertensive Wistar kyoto rats (SHR). Rats were divided into untreated SHR and SHR treated with a YBE-based oral formulation over four weeks. After treatment, blood pressure was measured, and cardiac function was assessed using the Langendorff technique to simulate ex vivo ischemic conditions. Prooxidant levels were assessed in plasma while antioxidant activity was evaluated in red blood cells. Histological analyses of heart, kidney, and liver samples were conducted to assess pathological changes induced by hypertension. Our results showed that the oral formulation loaded with ethanol YBE effectively reduced blood pressure, preserved myocardial function under ischemic stress, and decreased oxidative stress markers in blood. Importantly, our formulation with YBE demonstrated potential in attenuating structural kidney damage associated with hypertension. Overall, these findings suggest a cardioprotective effect of orally administered YBE formulation, highlighting its potential as an herbal supplement. However, clinical studies are warranted to validate these findings and explore the extract's suitability for clinical use. [ABSTRACT FROM AUTHOR]

In addition to their usual use in the treatment of cardiovascular disease, weak evidence is available for the potential of combined use of neprilysin inhibitor (sacubitril) and AT1 receptor antagonist (valsartan) to promote browning of white adipose tissue (WAT) in rats with metabolic syndrome (MetS). This study involved 32 male Wistar albino rats divided into four groups: CTRL—healthy control rats; ENT—healthy rats treated with sacubitril/valsartan; MS—rats with MetS; MS + ENT—rats with MetS treated with sacubitril/valsartan. After finishing the experimental protocol, different WAT depots were isolated for further analysis of molecular pathways. Molecular docking and molecular dynamics studies were used for in silico assessment of the binding affinity of sacubitril and valsartan towards subunits of mechanistic target of rapamycin complex 1 (mTORC1). Sacubitril/valsartan treatment markedly diminished morphological changes in adipose tissue, resulting in smaller lipid size and multilocular lipid droplet structure in WAT. We showed significantly higher protein expression of uncoupling protein‐1 (UCP‐1) and mTORC1 in WAT of MS + ENT rats, correlating with increased relative gene expression of browning‐related markers in tissue of rats treated with sacubitril/valsartan compared with MS group of rats. In silico analysis showed that sacubitrilat and valsartan exhibited the highest binding affinity against mTOR and mLST8, forming stable complexes with these mTORC1 subunits. The observed results confirmed strong potential of combined sacubitril/valsartan treatment to increase browning markers expression in different WAT depots in MetS condition and to form permanent complexes with mTOR and mLST8 subunits over the time. [ABSTRACT FROM AUTHOR]

Despite the numerous efforts to find an appropriate therapeutic modality, diabetic wounds remain a global unsolved problem. Therefore, our study aimed to develop a topical formulation loaded with pine tar and to investigate its wound-healing capacity. After phytochemical profiling of pine tar, an oil-in-water emulsion with 1% pine tar was prepared. The physical, chemical, and microbiological stability of prepared pine tar cream (PTC) was assessed during six months. Additionally, safety potential was examined in healthy rats, while wound-healing potential was accessed by creating excision wounds in diabetic rats. Diabetic animals were divided into four groups: untreated or topically treated with either the cream base, PTC, or silver sulfadiazine cream. Wound healing was monitored at the following time points (0, 7, 14, and 21 days) through macroscopic, biochemical, and histological examinations. Our PTC formula showed good physicochemical properties and remained stable and compatible for cutaneous application. PTC showed a remarkable increase in wound closure rate and led to attenuation of morphological alterations in skin samples. These findings were associated with significantly improved redox status and enhanced hydroxyproline levels in PTC relative to the untreated and cream base groups. Our results demonstrated that PTC might serve as a promising tool for the management of diabetic wounds. [ABSTRACT FROM AUTHOR]

An endometrial polyp is most commonly a benign, localized proliferation of the glands and the endometrial stroma, covered with epithelium and protruding above the level of the mucosa. These polyps are most often diagnosed during investigation into the causes of irregular menstrual bleeding or infertility. It is produced in the highest concentration during the secretory phase of the endometrial cycle. The level of glycodelin reaches its peak 12 days after ovulation. The aim of this paper was to determine the changes in the immunohistochemical expression of glycodelin at the level of the endometrium and in the tissue of the polyp, before and after hysteroscopic polypectomy, in infertile female patients with an endometrial polyp, and in the endometrial tissue of female patients without an endometrial polyp. The study included 82 infertile female patients. The infertile patients were divided into two groups. The first was the experimental group which included 56 infertile female patients who had an endometrial polyp. The second group was the control group, composed of 26 infertile female patients who did not have an endometrial polyp. The results obtained primarily indicate the existence of changes in the immunohistochemical expression of the cytokine glycodelin in the female patients from both the experimental and the control group, not only prior to but also after hysteroscopy. A larger number of patients who have an endometrial polyp show a lack of glycodelin expression, more pronouncedly so in the bioptate of the endometrium than in the endometrial polyp. [ABSTRACT FROM AUTHOR]

This study aimed to examine the effects of a 14-day treatment with lady's bedstraw methanol extract on doxorubicin-induced cardiotoxicity through functional, biochemical and histological examinations. We used 24 male Wistar albino rats divided into the following groups: control (CTRL), doxorubicin (DOX), and DOX + GVE (Galium verum extract). GVE was administered orally at a dose of 50 mg/kg per day for 14 days, while a single dose of doxorubicin was injected into the DOX groups. After accomplishing treatment with GVE, cardiac function was assessed, which determined the redox state. During the autoregulation protocol on the Langendorff apparatus, ex vivo cardiodynamic parameters were measured. Our results demonstrated that the consumption of GVE effectively suppressed the disturbed response of the heart to changes in perfusion pressures caused by administration of DOX. Intake of GVE was associated with a reduction in most of the measured prooxidants in comparison to the DOX group. Moreover, this extract was capable of increasing the activity of the antioxidant defense system. Morphometric analyses showed that rat hearts treated with DOX showed more pronounced degenerative changes and necrosis compared to the CTRL group. However, GVE pretreatment seems to be able to prevent the pathological injuries caused by DOX injection via decrease in oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Introduction. Dysplasia epiphysealis hemimelica, also known as Trevor’s disease, is an extremely rare skeletal developmental disorder of unknown etiology, characterized by an osteocartilaginous outgrowth of one or more epiphyses or of a tarsal bone during childhood. Case report. We presented a sporadic case of dysplasia epiphysealis hemimelica developed in the talus. A 6- year-old boy complained of swelling of his right ankle joint, with painful and reduced movements. Radiographies suggested excessive overgrowth of the dorsomedial aspect of the talus. The tumor was surgically excised and the gross and histological findings were consistent with those of osteochondroma. Conclusion. Dysplasia epiphysealis hemimelica is diagnosed by clinical, radiographic and histopathological examination. Early diagnosis is important for the condition to be treated before the deformity becomes disabling.

Byline: Vladan. Popovic, Neda. Milosavljevic, Marija. Radojevic, Radisa. Vojinovic, Nikola. Nedovic, Slobodanka. Mitrovic, Jasmina. Nedovic, Aleksandar. Tomasevic INTRODUCTION: To define indications for adjuvant radiotherapy in patients with endometrial cancer, the [...]

Aim: To investigate the influence of strain differences in immune responses on the pathogenesis of experimental periapical lesions in Dark Agouti (DA) and Albino Oxford (AO) inbred strains of rats. Methodology: Periapical lesions were induced in male DA and AO rats by pulp exposure of the first mandibular right molars to the oral environment. Animals were killed 21 days after pulp exposure. The mandibular jaws were retrieved and prepared for radiographic, pathohistological, immunohistochemical analysis, real‐time PCR and flow cytometry. Blood samples and the supernatant of periapical lesions were collected for measurement of cytokines and oxidative stress marker levels. Statistical analysis was performed using the Kruskal–Wallis H and Mann–Whitney U non‐parametric tests or parametric One‐Way anova and Independent Samples T‐test to determine the differences between groups depending on the normality of the data. A significant difference was considered when p values were <.05. Results: DA rats developed significantly larger (p <.05) periapical lesions compared to AO rats as confirmed by radiographic and pathohistological analysis. The immunohistochemical staining intensity for CD3 was significantly greater in periapical lesions of DA rats compared to AO rats (p <.05). In DA rats, periapical lesions had a significantly higher (p <.05) percentage of CD3+ cells compared to AO rats. Also, the percentage of INF‐γ, IL‐17 and IL‐10 CD3+CD4+ cells was significantly higher in DA rats (p <.05). DA rats had a significantly higher Th17/Th10 ratio. RT‐PCR expression of IL‐1β, INF‐γ and IL‐17 genes was significantly higher in periapical lesions of DA compared to AO rats (p <.05). The receptor activator of nuclear factor kappa‐Β ligand/osteoprotegerin ratio was higher in DA compared to AO rats with periapical lesions (p <.05). Systemic levels of TNF‐α and IL‐6 were significantly higher in DA compared to AO rats (p <.05). Levels of lipid peroxidation measured as thiobarbituric acid reactive substances and reduced glutathione were significantly higher (p <.05) in the supernatant in the periapical lesions of DA rats. Conclusion: After pulp exposure, DA rats developed much larger periapical lesions compared to AO rats. Genetically determined differences in immunopathology have been demonstrated to be a significant element defining the severity of periapical lesions. [ABSTRACT FROM AUTHOR]

Up until now, the specific mechanisms involved in doxorubicin (DOX)-induced cardiotoxicity have not been fully elucidated. Since thiamine deficiency is associated with myocardial dysfunction and it may lead to cardiomyopathy, we aimed to investigate whether thiamine (Vitamin B1) treatment provides cardioprotection and modulates DOX mediated subchronic cardiotoxicity as well as to determine possible mechanisms of its effects. The study involved 48 Wistar albino rats divided into four groups: healthy non-treated rats and healthy rats treated with thiamine and DOX rats without treatment and DOX rats treated with thiamine. DOX was applied as a single i.p.injection (15mg/kg), while thiamine treatment lasted 7days (25mg/kg/dayi.p.). Before and after the treatment hemodynamic changes were monitored in vivo by echocardiography. When the protocol was completed, animals were sacrificed and rat hearts were isolated in order to evaluate parameters of cardiac oxidative stress [superoxide anion radical-O2−, hydrogen peroxide-H2O2, nitric oxide-NO−, index of lipid peroxidation-thiobarbituric acid (TBA) reactive substances (TBARS), superoxide dismutase – SOD, catalase (CAT), and reduced glutathione-GSH] and apoptosis (Bax, Bcl-2, caspases). DOX treatment significantly reduced the ejection fraction, while thiamine treatment led to its minor increase in the DOX-treated group. In that sense, heart oxidative stress markers were significantly increased in DOX-treated rats, while therapeutic dose of thiamine decreased the levels of free radicals. Our study demonstrated the promising ameliorative effects of thiamine against DOX-induced cardiotoxicity through modulation of oxidative stress, suppression of apoptosis, and possibility to improve myocardial performance and morphometric structure of rats' hearts. [ABSTRACT FROM AUTHOR]