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© 2022 Wiley-VCH GmbH.Testicular ischaemia reperfusion (I/R) injury results with serious dysfunctions in testis. This study aims to explore effects of soluble guanylate cyclase (sGC) stimulator Riociguat on experimental testicular I/R injury in rats. Twenty-one male rats were divided into three groups (Control, IR and IRR). The control group was not exposed to any application. Bilateral testis from IR and IRR animals were rotated 720° in opposite directions for 3 h to induce experimental testicular ischaemia. Animals in IR and IRR groups were subjected to 3 h of reperfusion. Isotonic and Riociguat were administered to the animals 30 min prior reperfusion by oral gavage. At the end of experiment, animals were sacrificed and tissue samples were used for analyses. Riociguat treatment significantly decreased tissue malondialdehyde and Luminol levels compared to the IR group (p < 0.05). The pathological changes, pro-apoptotic proteins (Bax, Caspase 3, and Caspase 9) and apoptotic index in the IR group were down regulated in Riociguat treated animals (p < 0.05). Riociguat treatment was also significantly increased anti-apoptotic Bcl-2 expression, but alleviated tissue injury via modulating pro-inflammatory cytokine IL-1β levels and significantly (p < 0.05) down-regulating NF-κB activity. Moreover, mTOR and ERK phosphorylation increased in IR group (p < 0.05), but Riociguat treatment reduced protein phosphorylation. Our experiment indicated that targeting sGC might support surgical interventions in testicular I/R injury by modulating oxidative stress, inflammation, and apoptotic protein expression levels, but more detailed studies are required to explore the protective activity of Riociguat and underlying mechanisms in testicular I/R injury.

In this study, investigation on the essential oils and ethanol extracts of naturally grown and cultivatedSatureja macrantha samples were reported. The essential oil, flavour and terpenoid-steroid-flavonoid contents of S.macrantha samples were determined by GC-MS and their phenolic contents by LC-MS/MS. Besides, the biologicalactivities of the samples were investigated for their antioxidant, anti-Alzheimer, antimicrobial, cytotoxic,antityrosinase, antiurease, antielastase and anticollagenase properties. The phenolic content and antioxidant capacityof the cultivated sample were higher than those of the naturally grown sample. According to the GC-MS results,terpinene-4-ol (30.9%) and p-cymene (56.7%) were determined as the major components in the essential oils of thenaturally grown and cultivated S. macrantha, respectively. The flavour analysis results showed that cis-sabinenehydrate (20.7%) and carvacrol (42.2%) were found to be the major components in the naturally grown and cultivatedsamples, respectively. While the naturally grown sample was rich in abietane diterpenoids (ferruginol (17.5 mganalyte/g extract) and sugiol (4.2 mg analyte/g extract)), these components were not detected in the cultivatedsample. The rosmarinic acid content (0.20 and 24.87 mg analyte/g extract, respectively) of the cultivated samplewas found to be significantly higher than that of the natural sample. The biological activities of the samples weredetermined to be changed in parallel with their chemical contents that are due to factors such as climatic conditions,and soil structure.

Since ancient time, Salvia L. species have been commonly used to treat colds, bronchitis, tuberculosis, heart diseases, and menstrual and digestive disorders in traditional medicine all around the world. They have been also used as tea and spice. Studies indicated that diterpenes and triterpenes isolated from Salvia species possess various pharmacological and biological effects such as anti-inflammatory, antiviral, cytotoxic, antioxidant, and hepatotoxic activities. Flavones were also shown to have antimicrobial, antioxidant, and cytotoxic potentials. Salvia extracts also exhibit anti-Alzheimer, antiseptic, cardiovascular, antihypertensive, and antituberculous effects. To investigate the effects of 63 secondary metabolites from Salvia species on cell viability and apoptosis, Salvia secondary metabolites including 25 phenolics, 4 fatty acids, 19 abietane diterpenoids, 12 triterpenoids, and three steroids were examined on healthy cell line (PDF), breast cancer (MCF-7), and colon cancer (HT-29) cell lines using MTT method. In addition, the effects of rosmarinic acid, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, carnosic acid, carnosol, cryptotanshinone, beta-sitosterol, and ursolic acid on pro-apoptotic Bax and antiapoptotic Bcl-2 protein expression levels were investigated by Western Blot method. Practical applications Phenolic compounds (apigenin, chrysin, and luteolin) and diterpenes (especially dihydrotanshinone I, carnosic acid, and carnosol), and almost all of the triterpenes exhibited high toxic effects on healthy cell line. Cytotoxic effects of cryptotanshinone, 12-hydroxy abieta-1,3,5(10),8,11,13-hexaene, 12-demethylmulticauline, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, ursolic acid, and 3-acetyl lupeol were relatively higher than their toxic effects. Acetyl royleanone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone were found to have anticancer potential based on their modulating effects on the expression levels of Bax and Bcl-2 proteins which play important roles in the regulation of apoptosis. The results of the present study showed that acetyl royleanone, cryptotanshinone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone have potential to be used in the pharmaceutical industry.

WOS:000691376800017 Abstract: To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. Cannabinoids, the main constituents of cannabis (Cannabis sativa L.), are therapeutic compounds that have received international attention in the health field due to their therapeutic properties. Recently, they have been tested for the treatment of COVID-19 due to their antiviral properties. Indeed, cannabinoid-type compounds, and in particular cannabidiol (CBD), isolated from glandular trichomes found in the calyx of cannabis flowers with reported antiviral properties is hypothesized to be a therapeutic option in the ministration of SARS-CoV-2 consorted with COVID-19 disease. The relevant articles were determined from the database search published mainly in Web of Science, Google scholar, PubMed, Crossref, and ClinicalTrials.gov database during the pandemic period. The articles were evaluated for the therapeutic potentials, mechanisms of action of cannabinoids, the roles of the ECS in the immune system, impact of cannabinoids in SARS-CoV-2 septic, especially if they address the application of cannabinoids as drugs for the curability and management of SARSCoV-2 and its novel variants. Although the evidence needed to be considered using cannabinoids in the control and treatment of viral diseases is currently in its infancy, they already offer an opportunity for clinicians due to their effects in relieving pain, improving appetite, and improving childhood epilepsy, especially in cancer and human immunodeficiency virus (HIV/AIDS) patients. In addition to these, the most recent scientific evidence emphasizes their use in the treatment of the coronavirus infected patients. In brief, all preclinic and clinic studies that have been reported show that, through the cannabinoid system, cannabinoids, particularly CBD, have many mechanisms that are effective in the treatment of patients infected by SARS-CoV-2. Thus, more extensive studies are necessary in this area to fully identify the effects of cannabinoids on SARS-CoV-2.

This study examined the effects of black cumin seed oil treatment on oxidative stress and the expression of radixin and moesin in the liver of experimental diabetic rats.Eighteen rats were divided into 3 equal groups (control, diabetes, treatment). The control group was not exposed to any experimental treatment. Streptozotocin was administered to the rats in the diabetes and treatment groups. A 2.5 mL/kg dose of black cumin seed oil was administered daily for 56 days to the treatment group. At the conclusion of the experiment, the blood level of malondialdehyde (MDA) and glutathione (GSH) was measured. The expression level and the cellular distribution of radixin and moesin in the liver were analyzed.The plasma MDA (3.05±0.45 nmol/mL) and GSH (78.49±20.45 μmol/L) levels in the diabetes group were significantly different (p0.01) from the levels observed in the control group (MDA: 1.09±0.31 nmol/mL, GSH: 277.29±17.02 μmol/L) and the treatment group (MDA: 1.40±0.53 nmol/mL, GSH: 132.22±11.81 μmol/L). Immunohistochemistry and western blotting analyses indicated that while the level of radixin was not significantly between the groups (p0.05) and moesin expression was significantly downregulated (p0.05) in the experimental group, the treatment was ineffective.The administered dose was sufficient to prevent oxidative stress, but was not sufficient to alleviate the effects of diabetes on moesin expression in hepatic sinusoidal cells.

Recycling wastes and providing their use in useful fields attract attention every day. In our study, with the extract prepared from the parts of the Cynara scolymus L. (artichoke) plant that is not suitable for human consumption, silver nanoparticles were easily synthesized in an ec-friendly, energy-free way. Characterization of the obtained nanoparticles was done with a UV-visible spectrophotometer (UV-Vis.), fourier transform infrared spectroscopy (FTIR), X-ray diffraction diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), and zeta potential analysis data. In these data, it was determined that AgNPs have a maximum absorbance at 458.8 nm wavelength, a crystal nanosize of 28.78 nm, and a spherical appearance. The zeta potential of (-) 16.9 mV indicates that silver nanoparticles exhibit a stable structure. Particles show antimicrobial effects on pathogenic species at concentrations of 0.03-0.25 μg/ml, and it was determined by using the minimum inhibition concentration (MIC) microdilution method. By examining their cytotoxic effects on U118, CaCo-2, and Skov-3 cancer cell lines and healthy HDF cell lines by the MTT method, concentrations of inhibitive effects on survival were determined.

Zn(II) complex of Schiff base derived from the condensation of 4-aminopyrimidine-2(1H)-one with salicylaldehyde was prepared and characterized by various physico‐chemical and spectral methods for structure determination. The cytotoxic activity of the Zn(II) complex was investigated in comparison with 5-fluorouracil (5-FU) against two different human brain tumor cell lines (T98G and U118), while primer human dermal fibroblast cells (HDF) was used as control for biocompatibility. Then, the effectiveness of electroporation (EP) on cytotoxic activities of these compounds has been examined. The cytotoxicities of the 5-FU and new Zn(II) complex, alone or in combination with electroporation, were determined by MTT assay. The Zn(II) complex showed good cytotoxicity against T98G and U118 brain tumor cell lines with IC50 = 282.47 and 297.91 μM respectively, while it was safe on HDF healthy cells with IC50 = 826.72 μM. The 5-FU exhibited less cytotoxicity compared to the Zn(II) complex against T98G (IC50 = 382.35 μM) and U118 (IC50 = 396.56 μM) tumor cell lines. The combined application of Zn (II) + EP decreased the IC50 value by 5.96-fold in T98G cells and 4.76-fold in U118 cells. EP showed a similar effect in its combined application with 5-FU, resulting in a decrease of the IC50 value of 4.22-fold in the T98G cells and 3.84-fold in the U118 cells. In a conclusion, the Zn(II) complex exhibited an anticancer potential against both brain tumor cell lines (T98G and U118) and EP greatly increased the cytotoxicity of Zn(II) complex and 5-FU on these chemotherapy-resistant cells.

Background: Behcet’s Disease (BD) is a multisystemic inflammatory disorder affecting large vessels, lungs joints, gastrointestinal and neurological systems. The pathogenesis of BD remains poorly understood. Identifying the key signaling pathway is crucial for a complete understanding of the pathogenesis of BD. Objective: The aim of this study was to determine mRNA expression level of Src family kinases (SFKs) members and their involvement in lipopolysaccharide (LPS)-induced mitogen-activated protein kinases (MAPKs) regulation in peripheral blood mononuclear cells (PBMCs) of active BD patients. Methods: Twenty- five active BD patients and twenty-five healthy controls were included in the study. PBMCs were isolated from total blood by density gradient centrifugation. The mRNA expression levels of SFKs members were measured by real-time quantitative PCR (RT-qPCR). The effect of SFKs activity on LPS-induced activation MAPKs (Erk1/2, p38 and JNK) was examined by Western blot. Results: The mRNA expression levels of Hck, Src, Lyn, Yes and Fyn were found to be slightly decreased in active BD patients compared to the control subjects, but a slight change in mRNA level of SFKs members did not impact on protein levels and protein activity. LPS-induced Erk1/2 phosphorylation was significantly increased in the absence of SFKs activity in active BD patients. However, inhibition of SFKs activity had no effect on LPS-induced phosphorylation of p38 and JNK in both controls and active BD patients. Conclusion: SFKs downregulate LPS-induced Erk1/2 phosphorylation in PBMCs of active BD patients.

Background/aim: In this experimental study, we aimed to evaluate the late period effects of the combination of Ankaferd Blood Stopper (ABS), which has bone wound healing effects, and ß-tricalcium phosphate (TCP) on the regeneration of bone tissue through histopathological, immunohistochemical, and radiological (dual energy X-ray absorptiometry - DEXA) methods in nondiabetic rats.Materials and methods: Sixty-four Wistar albino male rats were used. In the calvaria of the rats, a bone defect 7.0 mm in diameter was created. These rats were divided into 4 different groups. Group 1 was the control group without any treatment, a 0.125 mL B-TCP graft was applied to Group 2, a 0.125 mL ABS was applied to Group 3, and a 0.125 mL (ß-TCP + ABS) mixture was applied to group 4. Half of the rats were sacrificed on day 28 and the other half on day 56. Histopathological, immunohistochemical, and DEXA analyses of the specimens were performed after the experiment.Results: As a result of the histopathological analysis, osteoblastic activity and new bone formation were found to be significantly higher in Group 2, Group 3, and Group 4 than the control group on day 28 (P < 0.05). However, inflammatory cell infiltration and vascular dilatation and hemorrhage decreased significantly compared to the control group (P < 0.05). The histopathological analysis in rats on day 56 showed that osteoblastic activity in Group 2 and Group 4 was significantly higher than in the control group, but there was a statistically significant decrease in inflammatory cell infiltration and vascular dilatation and hemorrhage compared to the control group (P < 0.05). New bone formation in Group 2, Group 3, and Group 4 was significantly higher than in the control group. Western blotting findings revealed that the osteonectin and osteopontin expression on day 28 was increased significantly in Group 2 and Group 4. DEXA analyses revealed that BMC values in Group 2 and Group 4 on day 28 were significantly higher than in the control group (P < 0.05). There was no significant difference in bone mineral density values on the 28th and 56th days (P > 0.05). Conclusion: The use of both ß-TCP + ABS and only ABS had positive effects on wound healing and bone formation in nondiabetic rats.