Enhancement of enzyme activity by laser-induced energy propulsion of upconverting nanoparticles under near-infrared light: A comprehensive methodology for in vitro and in vivo applications.

If the appropriate immobilization method and carrier support are not selected, partial decreases in the activity of enzymes may occur after immobilization. Herein, to overcome this challenge, an excitation mechanism that enables energy transfer was proposed. Modified upconverting nanoparticles (UCNPs) were constructed and the important role of near-infrared (NIR) excitation in enhancing the catalytic activity of the enzyme was demonstrated. For this purpose, UCNPs were first synthesized via the hydrothermal method, functionalized with isocyanate groups, and then, PEG-L-ASNase was immobilized via covalent binding. UCNPs with and without PEG-L-ASNase were extensively characterized by different methods. These supports had immobilization yield and activity efficiency of >96 % and 78 %, respectively. Moreover, immobilized enzymes exhibited improved pH, thermal, and storage stability. In addition, they retained >65 % of their initial activity even after 20 catalytic cycles. Biochemical and histological findings did not indicate a trend of toxicity in rats due to UCNPs. Most importantly, PEG-L-ASNase activity was triggered approximately 5- and 2-fold under in vitro and in vivo conditions, respectively. Overall, it is anticipated that this pioneering work will shed new light on the realistic and promising usage of NIR-excited UCNPs for the immobilization of enzymes in expensive and extensive applications.

Does apocynin increase liver regeneration in the partial hepatectomy model?

BACKGROUND: Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats. METHODS: A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. RESULTS: In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). DISCUSSION: Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.

Modeling Based on Ensemble Learning Methods for Detection of Diagnostic Biomarkers from LncRNA Data in Rats Treated with Cis-Platinum-Induced Hepatotoxicity.

BACKGROUND: The first aim of this study is to perform bioinformatic analysis of lncRNAs obtained from liver tissue samples from rats treated with cisplatin hepatotoxicity and without pathology. Another aim is to identify possible biomarkers for the diagnosis/early diagnosis of hepatotoxicity by modeling the data obtained from bioinformatics analysis with ensemble learning methods. METHODS: In the study, 20 female Sprague-Dawley rats were divided into a control group and a hepatotoxicity group. Liver samples were taken from rats, and transcriptomic and histopathological analyses were performed. The dataset achieved from the transcriptomic analysis was modeled with ensemble learning methods (stacking, bagging, and boosting). Modeling results were evaluated with accuracy (Acc), balanced accuracy (B-Acc), sensitivity (Se), specificity (Sp), positive predictive value (Ppv), negative predictive value (Npv), and F1 score performance metrics. As a result of the modeling, lncRNAs that could be biomarkers were evaluated with variable importance values. RESULTS: According to histopathological and immunohistochemical analyses, a significant increase was observed in the sinusoidal dilatation and Hsp60 immunoreactivity values in the hepatotoxicity group compared to the control group (p < 0.0001). According to the results of the bioinformatics analysis, 589 lncRNAs showed different expressions in the groups. The stacking model had the best classification performance among the applied ensemble learning models. The Acc, B-Acc, Se, Sp, Ppv, Npv, and F1-score values obtained from this model were 90%, 90%, 80%, 100%, 100%, 83.3%, and 88.9%, respectively. lncRNAs with id rna-XR_005492522.1, rna-XR_005492536.1, and rna-XR_005505831.1 with the highest three values according to the variable importance obtained as a result of stacking modeling can be used as predictive biomarker candidates for hepatotoxicity. CONCLUSIONS: Among the ensemble algorithms, the stacking technique yielded higher performance results as compared to the bagging and boosting methods on the transcriptomic data. More comprehensive studies can support the possible biomarkers determined due to the research and the decisive results for the diagnosis of drug-induced hepatotoxicity.

Effects of the apricot diets containing sulfur dioxide at different concentrations on rat testicles.

Due to its antioxidant and antimicrobial properties, sulfur dioxide (SO2) is widely used in foods and beverages to prevent the growth of microorganisms and to preserve the color and flavor of fruits. However, the amount of SO2 used in fruit preservation should be limited due to its possible adverse effects on human health. The present study was designed to investigate the effects of different SO2 concentrations in apricot diets on rat testes. Animals were randomly divided into six groups. The control group was fed a standard diet, and the other groups were fed apricot diet pellets prepared with (w/w) 10% dried apricots containing SO2 at different concentrations (1500 ppm, 2000 ppm, 2500 ppm, 3000 ppm, and 3500 ppm/kg) for 24 weeks. After sacrification, testicles were evaluated biochemically, histopathologically, and immunohistopathologically. Our results showed that an apricot diet containing 1500 ppm and 2000 ppm SO2 did not cause significant changes in testis. However, it was determined that tissue testosterone levels decreased as the amount of SO2 (2500 ppm and above) increased. Apricot diet containing 3500 ppm SO2 caused a significant increase in spermatogenic cell apoptosis, oxidative damage, and histopathological changes. In addition, a decrease in the expression of connexin-43, vimentin, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) was observed in the same group. In summary, the results show that sulfurization of apricot at high concentrations such as 3500 ppm may lead to male fertility problems in the long term through mechanisms such as oxidative stress, spermatogenic cell apoptosis, and inhibition of steroidogenesis.

Angiotensin II type 2 receptor agonist treatment of doxorubicin induced heart failure.

Doxorubicin (DOX) is an anthracycline derivative used for treatment of malignancies; however, its clinical use is limited by its cardiotoxicity. We investigated the effects of angiotensin II type 2 receptor agonist compound 21 (C21) on DOX induced heart failure in rat heart. We compared C21 with losartan (LOS), an AT 1 receptor antagonist used for treating heart failure. We allocated 40 rats into five groups of eight: saline treated control group, DOX group administered a single 20 mg/kg dose of DOX, DOX + C21 group administered 0.3 mg/kg C21 for 21 days following the 20 mg/kg dose of DOX, DOX + losartan (LOS) group administered a 21 day regimen of 20 mg/kg LOS following the single dose of DOX, and a DOX + LOS + C21 group administered 0.3 mg/kg C21 and 20 mg/kg LOS for 21 days following the single dose of DOX. We assessed histopathology and conducted echocardiograpic and hemodynamic measurements. Left ventricular ejection fraction (EF) was reduced only in the DOX treated group. C21, LOS and C21 + LOS therapy prevented decreased EF due to DOX. Less histopathology was observed in the DOX + LOS + C21 group than for the other treatment groups. Application of C21 decreased DOX induced cardiac injury similar to LOS. Combined use of C21 and LOS was most beneficial for DOX induced heart failure.

Experimental heart failure models in small animals.

Heart failure (HF) is one of the most critical health and economic burdens worldwide, and its prevalence is continuously increasing. HF is a disease that occurs due to a pathological change arising from the function or structure of the heart tissue and usually progresses. Numerous experimental HF models have been created to elucidate the pathophysiological mechanisms that cause HF. An understanding of the pathophysiology of HF is essential for the development of novel efficient therapies. During the past few decades, animal models have provided new insights into the complex pathogenesis of HF. Success in the pathophysiology and treatment of HF has been achieved by using animal models of HF. The development of new in vivo models is critical for evaluating treatments such as gene therapy, mechanical devices, and new surgical approaches. However, each animal model has advantages and limitations, and none of these models is suitable for studying all aspects of HF. Therefore, the researchers have to choose an appropriate experimental model that will fully reflect HF. Despite some limitations, these animal models provided a significant advance in the etiology and pathogenesis of HF. Also, experimental HF models have led to the development of new treatments. In this review, we discussed widely used experimental HF models that continue to provide critical information for HF patients and facilitate the development of new treatment strategies.

Effects of apocynin on sciatic nerve injury in rabbits.

We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.

Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II-induced hypertension.

The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin-angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II-induced hypertension in rats. Sprague Dawley rats were subject to 4-week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 µg/kg), AVE0991 (576 µg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail-cuff plethysmography at 1, 15, and 29 days post-treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin-A (CYP-A), monocyte chemoattractant protein-1 (MCP-1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase-2 and -9, NADPH oxidase-4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP-1 and CYP-A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin-converting enzyme-2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II-induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.

An experimental rat model of electric shock injury with isolated electric shock and water conduction: the histopathological changes on the skin and internal organs and the effect on biochemical parameters.

It is difficult to determine the cause of death in electric shock injuries when no trace can be determined on the skin, and this is accepted as a reason for negative autopsy. We aimed to determine useful parameters in the definition of the cause of deaths associated with electric shock and particularly those formed with water conduction. This study used a total of 42 rats, applied with fatal electric shock formed of isolated electric shock at 220 V and with water conduction. The serum NT-ProBNP and H-FABP levels were examined together with histopathological changes in the brain, cerebellum, brainstem, heart, liver and skin and the Bax, caspase-3 and HSP-60 antibody status in these tissues. A statistically significant difference was determined between the groups in respect of the serum H-FABP values and the immunohistochemical staining of the samples taken from the organs. In conclusion, this study is the first in literature with an experimental model of electric shock with water conduction. Using immunohistochemical and biochemical markers in deaths associated with isolated electric shock and electric shock with water conduction, the results of this study can contribute to the clarification of one of the reasons for negative autopsy in forensic medicine.

Fast Curing Multifunctional Tissue Adhesives of Sericin-Based Polyurethane-Acrylates for Sternal Closure.

The use of wire cerclage after sternal closure is the standard method because of its rigidity and strength. Despite this, they have many disadvantages such as tissue trauma, operator-induced failures, and the risk of infection. To avoid complications during sternotomy and promote tissue regeneration, tissue adhesives should be used in post-surgical treatment. Here, we report a highly biocompatible, biomimetic, biodegradable, antibacterial, and UV-curable polyurethane-acrylate (PU-A) tissue adhesive for sternal closure as a supportive to wire cerclage. In the study, PU-As were synthesized with variable biocompatible monomers, such as silk sericin, polyethylene glycol, dopamine, and an aliphatic isocyanate 4,4'-methylenebis(cyclohexyl isocyanate). The highest adhesion strength was found to be 4322 kPa, and the ex vivo compressive test result was determined as 715 kPa. The adhesive was determined to be highly biocompatible (on L-929 cells), biodegradable, and antibacterial (on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus bacteria). Finally, after opening the sternum of rats, the adhesive was applied to bond the bones and cured with UV for 5 min. According to the results, there was no visible inflammation in the adhesive groups, while some animals had high inflammation in the cyanoacrylate and wire cerclage groups. These results indicate that the adhesive may be suitable for sternal fixation by preventing the disadvantages of the steel wires and promoting tissue healing.

Effects of taurine and apocynin on the zone of stasis.

BACKGROUND: Among the zones of coagulation, hyperemia and stasis that occur in the burned area, the most intense metabolic process and the highest sensitivity to recovery with treatment is the zone of stasis.This metabolic process is related to how well the tissues in the zone of stasis can cope with oxidative stress. If the tissues in the zone of stasis are saved, the burn area will potentially heal faster and with less scar. In this study, we examined the effects of taurine amino acids and apocynin molecules on saving the tissues in the burn zone of stasis. METHODS: The study was conducted with 48 rats. The burn zone of stasis was created according to the pattern previously described in the literature as comb burn model. In the 21-day study, biopsies were taken for histological examination on the 3rd, 7th and 21st days of the study. In addition, macroscopic photographic analysis was performed. Biopsies were taken for biochemical analysis on the 21st day. Histologically, inflammation, reepithelialization, and collagenization were evaluated, and the CD34 immunoreactivity was analysed. Biochemically, CAT, SOD, tGSH, TAS, TOS, MDA and PPC values were determined. RESULTS: In the histological examination, on the 3rd, 7th and 21st days, inflammation was found to be reduced in the groups given taurine and apocynin on the 3rd day. On the 7th day, better reepithelialization and collagenization were observed in the group given taurine. Significant reepithelialization, collagenization and hair follicle development were observed in the groups given taurine and apocynin on the 21st day. In the biochemical analysis, the effects of apocynin on antioxidant enzymes were determined to be prominent. While we found no significant difference on the 3rd and 7th days in the photographic analysis, taurine and apocynin were observed to act synergistically on the 21st day and significantly reduced the burned areas. CONCLUSION: On the 3rd day, taurine and apocynin prevented inflammation, the effects of taurine in the zone of stasis in the early period (7th day) are more pronounced, the effect of apocynin on antioxidant enzymes is more pronounced. In the late period (21st day), taurine and apocynin were found to be more effective in saving the zone of stasis by creating a synergistic effect.

Effects of Low- and High-Dose Valproic Acid and Lamotrigine on the Heart in Female Rats.

Epilepsy is a chronic neurological disease that affects more than 50 million people worldwide. Antiepileptic drugs (AEDs) are the mainstay of treatment for most patients with epilepsy. However, AEDs have been reported to be associated with adverse cardiac effects. In this study, it was aimed to investigate the possible cardiac effects of low-dose (LD) and high-dose (HD) treatment of valproic acid (VPA) and lamotrigine (LTG), which are commonly used AEDs, in rats without epilepsy. Rats were randomly grouped as control, LD-VPA, HD-VPA, LD-LTG, and HD-LTG. The cardiac effects of AEDs were evaluated using immunohistological, biochemical, and hemodynamic parameters. A dose-dependent increase in the intensity of caspase-3 staining was detected in the VPA and LTG groups. The intensity of connexin-43 and troponin-T staining in the VPA groups and desmin staining in the LTG groups was significantly reduced. Biochemically, HD-VPA and HD-LTG administrations caused a significant increase in MDA level in myocardial tissue. In addition, as a result of hemodynamic evaluations, cardiac functions were found to be affected and blood pressure increased in HD-LTG group. The results of present study support that VPA and LTG treatment can increase cardiac risk markers.

Dose-dependent subacute cardiovascular effects of modafinil in rats.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

The effect of genistein on cisplatin induced ototoxicity and oxidative stress.

OBJECTIVE: Cisplatin is an antineoplastic agent used in adults and children for the treatment of various malignant diseases. It can cause irreversible ototoxicity. Genistein is a phytoestrogen. Genistein functions as an antioxidant and cell cycle inhibitor by inhibiting the DNA topoisomerase and tyrosine protein kinase enzymes. The protective effect of genistein in preventing cisplatin-induced ototoxicity and levels of the oxidative stress was investigated. METHODS: 32 Sprague Dawley rats were used in 4 groups (control, cisplatin, cisplatin + genistein, genistein). Otoacoustic emission measurements of the distortion product were performed on the 1st, 2nd and 5th days of the test protocol. Serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, total antioxidant status, total oxidant status and oxidative stress index measurements were made. RESULTS: The hearing of the cisplatin + genistein group was found to be better than that of the cisplatin group. While the malondialdehyde, total oxidant status and oxidative stress index parameters decreased significantly in the cisplatin + genistein group compared to the cisplatin group, superoxide dismutase increased significantly (p < 0.05). CONCLUSION: Genistein showed positive effects against ototoxicity with its antioxidant effect. LEVEL OF EVIDENCE: Level 3.

Effects of antiepileptic drugs on ovaries of female Wistar rats.

Valproate (VPA) induced changes in ovarian morphology are observed in humans with epilepsy and in non-epileptic animals. The effects of lamotrigine (LTG) on female reproduction is not well known. We investigated whether LTG might be a safer drug for use with patients of reproductive age. Forty Wistar albino female rats were divided into five groups. The control group was injected with saline-vehicle solution. The low dose (LD)-VPA group was injected with 100 mg/kg VPA. The high dose (HD)-VPA group was injected with 500 mg/kg VPA. The LD-LTG group was injected with 10 mg/kg LTG. The HD-LTG group was injected with 50 mg/kg LTG. We evaluated histological and biochemical changes in the ovaries. The number of atretic and cystic follicles was increased in the HD-VPA and HD-LTG groups compared to the control group. A significant increase in malondialdehyde level was found in the VPA groups compared to the control and LTG groups. No significant differences in total glutathione levels or superoxide dismutase activity were found among study groups. Catalase activity was significantly higher in HD-VPA and HD-LTG groups compared to the control, LD-VPA and LD-LTG groups. Prevalence and intensity of caspase-3 immunoreactivity in the luteal cells were significantly greater in the HD-LTG group compared to the control group. VPA administration caused polycystic ovarian syndrome-like changes in the ovary. We found that LD-LTG, which reflects the dose for humans, might be a safer option for use during the reproductive age.

Protective effects of apocynin against ionizing radiation-induced hepatotoxicity in rats.

Radiation hepatotoxicity is thought to be due to free oxygen radicals. We investigated the protective effects of apocynin (APO) against ionizing radiation induced oxidative stress in liver tissue following whole body ionizing radiation. We divided rats into four groups. The control group was injected intraperitoneally (i.p.) with saline for five consecutive days. A second group was injected i.p. with saline for 5 days and after 24 h, a single-dose of radiation (800 cGy) was administered to the whole abdomen. A third group was injected i.p. with 20 mg/kg APO for 5 days. A fourth group was injected i.p. with APO for 5 days and after 24 h, the rats were exposed to radiation. Ionizing radiation induced hepatotoxicity was demonstrated biochemically by significant changes in oxidative and antioxidant parameters. Our findings suggest that APO treatment may be protective against radiation induced hepatic injury by decreasing oxidative stress and increasing antioxidant activity.

Histological assessment of liver and stomach damage caused by pyridazinone derivative antidepressant agents.

Depression is a serious psychological disorder that affects a significant population. We investigated the antidepressant activities of four pyridazinone derivatives that contain the hydrazide moiety using the forced swimming test (FST). The compounds tested exhibited good antidepressant activity compared to duloxetine. The most promising compound was compound 2, which reduced the duration of immobility during FST. The toxic effects of the four compounds on the histomorphology of the liver and stomach tissue also was evaluated.

Photocrosslinkable gelatin/collagen based bioinspired polyurethane-acrylate bone adhesives with biocompatibility and biodegradability.

Hard or soft tissue adhesives have been presented as a promising candidate to replace traditional wound closure methods. However, there are mechanical strength problems in biological adhesives and biocompatibility problems in synthetic-based adhesives. At this point, we aimed to remove all these disadvantages and produce a single adhesive that contains all the necessary features and acrylate functionalized UV-curable polyurethane formulations were produced with high crosslink density, high adhesion strength, biocompatibility and injectable property for easy application as potential biomedical adhesives. Aliphatic isophorone diisocyanate (IPDI) was used as the isocyanate source and ß-cyclodextrin was used for host-guest relationship with gentamicin by crosslinking. Proteins (gelatin (GEL), collagen (COL)) and PEGs of various molecular weight ranges (P200, P400, P600) were selected as the polyol backbone for polyurethane synthesis due to their multiple biological activities such as biocompatibility, biodegradability, biomimetic property. Several techniques have been used to characterize the structural, thermal, morphological, and various other physicochemical properties of the adhesive formulations. Besides, the possibility of its use as a hard tissue adhesive was investigated by evaluating the tissue adhesion strength in vitro and ex vivo via a universal testing analyzer in tensile mode. Corresponding adhesive formulations were evaluated by in vitro and in vivo techniques for biocompatibility. The best adhesion strength results were obtained as 3821.0 ±â€¯214.9, and 3722.2 ±â€¯486.8 kPa, for IPDI-COL-P200 and IPDI-GEL-P200, respectively. Good antibacterial activity capability toward Escherichia coli Pseudomonas aeruginosa, and Staphylococcus aureus were confirmed using disc diffusion method. Moreover, cell viability assay demonstrated that the formulations have no significant cytotoxicity on the L929 fibroblast cells. Most importantly, we finally performed the in vivo biodegradability and in vivo biocompatibility evaluations of the adhesive formulations on rat model. Considering their excellent cell/tissue viability, fast curable, strong adhesion, high antibacterial character, and injectability, these adhesive formulations have significant potential for tissue engineering applications.

Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs.

Immunosuppressive drugs used in the transplantation period are generally defined as induction and maintenance therapy. The use of immunosuppressants, which are particularly useful and have fewer side effects, decreased both mortality and morbidity. Many drugs such as steroids, calcineurin inhibitors (cyclosporine-A, tacrolimus), antimetabolites (mycophenolate mofetil, azathioprine), and mTOR inhibitors (sirolimus, everolimus) are used as immunosuppressive agents. Although immunosuppressant drugs cause many side effects such as hypertension, infection, and hyperlipidemia, they are the agents that should be used to prevent organ rejection. This shows the importance of individualized drug use. The optimal immunosuppressive therapy post-transplant is not established. Therefore, discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard.Our review discussed the mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation.

Preoperative and Postoperative Endogenous Melatonin and Anxiety Levels and Their Correlation in Living Liver Donors.

OBJECTIVES: High anxiety levels may lead to mental and physical changes that may affect quality of life. Melatonin has anxiolytic properties. It has been reported that administration of melatonin reduces anxiety. In this study, we examined the preoperative and postoperative anxiety levels of living liver donors and the correlation between anxiety levels and endogenous melatonin levels. MATERIALS AND METHODS: This prospective clinical study included 56 living liver donors who underwent right hepatectomy (39 women, 17 men; average age of 29 ± 7 years). The anxiety levels were evaluated by using the Spielberger State-Trait Anxiety Inventory Test with a form for this test used to measure the current state of anxiety score and another form used to measure the underlying anxiety score of the patient. These forms were applied preoperatively and postoperatively. Blood samples were taken simultaneously for melatonin levels. Melatonin levels were measured using high-pressure liquid chromatography. Our primary outcomes were to determine the preoperative and postoperative endogenous melatonin and anxiety levels of living liver donors and to investigate their correlations. RESULTS: A statistically significant difference was observed between preoperative and postoperative state of anxiety scores. The preoperative and postoperative underlying anxiety scores were similar. A statistically significant difference was found between the preoperative endogenous melatonin level and postoperative endogenous melatonin level. A significant correlation was not observed between the preoperative and postoperative current and underlying anxiety levels or endogenous melatonin levels. CONCLUSIONS: Living liver donors had high anxiety levels during the preoperative and postoperative periods. A significant decrease was identified in the postoperative hour 24 endogenous melatonin level. These results may lay the foundation for interventions that can identify emotional changes as well as control and improve the mental health of living liver donors.