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Dentin tissue can act as a reservoir for bioactive molecules that create signals for cellular proliferation and differentiation to initiate tissue regeneration. Therefore, the aim of this study is to compare the cell viability, inflammatory response, and antimicrobial activity of bovine dentin grain-added calcium-hydroxide (CH-BDG) with different pulp-capping materials.

Aim: In this study, sensitivity and specificity of the albumin-bilirubin (ALBI) score were investigated to detect significant liver fibrosis, and these findings were then compared to fibrosis-4 (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) scores. Material and Methods: A total of 69 patients were included in the study. Of these patients, 54 (78.3%) were male and 15 (21.7%) were female. Serology, molecular analysis, biochemical parameters, and pathology results of the patients who underwent a liver biopsy due to a chronic hepatitis B virus (HBV) infection, were retrospectively evaluated. ALBI, APRI, and FIB-4 scores were calculated. To predict the fibrosis stage, F≥2 and F≥4, ALBI, APRI, and FIB-4 scores were investigated using the receiver operator characteristic (ROC) curve analysis. Results: The area under the ROC curve with 95% confidence interval (CI) for the ALBI, APRI, and FIB-4 scores were 0.613 (95% CI: 0.463-0.762, p=0.160), 0.658 (95% CI: 0.513-0.803, p=0.040), and 0.731 (95% CI: 0.570-0.891, p=0.004), respectively, to predict the F≥2, and 0.758 (95% CI: 0.544-0.971, p=0.090), 0.604 (95% CI:0.451-0.757, p=0.490), and 0.923 (95% CI: 0.856-0.990, p=0.005), respectively, in prediction of F≥4. The sensitivity and specificity rates of the ALBI score were 61.1% and 64.7%, respectively, for the cut-off value of -2.81 in predicting F≥2, and 75.0% and 70.8% for the cut-off value of -2.78 in predicting F≥4. Conclusion: ALBI scores can be used to detect F≥2 in patients with chronic HBV. However, it is not yet clear whether this approach is superior to other non-invasive methods for detecting F≥4.

Aluminum alloys have inherent tendencies to produce casting defects caused by alloying or metal melt flow inside the mold. The traditional detection method for these defects includes reduced pressure tests, which assess metal quality in a destructive manner. This leaves a gap between metal quality assessments and tensile test correlations. Computed tomography (CT) scans offer crucial assistance in evaluating the internal quality of castings without damaging the structure. This provides a valuable opportunity to couple mechanical tests with numerical methods such as finite element analysis to predict the mechanical performance of the alloy. The present study aims to evaluate the internal quality of cast aluminum alloys using CT scans and to correlate the defect metrics obtained from CT scans with mechanical test results. The Gurson-type material model and finite element methodology have been used to validate the correlation studies. Therefore, we propose a more holistic approach to predicting the behavior of metals by coupling damage models with CT scans and mechanical tests. The study investigates several CT metrics such as the defect volume, total defect surface, biggest defect surface, and projected area of defects. The conclusion reveals that CT scans provide crucial assistance in evaluating the internal quality of castings, and CT defect metrics can be used to build correlations between mechanical tests and CT evaluations. The study also suggests that the concept of adjusted representative material yield parameter (ARMY) or computed representative material yield parameter (CRMY) can be used to correlate CT metrics with mechanical strength in cast materials and parts for a given aluminum alloy. Overall, the study proposes a more comprehensive methodology to assess the quality of cast aluminum alloys and couple the quality to mechanical performance.

Introduction This study aimed to reveal the utility of age-platelet (AP) index and aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), which are non-invasive markers, in patients with chronic Hepatitis C virus (HCV) infection in prediction of fibrosis and evaluate whether viral markers could be used for that purpose or not. Methods A total of treatment-naïve 49 patients with chronic HCV who underwent liver biopsy were included in this retrospective study. Anti-HCV S/CO and HCV-RNA viral load (copy/ml) values measured simultaneously with biopsy were determined. AP index and AAR score were calculated and compared. Results Staging of liver biopsy samples of 49 HCV patients was assessed. Comparable diagnostic accuracies of AP index and AAR in prediction of significant fibrosis (F≥2) were showed with ROC curve analysis. The areas under the ROC (AUROCs) were 0.713 and 0.506 respectively. Diagnostic accuracy of API in prediction of significant fibrosis was superior to that of AAR (p=0.03). AUROC of HCV-RNA viral load in prediction of F≥2 was 0.531. Anti-HCV S/CO value (AUROC=0.464) was not found as a suitable marker in prediction of fibrosis. Conclusions AP index, AAR score and HCV viral load among non-invasive markers assessed in this study were useful in predicting significant fibrosis. Especially API was the most useful test in predicting significant fibrosis. AP index can be preferred in patients with near normal ALT values.

Detailed and accurate measurements can be done by using laser scanning technology compared to conventional methods in documentation of cultural heritage. Accuracy of measured data directly affects the protection of historical buildings and decision-making process. By processing laser scanning data, multipurpose 3d models can be obtained and all work and results can be shared via internet. Moreover, a detailed analysis of the building can be made with this data and it can be transferred to all related engineering and archeological fields. Despite the advantages of this technology, it has not been used widely yet in production of architectural projects. High cost of equipment and data processing software have been seen as main obstacles for widespread using of this technology. As well as, lack of integration of this topic into architectural education and less number of researcher studying in this field restrict the use of laser scanner. In this paper, evaluations were made in order to define the possibilities by using laser scanner technologies in process of restoration projects of which number is getting increased in last decades in Turkey. Positive and negative aspects of technology observed in survey process were given with a case study, a small traditional house in province of Aksaray and some reviews related to potential use of laser scanner technologies were made in Turkey.

Art of animation has developed very rapidly from the aspects of script, sound and music, motion, character design, techniques being used and technological tools being developed since the first years until today. Techical variety attracts a particular attention in the art of animation. Being perceived as a kind of illusion in the beginning; animations commonly used the Flash Sketch technique. And then tools like Magical Lantern, Thaumatrope, Phenakisticope and Zeotrap were developed and started to be used intensely in the first years of the art of animation. Today, on the other hand, the art of animation is affected by developments in the computer technology. It is possible to create three dimensional and two dimensional animations with the help of various computer softwares. Cut-out technique is among the important techniques being used in the art of animation. Cut-out animation technique is based on the art of paper cutting. This study titled “Cut-out Animation as an Technic and Development Inside History Process” will embrace the art of paper cutting, the relationship between the art of paper cutting and cut-out animation, its development within the historical process, animation artists producing artworks in this field, important cut-out animations and their technical properties.

Objective: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. Material and Method: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. Results: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. Conclusion: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.

Purpose: Anastomotic leaks following intestinal operations may cause devastating effects on patients. Ischemia may also occur at the intestinal walls in the presence of strangulations. In this study, we examined the effects of human recombinant (Hr)-epidermal growth factor (EGF) given at a single intramural dose into the intestinal walls and daily intraperitoneal cavity on ischemia and the healing process of anastomosis. Materials and Methods: Sixteen male New Zeland white rabbits were randomly divided into four groups (n = 4 in each group). In Group 1, two different segments of ileum were identified and, then, transected and the free ends were sutured each other. In the other groups, ischemia was induced by ligating the mesenteric vascular arcade. After the ischemic induction, Group 2 received intramural injections of %0.9 saline, Group 3 received intramural injections of a single dose of EGF, and Group 4 received intramural and intraperitoneal injections of EGF. Bursting pressures and tissue hydroxyproline levels were analyzed. Necrosis, fibroblastic activity, collagen deposition and neovascularization were also studied. Results: The mean levels of bursting pressures in Group 4 (148.6 ± 25.3 mmHg) were higher than Group 2 (70 ± 21.5 mmHg) (p = 0.001). The mean level of bursting pressures was not statistically significant between Group 1 (170.1 ± 35 mmHg) and Group 4 (p = 0.073). Hydroxyproline levels in Group 2 were lower than Groups 3 and 4. There was a statistically significant difference in the mucosal ischemia, mucosal healing and degree of adhesion, but not in the mural anastomotic healing among the groups. Conclusions: Intramural injection with daily intraperitoneal administration of low-dose EGF enhances the bursting pressure and collagen accumulation in ischemic anastomosis, improving many histological variables associated with ischemic intestinal anastomosis.

Background: Intraabdominal adhesions remain a significant cause of morbidity and mortality. Moreover, intraabdominal adhesions can develop in more than 50% of abdominal operations. Aims: We compared the anti-adhesive effects of two different agents on postoperative adhesion formation in a cecal abrasion model. Study Design: Experimental animal study. Methods: Forty Wistar albino type female rats were anesthetized and underwent laparotomy. Study groups comprised Sham, Control, Mitomycin-C, 4% Icodextrin, and Mitomycin-C +4% Icodextrin groups. Macroscopic and histopathological evaluations of adhesions were performed. Results: The frequencies of moderate and severe adhesions were significantly higher in the control group than the other groups. The mitomycin-C and Mitomycin-C +4% Icodextrin groups were associated with significantly lower adhesion scores compared to the control group and 4% Icodextrin group scores (p=0.002 and p=0.008, respectively). The adhesion scores of the Mitomycin-C group were also significantly lower than those of the 4% Icodextrin group (p=0.008). Conclusion: Despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials

Angiomyofibroblastoma (AMFB) is a rare seen mesenchymal tumor that is categorized as a genital stromal tumor. It is commonly seen in the middle-aged women usually affecting the labia majora and rarely the vagina. A variant called AMFB-like tumors are also rarely seen in male patients. AMFB with its clinical presentation and location can be wrongly diagnosed as an aggressive angiomyxomas, bartholin cyst or lower genital tract lipomas. In the patients who are applying because of the vulvar mass, AMFB should not be forgotten for the pre-diagnosis. The treatment is generally simple surgical excision.In this case, AMFB was reported with a wrongly pre-diagnosis as a bartholin cyst to which a medical treatment had been given. [Cukurova Med J 2015; 40(4.000): 822-825]

Angimyofiblastomlar(AMFB), genital stromal tümörler içerisinde yer alan,nadir izlenen benign mezenkimal tümörlerdir. Genellikle orta-yaş bayanlarda görülüp, sıklıkla labium majörü daha az sıklıklada vajinayı etkileyebilmektedir. AMFB benzeri tümörler adı altında, nadiren erkekler de görülebilmektedir. Yerleşim yeri ve klinik prezentasyonu ile bartolin kistleri, alt genital tract lipomları veya nadiren de agresif anjiyomiksomalar ile karışabilmektedir. Vulvar kitle ile başvuran hastalarda, ön tanıda AMFB ler unutulmamalıdır. Tedavisi genellikle basit cerrahi eksizyondur.Bu olguda, bartolin kist yanlış ön tanısı ile medikal tedavi verilen AMFB olgusundan bahsedildi

Appendiks intussussepsiyonu nadir görülen ve semptomlarının apandisite olan benzerliği nedeniyle hem klinik hem de radyolojik olarak preoperatif tanısı oldukça güç olan bir durumdur. Burada akut batın bulguları ile başvuran tanı ve tedavi sonrasında appendiks intussussepsiyonu olarak değerlendirilen olguyu bildirdik. Diagnostik görüntüleme yöntemleri gelişmiş olsa da bazen preoperatif dönemde tanı koymada yardımcı olmamaktadırlar. Bu yüzden doktorlar akut batın ile başvuran hastalarda akut apandisit, tümör ve ek olarak intussussepsiyonu alternatif tanı olarak düşünmeleri önerilir.

Intussusception of the appendix is a rare condition. As the symptoms can mixed with acute apandicitis, the diagnosis is difficult both clinically and radiologically at the preoperative period. This article reports a case of appendiceal intussusception who was presented as acute abdomen. Although diagnostic imaging was improved, sometimes preoperative findings are not enough helpful for the diagnosis. Therefore doctors should consider alternative diagnosis such as appendicitis, tumor in addition to intussusception at acute abdomen . [Cukurova Med J 2012; 37(4.000): 238-242]

Background: Harmonic Scalpel and PlasmaKinetic have become popular with the promise of quick and effective vascular control. Their excellent outcomes encouraged surgeons to use these instruments for closure of the bile ducts with little or no data, establishing their efficacy or safety. Aim: The aim of this experimental study was to compare the safety and feasibility of different cystic duct closure methods (suture ligation, clip application, Harmonic Scalpel and PlasmaKinetic). Methods: Sixty non-perforated gallbladders extracted during laparoscopic cholecystectomy were studied in this ex vivo study. Gallbladders were randomly divided into four groups and the distal end of cystic ducts remaining with sacs was reclosed by one of the four different methods. By means of a catheter, air insufflation was administered into gallbladders with a pressure-controlled pump. Bursting pressure and lateral thermal injury were measured for each group, and groups were compared with each other. Results: In the Harmonic Scalpel group, a 1.4 mm lateral thermal injury was detected, while it was 1.6 mm in the PlasmaKinetic group. But, in terms of bursting pressure, there was not a statistically significant difference between the groups. Conclusion: Cystic duct closure with the new devices may be an alternative to surgical clips. Further trials are needed to evaluate the feasibility and safety of PlasmaKinetic usage in the clinical setting. [Arch Clin Exp Surg 2012; 1(3.000): 168-171]

Objective: The aim of this study was to determine the potential, protective effects of amlodipine in an experimental, ischemia-reperfusion (I/R) model in the rabbit small intestine. Materials and Methods: The rabbits were divided into four groups: sham-operated, amlodipine (10 mg/kg) + sham-operated, I/R, and I/R + amlodipine (10 mg/kg) groups. An intestinal I/R model was applied to the rabbits. The superior mesenteric artery was occluded for 1 h with an atraumatic vascular clamp and then was reperfused for 2 h. Animals in the amlodipine and I/R + amlodipine groups received the amlodipine by oral gavage. At the end of the 2-h-reperfusion period, the animals were sacrificed. Results: Pretreatment with amlodipine significantly increased SOD activity and GSH levels to values close to those found in the serum from the I/R group. Rabbits in the I/R group showed high levels of serum MDA. Amlodipine pretreatment significantly reduced the serum MDA levels compared to the I/R group, although the MDA levels in the I/R + amlodipine group were still higher than in the sham-operated group. The I/R damage was ameliorated by amlodipine pretreatment, as evidenced by histopathological analysis. Conclusion: The present study is the first to report an attenuation of I/R-induced intestinal injury by the systemic administration of amlodipine.

Introduction. Ingestion of corrosive substances may lead to stricture formation in esophagus as a late complication. Full thickness injury seems to exterminate tissue stem cells of esophagus. Mesenchymal stem cells (MSCs) can differentiate into specific cell lineages and have the capacity of homing in sites of injury. Aim and Methods. We aimed to investigate the efficacy of MSC transplantation, on prevention of esophageal damage and stricture formation after caustic esophagus injury in rats. 54 rats were allocated into four groups; 4 rats were sacrificed for MSC production. Group 1, untreated controls (n: 10). Group 2, membrane labeled MSCs-treated rats (n: 20). Group 3, biodistribution of fluorodeoxyglucose labeled MSCs via positron emission tomography (PET) imaging (n: 10). Group 4, sham operated (n: 10). Standard caustic esophageal burns were created and MSCs were transplanted 24 hours after. All rats were sacrificed at the 21st days. Results. PET scan images revealed the homing behavior of MSCs to the injury site. The histopathology damage score was not significantly different from controls. However, we demonstrated Dil labeled epithelial and muscle cells which were originating from transplanted MSCs. Conclusion. MSC transplantation after caustic esophageal injury may be a helpful treatment modality; however, probably repeated infusions are needed.

Giant symplastic leiomyoma of the gluteal region is a rarely seen situation. It is accepted as a benign illness. A 36-year- old woman presented to general surgery clinic because of a mass on her right thigh. On physical examination, there was a 7 x 6 cm mass that was mobile and bulging up from the surface of skin, 3 cm from her anus. Pathologic examination revealed symplastic leiomyoma. Leiomyomas are benign smooth muscle tumors. After excision, dermal lesions have a 40% recurrence rate. Even if mitotic activity can be shown microscopically, follow-up is important and unnecessary treatment for symplastic leiomyoma must be avoided. [Arch Clin Exp Surg 2015; 4(2.000): 101-102]

NLRP1 is predominantly overexpressed in breast cancer tissue, and the evaluated activation of NLRP1 inflammasome is associated with tumor growth, angiogenesis, and metastasis. Therefore, targeting NLRP1 activation could be a crucial strategy in anticancer therapy. In this study, we investigated the hypothesis that NLRP1 pathway may contribute to the cytotoxic effects of celecoxib and nimesulide in MDA-MB-231 cells. First of all, IC 50 values and inhibitory effects on the colony-forming ability of drugs were evaluated in cells. Then, the alterations in the expression levels of NLRP1 inflammasome components induced by drugs were investigated. Subsequently, the release of inflammatory cytokine IL-1β and the activity of caspase-1 in drug-treated cells were measured. According to our results, celecoxib and nimesulide selectively inhibited the viability of MDA-MB-231 cells. These drugs remarkably inhibited the colony-forming ability of cells. The expression levels of NLRP1 inflammasome components decreased in celecoxib-treated cells, accompanied by decreased caspase-1 activity and IL-1β release. In contrast, nimesulide treatment led to the upregulation of the related protein expressions with unchanged caspase-1 activity and increased IL-1β secretion. Our results indicated that the NLRP1 inflammasome pathway might contribute to the antiproliferative effects of celecoxib in MDA-MB-231 cells but is not a crucial mechanism for nimesulide., (© 2024. The Author(s).)

Objectives: In recent years, there has been a growing interest in targeting ferroptosis for the treatment and prevention of multiple cancers. This study aimed to assess the contribution of ferroptosis to the antiproliferative effects of genistein (GN) and daidzein (DZ) in breast cancer cell lines., Methods: MDA-MB-231 and MCF-7 cells were employed as an in vitro model. The antiproliferative effects of GN and DZ were determined by WST-1 assay in the presence of specific inhibitors of different cell death pathways. The mRNA expressions of Gpx4 and Fsp-1, the levels of lipid peroxidation, glutathione (GSH)/glutathione disulfide (GSSG) ratio, and intracellular iron ion content were assessed in GN- or DZ-treated cells., Results: GN and DZ were found to cause ferroptotic cell death in MDA-MB-231, as confirmed by the reversal of viability when cells were pretreated with ferrostatin-1. Furthermore, both phytochemicals induced biochemical markers of ferroptosis, including lipid peroxidation and iron ions levels, and decreased GSH/GSSG levels. The mRNA expression levels of the main anti-ferroptotic genes, Gpx4 and Fsp-1, were diminished by the treatment of both phytochemicals. Surprisingly, ferroptosis did not play a role in GN- or DZ-induced cell death in MCF-7 cells., Conclusion: Our findings highlight the potential of GN and DZ as ferroptosis inducers in triple-negative breast cancer cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Objectives: Previous studies have shown that gene expressions can be regulated in the hippocampus of rats after seizures induced by kainic acid (KA). The aim of this study was to examine the potential regulatory impact of KA administration on gene expression levels of enzymes responsible for drug metabolism in rat hippocampal tissue., Materials and Methods: Rats received intraperitoneal injections of KA and saline at a dose of 10 mg/kg. Behavioral changes were observed in experimental animals following the administration of KA. Four hours after receiving treatments, all rats were decapitated, and the brains were removed. Hippocampal tissues were used for total RNA isolation, and cDNA synthesis was performed by reverse transcription polymerase chain reaction (PCR). Gene expression levels of enzymes responsible for drug metabolism were determined by quantitative PCR using the RT 2 Profiler PCR Array Rat Drug Metabolism PCR array system containing the relevant primers for a total of 84 genes. The gene expression levels of drug-metabolizing enzymes were quantified using the comparative Ct (2 -ΔΔ(delta delta)Ct ) method. The Student's t-test was used for data analysis., Results: Our results indicate that KA treatment caused significant changes in the gene expression levels of metallothionein 3, glucose phosphate isomerase, adenosine triphosphate-binding cassette protein C1, cytochrome P450 enzymes (Cyp2c6v1, Cyp3a23/3a1, Cyp2c7), glutathione peroxidase 1, 4, and 5, glutamic acid decarboxylase 1 and 2, paraoxonase 2, carbohydrate sulfotransferase 1, glutathione S-transferases (Gsta3, Gstm1, Gstm4), microsomal glutathione S-transferase 3, carboxylesterase 2C, fatty acid amide hydrolase, pyruvate kinase-muscle, arachidonate 5-lipoxygenase, apolipoprotein E, cytochrome b5 reductase 5, xanthine dehydrogenase, N-acetyltransferase 1, glucokinase regulator, hexokinase 2, myristoylated alanine rich protein kinase C substrate, and stannin in the hippocampus compared with the control ( p < 0.05)., Conclusion: As a conclusion, it can be said that the seizure activity triggered by KA has the potential to change the gene expression levels of the enzymes responsible for drug metabolism in the hippocampus of rats., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright© 2024 The Author. Published by Galenos Publishing House on behalf of Turkish Pharmacists’ Association.)

Study Design: Pre-clinical animal experiment., Objective: In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron-dependent non-apoptotic cell death, is shown to be influential in the pathogenesis of SCI., Methods: The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow-up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe 2+ levels were measured by spectrophotometry. Glutathione peroxidase-4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4-hydroxynonenal (4-HNE)-modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso-Beattie-Bresnahan test., Results: Silibinin achieved significant suppression in MDA and 4-HNE levels compared to the SCI both in 72-h and 6 weeks group ( p  < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups ( p  < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group ( p  < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups ( p  < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI ( p  < 0.05)., Conclusion: Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

A series of tacrine-donepezil hybrids were synthesized as potential multifunctional anti-Alzheimer's disease (AD) compounds. For this purpose, tacrine and the benzylpiperidine moiety of donepezil were fused with a hydrazone group to achieve a small library of tacrine-donepezil hybrids. In agreement with the design, all compounds showed inhibitory activity toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC 50 values in the low micromolar range. Kinetic studies on the most potent cholinesterase (ChE) inhibitors within the series showed a mixed-type inhibition mechanism on both enzymes. Also, the docking studies indicated that the compounds inhibit ChEs by dual binding site (DBS) interactions. Notably, tacrine-donepezil hybrids also exhibited significant neuroprotection against H 2 O 2 -induced cell death in a differentiated human neuroblastoma (SH-SY5Y) cell line at concentrations close to their IC 50 values on ChEs and showed high to medium blood-brain barrier (BBB) permeability on human cerebral microvascular endothelial cells (HBEC-5i). Besides, the compounds do not cause remarkable toxicity in a human hepatocellular carcinoma cell line (HepG2) and SH-SY5Y cells. Additionally, the compounds were predicted to also have good bioavailability. Among the tested compounds, H4, H16, H17, and H24 stand out with their biological profile. Taken together, the proposed novel tacrine-donepezil scaffold represents a promising starting point for the development of novel anti-ChE multifunctional agents against AD., (© 2024 The Authors. Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

In this study, a group of 4-substituted benzoyltaurinamide derivatives were designed, synthesized, and investigated for their anticancer activity against three cancer cell lines and one nontumorigenic cell line by MTT assay. Among the final compounds, methoxyphenyl derivatives 14, 15, 16 were found to be effective against all the tested cancerous cell lines with promising selectivity. The most active compounds were further evaluated to determine the molecular mechanism of their anticancer activity by using western blot assay and the Annexin V-FITC/PI test. Compound 14 (in SH-SY5Y and MDA-MB-231 cell lines) and 15 (in SH-SY5Y cell line) were found to induce intrinsic apoptotic pathway by upregulating BAX, caspase-3, and caspase-9, while downregulating Bcl-2 and Bcl-xL expression levels. According to mechanistic studies, compounds displayed their anticancer activity via three different mechanisms: a. caspase-dependent, b. caspase-independent, and c. caspase-dependent pathway that excluded caspase-9 activation. As a result, this study provides interesting data which can be used to design new taurine-based anticancer derivatives., Competing Interests: CONFLICT OF INTEREST: The authors have declared no conflict of interest., (Copyright © 2020 The Author(s).)

It has been known for centuries that exogenous cannabinoids, such as tetrahydrocannabinol have anticonvulsant activity. Recent studies have advanced our understanding of the endogenous cannabinoid system and renewed the interest in cannabinoids as a potential treatment for epilepsy. The endogenous cannabinoid system is rapidly activated after seizure activity but still little is known about the molecular mechanisms underlying the role of the cannabinoid system in epilepsy. In this study epileptiform activity was induced by kainic acid (KA) and effects of the CB1 receptor agonists N-(2-Chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA) on G-protein signaling using the agonist-stimulated [(35)S]GTPγS binding assay were evaluated. Control and KA treated rat hippocampus and cortex membranes were used. Our results showed that the ACEA displayed a high potency and efficacy in stimulating the G-proteins and when compared to the control animals, significant enhancements were observed in tissues from the KA treated animals. Potency and efficacy values were in particular increased in the hippocampus tissues. Furthermore, gene expression levels of the cannabinoid receptor 1 (CB1) receptor and cannabinoid receptor interacting protein 1 (CRIP1) were measured by RT-PCR, where both CB1 and CRIP1 expressions were found to be elevated in the KA treated animals., (Copyright © 2011 Elsevier B.V. All rights reserved.)