Nilotinib exhibits less toxicity than imatinib and influences the immune state by modulating iNOS, p-p38 and p-JNK in LPS/IFN gamma-activated macrophages.

In this study, we aimed to analyze the effects of first and second-generation Bcr-Abl tyrosine kinase inhibitors, imatinib and nilotinib on LPS/IFN gamma activated RAW 264.7 macrophages. Our data revealed that imatinib was less effective on nitrite levels and more toxic on macrophages compared to nilotinib. Therefore, we further analysed the effect of nilotinib on various inflammatory markers including iNOS, COX-2, NFkB, IL-6, p-ERK, p-p38 and p-JNK in LPS/IFN gamma activated RAW264.7 macrophages. Spectrophotometric viability test and Griess assay,western blot, RT-PCR and luciferase reporter assays were used to analyze the biological activity of nilotinib. Our findings revealed that nilotinib decreases nitrite levels, iNOS mRNA, iNOS and p-p38 protein expressions significantly whereas induces IL-6 mRNA and p-JNK protein expressions at particular doses. We did not find significant effect of nilotinib on COX-2, p-ERK and nuclear p65 proteins and NFkB transcriptional activity. In addition, the binding mode of nilotinib to iNOS protein was predicted by molecular docking. According to the docking analyses, nilotinib exhibited hydrophobic interactions between MET349, ALA191, VAL346, PHE363, TYR367, MET368, CYS194, TRP366 residues at the binding pocket and the molecule as well as van der Waals interactions at specific residues. In conclusion, our results reveal that, in addition to its anticancer activity, nilotinib can exhibit immune modulatory effects on macrophages through its effects on iNOS, IL-6, p-p38 and p-JNK.

Some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives overcome imatinib resistance by induction of apoptosis and reduction of P-glycoprotein activity.

Imatinib (IMA) is a tyrosine kinase inhibitor (TKI) introduced for the chronic myeloid leukemia (CML) therapy. Emergence of IMA resistance leads to the relapse and failure in CML therapy. Benzimidazole is a heterocyclic organic compound which is widely investigated for the development of anticancer drugs. In this study, we aimed to explore the anticancer effects of some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives on K562S (IMA-sensitive) and K562R (IMA-resistant) cells. To analyze the cytotoxic and apoptotic effects of the compounds, K562S, K562R, and L929 cells were exposed to increasing concentrations of the derivatives. Cytotoxic effects of compounds on cell viability were analyzed with MTT assay. Apoptosis induction, caspase3/7 activity were investigated with flow cytometry and BAX, BIM, and BAD genes expression levels were analyzed with qRT-PCR. Rhodamine123 (Rho-123) staining assays were carried out to evaluate the effect of compounds on P-glycoprotein (P-gp) activity. The hit compounds were screened using molecular docking, and the binding preference of each compounds to BCR-ABL protein was evaluated. Our results indicated that compounds triggered cytotoxicity, caspase3/7 activation in K562S and K562R cells. Rho-123 staining showed that compounds inhibited P-gp activity in K562R cells. Overall, our results reveal some benzimidazole derivatives as potential anticancer agents to overcome IMA resistance in CML.

Novel indole retinoid derivative induces apoptosis and cell cycle arrest and modulates AKT and ERK signaling in HL-60 cells.

Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in high-risk patients or patients with failed responses to chemo drugs. Discovery and development of more effective new agents with lower side effects is the main aim of leukemia treatment. In this study, a novel retinoid compound with tetrahydronaphthalene ring was synthesized and evaluated for anticancer activity in human chronic and acute myeloid leukemia cell lines K562 and HL-60. Novel N-(1H-indol-1-yl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide was synthesized based on molecular hybridization of the two different bioactive structures retinoid head and indole. The effects of the synthesized carboxamide compound, which was referred to as compound 5, were determined in K562 chronic myeloid leukemia and HL-60 acute myeloid leukemia cell lines and L929 fibroblast cell line, which served as a control. Colorimetric MTT and caspase3 activity tests, flow cytometry, western blot, and microscopic examinations were used to evaluate biological activity. Compound 5 more effectively induced cell death in HL60 cells in comparison to K562 cells and L929 fibroblast cells. Therefore, further mechanism of cell death was investigated in HL60 cell line. It was found that compound 5 induced remarkable cytotoxicity, caspase3 activation, and PARP fragmentation in HL60 cells. Flow cytometric staining showed that the percentage of cells arrested in G0/G1 was also increased with compound 5 treatment. Important modulator proteins of cell proliferation p-ERK, p-AKT, and p-m-TOR were also found to be inhibited with compound 5 treatment. Collectively, our results reveal compound 5, which is a novel indole retinoid compound as a potential active agent for the treatment of acute promyelocytic leukemia.

Global Effects of SARS-CoV-2 Era on Kidney Transplantation Activities: Analysis of WHO Data.

BACKGROUND: Uncertainty raises questions in kidney transplant during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic regarding the recipient, the donor, and health care professionals. The pandemic not only has disrupted kidney transplanted patients but also has influenced transplant systems, donation chains, and timely and safe transplant surgeries. In the present study, we aimed to explore the global effects of the SARS-CoV-2 pandemic on kidney transplant. METHODS: We collected transplantation statistics and SARS-CoV-2 pandemic data from the World Health Organization website on June 15, 2021. Spearman correlation analysis was applied to assess the strength of a monotonic relationship among quantitative variables. We also demonstrated the clinical characteristics of our kidney recipients with SARS-CoV-2 infection. RESULTS: Comparison of the mean of global kidney transplantation statistics between 2010 and 2019 with 2020 statistics showed a significant decrease in kidney transplant from living donors (P < .001). From the beginning of the pandemic to June 15, 2021, 1 of the 43 kidney transplant patients we treated in our clinic died of SARS-CoV-2 infection after discharge. Two of the patients we transplanted and saw in follow-up before the pandemic died of SARS-CoV-2 infection. CONCLUSION: While the overall kidney transplant numbers have increased in the year to date, kidney transplants decreased drastically at the onset of the pandemic.

Diagnostically challenging rupture of pancreaticoduodenal artery aneurysm: A case report.

Splanchnic artery aneurysms are rare vascular lesions with a high risk of rupture regardless of their size. Symptoms may vary from simple abdominal pain or vomiting to morbid conditions like haemorrhagic shock; however, most aneurysms are asymptomatic and difficult to diagnose. In this study, it was aimed to present the case of a 56-year-old female with a ruptured pancreaticoduodenal artery aneurysm treated by coil embolization.

Description and Outcomes of Three Different End-to-Side Microsurgical Techniques for the Anastomosis of Accessory Renal Artery With the Dominant Renal Artery in Kidney Transplantation.

BACKGROUND: In this study, we compared the outcomes of three different surgical microscope-assisted end-to-side anastomosis techniques between the dominant and accessory renal arteries during living donor kidney transplant. METHODS: The demographics, serum creatinine levels, warm and cold ischemia times, rate of complications, and incidence of delayed graft function of 135 kidney recipients were analyzed according to the type of arterial anastomosis. Group A (n = 98) had one dominant renal artery (DRA) with one end-to-side anastomosis to the external iliac artery (EIA) using a surgical microscope. Group B (n = 17) had one DRA plus one accessory renal artery (ARA) with two separate end-to-side anastomoses to the EIA using a surgical microscope. Group C (n = 20) had one DRA with end-to-side anastomosis to the EIA and one ARA with an ex vivo on-bench end-to-side anastomosis to the DRA using a surgical microscope. RESULTS: Compared with groups A and B, the cold ischemia time and the rate of delayed graft function were significantly higher in group C (P ≤ .001). At 6 months after transplant, group B demonstrated a higher creatinine value (2.40 ± 3.41 mg/dL) than group A and group B (P = .032). Also, the decrease in creatinine at postoperative month 6 was limited in group B as compared with groups A and C. CONCLUSIONS: An end-to-side anastomosis between ARA (group B) and DRA (group A) of the kidney graft using a surgical microscope on the bench ex vivo results in superior outcomes. Single arterial anastomosis techniques are associated with a better function in a 6-month follow-up than two separate arterial anastomoses.

A Comparative Analysis of Once-daily and Twice-daily Formulation of Tacrolimus in De Novo Kidney Transplant Recipients.

OBJECTIVES: We aimed to compare the once-daily and twice-daily formulation of tacrolimus concerning the efficiency and effects on graft function in de novo kidney transplant patients. METHODS: Twenty once-daily (TAC-OD) and twenty twice-daily (TAC-BID) tacrolimus administrated de novo kidney recipients who had received initial immunosuppressive therapy according to protocols at our institution (0.2 mg/kg of tacrolimus combined with 1000 milligrams of steroid taper plus 720 mg of mycophenolate and with 2.5mg/kg anti-thymocyte globulin) assessed concerning demographics, drug doses and blood concentration, and graft function. RESULTS: The mean tacrolimus blood concentration measurements were higher in the TAC-OD group in the first sixty days after transplantation, and the TAC-OD group showed more blood concentration overshoots/fluctuations in the first 30 days of the treatment. The initial drug dose was significantly higher in the TAC-OD group than the TAC-BID group (p=0.04). There was no meaningful difference among groups according to graft function (creatinine measurements) (p>0.05). CONCLUSION: Between de novo kidney recipients, the new TAC-OD formulation presents a similar short-term efficacy profile as TAC-BID. However, a higher daily dosage of TAC-OD is needed to achieve similar blood concentrations in the early postoperative period.

Approach of the Clinicians Practicing in Intensive Care Units to Brain Death Diagnosis and Training Expectations in Turkey: A Web-Based Survey.

BACKGROUND: For health professionals, recognizing and diagnosing brain death is vital for the development of organ transplantation. However, cadaveric organ donation rates remain insufficient, and this problem has become one of the most serious obstacles in the treatment of end-organ failure. OBJECTIVES: This study examines the attitude and knowledge level of clinicians who practice in intensive care units (ICUs) concerning the determination of brain death and describes the hindrances in diagnosing brain death. MATERIALS AND METHODS: A survey study was designed with 26 questions, including questions regarding the determination of characteristics of respondents' trainings, practicing preferences, and their knowledge and approach toward brain death diagnosis. Clinicians practicing in ICUs in Turkey were invited to the survey. RESULTS: A total of 244 surveys were fully completed. Physicians working at the university hospitals or university-affiliated hospitals answered the basic knowledge questions about brain death more accurately (P < .001). Also, physicians employed in university or university-affiliated hospitals feel more capable in diagnosing brain death (P = .002) and are more willing to receive education on the brain death issue (P < .001). CONCLUSION: There is a gap separating the practices suggested in guidelines and the daily practice of ICU clinicians working in state hospitals or private institutions. Academic organizations producing and leading the education curricula may assist in informing ICU clinicians who should be trained.

Synthesis of Some Benzimidazole-derived Molecules and their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability.

BACKGROUND: Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. OBJECTIVE: In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1Hbenzo[ d]imidazole-4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anticancer activities. METHODS: Compounds were tested by cell-free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer, and L929 fibroblast cell lines. RESULTS: Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells, whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. CONCLUSION: These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells, and further research will enlighten the underlying mechanisms of their effects.

Effect of Visceral, Subcutaneous and Retroperitoneal Adipose Tissue on Renal Function After Living Donor Nephrectomy: A Retrospective Analysis of 69 Cases.

PURPOSE: Recent studies reported that the presence of metabolic syndrome is closely correlated with impaired kidney function after living donor nephrectomy. Since the measurement of body mass index cannot differentiate the amount of body adipose tissue from total body weight, body mass index is not a reliable parameter for determining metabolic syndrome. In the present study, we investigated the correlation between body adipose tissue and kidney function recovery following living donor nephrectomy. MATERIALS AND METHODS: The patients who underwent living kidney donor nephrectomy consequently from July 2016 through December 2017 were enrolled in the study. We preoperatively measured the visceral (VAdT), retroperitoneal (RPAdT), and subcutaneous (SCAdT) adipose tissue volume by a computed tomography scan. Body mass index, adipose tissue measurements, and postoperative estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: The decrease between preoperative eGFR, and the first day, the first month and the sixth month eGFR after surgery were statistically significant (P = .001; P = .001; P = .001, respectively). The negative correlation between VAdT/SCAdT measurements and changes in eGFR at the first and the sixth postoperative month compared to preoperative eGFR were statistically significant (P = .049; P = .041, respectively). Additionally, RPAdT measurements and changes in eGFR at the first and the sixth postoperative month compared to preoperative eGFR (decreasing as RPAdT value increased) were statistically significant (P = .035; P = .026, respectively). CONCLUSION: According to a preoperative computed tomography scan, VAdT, RPAdT, and VAdT-to-SAdT ratio can predict impaired kidney function recovery. Furthermore, RPAdT measurement is a new variable to predict the impaired kidney function after living donor nephrectomy.

The Effect of Infrared Drying on Color, Projected Area, Drying Time, and Total Phenolic Content of Rose (Rose electron) Petals.

The effects of different drying temperatures (50, 60, 70 °C) on the quality of rose (Rose electron) petals were evaluated in this study. Drying time decreased from 1680 s to 600 s with increased infrared temperature. The temperature and time were increased from 50 °C to 70 °C and 30 min to 60 min, respectively, and a decrease in the fruit color quality was observed. The projected area (PA) of rose petals was affected significantly from temperature. After the drying process, the largest PA was observed as 33.35 cm2 (50 °C, 30 min), while the smallest achieved at 70 °C, 60 min (27.96 cm2). Depending on the temperature values (50, 60, 70 °C), the average projection area of dry samples of the rose petals decreased 2.17 times compared to the projection area of fresh samples. The dried samples demonstrated an increase in the total phenolic (TP) content compared to the fresh samples. The maximum TP (44.49 mg GAE/g) was achieved at 45 min and 70 °C rose petals sample. The results concluded that infrared drying for 45 min at 70 °C could be recommended for drying rose (rosa electron) petals.

Three-Dimensional Analysis of Binding Sites for Predicting Binding Affinities in Drug Design.

Understanding the interaction between drug molecules and proteins is one of the main challenges in drug design. Several tools have been developed recently to decrease the complexity of the process. Artificial intelligence and machine learning methods offer promising results in predicting the binding affinities. It becomes possible to do accurate predictions by using the known protein-ligand interactions. In this study, the electrostatic potential values extracted from 3-dimensional grid cubes of the drug-protein binding sites are used for predicting binding affinities of related complexes. A new algorithm with a dynamic feature selection method was implemented, which is derived from Compressed Images For Affinity Prediction (CIFAP) study, to predict binding affinities of Checkpoint Kinase 1 and Caspase 3 inhibitors.

Material Utilization of Cotton Post-Harvest Line Residues in Polymeric Composites.

This paper deals with a research focused on utilization of microparticle and short-fiber filler based on cotton post-harvest line residues in an area of polymeric composites. Two different fractions of the biological filler (FCR-reinforced cotton filler) of 20 and 100 µm and the filler with short fibers of a length of 700 µm were used in the research. The aim of the research was to evaluate mechanical characteristics of composites and adhesive bonds for the purpose of gaining new pieces of knowledge which will be applicable in the area of material engineering and assessing application possibilities of residues coming into being from agricultural products processing. Mechanical properties of the composite material produced by a vacuum infusion and tested at temperatures 20, 40, and 60 °C and adhesive bonds which were exposed to a low-cyclic loading, i.e., 1000 cycles at 30% to 70% from reference value of the maximum strength, were evaluated. Composite systems with the FCR adjusted in 5% water solution of NaOH showed higher strength values on average compared to untreated FCR. Unsuitable size of the FCR led to a deterioration of the strength. The filler in the form of 700 FCR microfibers showed itself in a positive way to composite materials, and the particle in the form of 20 FCR did the same to adhesive bonds. Results of adhesive bond cyclic tests at higher stress values (70%) demonstrated viscoelastic behavior of the adhesive layer.

Evaluation of Male Circumcision: Retrospective Analysis of One Hundred and Ninety-eight Patients.

Introduction Circumcision is the oldest and most frequently used surgical procedure. It dates back to at least 10,000 years from today. The debate on the benefits and necessity of circumcision is ongoing. In this study, we aimed to determine the complications and complication rate of circumcisions occurring in our circumcision clinic and to compare these with the complication rates in the world. Methods A total of 198 male patients circumcised between 2011 at 2019 at Bursa State Hospital was enrolled in the presented retrospective study. Demographic data of the patients were assessed and the height and weight of the patients were evaluated according to the child growth standards and weight for age percentile charts for boys of the World Health Organization (WHO). All early or late complications were noted after circumcision. Results The mean age of the patients was 93.57±40.12 (2-248) months. The mean follow-up time was 16.32±9.24 (2-35) months. Sixteen patients had bleeding, four patients had a penile hematoma, and 108 patients had penile edema. There is no statistically significant difference in the penile edema occurrence according to the weight of the patients (p=0.58).  Conclusion Circumcision is a frequently applied procedure. Like any other surgery, perioperative and postoperative complications can be observed. More importantly, a significant number of these complications can be prevented by careful surgery and postoperative care.

Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors.

In this study, a series of benzimidazoles bearing thiosemicarbazide chain or triazole and thiadiazole rings were designed and synthesized. Crystal and molecular structure of the compound 5c has been characterized by single crystal X-ray crystallographic analysis. EGFR kinase inhibitory potencies of synthesized compounds were compared with erlotinib in vitro and most of the compounds exhibited significant activities. Cell culture studies were also carried out for selected compounds and 12b was found to be the most active compound. To understand the binding mode of synthesized benzimidazoles, three compounds (12b, 16, 16c) were selected and placed on the binding site of EGFR tyrosine kinase based on their kinase inhibitor potencies and cell culture studies. Docking study indicated that compound 12b showed two-hydrogen bonding interactions with residues of LYS721 and THR830 at the binding pocket.

Evaluation of the Reliability, Utility, and Quality of the Information in Sleeve Gastrectomy Videos Shared on Open Access Video Sharing Platform YouTube.

BACKGROUND: The internet is a widely used source for obtaining medical information both by patients and physicians. YouTube® is a valuable information resource which can improve the learning experience of both public and medical professionals if appropriately used. In this study, we want to evaluate quality and accuracy of videos about sleeve gastrectomy procedure. METHODS: We included the first 100 videos returned by YouTube® search engine in response to "sleeve gastrectomy" keyword query to the study. The popularity of the videos was evaluated with an index called the video power index (VPI). Educational quality of videos was measured using the DISCERN score (DISCERN), Journal of American Medical Association (JAMAS) benchmark criteria, and Global Quality Scores (GQS). The technical quality was measured by Sleeve Gastrectomy Scoring System (SGSS) which was utilized by three bariatric surgeons. RESULTS: The source in 31% of the videos was a patient. The content in 53% of the videos was surgical technique. According to sources, videos uploaded by a university-affiliated physician had significantly higher DISCERN, JAMAS, GQS, and SGSS scores. Videos uploaded by a university-affiliated physician also had lower video power index than videos uploaded by patients. Surgical technique videos had significantly higher DISCERN, JAMAS, GQS, and SGSS scores. Patient experiences and advertisement videos had higher VPI scores. Also, negative correlations were found between video power index and JAMAS, GQS, and SGSS scores. CONCLUSIONS: Online information on sleeve gastrectomy is of low quality, and its contents are of unknown source and accuracy. However, educational potential of YouTube® cannot be ignored.

Fabry Disease Prevalence in Renal Replacement Therapy in Turkey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. OBJECTIVE: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. METHODS: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. RESULTS: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. CONCLUSIONS: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease.

Retrospective Analysis of the first 100 Kidney Transplants at the Istanbul Okan University, Health Application and Research Center.

OBJECTIVES: The renal transplant program of Istanbul Okan University Hospital started in August 2017. Five cadaveric and 95 living donor kidney transplants have been performed for over 16 months. In this study, we aimed to share our experiences regarding kidney transplantation. METHODS: In this study, a retrospective analysis of 100 patients who underwent kidney transplantation at the Istanbul Okan University over 16 months, the Health Application and Research Center was carried out. Patients' demographics, creatinine levels of donors and recipients, co-morbid conditions, postoperative complications, features of arterial anastomosis and arterial variations observed on computed tomography angiography of donor-patient were assessed. RESULTS: Mean age of donor patients was 44.05±13.76 (18-71) years. All living donors had computed tomography angiography for assessment of the vascular structure of both kidneys. Accessory right kidney artery was the most dominant vascular variation (16.5%). The primary cause of chronic renal disease was diabetes mellitus (36.4%) and hypertension (15.6%). Mean warm and cold ischemia time was 1.82±0.44 (1-3) and 40.25±6.12 (31-57) minutes, respectively. The most observed postoperative complication was stenosis of ureter anastomosis (4.1%). End-to-end arterial anastomosis between renal and internal iliac arteries was the most preferred anastomosis (57.2%). CONCLUSION: Increasing kidney transplantation, which is the most appropriate treatment in terms of cost-effectiveness, will be beneficial for patient health and economy of the country.

Apoptotic Effects of Some Tetrahydronaphthalene Derivatives on K562 Human Chronic Myelogenous Leukemia Cell Line.

BACKGROUND: Retinoids which are vitamin A (Retinol) derivatives have been suggested to mediate the inhibition of cancer cell growth and apoptosis. It has been reported that all trans retinoic acid (ATRA) exhibited suppressive effects on different types of leukemia including chronic myelogenous leukemia. OBJECTIVE: In the present study, we aim to find out the effects of 6 synthetic N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalene-2-yl)-carboxamide derivatives (compound 6-12) on cell viability and apoptotic pathways in K562 human chronic myelogenous leukemia cell line. METHODS: Cell viability and apoptosis were examined by spectrophotometric thiazolyl blue tetrazolium bromide (MTT) and caspase-3 assay, western blot, RT-PCR and flow cytometry. RESULTS: Our results indicated that compound 6 (5-(1,2-Dithiolan-3-yl)-N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)pentanamide), 8 (4-(3,4-Dimethoxyphenyl)-N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)butanamide) and 11 (E-3-(4-Hydroxy-3-methoxyphenyl)-N-(3,5,5,8,8-pentamethyl- 5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide) exhibited apoptotic effects in K562 human chronic myelogenous leukemia cell line and induced caspase 3, PARP cleavage, Bax/Bcl-2 ratio, Bad and Bim gene expressions. CONCLUSION: Some retinoid derivatives tested in this study induced apoptosis of K562 cells which suggest that these compounds may serve as potential agents in the treatment of chronic myelogenous leukemia.

Advances in small bowel transplantation.

Small bowel transplantation is a life-saving surgery for patients with intestinal failure. The biggest problem in intestinal transplantation is graft rejection. Graft rejection is the main reason for morbidity and mortality. Rejection has a negative effect on the survival of the graft. While 50%-75% of small bowel transplantation patients experience acute rejection, chronic rejection occurs in approximately 15% of patients. Immune monitoring is crucial after small bowel transplantation. Unlike other types of transplantation, there are no non-invasive or reliable markers to predict rejection in small bowel transplantation. The diagnosis of AR is confirmed by clinical symptoms, endoscopic appearance, and pathological specimens taken by endoscopy. Thus, histopathological examinations obtained by protocol biopsies remain as the gold standard for intestinal graft monitoring; however, biopsies have some complications, especially in small grafts. In addition to the high complication rate, biopsies are non-diagnostic; thus, multiple biopsies should be performed to exclude rejection. Therefore, auxiliary assays, such as measurements of citrulline and calprotectin in the blood, cytofluorographic examination of peripheral blood immune cells, cytokine profiling, and distinct gene-set-change measurements, are increasingly being used in small bowel transplantation. Developments in the understanding of genes seem to be promising that limited gene sets, taken from blood or from intestinal biopsies, will enhance pathological diagnosis. Bone marrow mesenchymal stem cell transplantation with SBT and tissue engineering are also promising procedures.