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In this study, the bioactive components, enzyme inhibitory, antioxidant and anticancer potentials of edible (L. sativa) and a new species (L. anatolica) of Lactuca were evaluated and compared. The quantitative analyzes of the bioactive components of L. sativa (LS) and L. anatolica (LA) were analyzed quantitatively by GC-MS and Orbitrab HPLC-HRMS. Antioxidant, enzyme inhibitory and anticancer properties were analyzed by various assays. In general, LA exhibited more stronger antioxidant properties compared to LS. The extracts showed similar inhibitory effects on these enzymes. It was determined that LS was dominant in terms of linoleic acid (23.71 %), while LA contained a high level of α-linolenic acid (31.70 %). LA and LS inhibited the viability of A549 and MCF-7 cells in a dose-dependent manner. IC50 values for LA, LS and cisplatin were determined as 120.3, 197.5, 4.3â µg/mL in A549â cell line and 286.2, 472.8, 7.2â µg/mL in MCF-7â cell line, respectively. It was revealed that LA and LS treatment at 50â µg/mL concentrations in A549 cells completely suppressed the colony forming capacity, and treatment with IC50 doses inhibited cell migration, and triggered apoptosis by regulating caspase-3, cPARP, p53 and p21. The findings of this study suggested that these species have significant pharmacological potential.
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BACKGROUND: Crush Syndrome is a major cause of morbidity and mortality following large-scale catastrophic earthquakes. Since there are no randomized controlled studies on Crush Syndrome, knowledge on this subject is limited to expert experience. The primary objective is to analyze the epidemiological and demographic characteristics, clinical outcomes, and mortality factors of earthquake victims after the Pazarcik and Elbistan earthquakes on February 6, 2023. METHODS: This cross-sectional and observational retrospective study evaluated 610 earthquake victims who presented to our center between February 6 and April 30, 2023. Among these patients, 128 with Crush Syndrome were included in the study. Patient information was gathered from hospital records during their stay and from national registries upon referral. The primary outcome was to identify risk factors for mortality. Demographic and laboratory data were analyzed by acute kidney injury (AKI) stages; mortality-affecting factors were identified through regression analysis. RESULTS: Of the 128 Crush Syndrome patients (100 adults, 28 children), 64 were female. The AKI rate was 32.8%. Among patients with AKI, the frequency of hemodialysis requirement was 69%, and the mortality rate was 14.2%. The overall mortality rate for patients with Crush Syndrome was 4.6%, compared to 3.9% (19/482) in earthquake victims without Crush Syndrome (p=0.705). Notably, low systolic blood pressure at admission was the only factor significantly affecting mortality in Crush Syndrome patients (Hazard Ratio [HR]: 1.088, p=0.021, 95% Confidence Interval [CI]). CONCLUSION: Our study highlights low systolic blood pressure upon admission as a significant risk factor for increased mortality in Crush Syndrome patients. This finding may contribute to the literature by emphasizing the importance of monitoring blood pressure under rubble and administering more aggressive fluid therapy to patients with low systolic blood pressure.
Subject(s)
Acute Kidney Injury , Crush Syndrome , Earthquakes , Adult , Child , Humans , Female , Male , Crush Syndrome/epidemiology , Crush Syndrome/etiology , Retrospective Studies , Cross-Sectional Studies , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapyABSTRACT
OBJECTIVE: Umbilical hernia repair can be easily performed simultaneously with laparoscopic cholecystectomy. The use of mesh is recommended for hernias larger than 1 cm. In this study, patients with primary repair of umbilical hernia simultaneously with laparoscopic cholecystectomy were evaluated. It aimed to present the effectiveness of this method and the effect of body mass index (BMI) on treatment results. METHODS: The records of patients who underwent primary repair of umbilical hernia simultaneously with laparoscopic cholecystectomy between 2014 and 2021 were reviewed retrospectively. Patients' age, gender, BMI, length of hospital stay, recurrence and reoperation information, and follow-up times were analyzed. The patients were examined in three groups according to their BMI, and the effect of BMI on treatment was investigated. RESULTS: patients were included in the study. Median values of the patients for age, BMI, hospitalization, and follow-up were 63 (28-94), 31 (20-51) kg/m2, 1 (1-25) days, and 23 (0.6-76) months, respectively. Recurrence was detected in 8 patients. BMI was <25 in one patient with recurrence and >30 in 5 patients. There was no significant correlation between length of stay, number of relapse and reoperation, and BMI (p>0.05). CONCLUSION: In our study, the recurrence rate was found to be higher than the studies reported with the use of mesh, and most of the patients with recurrence are obese, although it is not statistically significant. If the recurrence rate is acceptable, we believe that repair with primary suture is feasible in umbilical hernia.
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A new series of indole-carbohydrazide-phenoxy-N-phenylacetamide derivatives 7a-l were designed, synthesized, and screened for their α-glucosidase inhibitory abilities and cytotoxic effects. The results obtained in the α-glucosidase inhibition assay indicated that most of the synthesized derivatives displayed good to moderate inhibitory abilities (Ki values ranging from 14.65 ± 2.54 to 37.466 ± 6.46 µM) when compared with the standard drug acarbose (Ki = 42.38 ± 5.73 µM). Among them, 2-mehoxy-phenoxy derivatives 7l and 7h with 4-nitro and 4-chloro substituents on the phenyl ring of the N-phenylacetamide moiety, respectively, displayed the most inhibition effects. The inhibitory mechanism of these compounds was investigated by molecular docking studies. The in vitro cytotoxicity assay showed that only one compound, 2-methoxy-phenoxy derivative 7k with a 4-bromo substituent on the phenyl ring of the N-phenylacetamide moiety, exhibited moderate cytotoxicity against the human non-small-cell lung cancer cell line A549 and the rest of the compounds show almost no cytotoxicity. Further cytotoxic evaluations were also performed on compound 7k. The in silico pharmacokinetic study predicted that the selected compounds 7l and 7h are likely to be orally active.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Structure-Activity Relationship , Molecular Structure , Glycoside Hydrolase Inhibitors/pharmacology , alpha-Glucosidases/metabolism , Molecular Docking Simulation , Indoles/pharmacologyABSTRACT
BACKGROUND: Since cancer development is inevitable in patients with familial adenomatous polyposis (FAP), we aimed to determine the incidence of incidental malignancy in prophylactic colectomy specimens. METHODS: The files of patients who underwent prophylactic surgery for FAP between 2010 and 2020 were retrospectively reviewed. The incidence of incidental malignancy in histopathological specimens was examined and a comprehensive literature review was made. RESULTS: Fifty-five patients were included in the study, of whom 30 patients had a diagnosis of primary malignancy. Prophylactic colectomy was performed on 25 patients. The pathology results indicated that the specimens were benign in 12 patients (48%) and revealed carcinoma in situ in 11 patients (44%). Incidental malignancy was detected in 2 patients (8%). In the literature review, there were 243 patients who underwent prophylactic colectomy and incidental cancer was detected in 25 patients (10.3%) with the stages of 1 (7.4%), 2 (2.1%), and 3 (0.8%), respectively. CONCLUSIONS: Incidental cancer is not rare in patients who have undergone prophylactic colectomy for FAP. Hopefully. they are usually at early stages and unexpected advanced cancers are seen rarely.
Subject(s)
Adenomatous Polyposis Coli , Humans , Retrospective Studies , Adenomatous Polyposis Coli/complications , Adenomatous Polyposis Coli/epidemiology , Adenomatous Polyposis Coli/surgery , Colectomy/adverse effects , Anastomosis, Surgical , IncidenceABSTRACT
In this study, the therapeutic potential and phytochemical composition of ethanolic extract of Cephalaria elazigensis var. purpurea (CE), an endemic species, were investigated. For this purpose, the antiproliferative effect of CE on the MCF-7 human breast cancer cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and its effectiveness on colony formation and cell migration was analyzed with clonogenic assay and wound healing assay, respectively. In addition, the cell death detection ELISA (CDDE) assay was conducted to determine the pro-apoptotic capacity of CE. The IC50 value of the CE was determined as 324.2 ± 14.7 µg/mL. Furthermore, upon 1000 µg/mL CE treatment, there was 4.96-fold increase in the population of cells undergoing apoptosis compared to the untreated control cells. The antioxidant activity tests were performed by DPPH free radical, ABTS cation radical, ferric-ion reducing power (FRAP) and ferrous-ion chelating power (FCAP) assays. Antioxidant activity values for the DPPH, ABTS and FRAP assays were found to be 125.6 ± 6.3, 34.09 ± 0.1 and 123.4 ± 4.2 µmol TE/mg DE, respectively. We further determined the effect of CE ethanolic extract against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. CE plays an effective inhibitory role in AChE and BuChE (AChE: IC50: 10.54 µg/mL, BuChE: IC50: 6.84 µg/mL) respectively. Further, molecular docking stuy was conducted to understand the nature of the all compound against AChE an BChE. It is revealed that α-Linolenic acid shows lowest binding energy (-7.90 kcal/mol) towards AChE, on the other side, Linoleic acid shows good binding affinity (-7.40 kcal/mol) for BChE.Communicated by Ramaswamy H. Sarma.
Subject(s)
Antioxidants , Dipsacaceae , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Butyrylcholinesterase/metabolism , Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Dipsacaceae/metabolism , Molecular Docking Simulation , Plant Extracts/pharmacology , Plant Extracts/chemistryABSTRACT
IntroductionRoyal jelly (RJ) from the honey bee, Apis mellifera, is a traditional product that is widely used as a food supplement to support the medical treatment of various diseases.Material and methodsOur study continued for 8 weeks. 42 Wistar albino (8 weeks old) male rats were used in the study. The study included 6 groups; Group 1: Control group (fed with standard diet), Group 2: RJ (100 mg/kg, bw), Group 3: F-50 (50 mg/kg, bw), group 4: F-100 (100 mg/kg, bw) group 5: F-50 (50 mg/kg, bw) + RJ (100 mg/kg, bw) Group 6: F-100 (100 mg/kg, bw) + RJ (100 mg/kg, bw). Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) activities in liver tissue were determined by spectrophotometer. Liver tissue samples were examined histopathologically and various protein levels were determined by Western blotting technique.ResultsRJ caused a significant decrease in MDA level, Bcl-2, GSK3 and NF-κB protein expression levels, whereas induced a significant increase in GSH level, CAT activities and Bax, BDNF, caspase-6, caspase-3, Nrf-2 protein expression levels.ConclusionOur findings suggest RJ to be used as a hepatoprotective agent in the clinic to modulate the toxic effects of fluoride and other chemicals in the future.
Subject(s)
NF-kappa B , Oxidative Stress , Rats , Male , Animals , NF-kappa B/metabolism , Up-Regulation , Glycogen Synthase Kinase 3/metabolism , Caspases , Down-Regulation , Rats, Wistar , Antioxidants/pharmacology , Antioxidants/metabolism , Liver/metabolism , Glutathione/metabolismABSTRACT
Forty-two healthy adult male rats (Wistar albino, n = 42, 8 weeks old, starting weights 200-250 g) employed in this study were subdivided into six groups randomly with seven rats per group as follows: (i) Control group: received standard diet; (ii) RJ group: received standard diet supplemented with royal jelly; (iii) F50 group: received standard diet supplemented with fluoride (50 mg/kg BW); (iv) F100 group: received standard diet supplemented with fluoride (100 mg/kg BW); (v) F50 +RJ group: received standard diet supplemented with fluoride (50 mg/kg BW) and royal jelly; (iv) F100 +RJ group: received standard diet supplemented with fluoride (100 mg/kg BW) and royal jelly. The study continued for a total of eight weeks. Western blot analysis was conducted to determine the post-translational expression levels of NF-κB, Bax, Bcl-2, TNF-α, Caspase-3 and Caspase-6 proteins in pancreas tissue. The pancreatic tissue was subjected to histopathological evaluation. Furthermore, MDA, GSH and CAT activities were examined by spectrophotometric analyzes. Our findings demonstrate that, compared to the control and RJ groups, Bcl-2 protein expression was augmented and, conversely, Caspase-6, Caspase-3 and Bax protein levels were decreased upon fluoride treatment. A statistically significant increase in TNF-α and NF-κB protein expressions was observed in the groups with fluoride-induced damage compared to the control and RJ groups. The MDA levels were increased in all fluoride-treated rats compared to those in the control and RJ groups, whereas the CAT and GSH activities were reduced in all rats with fluoride- induced damage. Although there was not a great difference between the groups regarding histopathological findings, there was a tendency to decrease in the rate of damage upon royal jelly treatment.
Subject(s)
Antioxidants , NF-kappa B , Rats , Animals , Male , bcl-2-Associated X Protein/metabolism , Caspase 3/metabolism , NF-kappa B/metabolism , Antioxidants/metabolism , Fluorides/toxicity , Fluorides/metabolism , Caspase 6/metabolism , Oxidative Stress , Tumor Necrosis Factor-alpha/metabolism , Rats, Wistar , Fatty Acids/metabolism , Signal Transduction , Proto-Oncogene Proteins c-bcl-2/metabolism , Pancreas/metabolismABSTRACT
INTRODUCTION: Protective effect of royal jelly (RJ) on fluoride-induced nephrotoxicity was investigated in this study. METHODS: 42 healthy male Wistar rats (n = 42, 8 weeks of age) were divided equally into 6 groups with 7 rats in each; (1) Group-1: Controls fed with standard diet; (2) Group-2: RJ [100 mg/kg] bw (body weight), by oral gavage; (3) Group-3: Fluoride [50 mg/kg] bw, in drinking water; (4) Group-4: Fluoride [100 mg/kg] bw, in drinking water; (5) Group-5: RJ [100 mg/kg] bw, by oral gavage + Fluoride [50 mg/kg] bw, in drinking water; (6) Group-6: RJ [100 mg/kg] bw, by oral gavage + Fluoride [100 mg/kg] bw, in drinking water. After 8 weeks, all rats were decapitated and their kidney tissues were removed for further analysis. The protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, VEGF, GSK-3, BDNF, COX-2 and TNF-α proteins in kidney tissue were analysed by western blotting technique. RESULTS: RJ increased Bcl-2, COX-2, GSK-3, TNF-α and VEGF protein levels and a decreased caspase-3, caspase -6, caspase-9, Bax and BDNF protein levels in fluoride-treated rats. CONCLUSION: RJ application may have a promising therapeutical potential in the treatment of many diseases in the future by reducing kidney damage.
Subject(s)
Fatty Acids , Kidney Diseases , Animals , Male , Rats , Antioxidants/metabolism , bcl-2-Associated X Protein/metabolism , Biomarkers , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/pharmacology , Caspase 3/metabolism , Caspase 6/metabolism , Caspase 6/pharmacology , Caspase 9/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/pharmacology , Fluorides/toxicity , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3/pharmacology , Kidney , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Kidney Diseases/prevention & control , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/pharmacology , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism , Fatty Acids/pharmacologyABSTRACT
The study was carried out on 42 male rats divided into six groups with 7 rats in each group: two control groups, two injury groups and two treatment groups. One of the control groups received a basal diet while the other one was fed a basal diet supplemented with royal jelly (RJ) (100 mg/kg). The two injury groups were given 50 mg/kg and 100 mg/kg fluoride, respectively. The two treatment groups exposed to 50 mg/kg and 100 mg/kg fluoride were both fed basal diets with RJ (100 mg/kg). Lungs were taken for histopathological examination. Spectrophotometric analysis was utilized to determine Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) activities, and Western blotting technique was used to evaluate the levels of specific proteins. On one hand, our experiments revealed that RJ caused decreased MDA levels, and downregulation of COX-2, Bcl-2, GSK3 and TNF-α protein expressions. On the other hand, rolay jelly caused augmented GSH and CAT activities, as well as upregulated Bax, BDNF, caspase-3, caspase-6, caspase-9 protein expressions in rats injuried by the fluoride exposure. The results suggest that the application of RJ was very likely to have a healing effect on the degenerative changes seen in the examined tissue.
Subject(s)
Caspases , Tumor Necrosis Factor-alpha , Animals , Apoptosis , Caspases/metabolism , Cyclooxygenase 2 , Fatty Acids/pharmacology , Fluorides/toxicity , Glutathione/metabolism , Glycogen Synthase Kinase 3 , Lung , Male , Oxidative Stress , Rats , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
OBJECTIVE: To investigate factors that may have an effect on recurrence by retrospectively analysing the data of patients who were followed up and treated for idiopathic granulomatous mastitis in this clinic. STUDY DESIGN: Analytic study. PLACE AND DURATION OF STUDY: Department of General Surgery, Faculty of Medicine, Baskent University, Konya and Adana Practice and Research Hospitals between January 2010 and January 2021. METHODOLOGY: The data of patients who were histopathologically diagnosed with granulomatous mastitis were retrospectively analysed. The patients included in the study were divided into two groups: Recurrence (Group 1) and non-recurrence (Group 2). Patients with underlying etiological factors that may cause granulomatous inflammation such as infection, trauma, tuberculosis, sarcoidosis, and autoimmune disease were excluded from the study. The effects of other parameters (involvement area, follow-up duration, the time from the onset of complaints to diagnosis, side of involvement, breastfeeding, oral contraceptive use, redness, ulceration and/or discharge, preoperative histopathological diagnosis, diagnosis by any of the preoperative imaging techniques, preferred treatment method) on recurrence, were statistically analysed. RESULTS: Furthermore, the analysis results showed no significant difference between the groups with and without recurrence with regard to any of the other variables such as follow-up period, size of the involvement area, presenting complaints, breast-feeding, preferred treatment alternative (steroid, steroid + surgery, surgery), and preferred surgical technique (p>0.05). The time from the onset of complaints to diagnosis was significantly longer in the recurrence group (p=0.001). In addition, the frequency of oral contraceptive use was statistically significantly higher in the recurrence group (Odds ratio=7.6, p=0.044). CONCLUSION: The results of this study suggest that early diagnosis could prevent recurrence in patients with idiopathic granulomatous mastitis. Prospective randomised controlled studies are needed to support this thought. Key Words: Idiopathic granulomatous mastitis, Malignancy, Oral contraceptive, Steroid.
Subject(s)
Granulomatous Mastitis , Breast Feeding , Diagnosis, Differential , Female , Granulomatous Mastitis/diagnosis , Granulomatous Mastitis/epidemiology , Humans , Prospective Studies , Retrospective StudiesABSTRACT
Introduction Increases in spontaneous activity in the neurons of the auditory cortex are presumed as the pathophysiology of tinnitus. Objective To investigate the effectiveness of transcranial magnetic stimulation (TMS) in the treatment of tinnitus. Methods A total of 62 patients between the ages of 22 and 74 with chronic subjective tinnitus were enrolled in the study. The inclusion criteria were normal findings on an otolaryngologic examination and normal ranges of complete blood count, routine biochemical parameter levels, thyroid function, air-bone gap on pure-tone audiometry, and middle-ear pressure and stapedial reflex on tympanometry. The patients were randomized into 2 groups: 40 patients were placed in the treatment for TMS (tTMS) group, and the rest (22 patients) were placed in the sham TMS group. The frequency and severity of the tinnitus, as well as the tinnitus handicap inventory (THI) score of each patient were measured before and one month after the treatment, and the values were statistically evaluated. Results We observed a statistically significant improvement in the tTMS group ( p < 0.05 and p < 0.05 respectively) regarding the THI and tinnitus severity scores. The sham TMS group showed no significant improvement in terms of the THI ( p > 0.05). However, the tinnitus severity showed a significant increase in this group ( p < 0.05). The comparison of differences in the changes in the THI and the tinnitus severity scores showed a significant statistical improvement in the tTMS group compared with the sham TMS group ( p < 0.05 and p < 0.05 respectively). Conclusion Transcranial magnetic stimulation was found to be effective in the treatment of tinnitus, and may be adopted as a treatment for tinnitus after further comprehensive studies.
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Monopolar spindle-one binder (MOBs) proteins are evolutionarily conserved and contribute to various cellular signalling pathways. Recently, we reported that hMOB2 functions in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest in untransformed cells. However, the question of how hMOB2 protects cells from endogenous DNA damage accumulation remained enigmatic. Here, we uncover hMOB2 as a regulator of double-strand break (DSB) repair by homologous recombination (HR). hMOB2 supports the phosphorylation and accumulation of the RAD51 recombinase on resected single-strand DNA (ssDNA) overhangs. Physiologically, hMOB2 expression supports cancer cell survival in response to DSB-inducing anti-cancer compounds. Specifically, loss of hMOB2 renders ovarian and other cancer cells more vulnerable to FDA-approved PARP inhibitors. Reduced MOB2 expression correlates with increased overall survival in patients suffering from ovarian carcinoma. Taken together, our findings suggest that hMOB2 expression may serve as a candidate stratification biomarker of patients for HR-deficiency targeted cancer therapies, such as PARP inhibitor treatments.
Subject(s)
Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Cell Line, Tumor , DNA Damage , DNA Repair , Homologous Recombination , Humans , Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic useABSTRACT
Royal jelly is known to strengthen memory, provide antioxidative, antidiabetic, antitumor, anticancer, antibacterial, antiinflammatory, antihypertensive. In this study, 42 rats (n = 42) were used, and these rats were divided into 6 groups of 7 rats each. Groups: (i) Control Group: Group fed with standard diet; (ii) Royal Jelly (RJ) Group: RJ (100 mg/kg bw, gavage); (iii) F50 Group: Fluoride (50 mg/kg bw, drinking water); (iv) F100 Group: F (100 mg/kg bw, drinking water); (v) F50 + RJ Group: F (50 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage); (vi) F100 + RJ Group: F (100 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage). The rats were decapitated after 8 weeks, and their heart tissues were taken and examined. Lipid peroxidation by MDA (malondialdehyde) analyzes, GSH (glutathione) level and catalase activity were determined by spectrophotometer. Protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, BDNF, Gsk-3, Nrf-2 and NF-κB proteins in heart tissue were determined by western blotting technique and hearth tissue evaluated by histopathologically. As a result, MDA levels, Bcl-2, Gsk-3 and NF-κB protein expression levels were reduced, whereas GSH levels, caspase-3, caspase-9, caspase-6, Bax, BDNF and Nrf-2 protein levels were increased in the F50 + RJ and F100 + RJ groups compared to the F50 and F100 groups. According to the results of this study, it has been concluded that Royal jelly has the potential to be developed in to a drug for treatment of heart diseases in addition to providing protection against heart damage.
Subject(s)
Glycogen Synthase Kinase 3 , NF-kappa B , Animals , Apoptosis , Fatty Acids , Oxidative Stress , Rats , bcl-2-Associated X ProteinABSTRACT
This study attempts to evaluate the antioxidant, enzyme inhibitory, and anticancer properties as well as fatty acid compositions of endemic Saponaria prostrata WILLD. subsp. anatolica HEDGE. The gas chromatography-mass spectrometry (GC-MS) was used to determine the fatty acid content of methanol: dichloromethane extract from S. prostrata subsp. anatolica (SPA). Enzymatic activity was measured against acetylcholinesterase, butyrylcholinesterase and α-glucosidase. DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity and Ferric reducing antioxidant power assay (FRAP) were conducted to antioxidant properties. The anticancer effect of SPA on human MCF-7 breast cancer and human HCT116 colorectal cancer cell line was evaluated by WST-1 cell viability assay, colony formation assay and wound healing assay. In addition, human VEGF Elisa method was used to determine the anti-angiogenic effect, and the quantitative real-time PCR (qRT-PCR) method on p53, Bax and Bcl-2 mRNA levels were used to evaluate apoptosis. While high amounts of palmitic acid (40.8%), linoleic acid (17.75%) and α-linolenic acid (16.84%) were detected in the SPA, the total amount of unsaturated fatty acid (51.34%) was higher than the total amount of saturated fatty acid (48.66%). SPA displayed the most promising acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and α-glycosidase (AG) inhibitory activities (AChE: IC50: 18.03 µg/mL, BuChE: IC50: 44.24 µg/mL and AG: IC50: 210.85 µg/mL). The half maximum inhibitory concentration (IC50) of SPA in MCF-7 and HCT116 cells was determined as 259.79 µg/mL and 97.24 µg/mL, respectively. In addition, it was determined that SPA suppresses colony formation and wound closure, and suppresses angiogenesis as well as triggering apoptosis at a significant level. It is true that endemic S. prostrata subsp. anatolica is a potential source of functional food ingredients, but more analytical and in vivo experiments are needed to explore further secondary metabolite diversity and pharmacological properties.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antioxidants/chemistry , Fatty Acids/analysis , Plant Extracts/chemistry , Saponaria/chemistry , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/metabolism , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents, Phytogenic/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/metabolism , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/metabolism , Humans , Saponaria/metabolism , alpha-Glucosidases/chemistry , alpha-Glucosidases/metabolismABSTRACT
Resistance to chemotherapeutic drugs is a critical problem in cancer therapy, but the underlying mechanism has not been fully elucidated. TP53-induced glycolysis regulatory phosphatase (TIGAR), an important glycolysis and apoptosis regulator, plays a crucial role in cancer cell survival by protecting cells against oxidative stress-induced apoptosis. In the present study, we investigated whether TIGAR is involved in epithelial-mesenchymal transition (EMT) in doxorubicin (DOX)-resistant human non-small cell lung cancer (NSCLC), A549/DOX cells. We found that the expression of TIGAR was significantly higher in A549/DOX cells than in the parent A549â cell lines. siRNA-mediated TIGAR knockdown reduced migration, viability and colony survival of doxorubicin-resistant lung cancer cells. Also, TIGAR knockdown decreased pro-survival protein Bcl-2 and increased pro-apoptotic Bax and cleaved poly (ADP-ribose) polymerase (PARP). Moreover, TIGAR depletion significantly up-regulated both caspase-3 and caspase-9 expression. Furthermore, TIGAR depletion up-regulated the expression of E-cadherin and down-regulated the expression of vimentin. These results indicate that TIGAR knockdown may inhibit EMT in doxorubicin (DOX)-resistant human NSCLC and may represent a therapeutic target for a non-small lung cancer cells chemoresistance.
Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Phosphoric Monoester Hydrolases/metabolism , RNA, Small Interfering/metabolism , A549 Cells , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/deficiency , Apoptosis Regulatory Proteins/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cell Movement/drug effects , Cell Survival/drug effects , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/drug effects , Epithelial-Mesenchymal Transition/drug effects , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Phosphoric Monoester Hydrolases/deficiency , Phosphoric Monoester Hydrolases/genetics , Tumor Cells, CulturedABSTRACT
AIM: We aimed to evaluate the effect of PET taken before surgery on the treatment protocol in patients diagnosed with BC and whether PET resulted in changes in the disease stage. MATERIAL AND METHODS: BC patients in our hospital who underwent surgery between 2016-2020 were retrospectively analyzed. The effect of preoperative PET on the treatment protocol was evaluated in all. Patients were divided into subgroups depending on whether they underwent direct surgery without CTX or were operated on after CTX initiation. In addition, in the group that did not receive CTX, axillary findings of PET were compared with postoperative histopathological results, and axillary PPV, NPV, sensitivity and specificity of PET were determined. In this subgroup, the preoperative PET stage was compared with the postoperative histopathological stage, and any changes in the disease stage were compared. RESULTS: In our study, PET affected the treatment protocol of 19 patients (20%). PET resulted in staging differences in 57.6% overall, increased staging in four patients (8.8%) who did not receive early-stage CT, and lower staging in 22 (48.8%) patients in the group. In early-stage BC of PET, the PPV for axilla was 81.2%, the NPV was 65.5%, sensitivity was 56.5%, and specificity was 86.3%. DISCUSSION: Although PET has many limitations, the determination of the size of the primary tumor and the multiple foci at different locations according to PET findings helped us to easily determine the treatment protocol for patients planned for BCS. CONCLUSION: The preoperative routine use of PET, which can provide more information about metastasis and stage than other methods in patients undergoing BC surgery, may improve the management of treatment in these patients. KEY WORDS: Breast cancer, 18F FDG-PET/CT, Chemotherapy, Staging.
ABSTRACT
OBJECTIVES: This study aimed to evaluate the effect of quercetin on cochlear function and morphology, and its possible protective effect against acute cisplatin-induced ototoxicity in rats. MATERIALS AND METHODS: This prospective and controlled animal study was conducted on Wistar albino rats divided into four groups. Otoacoustic emission measures were performed three days after the first infiltration in Group 1 (saline), 2 (cisplatin), and 3 (quercetin). This interval was five days for Group 4 (cisplatin+quercetin). At the end of the study, the rats were decapitated with deep anesthesia, and histological changes in the cochleas were observed by light microscopy. RESULTS: Group 2 (cisplatin) revealed significant differences between the first and second measures in all frequencies. When compared to other group, the difference of the changes in Group 2 statistically significantly decreased, especially in higher frequencies. Morphologically, there were no acute changes in Group 1 and Group 3. Outer hair cell loss and the degeneration of stria vascularis and spiral ganglion were observed in both Groups 2 and 4; the damages in the latter were lesser. CONCLUSION: Quercetin does not have negative effect on cochlea, and it has protective effect on cisplatin-induced ototoxicity.
Subject(s)
Antineoplastic Agents/toxicity , Antioxidants/pharmacology , Cisplatin/toxicity , Ototoxicity/prevention & control , Quercetin/pharmacology , Analysis of Variance , Animals , Female , Organ of Corti/drug effects , Organ of Corti/pathology , Ototoxicity/pathology , Rats, Wistar , Stria Vascularis/drug effects , Stria Vascularis/pathologyABSTRACT
The family of MOBs (monopolar spindle-one-binder proteins) is highly conserved in the eukaryotic kingdom. MOBs represent globular scaffold proteins without any known enzymatic activities. They can act as signal transducers in essential intracellular pathways. MOBs have diverse cancer-associated cellular functions through regulatory interactions with members of the NDR/LATS kinase family. By forming additional complexes with serine/threonine protein kinases of the germinal centre kinase families, other enzymes and scaffolding factors, MOBs appear to be linked to an even broader disease spectrum. Here, we review our current understanding of this emerging protein family, with emphases on post-translational modifications, protein-protein interactions, and cellular processes that are possibly linked to cancer and other diseases. In particular, we summarise the roles of MOBs as core components of the Hippo tissue growth and regeneration pathway.