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1.
Article in English | MEDLINE | ID: mdl-38748229

ABSTRACT

Capecitabine is recommended as one of the first-line chemotherapy treatments for advanced or metastatic colorectal cancer. Researches have been conducted on capecitabine's impact on the viability of human colon cancer cells and its potential to induce apoptosis. However, even in cases initially responsive to treatment, the development of acquired resistance significantly limits its efficacy. Challenges still exist in effectively treating patients with chemotherapy, and developing new cytotoxic drugs is hindered by drug resistance. Fisetin alters the cell cycle, inducing apoptosis, inhibiting cancer cell proliferation, and enhancing the therapeutic effectiveness of chemotherapy drugs. This work aims to create a plan for reversing capecitabine resistance. For this purpose, the role of capecitabine and/or fisetin combinations in cell proliferation and apoptosis has been determined in both wild-type and capecitabine-resistant HT29 cells (CR/HT29). We developed capecitabine-resistant cell line from wild-type HT29 cells. This study demonstrated the effects of capecitabine, fisetin, and their combinations on both resistant and wild-type cells through experiments including cell survival skills, cell proliferation, wound healing, colony formation, hoechst staining, and western blot analysis. We established capecitabine-resistant cell lines. P-gp expression increased in CR/HT29 cells. Capecitabine effects on a CR/HT29 cells less than wild-type HT29 cells. The combination of fisetin and capecitabine in cell proliferation caused greater reductions in wild-type HT29 cells than in capecitabine-resistant cells. Fisetin has also additive effects on the apoptotic pathway in CR/HT29 cells. This study provides new perspectives on the combination of capecitabine and/or flavonoid treatment in resistant cells.

2.
Eur Rev Med Pharmacol Sci ; 27(15): 7180-7187, 2023 08.
Article in English | MEDLINE | ID: mdl-37606128

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the adverse effects of diabetes mellitus on the knee joint by using ultrasonography. PATIENTS AND METHODS: One hundred and two subjects with diabetes for 5 years and more were compared prospectively with 93 age and sex-matched healthy subjects. Individuals in both groups were aged between 40-55, had a body mass index below 30 kg/m2, and had no knee joint complaints. Femoral cartilage thickness, cartilage surface, quadriceps and patellar tendon thickness in both knees were assessed by ultrasonography using a 5-12 mHz linear transducer. RESULTS: According to ultrasonographic findings, thin and irregular femoral cartilage was more common in diabetic patients than in healthy controls (p<0.05). Diabetic patients had thinner quadriceps tendons compared to the control group (p<0.001). No statistically significant difference was recorded in patellar tendon thickness (right knee p=0.697, left knee p=0.639). The presence of effusion in the suprapatellar recess of the right knee was more common in diabetics than non-diabetics (p=0.006). CONCLUSIONS: Irregularity and thinning of the distal femoral cartilage in diabetics may indicate cartilage degeneration. In addition, the decrease in the thickness of the quadriceps tendon may lead to instability and adversely affect the knee joint. These sonographic findings may indicate early knee joint degeneration, so ultrasonography may help determine the possible risk of osteoarthritis in diabetic patients.


Subject(s)
Diabetes Mellitus , Osteoarthritis, Knee , Humans , Adult , Middle Aged , Knee Joint/diagnostic imaging , Tendons/diagnostic imaging , Cartilage
3.
Article | WPRIM (Western Pacific) | ID: wpr-832068

ABSTRACT

Objective@#The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear extinction depending on the phase of fear conditioning. Brain noradrenergic system has a role in fear conditioning. Data regarding the role of prazosin in traumatic stress are controversial. @*Methods@#In this study, we examined the effects of prazosin and the noradrenergic system in fear conditioning in a predator stress rat model. We evaluated the direct or indirect effects of stress and prazosin on noradrenaline (NA), gamma-aminobuytyric acid (GABA), glutamate, glycine levels and choline esterase activity in the amygdaloid complex, the dorsal hippocampus, the prefrontal cortex and the rostral pons. @*Results@#Our results demonstrated that prazosin might alleviate defensive behaviors and traumatic stress symptoms when given during the traumatic cue presentation in the stressed rats. However prazosin administration resulted in higher anxiety levels in non stressed rats when the neutral cue was presented. @*Conclusion@#Prazosin should be used in PTSD with caution because prazosin might exacerbate anxiety in non-traumatized subjects. However prazosin might as well alleviate stress responses very effectively. Stress induced changes included increased NA and GABA levels in the amygdaloid complex in our study, attributing noradrenaline a possible inhibitory role on fear acquisition. Acetylcholine also has a role in memory modulation in the brain. We also demonstrated increased choline esterase acitivity. Cholinergic modulation might be another target for indirect prazosin action which needs to be further studied.

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