Combination chemotherapy against colorectal cancer cells: Co-delivery of capecitabine and pioglitazone hydrochloride by polycaprolactone-polyethylene glycol carriers.

BACKGROUND: Colorectal cancer causes numerous deaths despite many treatment options. Capecitabine (CAP) is the standard chemotherapy regimen for colorectal cancer, and pioglitazone hydrochloride (PGZ) for diabetic disease treatment. However, free drugs do not induce effective apoptosis. This work aims to co-encapsulate CAP and PGZ and evaluate cytotoxic and apoptotic effects on HCT-119, HT-29 colorectal cancer cells, and human umbilical vein endothelial cells (HUVECs). METHOD: CAP, PGZ, and combination treatment nano-formulations were prepared by triblock (TB) (PCL-PEG-PCL) biodegradable copolymers to enhance drugs' bioavailability as anti-cancer agents. The Ultrasonic homogenization method was used for preparing nanoparticles. The physicochemical characteristics of nanoparticles were studied using 1H NMR, FTIR, DLS, and FESEM techniques. The zeta potential, entrapment efficiency, drug release, and storage stability were studied. Also, cell viability and apoptosis were examined by using MTT, acridine orange (AO), and propidium iodide (PI), respectively. RESULT: The smaller hydrodynamic size (236.1 nm), polydispersity index (0.159), and zeta potential (-20.8 mV) were observed in nanoparticles. Nanoparticles revealed a proper formulation and storage stability at 25 °C than 4 °C in 90 days. The synergistic effect was observed in (CAP-PGZ)-loaded TB nanoparticles in HUVEC, HCT-116, and HT-29 cells. In (AO/PI) staining, the high percentage of apoptotic cells in the (CAP-PGZ)-loaded TB nanoparticles in HUVEC, HCT-116, and HT-29 were calculated as 78 %, 71.66 %, and 69.31 %, respectively. CONCLUSION: The (CAP-PGZ)-loaded TB nanoparticles in this research offer an effective strategy for targeted combinational colorectal cancer therapy.

Laboratory methods: A concise review and update for COVID-19 diagnosis.

Since late December 2019, coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spread across the globe. The early, safe, sensitive, and accurate diagnosis of viral infection is required to decrease and control contagious infection and improve public health surveillance. The diagnosis generally is made by detecting SARS-CoV-2-related agents, including a range of nucleic acid detection-based, immunoassay-based, radiographic-based, and biosensor-based methods. This review presents the progress of various detection tools for diagnosing COVID-19 and addresses the advantages and restrictions of each detection method. Given that diagnosis of a contagious various like SARS-COV-2 can improve patient survival rates and break the transmission chain, there is no surprise that significant efforts should be made to reduce the limitations of tests that lead to false-negative results and to develop a substantial test for COVID-19 diagnosis.

MicroRNAs and drug resistance in colorectal cancer with special focus on 5-fluorouracil.

Colorectal cancer is globally one of the most common cancers in all age groups. The current chemotherapy combinations for colorectal cancer treatment include 5-fluorouracil-based regimens; however, drug resistance remains one of the main reasons for chemotherapy failure and disease recurrence. Many studies have determined colorectal cancer chemoresistance mechanisms such as drug efflux, cell cycle arrest, DNA damage repair, apoptosis, autophagy, vital enzymes, epigenetic, epithelial-mesenchymal transition, stem cells, and immune system suppression. Several microRNAs affect drug resistance by regulating the drug resistance-related target genes in colorectal cancer. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with colorectal cancer. This work reviews and discuss the role of selected microRNAs in 5-fluorouracil resistance and their molecular mechanisms in colorectal cancer.

MicroRNAs as therapeutic targets in breast cancer metastasis.

Breast cancer is a complex disease with multiple risk factors involved in its pathogenesis. Among these factors, microRNAs are considered for playing a fundamental role in the development and progression of malignant breast tumors. In recent years, various studies have demonstrated that several microRNAs exhibit increased or decreased expression in metastatic breast cancer, acting as indicators of metastatic potential in body fluids and tissue samples. The identification of these microRNA expression patterns could prove instrumental for the development of novel therapeutic molecules that either mimic or inhibit microRNA action. Additionally, an efficient delivery system mediated by viral vectors, nonviral carriers, or scaffold biomaterials is a prerequisite for implementing microRNA-based therapies; therefore, this review attempts to highlight essential microRNA molecules involved in the metastatic process of breast cancer and discuss recent advances in microRNA-based therapeutic approaches with potential future applications to the treatment sequence of breast cancer.

Performance of capecitabine in novel combination therapies in colorectal cancer.

Colorectal cancer is one of the most common cancers throughout the world, and no definitive cure has ever been found. Perhaps a new insight into the effectiveness of chemotherapy drugs could help better treat patients. Targeted therapies have significantly improved the median overall survival of colorectal cancer patients. One of the standard chemotherapy regimens used for colorectal cancer is capecitabine, which is important in monotherapy and combination therapies. Capecitabine, with other chemotherapeutic agents (irinotecan, oxaliplatin, perifosine, 17-allylamino-17-demethoxygeldanamycin, aspirin, celecoxib, statins, quinacrine, inositol hexaphosphate and inositol, cystine/theanine, curcumin, and isorhamnetin), and biological ones (antibodies) plays an important role in the inhibition of some signaling pathways, increasing survival, reducing tumor growth and side effects of capecitabine. However, some drugs, such as proton pump inhibitors, are negatively related to capecitabine; therefore, the purpose of this work is to review and discuss the performance of capecitabine combination therapies in colorectal cancer.

In-vitro study of homocysteine and aspirin effects on fibrinolysis: measuring fibrinolysis parameters.

Some studies suggest that increased homocysteine in blood leads to alterations in coagulation and fibrinolysis; however, the precise mechanism is not clear. The aim of this study was to compare different concentrations of homocysteine and aspirin on fibrinolysis in the plasma of healthy individuals in vitro. Different concentrations of homocysteine (200, 100, and 50 µmol/l) and aspirin (100, 10, and 1 mg/l) were added to the healthy people plasma citrate. They were incubated at 37°C for 24 h. Then, fibrinolysis parameters were analyzed by the turbidimetric procedure at 405 nm. The independent-samples t-test was utilized to compare them (P < 0.05). Findings revealed that homocysteine at 200 µmol/l with aspirin 100 ml/g had significant changes in the lysis maximum velocity (0.150 ±â€Š0.002), half-lysis time (218 ±â€Š5.77), the total lysis time (446 ±â€Š5.77), and lag time in lysis (119 ±â€Š3.60), compared to homocysteine at 200 µmol/l lysis maximum velocity (0.110 ±â€Š0.002), half-lysis time (278 ±â€Š7.63), the total lysis time (515 ±â€Š14.29), and lag time in lysis (176 ±â€Š3.60), respectively (P < 0.05). Homocysteine at 200 µmol/l with aspirin 1 ml/g did not significantly change in either parameter (P > 0.05). Homocysteine at 50 µmol/l with aspirin (100, 10, and 1 mg/l) had significant changes in all fibrinolysis parameters (P < 0.05), compared to homocysteine at 50 µmol/l. The other concentrations were compared in the same way. Aspirin (more than 1 mg/l) had more effect on higher concentrations of homocysteine. Aspirin increased velocity of clot lysis and decreased lysis time of clot in the presence of homocysteine.