Biomedical applications of electrospun polycaprolactone-based carbohydrate polymers: A review.

Carbohydrate used in biomedical applications is influenced by numerous factors. One of the most appealing characteristic of carbohydrates is their ability to reproduce from natural resources which makes them ecologically friendly. Due to their abundance, biocompatibility, and no contamination by residual initiators, the desire for polysaccharides in medical uses is growing. Research on fiber-based materials, with a variety of medical applications including bio-functional scaffolds, continues to yield novel and intriguing findings. Almost all biopolymers of diverse structural compositions are electrospun to fulfill biomedical usage criteria, and the electrospinning technique is widely employed in biomedical technologies for both in-vivo and in-vitro therapies. Due to its biocompatibility and biodegradability, polycaprolactone (PCL) is employed in medical applications like tissue engineering and drug delivery. Although PCL nanofibers have established effects in vitro, more research is needed before their potential therapeutic application in the clinic. Here we tried to focus mainly on the carbohydrate incorporated PCL-based nanofibers production techniques, structures, morphology, and physicochemical properties along with their usage in biomedicine.

Concomitant effects of paclitaxel and celecoxib on genes involved in apoptosis of triple-negative metastatic breast cancer cells.

Although triple-negative breast cancer accounts for less than one-fifth of breast cancers, it has a higher rate of metastasis and mortality. This study investigated the effects of combination treatment with paclitaxel and celecoxib on the expression of genes involved in the apoptosis of triple-negative metastatic breast cancer cells. MDA-MB-231 cells were cultured and then treated with certain concentrations of celecoxib (CLX), paclitaxel (PTX), and combination of them for 24 and 48 h. Cell viability was assessed by the MTT method. The real-time PCR method was utilized to assess the expression level of the genes involved in apoptosis. Western blotting was used for evaluating protein expression. IC50 values for CLX and PTX were 73.95 µM and 3.15 µM, respectively. The results demonstrated that PTX, CLX, and PTX + CLX significantly (p < 0.05) reduced cell viability. The comparison of combination treatment with PTX showed a significant increase in caspase 3 gene expression at both time points, in Bax gene expression after 48 h, and a remarkable decrease in Bcl-2 gene expression at both times. Western blotting results were in line with genes' expression. These findings indicate that a combination of PTX and CLX results in a significantly more reduction in cell viability of breast cancer cells. In addition, it seems CLX may be an effective agent in regulating the expression level of caspase 3, Bax, and Bcl-2 when combined with PTX.

Therapeutic application of mesenchymal stem cells derived exosomes in neurodegenerative diseases: A focus on non-coding RNAs cargo, drug delivery potential, perspective.

Despite the massive efforts advanced over recent years in emerging therapies for neurodegenerative diseases, effective treatment for these diseases is still an urgent need. The application of mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) as a novel therapy for neurodegenerative diseases holds great promise. A growing body of data now suggests that an innovative cell-free therapy, MSCs-Exo, may establish a fascinating alternative therapy due to their unique advantages over MSCs. Notable, MSCs-Exo can infiltrate the blood-brain barrier and then well distribute non-coding RNAs into injured tissues. Research shows that non-coding RNAs of MSCs-Exo are vital effectors that participate in the treatment of neurodegenerative diseases through neurogeneration and neurite outgrowth, modulation of the immune system, reducing neuroinflammation, repairmen of damaged tissue, and promotion of neuroangiogenesis. In addition, MSCs-Exo can serve as a drug delivery system for delivering non-coding RNAs to neurons in neurodegenerative conditions. In this review, we summarize the recent progress in the therapeutic role of non-coding RNAs of MSCs-Exo for various neurodegenerative diseases. This study also discusses the potential drug delivery role of MSCs-Exo and challenges and opportunities in the clinical translation of MSCs-Exo-based therapies for neurodegenerative diseases in the future.

Selumetinib: a selective MEK1 inhibitor for solid tumor treatment.

Cancer incidence is rapidly growing. Solid tumors are responsible for a majority of cancers. Recently, molecular-targeted agents have played a significant role in cancer treatment. Ras-Raf-MEK-ERK signaling pathway, is a substantial element in the survival, propagation, and drug resistance of human cancers. MEK is a specific part of the so-called cascade, and ERK proteins are its sole target. Furthermore, their downstream position in the Ras-ERK cascade, is noteworthy to direct their function in patients with upstream mutated genes. MEK1 mutations are responsible for initiating several solid tumors. Selumetinib (AZD6244) is a second-generation, selective, potent, and non-ATP competitive allosteric MEK1 inhibitor. The efficacy of selumetinib in various solid tumors such as colorectal cancer, lung cancer, neurofibroma, and melanoma is investigated. The present paper provides an overview of the MAPK cascade, the role of selumetinib as a MEK1/2 inhibitor, and the related findings of clinical trials for solid tumor treatment.

Venlafaxine can reduce the migraine attacks as well as amitriptyline: A noninferiority randomized trial.

OBJECTIVES: Migraine, as a primary headache, is among the leading causes of disability worldwide. The present study aimed at comparing the effects of venlafaxine (VLF) and amitriptyline (AMT) reducing the severity and the number of migraine attacks. METHODS: Patients with complaints of migraine attacks were randomly divided into two groups. The first group received amitriptyline at a dose of 25 mg every night, and the second group received venlafaxine at a dose of 37.5 mg daily. The duration of treatment was eight weeks. RESULTS: Eighty patients participated in the current study, out of which 57.5% were females. The mean age of the participants was 33 years, and the mean duration of disease was eight years. Both amitriptyline and venlafaxine significantly reduced the number of attacks per month (AMT: from 10.98 to 2.98, VLF: from 9.98 to 3.18), and six-item Headache Impact Test (HIT-6) score (AMT: from 67.78 to 49.73, VLF: from 66.65 to 48.88), and no significant difference was observed between the two drugs. The results demonstrated no significant relationship between age or disease duration with the score of the HIT-6. The decrease rate in the score of the HIT-6 in males was higher than that of females which shows the modifier role of the gender. Besides, it is noteworthy to mention that the adverse effects of amitriptyline exceeded the venlafaxine among the patients. CONCLUSION: The effectiveness of AMT and VLF in terms of their potential to reduce the intensity and duration of headaches was more noticeable in male patients than female patients. In terms of adverse drug reactions, patients in the amitriptyline group complained more about adverse drug reactions (ADR) than patients in the venlafaxine group. It seems that in similar conditions, venlafaxine could have priority over amitriptyline in migraine prophylaxis.