Advanced pharmaceutical bulletin最新文献

MicroRNAs are small RNAs with ability to attach to the large number of RNA that regulate gene expression on post-transcriptional level via inhibition or degradation of specific mRNAs. MiRNAs in cells are the primary regulators of functions such as cell growth, differentiation, and apoptosis and considerably influence cell function. The expression levels of microRNAs change in human diseases, including cancer. These changes highlight their essential role in cancer pathogenesis. Ubiquitous irregular expression profiles of miRNAs have been detected in various human cancers using genome-wide identification techniques, which are emerging as novel diagnostic and prognostic cancer biomarkers of high specificity and sensitivity. The measurable miRNAs with enhanced stability in blood, tissues, and other body fluids provide a comprehensive source of miRNA-dependent biomarkers for human cancers. The leading role of miRNAs as potential biomarkers in human cancers is discussed in this article. In addition, the interests and difficulties of miRNAs as biomarkers have been explored.

Brain, predisposed to local and metastasized tumors, has always been the focus of oncological studies. Glioblastoma multiforme (GBM), the most common invasive primary tumor of the brain, is responsible for 4% of all cancer-related deaths worldwide. Despite novel technologies, the average survival rate is 2 years. Physiological barriers such as blood-brain barrier (BBB) prevent drug molecules penetration into brain. Most of the pharmaceuticals present in the market cannot infiltrate BBB to have their maximum efficacy and this in turn imposes a major challenge. This mini review discusses GBM and physiological and biological barriers for anticancer drug delivery, challenges for drug delivery across BBB, drug delivery strategies focusing on SLNs and NLCs and their medical applications in on-going clinical trials. Numerous nanomedicines with various characteristics have been introduced in the last decades to overcome the delivery challenge. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were introduced as oral drug delivery nanomedicines which can be encapsulated by both hydrophilic and lipophilic pharmaceutical compounds. Their biocompatibility, biodegradability, lower toxicity and side effects, enhanced bioavailability, solubility and permeability, prolonged half-life and stability and finally tissue-targeted drug delivery makes them unique among all.

Quantum dots (QDs) are semiconductor materials that range from 2 nm to 10 nm. These nanomaterials (NMs) are smaller and have more unique properties compared to conventional nanoparticles (NPs). One of the unique properties of QDs is their special optoelectronic properties, making it possible to apply these NMs in bioimaging. Different size and shape QDs, which are used in various fields such as bioimaging, biosensing, cancer therapy, and drug delivery, have so far been produced by chemical methods. However, chemical synthesis provides expensive routes and causes serious environmental and health issues. Therefore, various biological systems such as bacteria, fungi, yeasts, algae, and plants are considered as potent eco-friendly green nanofactories for the biosynthesis of QDs, which are both economic and environmentally safe. The review aims to provide a descriptive overview of the various microbial agents for the synthesis of QDs and their biomedical applications for the diagnosis and treatment of cancer and SARS-CoV-2.

Extracellular vesicles (EVs) are a heterogeneous class of cell-derived vesicles that are responsible for eliciting a wide array of biological processes. After decades of intense investigation, the therapeutic potential of EVs will be finally explored in a series of upcoming clinical trials. EVs are rapidly changing the understanding of human physiology and will undoubtedly transform the field of medicine. The applicability of EVs as diagnostic biomarkers and treatment vectors has captured the attention of the scientific community and investors, facilitating the rapid progression of numerous EVs-based platforms. This mini-review provides an outline of the pioneering discoveries, and their respective significances, on progressing EVs toward clinical use. We focus the attention of the readers on several promising classes of EVs that hold major opportunities to translate in clinical practice. Market analysis and future challenges facing EVs-based therapies are also discussed.

Purpose: Evidence suggests that turmeric intake can improve antioxidant defense, blood pressure (BP), ageing and gut microbiota. The effects of turmeric concentrate (curcumin) intake on cardiovascular risk factors and exercise induced oxidative stress were investigated.

Methods: A randomized placebo-controlled study was performed to assess the effects of turmeric extract in healthy volunteers before and after a 30 min exercise bout. Participants (n=22) were given either turmeric concentrate or placebo supplements. Anthropometry, BP, pulse wave velocity (PWV), biomarkers of oxidative stress, perceived exertion and lipid peroxidation were assessed.

Results: In the turmeric group, the expected BP response to exercise following turmeric was blunted and the increase was not significant compared to basal values followed by a decrease in final BP and PWV values. There were no significant differences in all baseline parameters between the placebo and the curcumin groups (P>0.05). A significant increase was observed in urinary antioxidant power (P=0.031) and total polyphenol levels (P=0.022) post turmeric intervention. The distance ran by the participants taking turmeric was significantly longer (P=0.005) compared to basal value. Those who took the placebo did not show significant changes.

Conclusion: Our study suggests that turmeric concentrate intake can reduce BP and improve antioxidant, anti-inflammatory status and arterial compliance. Turmeric may improve exercise performance and ameliorates oxidative stress. Larger studies are warranted to validate these findings and test more cardiovascular risk factors.

Purpose: CD44 plays a pivotal role through tumorigenesis by regulating cancer cell metastasis, stemness, and chemosensitivity and is considered a promising therapeutic target for human cancers, including colorectal cancer (CRC). Therefore, the present research aimed to examine the simultaneous therapeutic effect of CD44 silencing and 5-fluorouracil (5-FU) on in vitro tumorigenesis of CRC cells.

Methods: CD44 expression was initially evaluated in TCGA datasets and CRC tissues. Furthermore, functional analysis was performed on HT-29 CRC cells overexpressing CD44. The cells were transfected with CD44 siRNA and then treated with 5-FU. Consequently, to explore the combination therapy effect on cell viability, migration, apoptosis, and chromatin fragmentation, we performed MTT assay, scratch assay, Annexin V/PI staining and DAPI staining assays, respectively. The spheroid and colony formation assays were further employed to investigate stemness features. The gene expression at protein and mRNA levels were explored using western blotting and qPCR.

Results: Our findings illustrated that CD44 was significantly overexpressed in CRC tissues compared to normal samples. The suppression of CD44 considerably promoted the chemosensitivity of HT-29 cells to 5-FU by apoptosis induction. Also, the combination therapy led to overexpression of apoptotic genes, including P53, caspase-3, and caspase-9, as well as downregulation of AKT1 expression. Furthermore, CD44 suppression, separately or combined with 5-FU, hindered stemness properties in HT-29 cells via downregulation of Sox2 and Nanog expression. Besides, the combination therapy remarkably downregulated MMPs and suppressed CRC cell migration.

Conclusion: Considering its involvement in chemosensitivity to 5-FU, CD44 could be suggested as a potential target for improving the efficiency of CRC chemotherapy.