Multiple functions of microfluidic platforms: Characterization and applications in tissue engineering and diagnosis of cancer

Microfluidic system, or lab-on-a-chip, has grown explosively. This system has been used in research for the first time and then entered in the clinical section. Due to economic reasons, this technique has been used for screening of laboratory and clinical indices. The microfluidic system solves some difficulties accompanied by clinical and biological applications. In this review, the interpretation and analysis of some recent developments in microfluidic systems in biomedical applications with more emphasis on tissue engineering and cancer will be discussed. Moreover, we try to discuss the features and functions of microfluidic systems. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding Bill & Melinda Gates Foundation

Application of nanoparticles in bone tissue engineering; A review on the molecular mechanisms driving osteogenesis

The introduction of nanoparticles into bone tissue engineering strategies is beneficial to govern cell fate into osteogenesis and the regeneration of large bone defects. The present study explored the role of nanoparticles to advance osteogenesis with a focus on the cellular and molecular pathways involved. Pubmed, Pubmed Central, Embase, Scopus, and Science Direct databases were explored for those published articles relevant to the involvement of nanoparticles in osteogenic cellular pathways. As multifunctional compounds, nanoparticles contribute to scaffold-free and scaffold-based tissue engineering strategies to progress osteogenesis and bone regeneration. They regulate inflammatory responses and osteo/angio/osteoclastic signaling pathways to generate an osteogenic niche. Besides, nanoparticles interact with biomolecules, enhance their half-life and bioavailability. Nanoparticles are promising candidates to promote osteogenesis. However, the interaction of nanoparticles with the biological milieu is somewhat complicated, and more considerations are recommended on the employment of nanoparticles in clinical applications because of NP-induced toxicities. © The Royal Society of Chemistry

Comparative evaluation of morphology and osteogenic behavior of human Wharton's jelly mesenchymal stem cells on 2D culture plate and 3D biomimetic scaffold

Expansion of seeded human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) on 2D culture plates and 3D nano-hydroxyapatite/chitosan/gelatin scaffolds, from morphology and osteoactivity points of view, were investigated. Cell attachment and spreading, temporal expression profiles of selected osteogenic gene and protein markers, intracellular alkaline phosphatase enzyme activity (ALP activity), and matrix mineralization were assayed over the course of the experiments. Morphological results demonstrated hWJ-MSCs had greater affinity to adhere onto the 3D scaffold surface, as the number and thickness of the filopodia were higher in the 3D compared with 2D culture system. Functionally, the intracellular ALP activity and extracellular mineralization in 3D scaffolds were significantly greater, in parallel with elevation of osteogenic markers at the mRNA and protein levels at all-time point. It is concluded that 3D scaffolds, more so than 2D culture plate, promote morphology and osteogenic behavior of WJ-MSCs in vitro, a promising system for MSCs expansion without compromising their stemness before clinical transplantation. © 2019 Wiley Periodicals, Inc

In vitro interaction of human Wharton's jelly mesenchymal stem cells with biomimetic 3D scaffold

Study of cell-biomaterial interaction is a crucial aspect of bone tissue engineering to find a state-of-the-art functional substitute. In present study, the Wharton's jelly mesenchymal stem cells (hWJ-MSCs) behavior on three-dimensional biomimetic nano-hydroxyapatite/chitosan/gelatin (nHA/CS/Gel) scaffolds was investigated. The outcome was assessed by histological, biochemical and morphological tests. Results indicated that hWJ-MSCs attached onto the scaffold surface through membrane filopodia, uniformly spread throughout the contacting surface. It only took 3 days for the seeded cells to appear deep inside the scaffold, reflecting proper hWJ-MSCs adhesion and migration, evidenced by both scanning electron microscope and hematoxilin and eosin assessments. Additionally, the present fabricated nHA/CS/Gel scaffold proved to be non-toxic as it supported cell proliferation measured by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Moreover, 3-week culture of hWJ-MSCs on scaffolds, immersed in osteogenic medium, rendered the microenvironment in favor of hWJ-MSCs differentiation into osteoblast cells and extracellular matrix secretion. Finally, osteoblasts were immunologically positive for various osteogenic markers including osteocalcin, osteopontin, osteonectin, and alkaline phosphatase. Present findings indicate that nHA/CS/Gel scaffold appropriately harbored hWJ-MSCs, stimulating their growth, migration, proliferation, and differentiation. hWJ-MSCs-loaded nHA/CS/gel substitute may therefore be considered as a suitable platform for the rising demand in in vivo bone repair studies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1166�1175, 2019. © 2019 Wiley Periodicals, Inc

Fabrication of cancellous biomimetic chitosan-based nanocomposite scaffolds applying a combinational method for bone tissue engineering

The aim of this study was to mimic the specific structure of bone and fabricate a biomimetic nano-hydroxyapatite (HA)/chitosan (Cs)/gelatin scaffolds using combination of particle leaching and freeze drying methods eliminating mold effects. To achieve an optimum structure, scaffolds with different gelatin/Cs weight ratio were fabricated. Morphological characterization of scaffolds by scanning electron microscopy method showed highly interconnected porous structures similar to cancellous bone with mean pore size ranging from 140 to 190 μm. Nano-HA crystals were dispersed homogeneously in the polymer matrix according to the energy-dispersive X-ray spectroscopy and transmission electron microscopy images. Fourier transform infrared and X-ray diffraction results disclosed that chemical interactions were formed between nano-HA, Cs, gelatin and crystallinity of each material decreased with blending. It was found that increasing the gelatin content significantly improved water uptake, degradation rate as well as attachment, infiltration and proliferation of Saos2 cells to the scaffolds. The presented results confirm that the designed biomimetic nano-HA /Cs/gelatin scaffolds can be used as promising substitutes for bone tissue engineering. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1882-1892, 2015. © 2014 Wiley Periodicals, Inc

Shelterin complex at telomeres: Implications in ageing

Different factors influence the development and control of ageing. It is well known that progressive telomere shorting is one of the molecular mechanisms underlying ageing. The shelterin complex consists of six telomere-specific proteins which are involved in the protection of chromosome ends. More particularly, this vital complex protects the telomeres from degradation, prevents from activation of unwanted repair systems, regulates the activity of telomerase, and has a crucial role in cellular senescent and ageing-related pathologies. This review explores the organization and function of telomeric DNA along with the mechanism of telomeres during ageing, followed by a discussion of the critical role of shelterin components and their changes during ageing. © 2020 Mir et al

Shelterin complex at telomeres: Roles in cancers

Telomeres, the nucleoprotein structures at the ends of eukaryotic chromosomes, have multiple roles in tumorigenesis. The shelterin complex consists of six telomere-specific proteins that are involved in the protection of the telomeres. The shelterin complex protects the telomeres from degradation, prevents the activation of unwanted repair systems, and regulates the activity of telomerase. However, alteration in the structure and function of the shelterin complex proteins may lead to tumorigenesis and cancer progression. The shelterin complex biology revealed that the manipulation of the shelterin proteins could be a new strategy in cancer therapy. In this review, we focused on shelterin components' roles in the diagnosis, prevention, and treatment of cancers. © 202