MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC.     

Early Osteogenic Marker Expression in hMSCs Cultured onto Acid Etching-Derived Micro- and Nanotopography 3D-Printed Titanium Surfaces

Polyetheretherketone (PEEK) titanium composite (PTC) is a novel interbody fusion device that combines a PEEK core with titanium alloy (Ti6Al4V) endplates. The present study aimed to investigate the in vitro biological reactivity of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) to micro- and nanotopographies produced by an acid-etching process on the surface of 3D-printed PTC endplates. Optical profilometer and scanning electron microscopy were used to assess the surface roughness and identify the nano-features of etched or unetched PTC endplates, respectively. The viability, morphology and the expression of specific osteogenic markers were examined after 7 days of culture in the seeded cells. Haralick texture analysis was carried out on the unseeded endplates to correlate surface texture features to the biological data. The acid-etching process modified the surface roughness of the 3D-printed PTC endplates, creating micro- and nano-scale structures that significantly contributed to sustaining the viability of hBM-MSCs and triggering the expression of early osteogenic markers, such as alkaline phosphatase activity and bone-ECM protein production. Finally, the topography of 3D-printed PTC endplates influenced Haralick’s features, which in turn correlated with the expression of two osteogenic markers, osteopontin and osteocalcin. Overall, these data demonstrate that the acid-etching process of PTC endplates created a favourable environment for osteogenic differentiation of hBM-MSCs and may potentially have clinical benefit.     

Enhancing the Therapeutic Potential of Mesenchymal Stromal Cell-Based Therapies with an Anti-Fibrotic Agent for the Treatment of Chronic Kidney Disease

Chronic kidney disease (CKD) affects 1 in 10 members of the general population, placing these patients at an increasingly high risk of kidney failure. Despite the significant burden of CKD on various healthcare systems, there are no effective cures that reverse or even halt its progression. In recent years, human bone-marrow-derived mesenchymal stromal cells (BM-MSCs) have been recognised as a novel therapy for CKDs, owing to their well-established immunomodulatory and tissue-reparative properties in preclinical settings, and their promising safety profile that has been demonstrated in patients with CKDs from several clinical trials. However, renal fibrosis (scarring), a hallmark of CKD, has been shown to impair the viability and functionality of BM-MSCs post-transplantation. This has suggested that BM-MSCs might require a pre-treatment or adjunct therapy that can enhance the viability and therapeutic efficacy of these stromal cells in chronic disease settings. To address this, recent studies that have combined BM-MSCs with the anti-fibrotic drug serelaxin (RLX), have demonstrated the enhanced therapeutic potential of this combination therapy in normotensive and hypertensive preclinical models of CKD. In this review, a critical appraisal of the preclinical data available on the anti-fibrotic and renoprotective actions of BM-MSCs or RLX alone and when combined, as a treatment option for normotensive vs. hypertensive CKD, is discussed.     

Potential for identification of wild night-flying moths by remote infrared microscopy

There are hundreds of thousands of moth species with crucial ecological roles that are often obscured by their nocturnal lifestyles. The pigmentation and appearance of moths are dominated by cryptic diffuse shades of brown. In this study, 82 specimens representing 26 moth species were analysed using infrared polarimetric hyperspectral imaging in the range of 0.95–2.5 µm. Contrary to previous studies, we demonstrate that since infrared light does not resolve the surface roughness, wings appear glossy and specular at longer wavelengths. Such properties provide unique reflectance spectra between species. The reflectance of the majority of our species could be explained by comprehensive models, and a complete parametrization of the spectral, polarimetric and angular optical properties was reduced to just 11 parameters with physical units. These parameters are complementary and, compared with the within-species variation, were significantly distinct between species. Counterintuitively to the aperture-limited resolution criterion, we could deduce microscopic features along the surface from their infrared properties. These features were confirmed by electron microscopy. Finally, we show how our findings could greatly enhance opportunities for remote identification of free-flying moth species, and we hypothesize that such flat specular wing targets could be expected to be sensed over considerable distances.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

Influence of Aging Parameters on the Tensile Properties and Quality Index of Al-9?Pct Si-1.8?Pct Cu-0.5?Pct Mg 354-Type Casting Alloys

The current study was carried out with a view to investigating the influence of age-hardening parameters, aging temperature and time, on the tensile properties and quality indices of a high-strength Al-9 pct Si casting alloy, namely, 354-Al-9 pct Si-1.8 pct Cu-0.5 pct Mg. Quality charts were used as an evaluation tool for selecting the optimum conditions to be applied, in practice, in order to develop high strength and optimum quality in 354 casting alloy. Aging at a low temperature of 428 K (155 °C) was observed to produce the greatest strength and optimum quality in the 354-type castings compared to aging at higher temperatures. The peak strength observed for 354 alloy may be attained after shorter aging times on the condition that the aging temperature is increased. The aging times required for reaching peak strength in 354 alloys are 72 hours, 40 hours, 8 hours, 1 hour, and 15 minutes at aging temperatures of 428 K, 443 K, 468 K, 493 K, and 518 K (155 °C, 170 °C, 195 °C, 220 °C, and 245 °C), respectively. Aging treatment at higher temperatures is accompanied by a reduction in the tensile properties and quality index values of the castings; however, it also introduces the possibility of a significant economical strategy for minimizing the time and the cost of this same treatment. Aging treatment at a lower temperature of 428 K (155 °C) produces fine and dense precipitates displaying smaller interparticle spacing, while at higher aging temperatures, such as 518 K (245 °C), the precipitates are coarser in size, less dense, and more widely dispersed. The quality charts developed in the course of the current research facilitate the interpretation and evaluation of the tensile properties of the 354 alloy. Such charts provide a logical evaluation tool, from the metallurgical point of view, for an accurate prediction of the influence of aging parameters studied on the properties of the alloys. Depending on the required level of tensile properties and based on the quality charts developed, it is possible to make a rigorous selection as to the most suitable aging parameters to be applied to the 354 alloy so as to obtain the best possible cost-effective compromise between alloy strength and quality.     

Survey questionnaire results of the current level of knowledge on trenchless technologies in China

With a growing population and densely populated urban environments, China is looking at alternative methods of underground pipeline installation and replacement of their aging infrastructure. Conventional open trench activities result in disruption to these urban centers through road closures, traffic delays, traffic detours, loss of access to homes and business, unsightliness, noise and general disruption for everyone. Trenchless technologies are a viable and sustainable solution to China’s buried infrastructure. Numerous challenges are present when promoting trenchless technologies in China including minimal local engineering knowledge, lack of trained contractors, lack of specifications, and system impact concerns raised by government owners. This paper presents the results of a survey questions obtained from a cross-section of 209 Chinese engineers from Shanghai, Beijing, Shengyang, Chongqing, and Guangzhou to gain a snapshot of the current level of knowledge on trenchless construction methods. The results reveal an understanding of trenchless technology in general; however, a lack of understanding of technologies such as lining of pipe, trenchless grouting, auger boring, and pipe bursting. Pipe jacking and horizontal directional drilling are currently by far the most recognized and understood trenchless technologies in China.