Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs (ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering. The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.
Knee osteoarthritis (OA) is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty (TKA). However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure. Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate focal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.
Given the limited spontaneous repair that follows cartilage injury, demand is growing for tissue engineering approaches for cartilage regeneration. There are two major applications for tissue-engineered cartilage. One is in orthopedic surgery, in which the engineered cartilage is usually used to repair cartilage defects or loss in an articular joint or meniscus in order to restore the joint function. The other is for head and neck reconstruction, in which the engineered cartilage is usually applied to repair cartilage defects or loss in an auricle, trachea, nose, larynx, or eyelid. The challenges faced by the engineered cartilage for one application are quite different from those faced by the engineered cartilage for the other application. As a result, the emphases of the engineering strategies to generate cartilage are usually quite different for each application. The statuses of preclinical animal investigations and of the clinical translation of engineered cartilage are also at different levels for each application. The aim of this review is to provide an opinion piece on the challenges, current developments, and future directions for cartilage engineering for both applications.
The stiffness and nanotopographical characteristics of the extracellular matrix (ECM) influence numerous developmental, physiological, and pathological processes in vivo. These biophysical cues have therefore been applied to modulate almost all aspects of cell behavior, from cell adhesion and spreading to proliferation and differentiation. Delineation of the biophysical modulation of cell behavior is critical to the rational design of new biomaterials, implants, and medical devices. The effects of stiffness and topographical cues on cell behavior have previously been reviewed, respectively; however, the interwoven effects of stiffness and nanotopographical cues on cell behavior have not been well described, despite similarities in phenotypic manifestations. Herein, we first review the effects of substrate stiffness and nanotopography on cell behavior, and then focus on intracellular transmission of the biophysical signals from integrins to nucleus. Attempts are made to connect extracellular regulation of cell behavior with the biophysical cues. We then discuss the challenges in dissecting the biophysical regulation of cell behavior and in translating the mechanistic understanding of these cues to tissue engineering and regenerative medicine.
Stem cell homing, namely the recruitment of mesenchymal stem cells (MSCs) to injured tissues, is highly effective for bone regeneration in vivo. In order to explore whether the incorporation of mimetic peptide sequences on magnesium-doped (Mg-doped) hydroxyapatite (HA) may regulate the homing of MSCs, and thus induce cell migration to a specific site, we covalently functionalized MgHA disks with two chemotactic/haptotactic factors: either the fibronectin fragment III1-C human (FF III1-C), or the peptide sequence Gly-Arg-Gly-Asp-Ser-Pro-Lys, a fibronectin analog that is able to bind to integrin transmembrane receptors. Preliminary biological evaluation of MSC viability, analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, suggested that stem cells migrate to the MgHA disks in response to the grafted haptotaxis stimuli.
Host-microbe interactions at the gastrointestinal interface have emerged as a key component in the governance of human health and disease. Advances in micro-physiological systems are providing researchers with unprecedented access and insights into this complex relationship. These systems combine the benefits of microengineering, microfluidics, and cell culture in a bid to recreate the environmental conditions prevalent in the human gut. Here we present the human-microbial cross talk (HuMiX) platform, one such system that leverages this multidisciplinary approach to provide a representative in vitro model of the human gastrointestinal interface. HuMiX presents a novel and robust means to study the molecular interactions at the host-microbe interface. We summarize our proof-of-concept results obtained using the platform and highlight its potential to greatly enhance our understanding of host-microbe interactions with a potential to greatly impact the pharmaceutical, food, nutrition, and healthcare industries in the future. A number of key questions and challenges facing these technologies are also discussed.
Method development has always been and will continue to be a core driving force of microbiome science. In this perspective, we argue that in the next decade, method development in microbiome analysis will be driven by three key changes in both ways of thinking and technological platforms: ① a shift from dissecting microbiota structureby sequencing to tracking microbiota state, function, and intercellular interaction via imaging; ② a shift from interrogating a consortium or population of cells to probing individual cells; and ③ a shift from microbiome data analysis to microbiome data science. Some of the recent method-development efforts by Chinese microbiome scientists and their international collaborators that underlie these technological trends are highlighted here. It is our belief that the China Microbiome Initiative has the opportunity to deliver outstanding “Made-in-China” tools to the international research community, by building an ambitious, competitive, and collaborative program at the forefront of method development for microbiome science.
Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics. Current research on the human microbiota has become much more sophisticated and more comprehensive. Therefore, we propose that research should focus on the host-microbe interaction and on cause-effect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease. and provide new therapeutic targets and treatment approaches in clinical practice.
The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract (GIT). Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease (NAFLD); obesity and diabetes, which are characterized as “lifestyle diseases” of the industrialized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the reader with an updated overview of the importance of the gut microbiota for human health and the potential to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile (C. difficile) infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial microbes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.
Colorectal cancer (CRC) is a multistage disease resulting from complex factors, including genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle. Recent accumulating evidence suggests that the gut microbiota is a new and important player in the development of CRC. Imbalance of the gut microbiota, especially dysregulated gut bacteria, contributes to colon cancer through mechanisms of inflammation, host defense modulations, oxidative stress, and alterations in bacterial-derived metabolism. Gut commensal bacteria are anatomically defined as four populations: luminal commensal bacteria, mucus-resident bacteria, epithelium-resident bacteria, and lymphoid tissue-resident commental bacteria. The bacterial flora that are harbored in the gastrointestinal (GI) tract vary both longitudinally and cross-sectionally by different anatomical localization. It is notable that the translocation of colonic commensal bacteria is closely related to CRC progression. CRC-associated bacteria can serve as a non-invasive and accurate biomarker for CRC diagnosis. In this review, we summarize recent findings on the oncogenic roles of gut bacteria with different anatomical localization in CRC progression.
The steady increase of IgE-dependent allergic diseases after the Second World War is a unique phenomenon in the history of humankind. Numerous cross-sectional studies, comprehensive longitudinal cohort studies of children living in various types of environment, and mechanistic experimental studies have pointed to the disappearance of “protective factors” related to major changes in lifestyle and environment. A common unifying concept is that of the immunoregulatory role of the gut microbiota. This review focuses on the protection against allergic disorders that is provided by the farming environment and by exposure to microbial diversity. It also questions whether and how microbial bioengineering will be able in the future to restore an interplay that was beneficial to the proper immunological development of children in the past and that was irreversibly disrupted by changes in lifestyle. The protective “farming environment” includes independent and additional influences: contact with animals, stay in barns/stables, and consumption of unprocessed milk and milk products, by mothers during pregnancy and by children in early life. More than the overall quantity of microbes, the biodiversity of the farm microbial environment appears to be crucial for this protection, as does the biodiversity of the gut microbiota that it may provide. Use of conventional probiotics, especially various species or strains of Lactobacillus and Bifidobacterium, has not fulfilled the expectations of allergists and pediatricians to prevent allergy. Among the specific organisms present in cowsheds that could be used for prevention, Acinetobacter (A.) lwoffii F78, Lactococcus (L.) lactis G121, and Staphylococcus (S.) sciuri W620 seem to be the most promising, based on experimental studies in mouse models of allergic respiratory diseases. However, the development of a new generation of probiotics based on very productive research on the farming environment faces several obstacles that cannot be overcome without a close collaboration between microbiologists, immunologists, and bioengineers, as well as pediatricians, allergists, specialists of clinical trials, and ethical committees.
In recent decades, diseases concerning the gut microbiota have presented some of the most serious public health problems worldwide. The human host’s physiological status is influenced by the intestinal microbiome, thus integrating external factors, such as diet, with genetic and immune signals. The notion that chronic inflammation drives carcinogenesis has been widely established for various tissues. It is surprising that the role of the microbiota in tumorigenesis has only recently been recognized, given that the presence of bacteria at tumor sites was first described more than a century ago. Extensive epidemiological studies have revealed that there is a strong link between the gut microbiota and some common cancers. However, the exact molecular mechanisms linking the gut microbiota and cancer are not yet fully understood. Changes to the gut microbiota are instrumental in determining the occurrence and progression of hepatocarcinoma, chronic liver diseases related to alcohol, nonalcoholic fatty liver disease (NAFLD), and cirrhosis. To be specific, the gut milieu may play an important role in systemic inflammation, endotoxemia, and vasodilation, which leads to complications such as spontaneous bacterial peritonitis and hepatic encephalopathy. Relevant animal studies involving gut microbiota manipulations, combined with observational studies on patients with NAFLD, have provided ample evidence pointing to the contribution of dysbiosis to the pathogenesis of NAFLD. Given the poor prognosis of these clinical events, their prevention and early management are essential. Studies of the composition and function of the gut microbiota could shed some light on understanding the prognosis because the microbiota serves as an essential component of the gut milieu that can impact the aforementioned clinical events. As far as disease management is concerned, probiotics may provide a novel direction for therapeutics for hepatocellular carcinoma (HCC) and NAFLD, given that probiotics function as a type of medicine that can improve human health by regulating the immune system. Here, we provide an overview of the relationships among the gut microbiota, tumors, and liver diseases. In addition, considering the significance of bacterial homeostasis, we discuss probiotics in this article in order to guide treatments for related diseases.
Gut and oral microflora are important factors in the pathogenesis and development of rheumatoid arthritis (RA). Recent studies have shown that probiotic supplements have beneficial consequences on experimental arthritis in rats. However, results from randomized clinical trials on the effects of probiotics have not been consistent. The aim of this study was to systematically review the existing evidence for the effects of probiotic intervention in RA. We included randomized controlled trials (RCTs) of RA patients receiving stable treatment with disease-modifying anti-rheumatic drugs (DMARDs) that: ① were combined with additional probiotic supplements or ② were combined with either no additional supplements or only a placebo treatment. Statistical analysis was performed using Review Manager 5.3.3. Six randomized clinical trials were eligible for inclusion in the meta-analysis, with 249 participants in total. The results showed that the probiotic intervention treatment has not yet achieved significant improvement in the American College of Rheumatology 20% improvement criteria (ACR20) score and the disease activity score in 28 joints (DAS28). The laboratory index C-reactive protein (CRP) (mg·L−1) was significantly reduced in the intervention group. The expression of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukine (IL)-1β was also significantly reduced, while IL-10 expression increased in the probiotic intervention groups. This article is the first systematic review and meta-analysis providing a comprehensive assessment of the benefits of treating RA with probiotics. We found that probiotic supplementation may show a limited improvement in RA therapy in existing reports because of a lack of sufficiently high-quality work on the part of clinicians. More multi-centered, large-sample RCTs are needed in order to evaluate the benefits of probiotics in RA treatment.
This paper introduces the high-speed electrical multiple unit (EMU) life cycle, including the design, manufacturing, testing, and maintenance stages. It also presents the train control and monitoring system (TCMS) software development platform, the TCMS testing and verification bench, the EMU driving simulation platform, and the EMU remote data transmittal and maintenance platform. All these platforms and benches combined together make up the EMU life cycle cost (LCC) system. Each platform facilitates EMU LCC management and is an important part of the system.
Our previous studies have shown that zein has good biocompatibility and good mechanical properties. The first product from a porous scaffold of zein, a resorbable bone substitute, has passed the biological evaluation of medical devices (ISO 10993) by the China Food and Drug Administration. However, Class III medical devices need quality monitoring before being placed on the market, and such monitoring includes quality control of raw materials, choice of sterilization method, and evaluation of biocompatibility. In this paper, we investigated four sources of zein through amino acid analysis (AAA) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in order to monitor the composition and purity, and control the quality of raw materials. We studied the effect of three kinds of sterilization method on a porous zein scaffold by SDS-PAGE. We also compared the changes in SDS-PAGE patterns when irradiated with different doses of gamma radiation. We found that polymerization or breakage did not occur on peptide chains of zein during gamma-ray (γ-ray) sterilization in the range of 20–30 kGy, which suggested that γ-ray sterilization is suitable for porous zein scaffolds. Regarding cell compatibility, we found a difference between using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and a cell-counting kit-8 (CCK-8) assay to assess cell proliferation on zein film, and concluded that the CCK-8 assay is more suitable, due to its low background optical density.
Based on observations and Coupled Model Intercomparison Project Phase 5 (CMIP5) results, multidecadal variations and trends in annual mean surface air temperature anomalies (SATa) at global, hemispheric, and hemispheric land and ocean scales in the past and under the future scenarios of two representative concentration pathways (RCPs) are analyzed. Fifteen models are selected based on their performances in capturing the temporal variability, long-term trend, multidecadal variations, and trends in global annual mean SATa. Observational data analysis shows that the multidecadal variations in annual mean SATa of the land and ocean in the northern hemisphere (NH) and of the ocean in the southern hemisphere (SH) are similar to those of the global mean, showing an increase during the 1900-1944 and 1971-2000 periods, and flattening or even cooling during the 1945-1970 and 2001-2013 periods. These observed characteristics are basically reproduced by the models. However, SATa over SH land show an increase during the 1945-1970 period, which differs from the other hemispheric scales, and this feature is not captured well by the models. For the recent hiatus period (2001-2013), the projected trends of BCC-CSM1-1-m, CMCC-CM, GFDL-ESM2M, and NorESM1-ME at the global and hemispheric scales are closest to the observations based on RCP4.5 and RCP8.5 scenarios, suggesting that these four models have better projection capability in SATa. Because these four models are better at simulating and projecting the multidecadal trends of SATa, they are selected to analyze future SATa variations at the global and hemispheric scales during the 2006-2099 period. The selected multi-model ensemble (MME) projected trends in annual mean SATa for the globe, NH, and SH under RCP4.5 (RCP8.5) are 0.17 (0.29) °C, 0.22 (0.36) °C, and 0.11 (0.23) °C·decade-1in the 21st century, respectively. These values are significantly lower than the projections of CMIP5 MME without model selection.
The possible mitigation of floods by dams and the risk to dams from floods are key problems. The People’s Republic of China is now leading world dam construction with great success and efficiency. This paper is devoted to relevant experiences from other countries, with a particular focus on lessons from accidents over the past two centuries and on new solutions. Accidents from floods are analyzed according to the dam’s height, storage, dam material, and spillway data. Most of the huge accidents that have been reported occurred for embankments storing over 10 hm3. New solutions appear promising for both dam safety and flood mitigation.