Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin.

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1ß, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.

Exposure to triphenyltin impairs gut integrity, disturbs gut microbiota, and alters fecal metabolites.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Alzheimer's pathogenic mechanisms and underlying sex difference.

AD is a neurodegenerative disease, and its frequency is often reported to be higher for women than men: almost two-thirds of patients with AD are women. One prevailing view is that women live longer than men on average of 4.5 years, plus there are more women aged 85 years or older than men in most global subpopulations; and older age is the greatest risk factor for AD. However, the differences in the actual risk of developing AD for men and women of the same age is difficult to assess, and the findings have been mixed. An increasing body of evidence from preclinical and clinical studies as well as the complications in estimating incidence support the sex-specific biological mechanisms in diverging AD risk as an important adjunct explanation to the epidemiologic perspective. Although some of the sex differences in AD prevalence are due to differences in longevity, other distinct biological mechanisms increase the risk and progression of AD in women. These risk factors include (1) deviations in brain structure and biomarkers, (2) psychosocial stress responses, (3) pregnancy, menopause, and sex hormones, (4) genetic background (i.e., APOE), (5) inflammation, gliosis, and immune module (i.e., TREM2), and (6) vascular disorders. More studies focusing on the underlying biological mechanisms for this phenomenon are needed to better understand AD. This review presents the most recent data in sex differences in AD-the gateway to precision medicine, therefore, shaping expert perspectives, inspiring researchers to go in new directions, and driving development of future diagnostic tools and treatments for AD in a more customized way.

Designing Better Cardiovascular Stent Materials - A Learning Curve.

Cardiovascular stents are life-saving devices and one of the top 10 medical breakthroughs of the 21st century. Decades of research and clinical trials have taught us about the effects of material (metal or polymer), design (geometry, strut thickness, and the number of connectors), and drug-elution on vasculature mechanics, hemocompatibility, biocompatibility, and patient health. Recently developed novel bioresorbable stents are intended to overcome common issues of chronic inflammation, in-stent restenosis, and stent thrombosis associated with permanent stents, but there is still much to learn. Increased knowledge and advanced methods in material processing have led to new stent formulations aimed at improving the performance of their predecessors but often comes with potential tradeoffs. This review aims to discuss the advantages and disadvantages of stent material interactions with the host within five areas of contrasting characteristics, such as 1) metal or polymer, 2) bioresorbable or permanent, 3) drug elution or no drug elution, 4) bare or surface-modified, and 5) self-expanding or balloon-expanding perspectives, as they relate to pre-clinical and clinical outcomes and concludes with directions for future studies.

Micro-/Nanotopography on Bioresorbable Zinc Dictates Cytocompatibility, Bone Cell Differentiation, and Macrophage Polarization.

Bioresorbable metals are quickly advancing in the field of regenerative medicine for their promises of tissue restoration without adverse consequences from their lifelong presence. Zn has recently risen to the top of bioresorbable metals with great potential as a medical implant. However, cell adhesion and colonization on the Zn substrate surface remains challenging, which could damper interfacial tissue-implant integration. Inspired by the fact that surface topography can regulate cell function and fate, we hypothesize that topography on bioresorbable Zn can dictate material biocompatibility, cell differentiation, and immunomodulation. To verify this, surface-engineered Zn plates with nano-, submicro-, and microtopographies were systematically investigated. The microscale topography exhibited increased adhesion, pronounced self-renewal, and enhanced osteogenic differentiation of bone cells as well as less macrophage inflammatory polarization, reduced platelet adhesion, and better hemocompatibility. Thus, surface topography could be a viable strategy to enhance bioresorbable Zn's biocompatibility and integration with surrounding tissues while reducing inflammation.

Salt Preform Texturing of Absorbable Zn Substrates for Bone-implant Applications.

Surface roughness is an important factor in improving the bone-implant contact area to enhance bone regeneration, yet this aspect has not been applied to absorbable metals. Textured zinc surfaces with varying degrees of surface roughness were produced using a salt-preform method with fine- and coarse-grained salts and compared to a polished control sample. The resulting surfaces were characterized by scanning electron microscopy (SEM), surface roughness, corrosion rates, and in vitro cytotoxicity. The resulting textured surfaces exhibit micron-sized cavities and increased roughness consistent with the initial salt particle size. The corrosion rate was shown to accelerate significantly as compared to the polished control sample, and pre-osteoblasts displayed healthy morphologies on the textures. The results confirm textured zinc surfaces support cell adhesion and can be used to control the corrosion rate. This study represents an important intermediate step that can be applied to porous absorbable metal scaffolds for bone-implant applications.

Zinc regulates vascular endothelial cell activity through zinc-sensing receptor ZnR/GPR39.

Zn2+ is an essential element for cell survival/growth, and its deficiency is linked to many disorders. Extracellular Zn2+ concentration changes participate in modulating fundamental cellular processes such as proliferation, secretion, ion transport, and cell signal transduction in a mechanism that is not well understood. Here, we hypothesize that the Zn2+-sensing receptor ZnR/G protein-coupled receptor 39 (GPR39), found in tissues where dynamic Zn2+ homeostasis takes place, enables extracellular Zn2+ to trigger intracellular signaling pathways regulating key cell functions in vascular cells. Thus, we investigated how extracellular Zn2+ regulates cell viability, proliferation, motility, angiogenesis, vascular tone, and inflammation through ZnR/GPR39 in endothelial cells. Knockdown of GPR39 through siRNA largely abolished Zn2+-triggered cellular activity changes, Ca2+ responses, as well as the downstream activation of Gαq-PLC pathways. Extracellular Zn2+ promoted vascular cell survival/growth through activation of cAMP and Akt as well as overexpressing of platelet-derived growth factor-α receptor and vascular endothelial growth factor A. It also enhanced cell adhesion and mobility, endothelial tubule formation, and cytoskeletal reorganization. Such effects from extracellular Zn2+ were not observed in GPR39-/- endothelial cells. Zn2+ also regulated inflammation-related key molecules such as heme oxygenase-1, selectin L, IL-10, and platelet endothelial cell adhesion molecule 1, as well as vascular tone-related prostaglandin I2 synthase and nitric oxide synthase-3. In sum, extracellular Zn2+ regulates endothelial cell activity in a ZnR/GPR39-dependent manner and through the downstream Gαq-PLC pathways. Thus, ZnR/GPR39 may be a therapeutic target for regulating endothelial activity.

Blood-Brain Barrier Integrity and Clearance of Amyloid-ß from the BBB.

Alzheimer's disease, a type of dementia, affects memory, behavior, and cognitive processes in affected individuals. It is one of the prominent diseases, accounting for 60-80% of dementia cases and affecting a significant population of persons over the age of 65 years. While rare, Alzheimer's disease (AD) may affect the younger population as well. With such a widespread number of persons affected with AD, scientists have undertaken the initiative to develop a cure for this devastating disease; however, it has been deemed quite challenging. A dysfunctional blood-brain barrier, with impaired ability to clear amyloid-ß from the brain, has been directly linked to the development of Alzheimer's disease. The blood-brain barrier restricts the flow of many substances into and out of the brain and serves as a selective and protective barrier to the brain. A proper functioning blood-brain barrier contributes to the maintenance and integrity of the brain. In turn, different systems and mechanisms within the blood-brain barrier are set in place to facilitate mediated passage of materials and substances between the brain and the bloodstream. In relation to AD, the mediation of amyloid-ß clearance is of great importance in maintaining the blood-brain barrier's integrity.

Corrigendum to "Metabolic Syndrome, Inflammation, and Cancer".

[This corrects the article DOI: 10.1155/2017/8259356.].

Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review.

Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept "bio-adaption" between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed.

Endothelialization of novel magnesium-rare earth alloys with fluoride and collagen coating.

Magnesium (Mg) alloys are promising scaffolds for the next generation of cardiovascular stents because of their better biocompatibility and biodegradation compared to traditional metals. However, insufficient mechanical strength and high degradation rate are still the two main limitations for Mg materials. Hydrofluoric acid (HF) treatment and collagen coating were used in this research to improve the endothelialization of two rare earth-based Mg alloys. Results demonstrated that a nanoporous film structure of fluoride with thickness of ~20 µm was formed on the Mg material surface, which improved the corrosion resistance. Primary human coronary artery endothelial cells (HCAECs) had much better attachment, spreading, growth and proliferation (the process of endothelialization) on HF-treated Mg materials compared to bare- or collagen-coated ones.

Three-Dimensional Bioprinting of Organoids: Past, Present, and Prospective.

Organoids are three-dimensional (3D) in vitro tissue models that are derived from stem cells and can closely mimic the structure and function of human organs. The ability to create organoids that recapitulate the complex cellular architecture of organs has emerged as an innovative technique in biomedical research and drug development. However, traditional methods of organoid culture are time consuming and often yield low quantities of cells, which has led to the development of 3D bioprinting of organoids from bioinks containing suspended cells and desired scaffolds. A comparison across different organoid-building techniques, focusing on 3D bioprinting and its benefits, may be helpful and was yet to be distinguished. The goal of this review is to provide an overview of the current state of 3D bioprinting of organoids and its potential applications in tissue engineering, drug screening, and regenerative medicine.

Effect of TiC Nanoparticles on a Zn-Al-Cu System for Biodegradable Cardiovascular Stent Applications.

Despite being a weaker metal, zinc has become an increasingly popular candidate for biodegradable implant applications due to its suitable corrosion rate and biocompatibility. Previous studies have experimented with various alloy elements to improve the overall mechanical performance of pure Zn without compromising the corrosion performance and biocompatibility; however, the thermal stability of biodegradable Zn alloys has not been widely studied. In this study, TiC nanoparticles were introduced for the first time to a Zn-Al-Cu system. After hot rolling, TiC nanoparticles were uniformly distributed in the Zn matrix and effectively enabled phase control during solidification. The Zn-Cu phase, which was elongated and sharp in the reference alloy, became globular in the nanocomposite. The strength of the alloy, after introducing TiC nanoparticles, increased by 31% from 259.7 to 340.3 MPa, while its ductility remained high at 49.2% elongation to failure. Fatigue performance also improved greatly by adding TiC nanoparticles, increasing the fatigue limit by 47.6% from 44.7 to 66 MPa. Furthermore, TiC nanoparticles displayed excellent phase control capability during body-temperature aging. Without TiC restriction, Zn-Cu phases evolved into dendritic morphologies, and the Al-rich eutectic grew thicker at grain boundaries. However, both Zn-Cu and Al-rich eutectic phases remained relatively unchanged in shape and size in the nanocomposite. A combination of exceptional tensile properties, improved fatigue performance, better long-term stability with a suitable corrosion rate, and excellent biocompatibility makes this new Zn-Al-Cu-TiC material a promising candidate for biodegradable stents and other biodegradable applications.

Endothelial Cells Promote Pseudo-islet Function Through BTC-EGFR-JAK/STAT Signaling Pathways.

Interactions between cells are of fundamental importance in affecting cell function. In vivo, endothelial cells and islet cells are close to each other, which makes endothelial cells essential for islet cell development and maintenance of islet cell function. We used endothelial cells to construct 3D pseudo-islets, which demonstrated better glucose regulation and greater insulin secretion compared to conventional pseudo-islets in both in vivo and in vitro trials. However, the underlying mechanism of how endothelial cells promote beta cell function localized within islets is still unknown. We performed transcriptomic sequencing, differential gene analysis, and enrichment analysis on two types of pseudo-islets to show that endothelial cells can promote the function of internal beta cells in pseudo-islets through the BTC-EGFR-JAK/STAT signaling pathway. Min6 cells secreted additional BTC after co-culture of endothelial cells with MIN6 cells outside the body. After BTC knockout in vitro, we found that beta cells functioned differently: insulin secretion levels decreased significantly, while the expression of key proteins in the EGFR-mediated JAK/STAT signaling pathway simultaneously decreased, further confirming our results. Through our experiments, we elucidate the molecular mechanisms by which endothelial cells maintain islet function in vitro, which provides a theoretical basis for the construction of pseudo-islets and islet cell transplants for the treatment of diabetes mellitus.

Efficient keystone species identification strategy based on tabu search.

As species extinction accelerates globally and biodiversity declines dramatically, identifying keystone species becomes an effective way to conserve biodiversity. In traditional approaches, it is considered that the extinction of species with high centrality poses the greatest threat to secondary extinction. However, the indirect effect, which is equally important as the local and direct effects, is not included. Here, we propose an optimized disintegration strategy model for quantitative food webs and introduced tabu search, a metaheuristic optimization algorithm, to identify keystone species. Topological simulations are used to record secondary extinctions during species removal and secondary extinction areas, as well as to evaluate food web robustness. The effectiveness of the proposed strategy is also validated by comparing it with traditional methods. Results of our experiments demonstrate that our strategy can optimize the effect of food web disintegration and identify the species whose extinction is most destructive to the food web through global search. The algorithm provides an innovative and efficient way for further development of keystone species identification in the ecosystem.

Customized Additive Manufacturing in Bone Scaffolds-The Gateway to Precise Bone Defect Treatment.

In the advancing landscape of technology and novel material development, additive manufacturing (AM) is steadily making strides within the biomedical sector. Moving away from traditional, one-size-fits-all implant solutions, the advent of AM technology allows for patient-specific scaffolds that could improve integration and enhance wound healing. These scaffolds, meticulously designed with a myriad of geometries, mechanical properties, and biological responses, are made possible through the vast selection of materials and fabrication methods at our disposal. Recognizing the importance of precision in the treatment of bone defects, which display variability from macroscopic to microscopic scales in each case, a tailored treatment strategy is required. A patient-specific AM bone scaffold perfectly addresses this necessity. This review elucidates the pivotal role that customized AM bone scaffolds play in bone defect treatment, while offering comprehensive guidelines for their customization. This includes aspects such as bone defect imaging, material selection, topography design, and fabrication methodology. Additionally, we propose a cooperative model involving the patient, clinician, and engineer, thereby underscoring the interdisciplinary approach necessary for the effective design and clinical application of these customized AM bone scaffolds. This collaboration promises to usher in a new era of bioactive medical materials, responsive to individualized needs and capable of pushing boundaries in personalized medicine beyond those set by traditional medical materials.

Guided Bone Regeneration Using Barrier Membrane in Dental Applications.

Guided bone regeneration (GBR) is a widely used technique in preclinical and clinical studies due to its predictability. Its main purpose is to prevent the migration of soft tissue into the osseous wound space, while allowing osseous cells to migrate to the site. GBR is classified into two main categories: resorbable and non-resorbable membranes. Resorbable membranes do not require a second surgery but tend to have a short resorption period. Conversely, non-resorbable membranes maintain their mechanical strength and prevent collapse. However, they require removal and are susceptible to membrane exposure. GBR is often used with bone substitute graft materials to fill the defect space and protect the bone graft. The membrane can also undergo various modifications, such as surface modification and biological factor loading, to improve barrier functions and bone regeneration. In addition, bone regeneration is largely related to osteoimmunology, a new field that focuses on the interactions between bone and the immune system. Understanding these interactions can help in developing new treatments for bone diseases and injuries. Overall, GBR has the potential to be a powerful tool in promoting bone regeneration. Further research in this area could lead to advancements in the field of bone healing. This review will highlight resorbable and non-resorbable membranes with cellular responses during bone regeneration, provide insights into immunological response during bone remodeling, and discuss antibacterial features.

Current progress of cerebral organoids for modeling Alzheimer's disease origins and mechanisms.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease that has emerged as a leading risk factor for dementia associated with increasing age. Two-dimensional (2D) cell culture and animal models, which have been used to analyze AD pathology and search for effective treatments for decades, have significantly contributed to our understanding of the mechanism of AD. Despite their successes, 2D and animal models can only capture a fraction of AD mechanisms due to their inability to recapitulate human brain-specific tissue structure, function, and cellular diversity. Recently, the emergence of three-dimensional (3D) cerebral organoids using tissue engineering and induced pluripotent stem cell technology has paved the way to develop models that resemble features of human brain tissue more accurately in comparison to prior models. In this review, we focus on summarizing key research strategies for engineering in vitro 3D human brain-specific models, major discoveries from using AD cerebral organoids, and its future perspectives.

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options.

BACKGROUND: An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS-related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. METHODS: The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients' sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein-protein interaction (PPI) network and their expression was validated using clinical specimens. RESULTS: A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low-risk group had a lower IC50 for the common chemotherapy drug, 5-FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. CONCLUSION: We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

Impairment of cerebral vascular reactivity and resting blood flow in early-staged transgenic AD mice: in vivo optical imaging studies.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder with progressive cognitive decline in aging individuals that poses a significant challenge to patients due to an incomplete understanding of its etiology and lack of effective interventions. While "the Amyloid Cascade Hypothesis," the abnormal accumulation of amyloid-ß in the brain, has been the most prevalent theory for AD, mounting evidence from clinical and epidemiological studies suggest that defects in cerebral vessels and hypoperfusion appear prior to other pathological manifestations and might contribute to AD, leading to "the Vascular Hypothesis." However, assessment of structural and functional integrity of the cerebral vasculature in vivo in the brain from AD rodent models has been challenging owing to the limited spatiotemporal resolution of conventional imaging technologies. Methods: We employed two in vivo imaging technologies, i.e., Dual-Wavelength Imaging (DWI) and Optical Coherence Tomography (OCT), to evaluate cerebrovascular reactivity (CVR; responsiveness of blood vessels to vasoconstriction as triggered by cocaine) in a relatively large field of view of the cortex in vivo, and 3D quantitative cerebrovascular blood flow (CBF) imaging in living transgenic AD mice at single vessel resolution. Results: Our results showed significantly impaired CVR and reduced CBF in basal state in transgenic AD mice compared to non-transgenic littermates in an early stage of AD progression. Changes in total hemoglobin (Δ[HbT]) in response to vasoconstriction were significantly attenuated in AD mice, especially in arteries and tissue, and the recovery time of Δ[HbT] after vasoconstriction was shorter for AD than WT in all types of vessels and cortical tissue, thereby indicating hypoperfusion and reduced vascular flexibility. Additionally, our 3D OCT images revealed that CBF velocities in arteries were slower and that the microvascular network was severely disrupted in the brain of AD mice. Conclusions: These results suggest significant vascular impairment in basal CBF and dynamic CVR in the neurovascular network in a rodent model of AD at an early stage of the disease. These cutting-edge in vivo optical imaging tools offer an innovative venue for detecting early neurovascular dysfunction in relation to AD pathology and pave the way for clinical translation of early diagnosis and elucidation of AD pathogenesis in the future.