MiR-18a affects hypoxia induced glucose metabolism transition in HT22 hippocampal neuronal cell line through the Hif1a gene.

Hypoxia can cause a variety of diseases, including ischemic stroke and neurodegenerative diseases. Within a certain range of partial pressure of oxygen, cells can respond to changes in oxygen. Changes in oxygen concentration beyond a threshold will cause damage or even necrosis of tissues and organs, especially for the central nervous system. Therefore, it is very important to find appropriate measures to alleviate damage. MiRNAs can participate in the regulation of hypoxic responses in various types of cells. MiRNAs are involved in regulating hypoxic responses in many types of tissues by activating the hypoxia-inducible factor (HIF) to affect angiogenesis, glycolysis and other biological processes. By analyzing differentially expressed miRNAs in hypoxia and hypoxia-related studies, as well as the HT22 neuronal cell line under hypoxic stress, we found that the expression of miR-18a was changed in these models. MiR-18a could regulate glucose metabolism in HT22 cells under hypoxic stress by directly regulating the 3'UTR of the Hif1a gene. As a small molecule, miRNAs are easy to be designed into small nucleic acid drugs, so this study can provide a theoretical basis for the research and treatment of nervous system diseases caused by hypoxia.

Iron and silicon modified biochar for enhancing cadmium removal from water: Unveiling the crucial role of iron-induced silicon dissolution.

The interaction mechanisms of silicon (Si) and active ingredient iron (Fe) on cadmium (Cd) removal are still unknown. Herein, the Fe/Si modified biochar (Fe/Si-BC) was synthesized to enhance Cd removal by pre-immersion of Fe and ball milling loading of Si. Detailed characterizations indicated that Fe and Si were successfully introduced into Fe/Si-BC, resulting in the formation of a new metallic silicate (Ca2.87Fe0.13(SiO3)2). The maximum Cd adsorption capacity of Fe/Si-BC (31.66 mg g-1) was 3.6 times and 2.5 times higher than that of Fe-BC (8.89 mg g-1) and Si-BC (11.03 mg g-1), respectively, deriving from an enhancement of Si dissolution induced by Fe introduction. The dissolved Si could capture and combine Cd to form CdSiO3 precipitation, which was strongly supported by the random forest regression and correlation between dissolved Si content and Cd adsorption capacity. This study advances the mechanistic insights into synergistic functions of Si and Fe in Cd removal.

Evidence that co-existing cadmium and microplastics have an antagonistic effect on greenhouse gas emissions from paddy field soils.

Accumulation of microplastics (MPs) and cadmium (Cd) are ubiquitous in paddy soil. However, the combined effects of MPs and Cd on physiochemical and microbial mechanisms in soils and the attendant implications for greenhouse gas (GHG) emissions, remain largely unknown. Here, we evaluated the influence of polylactic acid (PLA) and polyethylene (PE) MPs on GHG emissions from Cd-contaminated paddy soil using a microcosm experiment under waterlogged and drained conditions. The results showed that PLA significantly increased CH4 and N2O emission fluxes and hence the global warming potential (GWP) of waterlogged soil. Soils treated with MPs+Cd showed significantly reduced GWP compared to those treated only with MPs suggesting that, irrespective of attendant consequences, Cd could alleviate N2O emissions in the presence of MPs. Conversely, the presence of MPs in Cd-contaminated soils tended to alleviate the bioavailability of Cd. Based on a structural equation model analysis, both the MPs-derived dissolved organic matter and the soil bioavailable Cd affected indirectly on soil GHG emissions through their direct influencing on microbial abundance (e.g., Firmicutes, Nitrospirota bacteria). These findings provide new insights into the assessment of GHG emissions and soil/cereal security in response to MPs and Cd coexistence that behaved antagonistically with respect to adverse ecological effects in paddy systems.

The role of integrin αvß3 in biphasic calcium phosphate ceramics mediated M2 Macrophage polarization and the resultant osteoinduction.

Calcium phosphate ceramics-based biomaterials were reported to have good biocompatibility and osteoinductivity and have been widely applied for bone defect repair and regeneration. However, the mechanism of their osteoinductivity is still unclear. In our study, we established an ectopic bone formation in vivo model and an in vitro macrophage cell co-culture system with calcium phosphate ceramics to investigate the effect of biphasic calcium phosphate on osteogenesis via regulating macrophage M1/M2 polarization. Our micro-CT data suggested that biphasic calcium phosphate had significant osteoinductivity, and the fluorescence co-localization detection found increased F4/80+/integrin αvß3+ macrophages surrounding the biphasic calcium phosphate scaffolds. Besides, our study also revealed that biphasic calcium phosphate promoted M2 polarization of macrophages via upregulating integrin αvß3 expression compared to tricalcium phosphate, and the increased M2 macrophages could subsequently augment the osteogenic differentiation of MSCs in a TGFß mediated manner. In conclusion, we demonstrated that macrophages subjected to biphasic calcium phosphate could polarize toward M2 phenotype via triggering integrin αvß3 and secrete TGFß to increase the osteogenesis of MSCs, which subsequently enhances bone regeneration.

LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/ß-Catenin.

The Hippo signaling pathway inhibits cell growth, and its components and functions are highly conserved in mammals. LATS1 is a core component of the Hippo signaling pathway associated with lymphatic invasion, astrogliosis, apoptosis, and autophagy. Nevertheless, the role of Hippo/LATS1 in osteogenesis remains unclear. In this study, we used ribonucleic acid (RNA) lentiviruses to inhibit the expression of Lats1 in bone marrow-derived stem cells (BMSCs) and distraction osteogenic regions in rats. Increased osteogenic, proliferative, and migratory abilities of BMSCs were observed in Lats1-inhibited BMSCs, while these phenotypes were partially reversed by YAP1 inhibition. In vivo, we found that the LATS1/YAP1 axis promoted osteogenesis during distraction osteogenesis (DO). ß-catenin was positively correlated with YAP1 expression in vivo and in vitro. When YAP1 was strongly positive in the nucleus, ß-catenin expression was upregulated; when YAP1 expression was inhibited by verteporfin, ß-catenin was not expressed in the nucleus. These findings suggest that the LATS1/YAP1 signaling axis promotes DO by activating the Wnt/ß-catenin signaling pathway. This study provides insights into the molecular mechanism of osteogenesis and a potential therapeutic strategy for bone regeneration in DO by associating with LATS1/YAP1-ß-catenin.

Protective effects of baicalin on diethyl nitrosamine-induced liver cirrhosis by suppressing oxidative stress and inflammation.

Baicalin (BA) is a natural product extract with anti-inflammatory, antioxidant, and hepatoprotective properties. Given that the exact underlying mechanisms responsible for the impact of BA on liver cirrhosis remain ambiguous, a detailed investigation is sorely needed. Accordingly, a rat liver cirrhosis model was established via the intraperitoneal injection of diethyl nitrosamine (DEN, 100 mg/kg). Following the modeling, these rats were given BA (100 mg/kg) or N-acetylcysteine (NAC, 150 mg/kg) alone or in combination. The pathological morphology of rat liver tissues in each group was observed by hematoxylin and eosin staining and Masson's trichrome staining. The expression of fibrosis-related proteins was evaluated by Western blot, and the levels of liver function-related biochemical indexes, oxidative stress-related indexes, and inflammatory factors in the serum by enzyme-linked immunosorbent assays (ELISA). The level of mitochondrial reactive oxygen species was measured by flow cytometry. The results depicted that in the rat model of DEN-induced liver cirrhosis, BA reduced the expression of fibrosis-related proteins (collagen type I alpha 1, α-smooth muscle actin, and transforming growth factor-ß1), thereby alleviating the structural fibrosis of liver tissue. Furthermore, BA could diminish the level of mitochondrial reactive oxygen species, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), while promoting albumin, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels. Notably, all these effects of BA above were strengthened following the combined treatment of BA and NAC. On the whole, BA suppresses liver fibrosis by inhibiting oxidative stress and inflammation, thereby exerting a hepatoprotective effect.

Characterization of upper airway and analysis of potential risk factor associated with OSA in patients with unilateral temporomandibular ankylosis and micrognathia deformities.

OBJECTIVE: To ascertain the airway characteristics in patients with unilateral temporomandibular joint ankylosis and maxilla-mandibular deformities (UTMAMD) and investigate the potential risk factors associated with obstructive sleep apnea (OSA) among UTMAMD patients. METHODS: Authors conducted a retrospective single-center study to assess and compare study group consisting of a cohort of 32 patients diagnosed with UTMAMD between January 2011 and July 2022 with control group including 54 participants. The study group was further divided into two subgroups based on the presence or absence of OSA in patients. Parameters related to the upper airway were measured and analyzed using three-dimensional reconstruction of computed tomographic scans. The measurements of airway parameters were compared between study group and control group and between two subgroups. Pearson correlation analysis was used to identify the factors associated with the presence of OSA, and a multiple variable regression model was used to identify risk factors for OSA. RESULTS: Airway volume (VOL), Minimum cross-section area (min CSA), mean CSA, tilt in sagittal plane (TS), and tilt in sagittal plane (TC) in velopharynx; VOL, airway length (AL), min CSA, mean CSA, TS, TC, and airway deviation (AD) in glossopharynx; min CSA, TS, and AD in hypopharynx were found difference with significance between study group and control group. Lateral dimension/anterior-posterior dimension (LAT/AP) ratio in velopharynx and min CSA, TC, and LAT/AP ratio in glossopharynx were significant different between patients with UTMAMD with OSA and without OSA. CONCLUSIONS: The upper airway of patients with UTMAMD exhibits significant narrowing and distortion, rendering them susceptible to suffer from OSA. Patients with UTMAMD and OSA demonstrate more elliptical airways, and the glossopharyngeal LAT/AP ratio is a predictive indicator for the occurrence of OSA.

Comparison of Different Decompensation Approaches on Facial Profile in Orthodontic-Orthognathic Treatment for Skeletal Class III Patients.

BACKGROUND: The objective of the present study was to assess the hard and soft tissue differences of skeletal Class III malocclusion patients treated with orthodontic-orthognathic surgery treatment between two decompensation approaches including extraction of maxillary premolars in preoperative orthodontics and clockwise rotation of the maxilla in orthognathic surgery. METHODS: 22 skeletal Class III patients with the crowding of maxillary dental arch less than 3mm were included in this study. These patients were divided into two groups: extraction group and non-extraction group. Lateral cephalograms taken before preoperative orthodontic treatment and after postoperative orthodontic treatment were used to analyze the differences of hard and soft tissues between two groups. Independent t test was used to evaluate the differences of variables between extraction group and non-extraction group. RESULTS: After treatment, there was significant difference of Wits between extraction group and non-extraction group (- 4.34 mm vs - 2.82 mm, respectively, P <0.05). Co-Gn was significantly greater in non-extraction group than in extraction group (77.18 mm vs 71.58 mm, P <0.05). U1-SN and L1-MP in extraction group were significantly closer to the normal values than non-extraction group (P <0.05). Regarding the change of variables before and after orthodontic-orthognathic treatment, NLA (7.25° vs 1.46°, P <0.01) and G-Sn-Pog' (8.06° vs 4.62°, P <0.05) were significantly greater in extraction group than in non-extraction group. CONCLUSION: For patients with skeletal Class III malocclusion, extraction of maxillary premolars in preoperative orthodontic treatment can more effectively eliminate the dental compensation and achieve a more harmonious facial profile compared to clockwise rotation of the maxilla in orthognathic surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Preferential role of distinct phytochemicals in biosynthesis and antibacterial activity of silver nanoparticles.

Biosynthesis of silver nanoparticles (AgNPs) by plant extracts and its antibacterial utilization has attracted great attention due to the spontaneous reducing and capping capacities of phytochemicals. However, the preferential role and mechanisms of the functional phytochemicals from different plants on AgNPs synthesis, and its catalytic and antibacterial performance remain largely unknown. This study used three widespread arbor species, including Eriobotrya japonica (EJ), Cupressus funebris (CF) and Populus (PL), as the precursors and their leaf extracts as reducing and stabilizing agents for the biosynthesis of AgNPs. A total of 18 phytochemicals in leaf extracts were identified by ultra-high liquid-phase mass spectrometer. For EJ extracts, most kinds of flavonoids participated in the generation of AgNPs by a reduced content of 5∼10%, while for CF extracts, about 15∼40% of the polyphenols were consumed to reduce Ag+ to Ag0. Notably, the more stable and homogeneous spherical AgNPs with smaller size (≈38 nm) and high catalytic capacity on Methylene blue were obtained from EJ extracts rather than CF extracts, and no AgNPs were synthesized from PL extracts, indicating that flavonoids are superior than polyphenols to act as reducer and stabilizer in AgNPs biosynthesis. The antibacterial activities against Gram-positive (Staphylococcus aureus and Bacillus mycoides) and Gram-negative bacteria (Pseudomonas putida and Escherichia coli) were higher in EJ-AgNPs than that in CF-AgNPs, which confirmed the synergistic antibacterial effects of flavonoids combined with AgNPs in EJ-AgNPs. This study provides a significant reference on the biosynthesis of AgNPs with efficient antibacterial utilization underlying effect of abundant flavonoids in plant extracts.

Impact of different zero valent iron-based particles on anaerobic microbial dechlorination of 2,4-dichlorophenol: Comparison of dechlorination performance and the underlying mechanism.

The integration of iron-based materials and anaerobic microbial consortia has been extensively studied owing to its potential to enhance pollutant degradation. However, few studies have compared how different iron materials enhance the dechlorination of chlorophenols in coupled microbial systems. This study systematically compared the combined performances of microbial community (MC) and iron materials (Fe0/FeS2 +MC, S-nZVI+MC, n-ZVI+MC, and nFe/Ni+MC) for the dechlorination of 2,4-dichlorophenol (DCP) as one representative of chlorophenols. DCP dechlorination rate was significantly higher in Fe0/FeS2 +MC and S-nZVI+MC (1.92 and 1.67 times, with no significant difference between two groups) than in nZVI+MC and nFe/Ni+MC (1.29 and 1.25 times, with no significant difference between two groups). Fe0/FeS2 had better performance for the reductive dechlorination process as compared with other three iron-based materials via the consumption of any trace amount of oxygen in anoxic condition and accelerated electron transfer. On the other hand, nFe/Ni could induce different dechlorinating bacteria as compared to other iron materials. The enhanced microbial dechlorination was mainly due to some putative dechlorinating bacteria (Pseudomonas, Azotobacter, Propionibacterium), and due to improved electron transfer of sulfidated iron particles. Therefore, Fe0/FeS2 as a biocompatible as well as low-cost sulfidated material can be a good alternative for possible engineering applications in groundwater remediation.

Nitrogen-doped biochar (N-doped BC) and iron/nitrogen co-doped biochar (Fe/N co-doped BC) for removal of refractory organic pollutants.

The presence of refractory organic pollutants (ROPs) in the ecosystem is a serious concern because of their impact on environmental constituents as well as their known or suspected ecotoxicity and adverse health effects. According to previous studies, carbonaceous materials, such as biochar (BC), have been widely used to remove pollutants from ecosystems owing to their desirable features, such as relative stability, tunable porosity, and abundant functionalities. Nitrogen (N)-doping and iron/nitrogen (Fe/N) co-doping can tailor BC properties and provide supplementary functional groups as well as extensive active sites on the N-doped and Fe/N co-doped BC surface, which is advantageous for interaction with and removal of ROPs. This review investigates the impact of N-doped and Fe/N co-doped BC on the removal of ROPs through adsorption, activation oxidation, and catalytic reduction due to the synergistic Fe, N, and BC features that modify the physicochemical properties, surface functional groups, and persistent free radicals of BC to aid in the degradation of ROPs. Owing to the attractive properties of N-doped and Fe/N co-doped BCs for the removal of ROPs, this review focuses and evaluates previous experimental investigations on the manufacturing (including precursors and influencing parameters during manufacturing) and characterizations of N-doped and Fe/N co-doped BCs. Additionally, the effective applications and mechanisms of N-doped and Fe/N co-doped BCs in adsorption, activation oxidation, and reductive remediation of ROPs are investigated herein. Moreover, the application of N-doped and Fe/N co-doped BC for progressive environmental remediation based on their effectiveness against co-pollutants, regeneration, stability, affordability, and future research prospects are discussed.

Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites.

Multiple tumor exacerbations and treatment procedures, such as extracellular matrix remodeling, metabolic reprogramming, immunological evasion, and resistance to chemotherapy and radiotherapy, are influenced by intratumoral hypoxia. It is becoming increasingly clear how hypoxia interacts with the extracellular matrix and how this affects the growth of cancer. We analyzed the published sequencing results of hypoxia-stressed mouse kidney tumor cells and found that the expression of miR-29b was significantly downregulated. There are several sites that are complementary to the miR-29 seed sequence in the 3' non-coding regions (3'UTRs) of various extracellular matrix-related genes, including collagen IV. We analyzed the sequences of the 3'UTRs of different subunits of collagen IV in different species and constructed the corresponding phylogenetic trees. We found that the 3'UTRs of Col4a1 and Col4a4 may have been subjected to particular evolutionary pressures. By cloning the 3'UTRs of collagen IV subunits into the psiCHECKTM-2 vector, we found that seven of the eight sites in the Col4a3-Col4a6 gene complementary to miR-29 were significantly repressed by miR-29a, b (except for the 7774-7781 of Col4a3 gene). The inhibitory efficiency of miR-29a, b on these seven sites was between 27% and 57%. The research on the regulation of miR-29 and extracellular matrix by hypoxia can provide a theoretical basis for tumor and fibrosis research and treatment.

Presepsin Predicts Severity and Secondary Bacterial Infection in COVID-19 by Bioinformatics Analysis.

Introduction: Novel coronavirus pneumonia (COVID-19) is an acute respiratory disease caused by the novel coronavirus SARS-CoV-2. Severe and critical illness, especially secondary bacterial infection (SBI) cases, accounts for the vast majority of COVID-19-related deaths. However, the relevant biological indicators of COVID-19 and SBI are still unclear, which significantly limits the timely diagnosis and treatment. Methods: The differentially expressed genes (DEGs) between severe COVID-19 patients with SBI and without SBI were screened through the analysis of GSE168017 and GSE168018 datasets. By performing Gene Ontology (GO) enrichment analysis for significant DEGs, significant biological processes, cellular components, and molecular functions were selected. To understand the high-level functions and utilities of the biological system, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. By analyzing protein-protein interaction (PPI) and key subnetworks, the core DEGs were found. Results: 85 DEGs were upregulated, and 436 DEGs were downregulated. The CD14 expression was significantly increased in the SBI group of severe COVID-19 patients (P < 0.01). The area under the curve (AUC) of CD14 in the SBI group in severe COVID-19 patients was 0.9429. The presepsin expression was significantly higher in moderate to severe COVID-19 patients (P < 0.05). Presepsin has a diagnostic value for moderate to severe COVID-19 with the AUC of 0.9732. The presepsin expression of COVID-19 patients in the nonsurvivors was significantly higher than that in the survivors (P < 0.05). Conclusion: Presepsin predicts severity and SBI in COVID-19 and may be associated with prognosis in COVID-19.

Primary Neuroendocrine Tumor of the Breast: Current Understanding and Future Perspectives.

Primary neuroendocrine carcinoma of the breast (NECB) is characterized with heterogeneity, rarity, and poor differentiation, which is probably an underestimated subtype of breast cancer, including small cell NECs and large cell NECs. The diagnostic criteria for NECB have been constantly updated as the disease changes and the understanding increases. According to the latest WHO Classification, primary neuroendocrine neoplasm (NEN) of the breast consists of well-differentiated neuroendocrine tumors (NET), extremely aggressive neuroendocrine carcinomas (NEC) as well as invasive breast cancers of no special type (IBCs-NST) with neuroendocrine differentiation. The accurate diagnosis of NECB remains a challenge for its low incidence, which needs multi-disciplinary methods. For the rarity of the disease, there is a lack of large samples and prospective clinical research. For these invasive tumors, there are no standardized therapeutic guidelines or norms, and the treatment often refers to nonspecific breast cancer. In addition, the prognosis of such patients remains unknown. In 2003, the World Health Organization (WHO) listed NECB as an independent entity for the first time, while few features of NECB were clarified. In this review, it presents the WHO Classification, clinicopathologic characteristics, diagnosis, treatment, and prognosis of these patients. In addition, it summarizes the latest studies on molecular features of NECB, aiming to provide new therapeutic perspectives for the disease.

Effects of microplastics on greenhouse gas emissions and microbial communities in sediment of freshwater systems.

Microplastics can regulate greenhouse gas emissions from environmental systems and affect microbes in the environment. However, the effect of microplastics in freshwater sediment system is still not well studied. In this paper, polyethylene terephthalate (PET) particles with six different diameters of 5-2000 µm were added to freshwater sediment, PET exposing for 90 days was carried out and its effect on greenhouse gas emissions, nutrients cycle and microbial communities were studied. In the 5 µm experimental group, carbon dioxide (CO2) emissions were significantly promoted in the 7-30 days and nitrogen monoxide (N2O) emissions were significantly promoted in the 7 days after cultivation. Microplastics in the range of 300-800 µm significantly promoted CO2 emissions after three days of culture. In addition, microplastics increased the total organic carbon (TOC) content in freshwater sediment and changed microbial diversity, especially increased the microorganisms capable of degrading complex organics such as Saprospiraceae. There was a positive correlation between N2O emission and nitrate (NO3-) content in sediment after 3 days of culture, while greenhouse gas emission was mainly related to TOC content after 90 days of culture. These results showed that microplastics could affect the carbon and nitrogen cycling process of shallow lake ecosystem.

Multifunctional DNA dendrimer nanostructures for biomedical applications.

DNA nanomaterials have attracted ever-increasing attention over the past decades due to their incomparable programmability and multifunctionality. In particular, DNA dendrimer nanostructures, as a major research focus, have been applied in the fields of biosensing, therapeutics, and protein engineering, benefiting from their highly branched configuration. With the aid of specific recognition probes and inherent signal amplification, DNA dendrimers can achieve ultrasensitive detection of nucleic acids, proteins, cells, and other substances, such as lipopolysaccharides (LPS), adenosine triphosphate (ATP), and exosomes. By virtue of their void-containing structures and biocompatibility, DNA dendrimers can deliver drugs or functional nucleic acids into target cells in chemotherapy, immunotherapy, and gene therapy. Furthermore, DNA dendrimers are being applied in protein engineering for efficient directed evolution of proteins. This review summarizes the main research progress of DNA dendrimers, concerning their assembly methods and biomedical applications as well as the emerging challenges and perspectives for future research.

Deformation Assessment of the Manually Pre-Bent Titanium Miniplates in Orthognathic Surgery With Finite Element Analysis.

ABSTRACT: This study summarized the literature regarding the application of pre-bent titanium miniplates in orthognathic surgery and evaluated the extra deformation of the manually pre-bent titanium miniplates via finite element analysis for acquiring higher surgical accuracy. The literature was reviewed with a chart. Three models of titanium miniplates with different thicknesses (1.0 mm, 0.8 mm, 0.6 mm) were created using COMSOL Multiphysics software for biomechanical behavior analysis. The 3 models were virtually bent into 5 angles (15 degree, 30 degree, 45 degree, 60 degree, 80 degree). respectively to simulate the preoperative virtual bending, then to simulate the practical manual bending via finite element analysis. The stresses and displacements of these models were recorded. The models from virtual bending simulation and manual bending simulation were registered to analyze the deviations. The results showed that the maximum stress and the displacement deviations between the virtual bending models and the manual bending models increased with the thickness and bending angle of the pre-bent miniplate models. To improve the surgical accuracy, measures should be applied to the manually pre-bent titanium miniplates to reduce the extra deformation when the plate being thicker and the bending angle being larger.

Osteogenesis Differences Around Titanium Implant and in Bone Defect Between Jaw Bones and Long Bones.

The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.

Preclinical Evaluation of a Single Intravenous Infusion of hUC-MSC (BX-U001) in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease of the joints, which causes severe pain and excessive systemic circulation of harmful inflammatory cytokines. Current treatments are limited, with some patients not responding well, and some experiencing severe and detrimental side effects. Mesenchymal stem cells (MSC) are cell-based therapeutics being evaluated as potent immunomodulators in RA and may provide relief to patients not responding well to drug-based treatments. We evaluated the safety and efficacy of BX-U001 human umbilical cord tissue-derived mesenchymal stem cells (hUC-MSC) to treat RA, in support of a successful investigational new drug application. A collagen-induced arthritis (CIA) mouse model of RA was established in DBA/1 J mice. Mice from the treatment assessment group were given a tail vein infusion of hUC-MSC 24 days after primary RA induction, while control assessment (CA) group mice were given cell-free carrier solution. All animals were evaluated daily for RA symptoms via clinical scoring, blood was taken periodically for cytokine analysis, and mice were dissected at end point for histological analysis. A linear mixed model was used to compare the rate of change among groups. The clinical scores of TA group were significantly reduced compared with CA group (P < 0.01), indicating therapeutic effects. The histological scores of the joints in TA group were significantly lower than those in the CA group (P < 0.05), but had no significant difference compared with Healthy groups (P > 0.05). The concentration of (interleukin) IL-6 in TA group was significantly reduced by 80.0% (P < 0.0001) 2 days after treatment and by 93.4% at the experimental endpoint compared with levels prior to hUC-MSC injection. A single intravenous infusion of hUC-MSC (2 × 106 cells/mouse), to CIA-induced DBA/1 J mice, resulted in significant alleviation of RA symptoms and may provide significant therapeutic benefits in humans.

Optimization of a syngeneic murine model of bone metastasis.

Many cancers metastasize to the bones, particularly in cases of breast and prostate cancers. Due to the "vicious cycle" of cancer cells inducing bone resorption, which promotes further tumor growth, they are difficult to treat and may lead to extreme pain. These factors increase the urgency for emerging therapeutics that target bone metastases more specifically and effectively. Animal studies are essential to the development of any therapeutics, but also require robust animal models of human diseases. Robust animal models are often challenging to develop in the case of bone metastasis studies. Previous methods to induce bone metastasis include intracardiac, intravenous, subcutaneous via mammary fat pad, and intraosseous cancer cell injections, but these methods all have limitations. By contrast, the caudal artery route of injection offers more robust bone metastasis, while also resulting in a lower rate of vital organ metastases than that of other routes of tumor implantation. A syngeneic animal model of bone metastasis is necessary in many cancer studies, because it allows the use of immunocompetent animals, which more accurately mimic cancer development observed in immunocompetent humans. Here we present a detailed method to generate robust and easily monitored 4T1-CLL1 syngeneic bone metastases with over 95% occurrence in BALB/c mice, within two weeks. This method can potentially increase consistency between animals in bone cancer metastasis studies and reduce the number of animals needed for studying bone metastases in mice.