The effects of the COVID-19 pandemic period on stock market return and volatility. Evidence from the Pakistan Stock Exchange.

The COVID-19 pandemic has emerged as a significant event of the current century, introducing substantial transformations in economic and social activities worldwide. The primary objective of this study is to investigate the relationship between daily COVID-19 cases and Pakistan stock market (PSX) return volatility. To assess the relationship between daily COVID-19 cases and the PSX return volatility, we collected secondary data from the World Health Organization (WHO) and the PSX website, specifically focusing on the PSX 100 index, spanning from March 15, 2020, to March 31, 2021. We used the GARCH family models for measuring the volatility and the COVID-19 impact on the stock market performance. Our E-GARCH findings show that there is long-term persistence in the return volatility of the stock market of Pakistan in the period of the COVID-19 timeline because ARCH alpha (ω1) and GARCH beta (ω2) are significant. Moreover, is asymmetrical effect is found in the stock market of Pakistan during the COVID-19 period due to Gamma (ѱ) being significant for PSX. Our DCC-GARCH results show that the COVID-19 active cases have a long-term spillover impact on the Pakistan stock market. Therefore, the need of strong planning and alternative platform should be needed in the distress period to promote the stock market and investor should advised to make diversified international portfolio by investing in high and low volatility stock market to save their income. This study advocated the implications for investors to invest in low volatility stock especially during the period of pandemics to protect their return on investment. Moreover, policy makers and the regulators can make effective policies to maintain financial stability during pandemics that is very important for the country's economic development.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment.

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.

Clinical accuracy of partially guided implant placement in edentulous patients: A computed tomography-based retrospective study.

OBJECTIVES: This retrospective study was intended to evaluate the clinical accuracy of partially guided template in guiding implant placement in edentulous patients. METHODS: A total of 120 implants were placed in 24 patients with at least one completely edentulous arch with a partially guided system. Based on CBCT data, a repeatable method was used to measure linear and angular deviations of implants at 3D level in Mimics medical software. The influence of supporting tissue and implant region on the accuracy was assessed, followed by the evaluation of direction of linear deviations in biologically vital areas. RESULTS: Linear deviations of all implants were 1.91 ± 0.68 mm, 1.47 ± 0.68 mm, and 1.02 ± 0.69 mm at apical, apical lateral, and apical vertical levels. When at the cervical, cervical lateral, and cervical vertical levels, the linear deviations were 1.53 ± 0.65 mm, 0.98 ± 0.53 mm, and 1.01 ± 0.69 mm, respectively. Angular deviation of all implants was 7.14 ± 3.41°. Implants guided by mucosa + tooth-supported templates showed higher linear deviations at apical vertical level (1.21 ± 0.72 mm vs. 0.86 ± 0.63 mm, p < .05) and cervical vertical level (1.18 ± 0.72 mm vs. 0.87 ± 0.63 mm, p < .05) than mucosa-supported templates, and implants in maxilla were found higher angular deviation than mandible (7.89 ± 3.61° vs. 6.29 ± 2.97°, p < .05). CONCLUSIONS: The partially guided template served as clinically viable surgical assistance in implant placement in edentulous patients. When using mucosa + tooth-supported template or placing implants in maxilla, more caution was required, especially in biologically vital areas.

Simultaneous nitrate and sulfate biotransformation driven by different substrates: comparison of carbon sources and metabolic pathways at different C/N ratios.

Nitrate (NO3-) and sulfate (SO42-) often coexist in organic wastewater. The effects of different substrates on NO3- and SO42- biotransformation pathways at various C/N ratios were investigated in this study. This study used an activated sludge process for simultaneous desulfurization and denitrification in an integrated sequencing batch bioreactor. The results revealed that the most complete removals of NO3- and SO42- were achieved at a C/N ratio of 5 in integrated simultaneous desulfurization and denitrification (ISDD). Reactor Rb (sodium succinate) displayed a higher SO42- removal efficiency (93.79%) with lower chemical oxygen demand (COD) consumption (85.72%) than reactor Ra (sodium acetate) on account of almost 100% removal of NO3- in both Ra and Rb. Ra produced more S2- (5.96 mg L-1) and H2S (25 mg L-1) than Rb, which regulated the biotransformation of NO3- from denitrification to dissimilatory nitrate reduction to ammonium (DNRA), whereas almost no H2S accumulated in Rb which can avoid secondary pollution. Sodium acetate-supported systems were found to favor the growth of DNRA bacteria (Desulfovibrio); although denitrifying bacteria (DNB) and sulfate-reducing bacteria (SRB) were found to co-exist in both systems, Rb has a greater keystone taxa diversity. Furthermore, the potential carbon metabolic pathways of the two carbon sources have been predicted. Both succinate and acetate could be generated in reactor Rb through the citrate cycle and the acetyl-CoA pathway. The high prevalence of four-carbon metabolism in Ra suggests that the carbon metabolism of sodium acetate is significantly improved at a C/N ratio of 5. This study has clarified the biotransformation mechanisms of NO3- and SO42- in the presence of different substrates and the potential carbon metabolism pathway, which is expected to provide new ideas for the simultaneous removal of NO3- and SO42- from different media.

Endoscope-assisted maxillary sinus floor augmentation with a mini-lateral window: A retrospective study.

OBJECTIVES: The aim of this study was to evaluate the efficacy of endoscope-controlled sinus floor augmentation through a mini-lateral window, compared with traditional lateral window approach. MATERIALS AND METHODS: This retrospective research included 19 patients and 20 augmented sinuses using lateral window approach with simultaneous implant placement (test group: a 3-4 mm round osteotomy; control group: a 10 × 8 mm rectangular osteotomy). Preoperatively (T0), immediately after surgery (T1), and 6 months postoperatively (T2), cone-beam computed tomography (CBCT) scans were obtained. Residual bone height (RBH), lateral window dimension (LWD), endo-sinus bone gain (ESBG), apical bone height (ABH), and bone density were measured. Intraoperative and postoperative complications were recorded. Patients' evaluation of pain first day after surgery and a week later was assessed by visual analog scale (VAS). RESULTS: No significant difference was found in ESBG, ABH between the two groups at T1, T2 or their changes from T1 to T2. However, the increase of bone density value in the test group was significantly higher than control group (356.28 ± 149.59 vs. 242.99 ± 129.54; p < 0.05). The sinus perforation rate of test and control group was 10% and 20%, respectively. The VAS score of the test group at the first day after surgery was significantly lower than control group (4.20 ± 1.03 vs. 5.60 ± 1.71; p < 0.05). CONCLUSIONS: Endoscope-controlled maxillary sinus floor augmentation through a mini-lateral window yield similar result with traditional approach in terms of bone height gain. The modified approach could facilitate new bone formation, reducing sinus perforation rate and postoperative pain.

Implant survival rate and marginal bone loss with the all-on-4 immediate-loading strategy: A clinical retrospective study with 1 to 4 years of follow-up.

STATEMENT OF PROBLEM: Assessing peri-implant marginal bone loss (MBL) and its risk factors with cone beam computed tomography (CBCT) may clarify the risk factors for the all-on-4 (5 or 6) strategy and further improve its survival rate. PURPOSE: The purpose of this retrospective clinical study was to evaluate the implant survival rate, MBL, and associated risk factors of all-on-4 (5 or 6) prostheses after 1 to 4 years of follow-up with CBCT. MATERIAL AND METHODS: A total of 56 participants rehabilitated with 325 implants by using the all-on-4 (5 or 6) concept between October 2015 and December 2019 were included. Outcome measures were cumulative implant survival (life-table analysis) and MBL. Four CBCT scans, a scan immediately after surgery (T0), a scan 1 year after surgery (T1), a scan 2 years after surgery (T2), and a scan 3 to 4 years after treatment (T3), were obtained to evaluate the MBL. The Pearson correlation coefficient analysis and linear mixed models were performed to assess the potential risk factors for MBL (α=.05). RESULTS: The implant survival rate was 99.38%, and the prosthesis survival rate was 100%. The reductions in the vertical buccal bone height (△VBBH) were 0.74 ±0.10 mm (T0-T1), 0.37 ±0.12 mm (T1-T2), and 0.15 ±0.14 mm (T2-T3). Except for T2-T3, the △VBBH showed a significant difference at T0-T1 and T1-T2 (P≤.05). The alterations in vertical mesial bone height (VMBH), vertical distal bone height (VDBH), and vertical lingual bone height (VLBH) were similar to the trend observed in VBBH. The △VBBH (T0-T3) was negatively correlated with the horizontal buccal bone thickness (HBBT) (T0) (r=-.394, P<.001). Linear mixed models revealed that factors such as smoking (P=.001), mandible implant site (P<.001), immediate implant (P=.026), tilted implant (P<.001), female sex (P=.003), systemic disease (P=.025), and bruxism (P=.022) negatively affected MBL. The cantilever length (CL) also had a negative effect on MBL around the implants at the distal extension (P<.001). CONCLUSIONS: The high implant and prosthesis survival rates and low MBL confirmed the predictability of the all-on-4 (5 or 6) concept. Smoking, mandible implant site, systemic disease, bruxism, female sex, immediate implant, tilted implant, and CL were identified as potential risk factors for MBL.

Dental Reimplantation Treatment and Clinical Care for Patients with Previous Implant Failure-A Retrospective Study.

(1) Objectives: This study evaluated the clinical outcomes of dental implants placed in previously failed sites and discussed the risk factors that mattered in reimplantation. (2) Methods: All the cases by one specific implantologist during his first five years of clinical practice were screened, with a focus on those who received reimplantation. The clinical outcomes were assessed, including the implant survival, peri-implant health, and patients' satisfaction. (3) Results: 28 patients (31 implants) were recorded as failures from 847 patients (1269 implants), with a 2.4% overall failure rate at the implant level, of whom 19 patients (21 implants) received reimplantation treatment. After a mean follow-up of 33.7 ± 10.1 months (95% CI 29.1-38.3 months), 20 implants remained functional, but 1 implant revealed a secondary early failure, indicating a 95.2% overall survival rate. The mean probing depth (PD), modified sulcus bleeding index (mSBI), and marginal bone loss (MBL) of the surviving reinserted implants were 2.7 ± 0.6 mm (95% CI 2.5-3.0 mm), 0.7 ± 0.5 (95% CI 0.5-1.0), and 0.5 ± 0.6 mm (95% CI 0.3-0.8 mm), respectively. Embedded healing occurred more frequently in the reinserted implants than in the primary implants (p = 0.052). The patients' satisfaction suffered from implant failure, but a successful reimplantation could reverse it with close doctor-patient communication. (4) Conclusions: Reimplantation treatment was recommended, based on a thorough evaluation and consideration of the risk factors combined with effective communication with the patients.

Controlled release of silibinin in GelMA hydrogels inhibits inflammation by inducing M2-type macrophage polarization and promotes vascularization in vitro.

A dry socket is one of the most common complications after tooth extraction. The main etiologies are the loss of blood clots in the socket and the inflammation reaction caused by infection. Current studies on how to prevent dry sockets could not solve these two etiologies at the same time. Recent studies have demonstrated the anti-inflammation role of silibinin. In this study, silibinin was engineered into GelMA hydrogels (Sil-GelMA) with a concentration of 30 mM. The surface characteristics were observed by scanning electron microscopy and the successful loading of silibinin was detected by FTIR spectrometry. The Sil-GelMA hydrogels presented the sustained release ability of silibinin and slow degradation performance of GelMA. Furthermore, silibinin inhibited the inflammatory reaction by inducing M2-type macrophage polarization, promoting the secretion of anti-inflammatory factors (CD206, IL-10) and inhibiting the secretion of anti-inflammatory factors (IL-1ß, iNOS). Silibinin also increased the secretion of vascularization-related factor VEGF and promoted vascularization in vitro. This study suggested that the Sil-GelMA hydrogels not only had an anti-inflammatory effect, but also had the potential to promote vascularization. Based on these results, the Sil-GelMA hydrogels might provide a promising prospect for prevention of dry sockets in the future.

κ-Carrageenan Oligosaccharides Inhibit the Inflammation of Lipopolysaccharide-Activated Microglia Via TLR4/NF-κB and p38/JNK MAPKs Pathways.

Microglial inflammation plays an essential role in neurodegenerative disease. Our previous studies had shown that κ-carrageenan oligosaccharides (KOS) could inhibit the excessive activation of microglia that induced by LPS, while the interrelated mechanisms were still indistinct. Therefore, we detected the inflammatory signaling pathway on LPS-activated microglia that pretreat by different content of KOS to reveal the mechanism on KOS's inhibition of microglia inflammatory response. ELISA was used to detect the effects of KOS on the secretion of interleukin-1 (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PG-2) by LPS-activated microglia, respectively. The production of reactive oxygen species (ROS) and nitric oxide (NO) in microglia cells was detected by flow cytometry, and the protein expression of immunoinflammation-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protected the microglia from the over-activated inflammatory by inhibiting the release of inflammatory cytokines and the oxidative stress response. And KOS could reduce the expression of the protein that related to the TLR4/NF-κB and p38/JNK MAPKs pathways activated by LPS in microglia. However, there may be no specific target of KOS in cells. Therefore, KOS, a natural algal source oligosaccharide, has immunomodulatory effects and can be used as a potential intervention therapy for inflammatory related neurodegenerative diseases.

κ-Carrageenan oligosaccharides induce microglia autophagy through AMPK/ULK1 pathway to regulate their immune response.

Microglia are the main effector cells of immune response in central nervous system and are important targets for disease prevention and treatment. Κ-carrageenan Oligosaccharide (KOS), obtained by enzymatic hydrolysis from carrageenan of marine red algae, can inhibit the release of inflammatory factors from the over-activated microglia. The mechanism of microglia autophagy induced by KOS and its relationship with inflammation were studied to explore the development prospect of KOS in the research and treatment of inflammatory related diseases. The effect of KOS on inducing autophagy was detected by the secretion of cytokines by lipopolysaccharide (LPS)-activated microglia, respectively. The protein expression of autophagy-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protect the microglia from over-activated inflammatory by inducing the autophagy and inhibiting the release of inflammatory cytokines. And KOS could reduce the expression of the protein that related to the AMPK/ULK1 pathways in microglia, so as to regulate the autophagy pathway, and inhibit the inflammatory response of over-activated microglia. The study on the effect of KOS on microglia autophagy and excessive inflammatory response will provide a theoretical basis for further studies on the inhibition of nerve injury by regulating microglia autophagy and inflammatory response.

Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro.

Hypertension is a prevalent systemic disease in the elderly, who can suffer from several pathological skeletal conditions simultaneously, including osteoporosis. Benidipine (BD), which is widely used to treat hypertension, has been proved to have a beneficial effect on bone metabolism. In order to confirm the osteogenic effects of BD, we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro. The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD, as measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell cycle assay. With BD treatment, the osteogenic differentiation and maturation of MC3T3-E1 cells were increased, as established by the alkaline phosphatase (ALP) activity test, matrix mineralized nodules formation, osteogenic genetic test, and protein expression analyses. Moreover, our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD, while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK (receptor activator of nuclear factor-κB (NF-κB)) pathway. The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.

Melatonin up-regulates bone marrow mesenchymal stem cells osteogenic action but suppresses their mediated osteoclastogenesis via MT2 -inactivated NF-κB pathway.

BACKGROUND AND PURPOSE: Melatonin is a neurohormone involved in bone homeostasis. Melatonin directs bone remodelling and the role of bone marrow mesenchymal stem cells (BMMSCs) in the regulating melatonin-mediated bone formation-resorption balance remains undefined. EXPERIMENTAL APPROACH: Osteoporosis models were established and bone tissue and serum were collected to test the effects of melatonin on bone homeostasis. Melatonin receptors were knocked down, the NF-κB signalling pathway and receptor activator of NF-κB ligand (RANKL) expression were investigated. Communication between bone marrow mesenchymal stem cells and osteoclasts was detected with direct-contact or indirect-contact system. KEY RESULTS: Bone loss and microstructure disorder in mice were reversed after melatonin treatment, as a result of anabolic and anti-resorptive effects. In vitro, a physiological (low) concentration of melatonin promoted the bone marrow mesenchymal stem cells, osteogenic lineage commitment and extracellular mineralization but had no impact on extracellular matrix synthesis. After MT knockdown, especially MT2 , the positive effects of melatonin on osteogenesis were attenuated. The canonical NF-κB signalling pathway was the first discovered downstream signalling pathway after MT receptor activation and was found to be down-regulated by melatonin during osteogenesis. Melatonin suppressed BMMSC-mediated osteoclastogenesis by inhibiting RANKL production in BMMSCs and this effect only occurred when BMMSCs and osteoclast precursors were co-cultured in an indirect-contact manner. CONCLUSION AND IMPLICATIONS: Our work suggests that melatonin plays a crucial role in bone balance, significantly accelerates the osteogenic differentiation of bone marrow mesenchymal stem cells by suppressing the MT2 -dependent NF-κB signalling pathway, and down-regulates osteoclastogenesis via RANKL paracrine secretion.

The effect of surface immobilized NBD peptide on osteoclastogenesis of rough titanium plates in vitro and osseointegration of rough titanium implants in ovariectomized rats in vivo.

Successful osseointegration in dental implants depends on balanced activation of osteoclasts and osteoblasts. Osteoporosis up-regulates osteoclast activity, so it is desirable to find effective interventions to inhibit osteoclastogenesis and enhance the osseointegration of implants under these conditions. It has been reported that the NF-κB essential modulator (NEMO)-binding domain (NBD) peptide can prevent osteoclast formation and bone resorption. In this study, we conjugated NBD peptide onto the surface of rough pure titanium (Ti) using the layer by layer technique. We analyzed the surface characteristics and determined the successful NBD integration by the presence of trivial granular structures, increased S elements and hydrophilia. Importantly, we first reported that Ti surface-conjugated NBD peptide retained its inhibitory effects on osteoclastogenesis by reducing osteoclast sealing zone formation and function. These effects were mediated by a reduction in NFATc1 expression, which in turn regulated integrin ανß3 and MMP9 by targeting the P65 signaling pathway. In vivo TRAP staining suggested NBD-coating decreased osteoclast formation with less pseudopodia. Micro-CT and histomorphometric analysis demonstrated that NBD-coating enhanced pronounced osseointegration in vivo in ovariectomized rats. This study holds great promise for in vivo use of immobilized NBD peptide and offers an effective therapeutic approach to select more suitable Ti-implant surface modifications for improving implant osseointegration in osteoporotic patients.

Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin.

Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor-promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC-conditioned media (MSC-CM) showed that MSC-CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC-CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N-cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN-mediated PI3K/Akt/mTOR activation.

miR-21 promotes the differentiation of hair follicle-derived neural crest stem cells into Schwann cells.

Hair follicle-derived neural crest stem cells can be induced to differentiate into Schwann cells in vivo and in vitro. However, the underlying regulatory mechanism during cell differentiation remains poorly understood. This study isolated neural crest stem cells from human hair follicles and induced them to differentiate into Schwann cells. Quantitative RT-PCR showed that microRNA (miR)-21 expression was gradually increased during the differentiation of neural crest stem cells into Schwann cells. After transfection with the miR-21 agonist (agomir-21), the differentiation capacity of neural crest stem cells was enhanced. By contrast, after transfection with the miR-21 antagonist (antagomir-21), the differentiation capacity was attenuated. Further study results showed that SOX-2 was an effective target of miR-21. Without compromising SOX2 mRNA expression, miR-21 can down-regulate SOX protein expression by binding to the 3'-UTR of miR-21 mRNA. Knocking out the SOX2 gene from the neural crest stem cells significantly reversed the antagomir-21 inhibition of neural crest stem cells differentiating into Schwann cells. The results suggest that miR-21 expression was increased during the differentiation of neural crest stem cells into Schwann cells and miR-21 promoted the differentiation through down-regulating SOX protein expression by binding to the 3'-UTR of SOX2 mRNA.

Effects of the antihypertensive drug benidipine on osteoblast function in vitro.

The dihydropyridine-type calcium channel blocker, benidipine (BD) has been widely used in hypertension therapy. Previous studies have demonstrated that BD has a positive effect on bone metabolism. Inspired by this promoting phenomenon, the present study investigated the effects of BD on osteoblasts in vitro. Experiments were designed and performed, including an MTT assay, reverse transcription-polymerase chain reaction, western blot analysis, alkaline phosphatase activity measurements and alizarin red S staining. The results demonstrated that BD promoted osteoblast proliferation and osteogenic differentiation at concentrations from 1×10-6 to 1×10-9 M by upregulating Runx2, BMP2 and OCN gene expression levels. Overall, BD at appropriate concentrations has been demonstrated to have positive effects on osteoblast function in addition to its conventional clinical usage.

Effects of hierarchical micro/nano-textured titanium surface features on osteoblast-specific gene expression.

PURPOSE: To investigate the influence of hierarchical hybrid micro/nano-textured titanium surface features on osteoblast differentiation. MATERIALS AND METHODS: In this study, 3 different implant discs were produced: a hierarchical hybrid micro-/nanostructured titanium surface topography was modified using electrolytic etching (EE) technique, and a sandblasted, acid-etched (SLA) group and a machined (M) group were used as control groups. MG-63 cells were cultured on discs for 1 day to 7 days. The osteoblast response to the hierarchical hybrid micro-/nanostructured titanium surface was evaluated through the osteoblastic alkaline phosphatase (ALP) activity and gene (OCN, RUNX2, OPN, and Col-I) expression. RESULTS: On the first, third, fifth and seventh day, the ALP activity, OCN, RUNX2, OPN, and Col-I messenger RNA gene expression, levels of EE were higher in EE group than in M and SLA groups. CONCLUSION: Hierarchical hybrid micro-/nanostructured titanium surface has a favorable biocompatibility, which can promote osteoblast differentiation. It could possibly accelerate bone growth, promote bone formation at early stage, and guarantee the immediate loading and early stage loading in clinical practice.

Uniform magnesium silicate hollow spheres as high drug-loading nanocarriers for cancer therapy with low systemic toxicity.

Resulting from their versatile functionality, nanomaterials with low systemic toxicity have offered high-performance diagnostic and therapeutic capabilities. Here, we designed and synthesized uniform magnesium silicate hollow spheres as high drug-loading nanocarriers for cancer therapy. Through a classical Stöber method and a hydrothermal process, well-defined MgSiO3 hollow spheres were prepared in a facile route with inexpensive inhesion. Compared with routinely used mesoporous silica nanoparticles, our MgSiO3 hollow spheres with larger void space and mesoporous shell endowed the structures with a much higher storage capacity of guest molecules (2140 mg DOX g(-1)) and a much more sustained release of anticancer drugs. In detail, the release property and therapeutic efficacy of DOX-loaded nanoparticles were evaluated in vitro and in vivo. In vitro experiments revealed that these nanoparticles were mostly accumulated in lysosome, which facilitated continual drug release and efficient cancer cell destruction. We further demonstrated that these DOX-loaded nanoparticles could effectively suppress tumor growth compared to free DOX in vivo, as DOX-loaded-nanoparticle-treated mice survived over 15 days without obvious detectable tumor growth. Otherwise, long-term toxicity study was also evaluated, indicating their overall safety and great potential in biomedical applications.