Casual associations between blood metabolites and colon cancer.

BACKGROUND: Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer. AIM: To investigate causal associations between blood metabolites and colon cancer. METHODS: The study utilized a two-sample Mendelian randomization (MR) analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer. The primary method of analysis used was the inverse variance weighted model. To further validate the results several sensitivity analyses were performed, including Cochran's Q test, MR-Egger intercept test, and MR robust adjusted profile score. These additional analyses were conducted to ensure the reliability and robustness of the findings. RESULTS: After rigorous selection for genetic variation, 486 blood metabolites were included in the MR analysis. We found Mannose [odds ratio (OR) = 2.09 (1.10-3.97), P = 0.024], N-acetylglycine [OR = 3.14 (1.78-5.53), P = 7.54 × 10-8], X-11593-O-methylascorbate [OR = 1.68 (1.04-2.72), P = 0.034], 1-arachidonoylglycerophosphocholine [OR = 4.23 (2.51-7.12), P = 6.35 × 10-8] and 1-arachidonoylglycerophosphoethanolamine 4 [OR = 3.99 (1.17-13.54), P = 0.027] were positively causally associated with colorectal cancer, and we also found a negative causal relationship between Tyrosine [OR = 0.08 (0.01-0.63), P = 0.014], Urate [OR = 0.25 (0.10-0.62), P = 0.003], N-acetylglycine [0.73 (0.54-0.98), P = 0.033], X-12092 [OR = 0.89 (0.81-0.99), P = 0.028], Succinylcarnitine [OR = 0.48 (0.27-0.84), P = 0.09] with colorectal cancer. A series of sensitivity analyses were performed to confirm the rigidity of the results. CONCLUSION: This study showed a causal relationship between 10 blood metabolites and colorectal cancer, of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors. The other five blood metabolites are protective factors.

The global, regional, and national burden of stomach cancer attributed to smoking in 204 countries, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019.

INTRODUCTION: Understanding the current burden of stomach cancer linked to smoking and the variations in trends across different locations, is crucial for developing effective prevention strategies. In this study, we present findings on the age-standardized death rate (ASDR) and age-standardized disability-adjusted life years (DALYs) rate attributed to smoking in 204 countries and territories spanning 21 regions from 1990 to 2019. METHODS: The data for this study were obtained from the Global Burden of Disease Study (GBD) 2019, which assessed 369 diseases and injuries, as well as 87 risk factors in 204 countries and 21 regions. To assess the trend in ASDR and age-standardized DALYs rate, the estimated annual percentage change (EAPC) was utilized. RESULTS: Between 1990 and 2019, smoking was found to be associated with a decrease in ASDR (EAPC = -2.20) and age-standardized DALYs (EAPC = -2.42) rates for gastric cancer. As the sociodemographic index (SDI) increased, the decline in rates also increased gradually. However, the decline was smallest in regions with low SDI (EAPCASDR = -1.34; EAPCage-standardized DALYs rate = -1.38). In 21 regions, both ASDR and DALYs rates experienced a decline. The smallest decline in ASDR was observed in Western Sub-Saharan Africa, with an EAPC of -0.80, while the smallest decline in DALYs rate was found in Oceania, with an EAPC of -0.81. Among the 204 countries analyzed, the Dominican Republic showed the highest increase in ASDR and age-standardized DALYs rate (EAPCASDR = 1.19; EAPCage-standardized DALYs rate = 1.21), followed by Afghanistan (EAPCASDR = 1.09; EAPCage-standardized DALYs rate = 1.09) and Sao Tome and Principe (EAPCASDR = 1.05; EAPCage-standardized DALYs rate = 1.03). In the year 2019, the highest ASDR and age-standardized DALYs rate was observed in East Asia, with the highest rates occurring in Mongolia. CONCLUSIONS: The burden of stomach cancer worldwide, adjusted for age, and related to smoking, has shown a decline from 1990 to 2019. However, regional disparities have been identified, with some areas experiencing an increase in this burden. These regions with a higher burden emphasize the necessity for the implementation of strong tobacco control measures.

Multi-omic analysis revealed the therapeutic mechanisms of Alpinia oxyphylla fructus water extract against bladder overactivity in spontaneously hypertensive rats.

OBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. METHODS: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. RESULTS: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFß1, p-SMAD3, collagen III, Gq and PLCß1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. CONCLUSION: YZR's mechanisms of action in treating OAB involved the TGFß1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCß1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.

The burden of cervical cancer in China.

Objective: Trends in the incidence, disability-adjusted life-years (DALYs), and mortality rate of cervical cancer remain unknown. Methods: The average annual percent changes (AAPCs) and relative risks (RR) in the incidence, DALYs, and mortality rate were determined using a joinpoint regression analysis; the net age, period, and cohort effects on above rates were evaluated. Results: A significant increase in age-standardized incidence (AAPC, 0.9%; 95CI: 0.8, 1.1) but significant decreases in age-standardized DALYs (AAPC, -0.4%; 95%CI: -0.60, -0.20) and the mortality rate (AAPC, -0.4%; 95CI: -0.6, -0.3) were observed. As for age-specific rates, the incidence was higher in younger age groups, and the DALYs and mortality rate were lower in older age groups. The effects of age included a slight but significant increase in the RR with advancing age from 35 to 94 years; the period effect included a significant increase in the incidence over the 2005-2019 periods; and the cohort effect included a substantial increase in the incidence from earlier to later birth cohorts. Conclusions: The incidence of cervical cancer increased from 1990 to 2019, particularly in younger age groups, and the DALYs and mortality rate decreased in the older age groups. Furthermore, the incidence increased with age, period, and cohort.

[Textual research on history of Glycyrrhizae Radix et Rhizome processing].

The historical preparation methods of Glycyrrhizae Radix et Rhizoma were summarized and analyzed by consulting relevant literatures of herbal medicines and medical classics. This study also reviewed the records of Glycyrrhizae Radix et Rhizoma processing methods in previous editions of the Chinese Pharmacopoeia and the regulations on processing technology of Glycyrrhizae Radix et Rhizoma decoction pieces in China. This paper summarized the processing history of Glycyrrhizae Radix et Rhizoma and defined the development process of Glycyrrhizae Radix et Rhizoma processing. According to textual research from ancient times to today, there are many ways to process Glycyrrhizae Radix et Rhizoma. The processing methods without auxiliary materials include braising, frying, cooking, simmering and adding such auxiliary materials as wine, vinegar, salt, oil, ginger, honey, water and bile. There are 9 editions of the published Chinese Pharmacopoeia that document the processing of Glycyrrhizae Radix et Rhizoma, and 24 provinces and cities nationwide record the processing of Glycyrrhizae Radix et Rhizoma. At present, the 2015 edition of the Chinese Pharmacopoeia only records the processing technology of Glycyrrhizae Radix et Rhizoma honey, and the honey processing method is still widely usedtoday. Whether or not Zhigancao should be used uniformly for honey-processed Zhigancao today should be based on the processing methods of Chinese herbal medicine and its clinical use in previous ancient medical books. This paper provides a reference and historical basis for subsequent studies on other processing techniques of Glycyrrhizae Radix et Rhizoma, the rational selection of Glycyrrhizae Radix et Rhizoma varieties and the further development and utilization of corresponding medicinal materials.

Use of Polyphenol Tannic Acid to Functionalize Titanium with Strontium for Enhancement of Osteoblast Differentiation and Reduction of Osteoclast Activity.

Implant anchorage remains a challenge, especially in porous osteoporotic bone with high osteoclast activity. The implant surface is modified with osteogenic molecules to stimulate osseointegration. Strontium (Sr) is known for its osteogenic and anti-osteoclastogenic effects. In this study, Sr was immobilized on a titanium (Ti) surface using bioinspired polyphenol tannic acid (pTAN) coating as an ad-layer (Ti-pTAN). Two separate coating techniques were employed for comparative analysis. In the first technique, Ti was coated with a tannic acid solution containing Sr (Ti-pTAN-1Stp). In the second method, Ti was first coated with pTAN, before being immersed in a SrCl2 solution to immobilize Sr on Ti-pTAN (Ti-pTAN-2Stp). Ti-pTAN-1Stp and Ti-pTAN-2Stp augmented the alkaline phosphatase activity, collagen secretion, osteocalcin production and calcium deposition of MC3T3-E1 cells as compared to those of Ti and Ti-pTAN. However, osteoclast differentiation of RAW 264.7, as studied by TRAP activity, total DNA, and multinucleated cell formation, were decreased on Ti-pTAN, Ti-pTAN-1Stp and Ti-pTAN-2Stp as compared to Ti. Of all the substrates, osteoclast activity on Ti-pTAN-2Stp was the lowest. Hence, an economical and simple coating technique using pTAN as an adlayer preserved the dual biological effects of Sr. These results indicate a promising new approach to tailoring the cellular responses of implant surfaces.

Bioinspired polydopamine and polyphenol tannic acid functionalized titanium suppress osteoclast differentiation: a facile and efficient strategy to regulate osteoclast activity at bone-implant interface.

Osseointegration of metallic implants in porous osteoporotic bone remains a challenge. Surface modification of implants to reduce peri-implant osteoclastic bone resorption was explored in the study. Bioinspired polydopamine (pDOP) and polyphenol tannic acid (pTAN) are nature-derived universal coating systems that have emerged either as a sole coating or ad-layer for biomolecular conjugation on different biomaterials. The effects pDOP and pTAN on osteoclast development have not been reported before. In this study, osteoclast development was investigated on titanium (Ti) substrates coated with pDOP (Ti-pDOP) and pTAN (Ti-pTAN). The results showed that Ti-pDOP and Ti-pTAN coating reduced tartrate-resistant acid phosphatase activity and osteoclast cell number as compared with pristine Ti. Intriguingly, the reduction was higher on Ti-pTAN than on Ti-pDOP. Economical and biocompatible tannic acid serves as a superior coating in decreasing osteoclast activity when compared with that of pDOP coating and could be used to modulate osteoclast activity at bone-implant interfaces.

Beta-cyclodextrin modified mesoporous bioactive glass nanoparticles/silk fibroin hybrid nanofibers as an implantable estradiol delivery system for the potential treatment of osteoporosis.

Osteoporosis, a systemic skeletal disease prevalent in elderly women, is associated with post-menopausal estrogen deficiency. Although systemic administration of exogenous estradiol (E2) reduced fragility fractures, the treatment has adverse effects. Localized delivery technologies of E2 could be utilized to circumvent the systemic adverse effects of systemic administration. In this study, a localized E2 delivery system is developed. Mesoporous bioactive glass nanoparticles (MBGNPs) with inherent osteogenic properties are modified with ß-cyclodextrin (CD-MBGNPs) to enhance their affinity for E2. To ensure mechanical stability and integrity, E2 loaded CD-MBGNPs are further electrospun with silk fibroin (SF) to produce a nanofibrous mesh (E2@CD-MBGNPs/SF). The incorporation of MBGNPs in SF enhances in vitro apatite formation and sustains the constant release of E2. Moreover, osteoblast proliferation and differentiation markers such as alkaline phosphatase activity, collagen 1 and osteocalcin expression of MC3T3-E1 are augmented in CD-MBGNPs/SF and E2@CD-MBGNPs/SF as compared to SF nanofibers. On the other hand, osteoclast DNA, tartrate resistant acid phosphatase activity and multinucleated cell formation are reduced in E2@CD-MBGNPs/SF as compared to CD-MBGNPs/SF and SF. Hence the presence of CD-MBGNPs in SF stimulates osteoblast function whereas E2 incorporation in CD-MBGNPs/SF reduces osteoclast activity. This is the first report to develop CD-MBGNPs/SF as a localized delivery system for hydrophobic molecules such as estradiol to treat osteoporosis.

Development of mesoporous bioactive glass nanoparticles and its use in bone tissue engineering.

The incidence of bone disorders, from trauma, tissue degeneration due to ageing, pathological conditions to cancer, has been increasing. The pursuit for bone graft substitutes to assist in regenerating large bone defects is ever growing as a result of the shortage in conventional autografts and allografts, in addition to the associated risks of disease transmission. However, the use of alloplastic biomaterials is limited in clinical settings, as further investigations are required to address the properties of synthetic grafts to mimic the native bone tissue and deliver desirable biomolecules to facilitate bone regeneration. This review discusses the fundamental structure and properties of bone with the emphasis on organic and inorganic components that are important for the biomaterial design. The main focus will be on the advancement and usage of bioactive glass (BG) for bone tissue engineering due to its similarity to the natural inorganic constituent of bone. The various BG synthetic processes, modifications of composition, as well as the biomolecule delivery will be discussed in great detail. As the properties of BG are tuneable according to clinical needs, it creates a new paradigm in addition to displaying its superior potential for bone tissue engineering and translational medicine in the field of orthopedic surgery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2878-2887, 2018.

Modulation of Osteoclast Interactions with Orthopaedic Biomaterials.

Biomaterial integration in bone depends on bone remodelling at the bone-implant interface. Optimal balance of bone resorption by osteoclasts and bone deposition by osteoblasts is crucial for successful implantation, especially in orthopaedic surgery. Most studies examined osteoblast differentiation on biomaterials, yet few research has been conducted to explore the effect of different orthopaedic implants on osteoclast development. This review covers, in detail, the biology of osteoclasts, in vitro models of osteoclasts, and modulation of osteoclast activity by different implant surfaces, bio-ceramics, and polymers. Studies show that surface topography influence osteoclastogenesis. For instance, metal implants with rough surfaces enhanced osteoclast activity, while smooth surfaces resulted in poor osteoclast differentiation. In addition, surface modification of implants with anti-osteoporotic drug further decreased osteoclast activity. In bioceramics, osteoclast development depended on different chemical compositions. Strontium-incorporated bioceramics decreased osteoclast development, whereas higher concentrations of silica enhanced osteoclast activity. Differences between natural and synthetic polymers also modulated osteoclastogenesis. Physiochemical properties of implants affect osteoclast activity. Hence, understanding osteoclast biology and its response to the natural microarchitecture of bone are indispensable to design suitable implant interfaces and scaffolds, which will stimulate osteoclasts in ways similar to that of native bone.

Estradiol-Loaded Poly(ε-caprolactone)/Silk Fibroin Electrospun Microfibers Decrease Osteoclast Activity and Retain Osteoblast Function.

Estrogen, a steroid hormone, plays an important role in modulating osteoclast proliferation and development. Estrogen deficiency boosts osteoclast activity, leading to osteoporosis in elderly women. In this study, 17-ß estradiol (E2)-loaded poly(ε-caprolactone) (PCL)/silk fibroin (SF) electrospun microfibers were developed as a proposed localized E2 delivery system to treat osteoporotic fractures. PCL is a synthetic polymer known for its biocompatibility and excellent mechanical properties. The bioactivity of PCL was enhanced by mixing it with a natural SF polymer that has low immunogenicity and inherent bioactivity. Different ratios of PCL/SF blends were electrospun and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle measurement. PCL and SF at a ratio of 50:50 (PCL50/SF50) augmented cell proliferation of murine preosteoblast MC3T3-E1 cells and murine preosteoclast RAW 264.7 cells. Hence, PCL50/SF50 was selected and mixed with three concentrations of E2 to produce electrospun fiber mesh (0.1% E2@PCL/SF, 1% E2@PCL/SF, and 5% E2@PCL/SF). Sustained release of E2 was obtained for about 3 weeks at higher E2 concentration 5% E2@PCL/SF. An E2-loaded PCL50/SF50 elecrospun microfiber (1% E2@PCL/SF and 5% E2@PCL/SF) reduced tartrate-resistant acid phosphate activity, total DNA, and multinucleated cell formation of osteoclasts. On the other hand, the alkaline phosphatase activity and collagen I expression of osteoblasts were retained on all E2-loaded electrospun microfibers. The E2@PCL/SF system shows potential to be used for localized E2 delivery for the treatment of osteoporotic fractures.

Inhibition activity of a traditional Chinese herbal formula Huang-Lian-Jie-Du-Tang and its major components found in its plasma profile on neuraminidase-1.

Huang-Lian-Jie-Du-Tang (HLJDT), a traditional formula with four TCM herbs, has been used for hundred years for different diseases. The current study aimed to assess the inhibitory activity of HLJDT against H1N1 neuraminidase (NA-1), and identify potent NA-1 inhibitors from its plasma profile. The in vitro NA-1 study has shown that the water extract of HLJDT potently inhibited NA-1 (IC50 = 112.6 µg/ml; Ki = 55.6 µg/ml) in a competitive mode. The IC50 values of the water extracts of its four herbs were as follows: Coptidis Rhizoma, 96.1 µg/ml; Phellodendri Chinensis Cortex, 108.6 µg/ml; Scutellariae Radix, 303.5 µg/ml; Gardeniae Fructus, 285.0 µg/ml. Thirteen compounds found in the plasma profile of HLJDT were also identified as potent NA-1 inhibitors, which included jatrorrhizine, palmatine, epiberberine, geniposide, oroxylin A, berberine, coptisine, baicalein, wogonoside, phellodendrine, wogonin, oroxylin A-7-O-glucuronide and baicalin (sorted in ascending order by their IC50 values). Their inhibitory activities were consistent with molecular docking analysis when considering crystallographic water molecules in the ligand-binding pocket of NA-1. Our current findings suggested that HLJDT can be used as a complementary medicine for H1N1 infection and its potent active compounds can be developed as NA-1 inhibitors.

In Vitro Findings of Titanium Functionalized with Estradiol via Polydopamine Adlayer.

To improve orthopedic implant fixation and reduce post-operative complications, osteogenic molecules are delivered locally by immobilizing them on the surface of implants, which will modulate the biology of cell attachment and differentiation on the implant surface. Estradiol, a natural steroid hormone, maintains bone metabolism by decreasing bone resorption. It either directly or indirectly affects osteoclasts. In this work, estradiol was immobilized on a titanium surface by polydopamine adlayer. Immobilization of estradiol was confirmed by X-ray electron spectroscopy (XPS), immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Estradiol-modified substrates enhanced alkaline phosphatases activity (ALP) and calcium deposition of osteoblasts. However, these substrates did not decrease tartrate-resistant acid phosphatase (TRAP) activity and actin ring formation of the osteoclast. The scanning electron microscopic (SEM) images of estradiol-modified substrates showed the formation of estradiol crystals, which decreased the potency of immobilized estradiol. Despite having a successful immobilization of estradiol via the polydopamine technique, the bioavailability and potency of coated estradiol is reduced due to crystallization, suggesting that this is not a suitable system for localized estradiol delivery as tested in vitro here. Consequently, other suitable platforms have to be explored for immobilizing estradiol that will prevent crystal formation while preserving the biological activity.

Mechanical properties and antibiotic release characteristics of poly(methyl methacrylate)-based bone cement formulated with mesoporous silica nanoparticles.

The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based bone cements is investigated. The incorporation of MSNs to the bone cements (8.15wt%) shows no detrimental effects on the biomechanical properties of the freshly solidified bone cements. Importantly, there are no significant changes in the compression strength and bending modulus up to 6 months of aging in PBS buffer solution. The preserved mechanical properties of MSN-functionalized bone cements is attributed to the unchanged microstructures of the cements, as more than 96% of MSNs remains in the bone cement matrix to support the cement structures after 6 months of aging. In addition, the MSN-functionalized bone cements are able to increase the drug release of gentamicin (GTMC) significantly as compared with commercially available antibiotic-loaded bone cements. It can be attributed to the loaded nano-sized MSNs with uniform pore channels which build up an effective nano-network path enable the diffusion and extended release of GTMC. The combination of excellent mechanical properties and sustainable drug delivery efficiency demonstrates the potential applicability of MSN-functionalized PMMA bone cements for orthopedic surgery to prevent post-surgery infection.

In Vitro and In Vivo Effects of Norathyriol and Mangiferin on α-Glucosidase.

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 µM, which is more potent than mangiferin (IC50 = 358.54 µM) and positive drug acarbose (IC50 = 479.2 µM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p < 0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.

Spectrum-Effect Relationships Between Chemical Fingerprints and Antibacterial Effects of Lonicerae Japonicae Flos and Lonicerae Flos Base on UPLC and Microcalorimetry.

The traditional Chinese medicines Lonicerae Japonicae Flos (LJF, Jinyinhua in Chinese) and Lonicerae Flos (LF, Shanyinhua in Chinese) refer to the flower buds of five plants belonging to the Caprifoliaceae family. Until 2000, all of these were officially listed as a single item, LJF (Jinyinhua), in the Chinese Pharmacopoeia. However, there have recently been many academic controversies concerning the separation and combination of LJF and LF in administrative regulation. Till now there has been little work completed evaluating the relationships between biological activity and chemical properties among these drugs. Microcalorimetry and UPLC were used along with principal component analysis (PCA), hierarchical cluster analysis (HCA), and canonical correlation analysis (CCA) to investigate the relationships between the chemical ingredients and the antibacterial effects of LJF and LF. Using multivariate statistical analysis, LJF and LF could be initially separated according to their chemical fingerprints, and the antibacterial effects of the two herbal drugs were divided into two clusters. This result supports the disaggregation of LJF and LF by the Pharmacopoeia Committee. However, the sample of Lonicera fulvotomentosa Hsu et S. C. Cheng turned out to be an intermediate species, with similar antibacterial efficacy as LJF. The results of CCA indicated that chlorogenic acid and 3,4-Dicaffeoylquinic acid were the major components generating antibacterial effects. Furthermore, 3,4-Dicaffeoylquinic acid could be used as a new marker ingredient for quality control of LJF and LF.

The effects of silver, silicon-containing apatite towards bacteria and cell responses.

An integrated approach is proposed to incorporate silicon and silver into hydroxyapatite (HA) to enhance the biological response and reduce implant-related infection in bone substitutes. This study examined the responses of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacteria to silver, silicon-containing apatite (Ag,Si-HA). Scanning electron microscopy images revealed significant reduction in adherence of S. aureus and E. coli bacteria on Ag,Si-HA as compared to HA. The antibacterial property of Ag,Si-HA was shown from a 7-log reduction of S. aureus population in the test solution and on the sample's surface as compared to HA at day 7. Rapid inhibition of the adherent bacteria suggested that the antibacterial action of Ag incorporated in Ag,Si-HA could be attributed to the Ag(+) ions on the crystal surface rather than the released Ag(+) ions. Presence of Ag may influence the biological response of HA and as such, the long-term interaction between human adipose-derived mesenchymal stem cells and Ag,Si-HA was evaluated in-vitro. An alamarBlue™ assay showed higher cell proliferation for Ag,Si-HA as compared to HA from day 3 onwards. Immunofluorescence staining revealed well-spread actin cytoskeletons on Ag,Si-HA. In addition, signs of extracellular matrix secretion and biomineralization were observed on Ag,Si-HA at day 14 onwards. Results demonstrated enhanced bone differentiation on Ag,Si-HA, as indicated by a higher level of protein expressions (type 1 collagen and osteocalcin) from day 14 to 21. Therefore, the incorporation of Ag and Si complement each other by endowing HA with antibacterial property, and concurrently promoting biological performance of the cells.

Targeting of circulating hepatocellular carcinoma cells to prevent postoperative recurrence and metastasis.

Currently, the main treatment for hepatocellular carcinoma (HCC) involves the surgical removal of tumors or liver transplantation. However, these treatments are often not completely curative, as they are associated with a risk for postoperative recurrence and metastasis. Circulating tumor cells (CTCs) are increasingly recognized as the main source for recurrence and metastasis after radical hepatectomies are performed. Many studies have demonstrated the association between the presence of either pre- or postoperative CTCs and an increased risk for HCC recurrence. To improve the therapeutic outcome of HCC, a personalized, comprehensive and multidisciplinary approach should be considered, involving the application of appropriate diagnostic and therapeutic measures targeting HCC CTCs in different stages throughout the course of treatment. This article proposes some HCC CTC-based strategies for the treatment of HCC, including the monitoring of HCC CTCs before, during and after radical hepatectomy, therapeutic targeting of HCC CTCs, prevention of the generation and colonization of CTCs, as well as the use of CTC indexes for the selection of indications, prediction of prognoses, and planning of individualized therapeutic regimens. Innovation and technological development of therapies targeting CTCs, as well as their translation into clinical practice, will help to effectively reduce postoperative recurrence and metastasis, and significantly prolong the survival of HCC patients.

Enhanced endothelial differentiation of adipose-derived stem cells by substrate nanotopography.

Adipose-derived stem cells (ADSCs) have great potential as a cell source for tissue engineering and regenerative medicine because they are easier to obtain, have lower donor-site morbidity and are available in larger numbers than stem cells harvested using bone marrow aspiration. Until now, little has been known about how nanotopography affects the proliferation and endothelial differentiation of ADSCs. In the present study, two nanograting substrates with a period (ridge and groove) of about 250 and 500 nm, respectively, were fabricated on quartz and their effect on ADSC fate was investigated. The results showed that proliferation of ADSCs on nanograting substrates decreased while cell attachment was not significantly affected compared to a flat substrate. Endothelial differentiation of ADSCs on both flat and nanograting substrates can be induced with vascular endothelial growth factor, as shown by immunofluorescent staining. Quantitative real-time PCR analysis showed significantly enhanced upregulation of vWF, PECAM-1 and VE-cadherin at the gene level by ADSCs on the nanograting substrates. In vitro angiogenesis assay on Matrigel showed that nanograting substrates enhanced capillary tube formation. This study highlights the beneficial influence of nanotopography on the differentiation of ADSC into endothelial cells which play an important role in vascularization.