Regulatory effect of Ganoderma lucidum and its active components on gut flora in diseases.

Driven by the good developmental potential and favorable environment at this stage, Ganoderma lucidum is recognized as a precious large fungus with medicinal and nutritional health care values. Among them, polysaccharides, triterpenoids, oligosaccharides, trace elements, etc. are important bioactive components in G. lucidum. These bioactive components will have an impact on gut flora, thus alleviating diseases such as hyperglycemia, hyperlipidemia and obesity caused by gut flora disorder. While numerous studies have demonstrated the ability of G. lucidum and its active components to regulate gut flora, a systematic review of this mechanism is currently lacking. The purpose of this paper is to summarize the regulatory effects of G. lucidum and its active components on gut flora in cardiovascular, gastrointestinal and renal metabolic diseases, and summarize the research progress of G. lucidum active components in improving related diseases by regulating gut flora. Additionally, review delves into the principle by which G. lucidum and its active components can treat or assist treat diseases by regulating gut flora. The research progress of G. lucidum in intestinal tract and its potential in medicine, health food and clinical application were fully explored for researchers.

Intrawound vancomycin powder in orthopaedic surgery as surgical site wound infection prophylaxis: A meta-analysis.

A meta-analysis research was executed to appraise the consequence of intrawound vancomycin powder (IWVP) in orthopaedic surgery (OPS) as surgical site wound infection (SSWI) prophylaxis. Inclusive literature research till March 2023 was carried out and 2756 interconnected researches were revised. Of the 18 picked researches enclosed 13 214 persons with OPS were in the used researches' starting point, 5798 of them were utilising IWVP, and 7416 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to appraise the consequence of the IWVP in OPS as SSWI prophylaxis by the dichotomous approaches and a fixed or random model. IWVP had significantly lower SSWIs (OR, 0.61; 95% CI, 0.50-0.74, P < .001), deep SSWIs (OR, 0.57; 95% CI, 0.36-0.91, P = .02), and superficial SSWIs (OR, 0.67; 95% CI, 0.46-0.98, P = .04) compared with control in persons with OPS. IWVP had significantly lower SSWIs, deep SSWIs, and superficial SSWIs compared with control in persons with OPS. However, when interacting with its values, caution must be taken and more research is needed to confirm this finding.

Liver cancer cell-secreted exosomes promote bone metastasis of liver cancer by facilitating osteoclast differentiation through the miR-574-5p/BMP2 axis.

Bone metastasis of liver cancer leads to a worse prognosis with no appropriate treatment clinically. Exosomes are associated with tumor bone metastasis. This study aimed to investigate the effects of liver cancer cell-derived exosomes on bone metastasis. Exosomes were isolated from Hep3B cells, and the effects of osteoclast differentiation were assessed using TRAP assay. The expression of OPG and RANKL was assessed using qRT-PCR. The interaction of miR-574-5p and BMP2 was analyzed using luciferase reporter analysis, RNA pull-down, and qRT-PCR. We found that Hep3B cells promoted osteoclast differentiation of RANKL-induced Raw264.7 cells by secreting exosomes, with decreased OPG and increased RANKL expression. The exosomes were isolated from Hep3B cells, which promoted osteoclast differentiation. Exosomal miR-574-5p promoted osteoclastogenesis by targeting BMP2. Moreover, exosomes facilitated osteoclast differentiation, promoting bone metastasis by regulating miR-574-3p in vivo. In conclusion, liver cancer cell-derived exosomal miR-574-5p promoted osteoclastogenesis by regulating BMP2, thereby promoting bone metastasis in vivo. The findings suggest that liver cancer cell-released exosomes are the potential therapeutic approach for bone metastatic liver cancer. DATA AVAILABILITY STATEMENT: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Transcriptome Profiling Unveils a Critical Role of IL-17 Signaling-Mediated Inflammation in Radiation-Induced Esophageal Injury in Rats.

Elucidation of the molecular mechanisms involving the initiation and progression of radiation-induced esophageal injury (RIEI) is important for prevention and treatment. Despite ongoing advances, the underlying mechanisms controlling RIEI remain largely unknown. In the present study, RNA-seq was performed to characterize mRNA profiles of the irradiated rat esophagus exposed to 0, 25, or 35 Gy irradiation. Bioinformatics analyses including dose-dependent differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network, and immune infiltration were performed. 134 DEGs were screened out with a dose-dependent manner (35 Gy > 25 Gy > control, or 35 Gy < 25 Gy < control). GO and KEGG analyses showed that the most significant mechanism was IL-17 signaling-mediated inflammatory response. 5 hub genes, Ccl11, Cxcl3, Il17a, S100a8, and S100a9, were identified through the intersection of the DEGs involved in inflammatory response, IL-17 pathway, and PPI network. Additionally, immune infiltration analysis showed the activation of macrophages, monocytes, T cells, NKT cells, and neutrophils, among which macrophages, monocytes, and neutrophils might be the main sources of S100a8 and S100a9. Thus, these findings further our understanding on the molecular biology of RIEI and may help develop more effective therapeutic strategies.

Integration of Metabolomic and Clinical Data Improves the Prediction of Intensive Care Unit Length of Stay Following Major Traumatic Injury.

Recent advances in emergency medicine and the co-ordinated delivery of trauma care mean more critically-injured patients now reach the hospital alive and survive life-saving operations. Indeed, between 2008 and 2017, the odds of surviving a major traumatic injury in the UK increased by nineteen percent. However, the improved survival rates of severely-injured patients have placed an increased burden on the healthcare system, with major trauma a common cause of intensive care unit (ICU) admissions that last ≥10 days. Improved understanding of the factors influencing patient outcomes is now urgently needed. We investigated the serum metabolomic profile of fifty-five major trauma patients across three post-injury phases: acute (days 0-4), intermediate (days 5-14) and late (days 15-112). Using ICU length of stay (LOS) as a clinical outcome, we aimed to determine whether the serum metabolome measured at days 0-4 post-injury for patients with an extended (≥10 days) ICU LOS differed from that of patients with a short (<10 days) ICU LOS. In addition, we investigated whether combining metabolomic profiles with clinical scoring systems would generate a variable that would identify patients with an extended ICU LOS with a greater degree of accuracy than models built on either variable alone. The number of metabolites unique to and shared across each time segment varied across acute, intermediate and late segments. A one-way ANOVA revealed the most variation in metabolite levels across the different time-points was for the metabolites lactate, glucose, anserine and 3-hydroxybutyrate. A total of eleven features were selected to differentiate between <10 days ICU LOS vs. >10 days ICU LOS. New Injury Severity Score (NISS), testosterone, and the metabolites cadaverine, urea, isoleucine, acetoacetate, dimethyl sulfone, syringate, creatinine, xylitol, and acetone form the integrated biomarker set. Using metabolic enrichment analysis, we found valine, leucine and isoleucine biosynthesis, glutathione metabolism, and glycine, serine and threonine metabolism were the top three pathways differentiating ICU LOS with a p < 0.05. A combined model of NISS and testosterone and all nine selected metabolites achieved an AUROC of 0.824. Differences exist in the serum metabolome of major trauma patients who subsequently experience a short or prolonged ICU LOS in the acute post-injury setting. Combining metabolomic data with anatomical scoring systems allowed us to discriminate between these two groups with a greater degree of accuracy than that of either variable alone.

Antibiotic contamination control mediated by manganese oxidizing bacteria in a lab-scale biofilter.

Antibiotic micro-pollution is usually found at the ng/L-level in drinking water sources or discharge water of wastewater treatment plants. In this study, a novel approach mediated by manganese oxidizing bacteria (MnOB) in a biofilter was developed to control the pollution. The results indicated that the biogenic manganese oxide (MnOx) produced during the oxidation of the feeding manganese ions could coat the surface of the filtering sand effecting the simultaneous removal of antibiotics. It was found that the removal of antibiotics is insured as long as the feeding manganese was well removed and was not influenced by the hydraulic loading. The growth rate of the MnOB group revealed that the antibiotic concentration at 50 and 100 ng/L promoted their activity, but it was inhibited at 500 and 1000 ng/L. The structure of the bacterial community was stable in the presence of antibiotics (50 ng/L), but their extracellular processes changed. The removal performance of the feeding manganese seemed to relate to the extracellular processes of the dominant bacterial genus. Moreover, the freshly formed MnOx was a buserite-like material that was rich in Mn(III) and Mn(IV) (94.1%), favoring the degradation. The biofilter did not generate additional antibiotic resistant genes in the presence of antibiotics.

Iliac Aneurysms Treated with Endovascular Iliac Branch Device: A Systematic Review and Meta-analysis.

BACKGROUND: Iliac branch devices (IBDs) have been increasingly reported for treating aortoiliac aneurysms. However, there are still concerns regarding this device. The aim of this study was to evaluate the safety and outcomes of IBDs in treating aortoiliac aneurysms by performing a systematic review and meta-analysis. METHODS: The Medline, EMBASE, and Cochrane databases were systematically searched to identify studies on the management of aortoiliac aneurysms using IBDs. Studies were reviewed and selected using defined criteria by 2 independent investigators who abstracted data on the study characteristics, study quality, and outcomes. The extracted data were presented as a rate and converted through arcsine transformations. Individual studies were evaluated and analyzed for 7 outcomes, including technical success rate, 30-day mortality, 30-day patency, follow-up patency, endoleak rate, buttock claudication, and IBD-associated reintervention. The heterogeneity of the studies was determined using the chi-squared distribution-based Q test and quantified by I2 statistics. Meta-analyses were performed using both a random effects model and fixed effects model. RESULTS: Twenty-two studies with a total of 1064 patients met the inclusion criteria and were selected for analysis. The pooled technical success rate of IBD was 93% (95% confidence interval [CI]: 91-95%). After patients were treated with the IBD, the 30-day mortality rate was 2% (95% CI, 1-4%), 30-day patency rate was 93% (95% CI, 91-94%), follow-up patency was 86% (95% CI, 84-88%), endoleak rate was 12% (95% CI, 8-17%), buttock claudication rate was 6% (95% CI, 5-8%), and IBD-associated reintervention rate was 11% (95% CI, 8-14%). CONCLUSIONS: Our study demonstrates that treating aortoiliac aneurysm with IBD produces satisfactory outcomes in midterm follow-up.

Protective effects of 2,3,5,4-tetrahydroxystilbene-2-o-ß-D-glucoside against osteoporosis: Current knowledge and proposed mechanisms.

AIM: The aim of this study was to explore the mechanism underlying the protective effects of 2,3,5,4-tetrahydroxystilbene-2-o-ß-D-glucoside (TSG) against osteoporosis. METHOD: MC3T3-E1 mouse osteoblast precursor cells were used to analyze the protective effects of TSG on osteoblast apoptosis and differential inhibition induced by oxidative stress to determine the gene expression of forkhead transcription factor FKHRL1 (FoxO3a), T cell factors (TCFs), and downstream genes. A mouse model was used to assess the protective effects of TSG on ovariectomy-induced osteoporosis as well as on Cell Counting Kit-8 (CCK) gene expression, including that of FoxO3a. The mechanism underlying the protective effects of TSG against osteoporosis was further explored using high-throughput sequencing data. RESULTS: A CCK-8 assay in MC3T3-E1 cells and hematoxylin and eosin staining in mouse tissue indicated that cell viability and bone tissue development were inhibited by oxidative stress and ovariectomy and that TSG neutralized or attenuated this effect. The expression levels of FoxO3a, TCF, and downstream genes and the indices of oxidative stress were the same in MC3T3-E1 cells and the bone tissues of the mouse model. Bioinformatics analysis indicated that the cardiac muscle contraction and chemokine signaling pathway were disturbed in MC3T3-E1 cells treated with hydrogen peroxide. Gene ontology-biological process analysis revealed the influence of TSG treatment. CONCLUSION: Osteoporosis and cardiac diseases appear to share a common mechanism. In addition to Wnt/FoxO3a signaling, the immune system and the chemokine signaling pathway may contribute to the protective mechanism of TSG.

Defensive and adverse energy-related molecular responses precede tris (1, 3-dichloro-2-propyl) phosphate cytotoxicity.

To understand the potentially adverse effects of human exposure to tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) and explore the underlying molecular mechanisms, combined transcriptomic and metabolomic approaches were employed to investigate the molecular responses of two human cell lines exposed to different concentrations of TDCIPP. Comparative analyses of transcriptional and metabolic profiles of HepG2/C3A and A549 cells were performed after exposure to 1, 10 and 100 µM TDCIPP for 24 and 72 h. Stress responses (e.g. xenobiotic metabolism and ABC transporter pathways) were observed at the transcriptional level after 24-h exposure to a sub-cytotoxic concentration (10 µM). Transcription of an energy metabolism-related pathway (oxidative phosphorylation) was down-regulated more severely at 100 µM TDCIPP exposure, accompanied by the suppression of pathways relevant to cell proliferation (e.g. cell cycle and DNA replication), while no significant cytotoxic effects were observed. Functional metabolic changes were observed after 72 h in HepG2/C3A cells exposed to 100 µM TDCIPP that corresponded to changes detected at the transcriptional level after 24 h. Taken together, defensive responses to chemical exposure and energy-related changes both precede the cytotoxic effects of TDCIPP in HepG2/C3A cells.

Long-Term Fever After Hallux Valgus Surgery Secondary to Titanium Allergy: A Case Report and Review of the Literature.

We present the case of a patient who had experienced a fever of unknown cause for >7 months after surgical treatment for hallux valgus. A patch test revealed a positive reaction to a titanium alloy. All symptoms subsequently disappeared after we removed the implanted titanium screws. Histopathologic examination of the tissue surrounding the screws showed macrophage infiltration in the tissue. For >1 year after removal of the titanium screws, the patient's body temperature remained <37°C. These results support a diagnosis of titanium allergy in our patient. To the best of our knowledge, a long-term fever caused by an allergic reaction to mini-titanium screws of such a small size has not been reported. A review of 16 cases of titanium allergy reported in the published data confirmed that titanium allergy is extremely rare and that the clinical symptoms can vary. Titanium allergy should be suspected when a patient presents with a fever of unknown cause, delayed wound healing, dermatitis, or impaired fracture healing after internal fixation with titanium materials. A patch test for titanium or the lymphocyte transformation test could offer guidance for the clinical diagnosis of titanium allergy. Finally, we recommend that all patients should be asked whether they have a history of an allergy to any metal before surgery.

Gene expression and metabolic responses of HepG2/C3A cells exposed to flame retardants and dust extracts at concentrations relevant to indoor environmental exposures.

Humans are routinely exposed to mixtures of flame retardants (FRs) from multiple sources including indoor dust. As a model to explore the potential effects of FR exposure from indoor dust on human health, the molecular responses of human hepatoma cells (HepG2/C3A cells) to a defined mixture of FRs and to a dust extract were investigated using multiple non-targeted omics approaches. A solvent extract of an indoor dust standard reference material SRM2585 was used as the surrogate dust sample, while a mixture of four FRs (TCEP, TCIPP, TDCIPP and HBCD) was used to mimic the FR mixture in the indoor dust. Cytotoxicity tests indicated there were no significant changes to cell viability or cell integrity after a 24- or 72-h exposure of HepG2/C3A cells to the FR mixture or to the dust extract. However, transcriptomics revealed changes in gene expression associated with the metabolism of xenobiotics (e.g. CYP1A1, CYP1A2, CYP2B6) in the dust extract group but not in the FR mixture group after a 72-h exposure. Few metabolic or lipidomic changes were detected in response to either the FR mixture or to the dust extract group. Given that the dust extract contained components that elicited a biological response, in contrast to the lack of response induced by the FR mixture, our findings suggest that the most likely causes of the molecular responses to indoor dust exposure lie in components other than the four FRs investigated, e.g. caused by PAHs or PCBs.

Transcriptomic and metabolomic approaches to investigate the molecular responses of human cell lines exposed to the flame retardant hexabromocyclododecane (HBCD).

The potential for human exposure to the brominated flame retardant, hexabromocyclododecane (HBCD) has given rise to health concerns, yet there is relatively limited knowledge about its possible toxic effects and the underlying molecular mechanisms that may mediate any impacts on health. In this study, unbiased transcriptomic and metabolomic approaches were employed to investigate the potential molecular changes that could lead to the toxicity of HBCD under concentrations relevant to human exposure conditions using in vitro models. A concentration-dependent cytotoxic effect of HBCD to A549 and HepG2/C3A cells was observed based on MTT assays or CCK-8 assays with EC50 values of 27.4 µM and 63.0 µM, respectively. Microarray-based transcriptomics and mass spectrometry-based metabolomics revealed few molecular changes in A549 cells or HepG2/C3A cells following a 24-hour exposure to several sub-lethal concentrations (2 to 4000 nM) of HBCD. Quantification of the level of HBCD in the HepG2/C3A exposed cells suggested that the flame retardant was present at concentrations several orders of magnitude higher than those reported to occur in human tissues. We conclude that at the concentrations known to be achievable following exposure in humans, HBCD exhibits no detectable acute toxicity in A549 cells, representative of the lung, or in HepG2/C3A cells, that are hepatocytes with some xenobiotic metabolic capacity.

High-resolution mass spectrometry provides novel insights into products of human metabolism of organophosphate and brominated flame retardants.

The high resolution, accurate mass, and fast scanning features of the Orbitrap(TM) mass spectrometer, combined with the separation power of ultrahigh-performance liquid chromatography were applied for the first time to study the metabolic profiles of several organic flame retardants (FRs) present in indoor dust. To mimic real-life exposure, in vitro cultured HepG2 human hepatocyte cell lines were exposed simultaneously to various FRs in an indoor dust extract for 24 h. Target parent FRs, hexabromocyclododecanes (α-, ß-, and γ-HBCDs), tris-2-chloroethyl phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), were separated in a single run for the first time using alternating positive and negative heated ESI source. Further metabolite separation and identification was achieved using full scan (70,000 full width at half maximum (FWHM)), accurate mass (up to 1 ppm) spectrometry. Structural confirmation was performed via all ion fragmentation (AIF) spectra using the optional higher collisional dissociation (HCD) cell and MS/MS analysis. First insights into human metabolism of HBCDs revealed several hydroxylated and debrominated phase I metabolites, in addition to conjugated phase II glucuronides. Furthermore, various hydroxylated, oxidized, and conjugated metabolites of chlorinated phosphorous FRs were identified, leading to the suggestion of α-oxidation as a significant metabolic pathway for these compounds.

Ophiopogonin D: A new herbal agent against osteoporosis.

Excessive reactive oxygen species (ROS) play an important role in the development of osteoporosis. Ophiopogonin D (OP-D), isolated from the traditional Chinese herbal agent Radix Ophiopogon japonicus, is a potent anti-oxidative agent. We hypothesized that OP-D demonstrates anti-osteoporosis effects via decreasing ROS generation in mouse pre-osteoblast cell line MC3T3-E1 subclone 4 cells and a macrophage cell line RAW264.7 cells. We investigated OP-D on osteogenic and osteoclastic differentiation under oxidative status. Hydrogen peroxide (H2O2) was used to establish an oxidative damage model. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Then, we searched the molecular mechanism of OP-D against osteoporosis. Our results revealed that OP-D significantly promoted the proliferation of MC3T3-E1 cells and improved some osteogenic markers. Moreover, OP-D reduced TRAP activity and the mRNA expressions of osteoclastic genes in RAW264.7 cells. OP-D suppressed ROS generation in both MC3T3-E1 and RAW264.7 cells. OP-D treatment reduced the activity of serum bone degradation markers, including CTX-1 and TRAP. Further research showed that OP-D displayed anti-osteoporosis effects via reducing ROS through the FoxO3a-ß-catenin signaling pathway. In summary, our results indicated that the protective effects of OP-D against osteoporosis are linked to a reduction in oxidative stress via the FoxO3a-ß-catenin signaling pathway, suggesting that OP-D may be a beneficial herbal agent in bone-related disorders, such as osteoporosis.

Gastrodin: an ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species.

Increased levels of reactive oxygen species (ROS) are a crucial pathogenic factor of osteoporosis. Gastrodin, isolated from the traditional Chinese herbal agent Gastrodia elata, is a potent antioxidant. We hypothesized that gastrodin demonstrates protective effects against osteoporosis by partially reducing reactive oxygen species in human bone marrow mesenchymal stem cells (hBMMSCs) and a macrophage cell line (RAW264.7 cells). We investigated gastrodin on osteogenic and adipogenic differentiation under oxidative stress in hBMMSCs. We also tested gastrodin on osteoclastic differentiation in RAW264.7 cells. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results showed that gastrodin significantly promoted the proliferation of hBMMSCs, improved some osteogenic markers, reduced lipid generation and inhibited the mRNA expression of several adipogenic genes in hBMMSCs. Moreover, gastrodin reduced the number of osteoclasts, TRAP activity and the expression of osteoclast-specific genes in RAW264.7 cells. Gastrodin suppressed the production of reactive oxygen species in both hBMMSCs and RAW264.7 cells. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our data revealed that gastrodin treatment reduced the activity of serum bone degradation markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones. Gastrodin decreased osteoclast numbers in vivo by TRAP staining. To conclude, these results indicated that gastrodin shows protective effects against osteoporosis linking to a reduction in reactive oxygen species, suggesting that gastrodin may be useful in the prevention and treatment of osteoporosis.

Ginsenoside-Rb2 displays anti-osteoporosis effects through reducing oxidative damage and bone-resorbing cytokines during osteogenesis.

Reactive oxygen species (ROS) are a significant pathogenic factor of osteoporosis. Ginsenoside-Rb2 (Rb2), a 20(S)-protopanaxadiol glycoside extracted from ginseng, is a potent antioxidant that generates interest regarding the bone metabolism area. We tested the potential anti-osteoporosis effects of Rb2 and its underlying mechanism in this study. We produced an oxidative damage model induced by hydrogen peroxide (H2O2) in osteoblastic MC3T3-E1 cells to test the essential anti-osteoporosis effects of Rb2in vitro. The results indicated that treatment of 0.1 to 10µM Rb2 promoted the proliferation of MC3T3-E1 cells, improved alkaline phosphatase (ALP) expression, elevated calcium mineralization and mRNA expressions of Alp, Col1a1, osteocalcin (Ocn) and osteopontin (Opn) against oxidative damage induced by H2O2. Importantly, Rb2 reduced the expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and inhibited the H2O2-induced production of ROS. The in vivo study indicated that the Rb2 administered for 12weeks partially decreased blood malondialdehyde (MDA) activity and elevated the activity of reduced glutathione (GSH) in ovariectomized (OVX) mice. Moreover, Rb2 improved the micro-architecture of trabecular bones and increased bone mineral density (BMD) of the 4th lumbar vertebrae (L4) and the distal femur. Altogether, these results demonstrated that the potential anti-osteoporosis effects of Rb2 were linked to a reduction of oxidative damage and bone-resorbing cytokines, which suggests that Rb2 might be effective in preventing and alleviating osteoporosis.

Adenovirus-mediated transfer of VEGF into marrow stromal cells combined with PLGA/TCP scaffold increases vascularization and promotes bone repair in vivo.

INTRODUCTION: Large osseous defect remains a serious clinical problem due to the lack of sufficient blood supply and it has been proposed that this situation can be relieved by accelerating the formation of new vessels in the process of bone defect repair. The aim of this study was to develop a new type of artificial bone by transferring the VEGF gene into marrow stromal cells (MSCs) and seeding them into a porous scaffold. MATERIAL AND METHODS: An adenovirus vector was employed to transfer the VEGF gene into MSCs and expression of the exogenous gene was confirmed by ELISA. Next the transduced cells were seeded into a collagen I modified PLGA/TCP scaffold. The constructed new complex artificial bone was then assessed for biocompatibility in vitro and blood vessel formation and bone formation in vivo. RESULTS: We found that adenovirus mediated VEGF gene transfer into MSCs sustained VEGF expression in MSCs for 3 weeks. Porous scaffold PLGA/TCP made by rapid prototyping technology exhibited improved biocompatibility resulting from crosslinking with collagen I. Furthermore, the in vivo study showed that large amounts of blood vessels were detected histologically 1 week after artificial bone implantation, and significant bone formation was detected 8 weeks after implantation. CONCLUSIONS: Our findings suggest that gene transfer of VEGF into MSCs combined with PLGA/TCP scaffold enhances bone repair in vivo by promoting vascularization.

Estrogen improves the proliferation and differentiation of hBMSCs derived from postmenopausal osteoporosis through notch signaling pathway.

Estrogen deficiency is the main reason of bone loss, leading to postmenopausal osteoporosis, and estrogen replacement therapy (ERT) has been demonstrated to protect bone loss efficiently. Notch signaling controls proliferation and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Moreover, imperfect estrogen-responsive elements (EREs) were found in the 5'-untranslated region of Notch1 and Jagged1. Thus, we examined the molecular and biological links between estrogen and the Notch signaling in postmenopausal osteoporosis in vitro. hBMSCs were obtained from healthy women and patients with postmenopausal osteoporosis. Notch signaling molecules were quantified using real-time polymerase chain reaction (real-time PCR) and Western Blot. Luciferase reporter constructs with putative EREs were transfected into hBMSCs and analyzed. hBMSCs were transduced with lentiviral vectors containing human Notch1 intracellular domain (NICD1). We also used N-[N-(3, 5-diflurophenylacetate)-l-alanyl]-(S)-phenylglycine t-butyl ester, a γ-secretase inhibitor, to suppress the Notch signaling. We found that estrogen enhanced the Notch signaling in hBMSCs by promoting the expression of Jagged1. hBMSCs cultured with estrogen resulted in the up-regulation of Notch signaling and increased proliferation and differentiation. Enhanced Notch signaling could enhance the proliferation and differentiation of hBMSCs from patients with postmenopausal osteoporosis (OP-hBMSCs). Our results demonstrated that estrogen preserved bone mass partly by activating the Notch signaling. Because long-term ERT has been associated with several side effects, the Notch signaling could be a potential target for treating postmenopausal osteoporosis.

MicroRNA­125b suppresses the proliferation and osteogenic differentiation of human bone marrow­derived mesenchymal stem cells.

The regressive biological function of human bone marrow­derived mesenchymal stem cells (hBMSCs) is one of the key factors resulting in the decrease of bone mass in senile osteoporosis. MicroRNAs (miRs) are non­coding small RNAs involved in various gene regulation processes. Whether any miR(s) are involved in the progression of osteoporosis by regulating the biological function of hBMSCs remains to be elucidated. The present study aimed to compare the expression levels of miR­125b in hBMSCs derived from senile osteoporotic patients with that of control (normal) subjects. A significantly upregulated expression of miR­125b in osteoporotic hBMSCs was detected. To elucidate the biological function of miR­125b in senile osteoporosis, the effects of miR­125b expression on proliferation and osteogenic differentiation of hBMSCs were assessed using gain­ and loss­of­function studies. It was evident that the overexpression of a miR­125b mimic was able to suppress the proliferative and osteogenic differentiation of senile hBMSCs. In contrast, repression of the function of miR­125b by transfection of an miR­125b inhibitor promoted the proliferation and osteogenic differentiation of hBMSCs. Furthermore, the potential target gene of miR­125b, osterix (Osx), was examined. The results of the present study strongly suggested that miR­125b may regulate osteogenic differentiation of hBMSCs through the modulation of Osx expression.

Comparison of protein expression profiles of the hepatopancreas in Fenneropenaeus chinensis challenged with heat-inactivated Vibrio anguillarum and white spot syndrome virus.

Fenneropenaeus chinensis (Chinese shrimp) culture industry, like other Penaeidae culture, has been seriously affected by the shrimp diseases caused by bacteria and virus. To better understand the mechanism of immune response of shrimp to different pathogens, proteome research approach was utilized in this study. Firstly, the soluble hepatopancreas protein samples in adult Chinese shrimp among control, heat-inactivated Vibrio-challenged and white spot syndrome virus-infected groups were separated by 2-DE (pH range, 4-7; sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and pH range, 3-10; tricine-SDS-PAGE). Then the differentially expressed protein spots (≥1.5-fold or ≤0.67-fold averagely of controls) were analyzed by LC-ESI-MS/MS. Using Mascot online database searching algorithm and SEQUEST searching program, 48 and 49 differentially expressed protein spots were successfully identified in response to Vibrio and white spot syndrome virus infection, respectively. Based on these results, we discussed the mechanism of immune response of the shrimp and shed light on the differences between immune response of shrimp toward Vibrio and white spot syndrome virus. This study also set a basis for further analyses of some key genes in immune response of Chinese shrimp.