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Purpose: Dietary protein, as important macronutrient, is vital for intestinal function and health status. We aimed to determine the effects of dietary protein source on growth performance and intestinal function of neonates with intrauterine growth retardation (IUGR) in a pig model. Methods: Eighteen pairs of IUGR and normal birth weight (NBW) weaned pigs were allotted to be fed starter diet containing soybean protein concentrate (SPC) or spray-dried porcine plasma (SDPP) for 2 weeks. Growth performance, antioxidant variables, intestinal morphology and absorption capability, microbiota composition and short-chain fatty acids (SCFA) were assessed. Results: IUGR led to poor growth performance, absorption capability and changes on antioxidant variables, while SDPP diet improved the growth performance, diarrhea index, intestinal morphology and antioxidant variables of IUGR or NBW pigs relative to that fed SPC diet. Importantly, SDPP diet improved bacterial diversity and increased the abundance of phylum Firmicutes, but decreased the phylum Proteobacteria in colonic digesta, associating with higher genera Lactobacillus and lower genera Escherichia–Shigella, linking to the increased concentration of SCFA. Conclusions: Our findings indicate that IUGR impairs the growth rate, intestinal function and oxidative status of weaned pigs, which could be partly improved by SDPP diet either for IUGR or NBW pigs, associating with the better antioxidant capability, composition of microbiotas and their metabolites. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1-34 (60 μg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats. [ABSTRACT FROM AUTHOR]

Reduced cerebral blood flow in Alzheimer's disease (AD) may occur in early AD, which contributes to the pathogenesis and/or pathological progression of AD. Reversing this deficit may have therapeutic potential. Certain traditional Chinese herbal medicines (e.g., Saponin and its major component Xueshuantong [XST]) increase blood flow in humans, but whether they could be effective in treating AD patients has not been tested. We found that systemic XST injection elevated cerebral blood flow in APP/PS1 transgenic mice using two-photon time-lapse imaging in the same microvessels before and after injection. Subchronic XST treatment led to improved spatial learning and memory and motor performance in the APP/PS1 mice, suggesting improved neural plasticity and functions. Two-photon time lapse imaging of the same plaques revealed a reduction in plaque size after XST treatment. In addition, western blots experiments showed that XST treatment led to reduced processing of amyloid-β protein precursor (AβPP) and enhanced clearance of amyloid-β (Aβ) without altering the total level of AβPP. We also found increased synapse density in the immediate vicinity of amyloid plaques, suggesting enhanced synaptic function. We conclude that targeting cerebral blood flow can be an effective strategy in treating AD. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC.Methods: We used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively.Results: Expression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-β signaling.Conclusions: IQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-β signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC. [ABSTRACT FROM AUTHOR]

Objectives. Several animal studies have demonstrated the positive effects of platelet-rich plasma (PRP) on disc degeneration retardation. The present meta-analysis was to verify the efficacy of PRP in retarding disc degeneration in animal. Methods. Relevant studies were identified and evaluated according to our inclusion and exclusion criteria. The standardized mean difference (SMD) and related 95% confidence interval (95% CI) were estimated to assess PRP efficiency. Results. In total, eleven studies were included in this meta-analysis. Significant differences were found in the PRP treatment group, which showed increased disc height (SMD = 2.66, 95% CI: 1.86, 3.47, p=0.000), increased MRI T2 signal intensity (SMD = −3.29, 95% CI: −4.44, −2.13, p=0.000), and decreased histological degeneration grade (SMD = −4.28, 95% CI: −5.26, −3.30, p=0.000). However, no significant increase in collagen II expression was found (SMD = 25389.74, 95% CI: −27585.72, 78365.21, p=0.348). Apart from the subgroup analysis of the disc height based on animal species (pig) and disc degeneration model (chymopapain induction), other subgroup analysis based on animal species (rabbit and rat), study design, disc degeneration model, and follow-up period demonstrated that PRP treatment can significantly restore disc height and increase MRI T2 signal intensity. Conclusions. PRP treatment is potentially effective in restoring disc height of rodent rabbit and rat, reducing histological degeneration grade, and increasing MRI T2 image signal. PRP injection may be promising therapy for retarding disc degeneration. [ABSTRACT FROM AUTHOR]

Surface modification techniques have been applied to generate titanium implant surfaces that promote osseointegration for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Strontium (Sr) promotes osteoblast proliferation and inhibits osteoclast proliferation and positively affects bone regeneration. The aim of this study was to confirm the effects of strontium-substituted hydroxyapatite (Sr-HA) coating via electrochemical deposition on implant's osseointegration in the osteoporotic condition. Female Sprague Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group HA; group 5 % Sr-HA; group 10 % Sr-HA; and group 20 % Sr-HA. Afterward, all rats from groups HA, 5 % Sr-HA, 10 % Sr-HA, and 20 % Sr-HA received implants with hydroxyapatite coating containing 0, 5, 10, and 20 % Sr. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All treatment groups increased new bone formation around the surface of titanium rods and push-out force; group 20 % Sr-HA showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant differences in bone formation and push-out force was observed between groups 5 % Sr-HA and 10 % Sr-HA. This finding suggests that Sr-HA coating can improve implant osseointegration, and the 20 % Sr coating exhibited the best properties for implant osseointegration among the tested coatings in osteoporosis rats. [ABSTRACT FROM AUTHOR]

Background: The maintenance of nucleus pulposus (NP) viability in vitro is difficult. The annulus fibrosus (AF) pathway reflects one nutrient transport channel and may have an important effect on NP viability in disc organ cultures. The present study describes a feasible disc pre-treatment involving the AF and investigates its efficacy in improving NP bioactivity in an in vitro disc bioreactor culture.Methods: Rabbit discs that were randomly assigned to the experimental group (EG) were pretreated via the surgical removal and controlled trypsinization of the outer AF. The discs in the control group (CG) did not receive any special treatment. All discs were organ-cultured in a self-developed bioreactor. Solute transport into the central NP was measured using a methylene blue solution. On days 7 and 14, histological properties, cell viability, cell membrane damage, gene expression and matrix composition within the NP in these two groups were compared with each other and with the corresponding parameters of fresh NP samples. Additionally, the structures of the outer AF and the cartilage endplate (CEP) following pre-treatment were also assessed.Results: The outer AF in the EG became disorganized, but no specific changes occurred in the CEP or the inner AF following pre-treatment. The discs in the EG exhibited increased penetration of methylene blue into the central NP. On days 7 and 14, the NP bioactivity in the EG was improved compared with that of the CG in terms of cell viability, cell membrane damage, gene expression profile and matrix synthesis. Moreover, cell viability and matrix synthesis parameters in the EG were more similar to those of fresh samples than they were to the same parameters in the CG on day 14.Conclusions: Using this disc pre-treatment, i.e., the surgical removal and controlled trypsinization of the outer AF, NP bioactivity was better maintained for up to 14 days in an in vitro disc bioreactor culture. [ABSTRACT FROM AUTHOR]

Background: Many researches have investigated the changes associated with immobilization-induced osteoarthritis (OA). However, there are only few studies focusing on the effect of unilateral knee immobilization on cartilage matrix changes in the contralateral mobile knee. The aim of the present study was to investigate the influence of immobilization on the cartilage matrix in the contralateral mobile knees in a rabbit model of OA induced by immobilization.Methods: Right knees (experimental knees) of eighteen mature female rabbits were immobilized at an extension of 180° with orthopedic casting tape for 2, 4, or 8 weeks. Left knees (contralateral knees) of the immobilized rabbits were not subjected to immobilization. The knees of six non-immobilized rabbits were designated as control knees. Following immobilization, cartilage specimens from the medial femoral condyle underwent macroscopic, histological, immunohistochemical, and biochemical evaluations.Results: Roughness of cartilage surface was detected in the experimental knees at 2 weeks, and cartilage degeneration was further developed. In the contralateral knee, cartilage showed degenerative changes after 4 weeks. Safranin-O staining and glycosaminoglycan (GAG) contents were reduced in the experimental knees following immobilization and in the contralateral intact knees after 4 and 8 weeks. Type II collagen staining was gradually reduced, type I collagen accumulation was obviously detected in the upper and middle layers of cartilage in experimental knees after 8 weeks, and the collagen orientation was gradually disorganized in both knees at 4 and 8 weeks. For both experimental and contralateral knees, collagen contents were significantly decreased at 8 weeks, and Mankin and Osteoarthritis Research Society International (OARSI) scores increased over time.Conclusion: OA developed in the contralateral intact knee with the progress of OA in the immobilized knee in a rabbit model of immobilization-induced OA. [ABSTRACT FROM AUTHOR]

Abstract: The primo-vascular system was visualized in the mesentery surrounding the small intestine of a dog using Trypan blue. This structure, which was first observed in a rat, formed a network as primo-vessel branches were joined to primo-nodes. Other characteristic features of the primo-vascular system, such as bundles of tubes with fibrous extracellular matrix in a primo-vessel and a broken-line alignment of rod-shaped nuclei along the primo-vessel, were observed. Blood vessels, lymph vessels, and primo-vessels were present in the same mesentery, and they could clearly be distinguished by histological differences. [Copyright &y& Elsevier]

Objective: Disruption of B cell homeostasis and subsequent dominance of effector B cell subsets are critical for the development of systemic lupus erythematosus (SLE). Revealing the key intrinsic regulators involved in the homeostatic control of B cells has important therapeutic value for SLE. This study was undertaken to determine the regulatory role of the transcription factor Pbx1 in B cell homeostasis and lupus pathogenesis. Methods: We constructed mice with B cell–specific deletion of Pbx1. T cell–dependent and T cell–independent humoral responses were induced by intraperitoneal injection of nitrophenyl‐containing hapten (NP) conjugated to keyhole limpet hemocyanin or NP‐Ficoll. The regulatory effects of Pbx1 on autoimmunity were observed in a Bm12‐induced lupus murine model. We investigated mechanisms of Pbx1 using RNA sequencing, the cleavage under targets and tagmentation assay, and chromatin immunoprecipitation–quantitative polymerase chain reaction assay. We transduced B cells from SLE patients with plasmids that overexpressed PBX1 to explore the in vitro therapeutic efficacy of PBX1. Results: Pbx1 was specifically down‐regulated in autoimmune B cells and negatively correlated with disease activity. The deficiency of Pbx1 in B cells resulted in excessive humoral responses following immunization. In the Bm12‐induced lupus model, mice with B cell–specific Pbx1 deficiency displayed enhancements in germinal center responses, plasma cell differentiation, and autoantibody production. Pbx1‐deficient B cells had increased survival and proliferative advantages after activation. Pbx1 regulated genetic programs by directly targeting critical components of the proliferation and apoptosis pathways. In SLE patients, PBX1 expression was negatively correlated with effector B cell expansion; when PBX1 expression was enforced, the survival and proliferative capacity of SLE B cells were attenuated. Conclusion: Our study reveals the regulatory function and mechanism of Pbx1 in adjusting B cell homeostasis and highlights Pbx1 as a therapeutic target in SLE. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) represents a promising modality that provides the possibility of non-invasively eliminating solid tumors in a site-directed manner. In light of the complexity and heterogeneity of tumors, more and more studies are attempting to combine SDT with other therapeutic methods so as to achieve better tumor treatment effect, which sheds new light on the potential of SDT-based synergistic therapeutics. Herein, the representative studies of SDT-instructed multimodal synergistic cancer therapy are comprehensively presented, such as sono-chemotherapy, sono-radiotherapy, sono-immunotherapy, and sono-chemodynamic therapy, etc., and their incorporate mechanisms are discussed in detail. The current challenges and future prospects to promote the advanced development of SDT-based nanomedicines in this burgeoning research field are highlighted. It is believed that such an emerging synergistic therapeutic modality based on SDT will play a more significant role in the field of tumor precision treatment medicine. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Parathyroid hormone (PTH) enhances bone healing. Strontium ranelate (SR) is an antiresorptive agent that increases bone formation. Reports about combined effects of PTH and SR on local bone regeneration in osteoporotic subjects are limited. We aimed at investigating the efficacy of PTH and SR for promoting new bone formation in critical‐sized defects of ovariectomized rats. Materials and Methods: Parathyroid hormone‐ and/or SR‐containing poloxamer implant tablets with/without chitosan microparticles were delivered locally to calvarial defects of 90 Wistar rats. Biopsies were analyzed histologically and histomorphometrically at 4 and 8 weeks of healing. Results: Histomorphometry revealed that PTH alone promoted new bone formation at 4 weeks but the efficiency declined in 8 weeks. There was no positive effect of SR alone on bone formation at 4 or 8 weeks. Calvarial defects treated with PTH+SR combinations showed statistically significant greater new bone formation than either treatment alone at both time intervals. Tissue responses were modest and supported the good biocompatibility of the biomaterials used. Conclusion: Parathyroid hormone and SR combinations can be effective for calvarial bone regeneration of ovariectomized rats. PTH plus SR may have potential use as bone graft material in orthopedic and dental surgery to enhance bone healing and osseointegration. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this research was to assess the performance of a modified bovine stent valve implanted transventricularly in the pulmonary position in sheep with a 3-month follow-up period.Materials and Methods: Seven modified pulmonary bovine stent valves were transventricularly implanted in the pulmonary position into seven sheep using a delivery system. Stent valve performance was investigated and evaluated hemodynamically, angiographically, and with echocardiograms before, immediately after, and 3 months following implantation. Macroscopic, histologic, and radiographic examinations were performed on the explanted graft at 3 months.Results: The modified stent valves were all deployed and implanted successfully in the pulmonary position in seven sheep. Angiographic, echocardiographic, hemodynamic, and macroscopic analyses confirmed firm anchoring of the stents in the target position in the early and 3-month follow-up period. All modified stent valves showed satisfactory function, except one moderate stenosis (32 mmHg gradient) with mild regurgitation that was discovered at 3 months. All seven valves were free of any calcification and thrombus formation at postmortem macroscopic examination, which was confirmed by histologic and radiographic examination. All stents were intact without any fracture at microscopic or radiographic examination.Conclusions: Transventricular implantation of a modified nitinol pulmonary valve stent showed good structural and functional outcomes without stent fracture or migration. [ABSTRACT FROM AUTHOR]

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic osseous integration of the implant, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings still limited. This study aims to investigate effects of PTH+SIM on osseous integration of the implant in OVX rats. Female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group control; group SIM; group PTH and group PTH+SIM. Afterwards, all OVX rats received hydroxyapatite (HA)-coated titanium rods (external diameter and length are 1.5mm and 20mm) in the femoral medullary canal. Subsequently, the animals from group SIM, group PTH and group PTH+SIM received human parathyroid hormone 1-34 (60μg/kg, three times a week), SIM (5mg/kg daily), or both for 12 weeks. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All groups increased new bone formation around the surface of titanium rods and push-out force; group PTH+SIM showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant difference observed in bone formation and push-out force between groups SIM and PTH. This finding suggests that intermittent administration of PTH or SIM alone has an effect to increase new bone formation on the surface of HA-coated implants in the osteoporotic condition, and the additive effects of combination PTH and SIM on osseous integration of the implant in OVX rats. [ABSTRACT FROM AUTHOR]

In this study, we tested the effect of Teriparatide (PTH) in combination with β-tricalcium phosphate (β-TCP) as a bone void filler in an ovariectomised rat distal femoral metaphysis model.β-TCP is a completely resorbable synthetic calcium phosphate and the Teriparatide is a drug that can promote bone formation in the condition of osteoporosis. A critical size defect of 3mm in diameter, a through-hole bone defect, was drilled into each distal femur of the ovariectomised rats. The hole was filled with β-TCP and the rat was injected PTH Teriparatide (30μg/kg) in peritoneum 5 times per week. After 4and 8 weeks the animals were killed and the degree of bone healing analysed. In total, 60 animals were investigated. When the β-TCP and PTH were used, histological, biochemistry and histomor-phometric evaluations revealed significantly better bone healing in terms of quantity and quality of the newly formed bone. The Ovariectomised rats which suffer from femur metaphysis defect are cured by embedding β-tricalcuim phosphate and intermittently cured by parathyroid hormone (PTH). [ABSTRACT FROM AUTHOR]

The Qing' E Formula (QEF) is a compound preparation that was originally recorded in the 'Prescriptions of the Bureau of Taiping People's Welfare Pharmacy' during the Song Dynasty (10th century CE). It consists of four Chinese medicinal herbs, Eucommiae Cortex (Eucommia ulmoides), Psoraleae Fructus (Psoralea corylifolium), Juglandis Semen (Juglans regia), and Garlic Rhizoma. According to traditional Chinese medicine (TCM), QEF has the ability to tonify the kidney and strengthen muscle and bone. According to the 'kidney governing bone' theory in TCM, QEF is also used to treat the symptoms of climacteric syndrome, especially osteoporosis caused by reduced production of estrogen during the perimenopausal period; however, the therapeutic roles of the individual components of the QEF and their compatibility within the formula has not been investigated. In this study, the compatibility mechanism and estrogen-like action properties of the four herbal components in the QEF was elucidated according to the organizing principle of Chinese medicine formulas using both in vitro and in vivo models. The estrogen-like effects of QEF and its herbal components were investigated in MCF7 and HEK293 cells as well as ovariectomized (OVX) rats. The estrogen-like effects of the QEF and its components were analyzed in vitro using Cell Counting Kit-8 and Luciferase reporter gene assays. In the in vivo studies, the blood plasma levels of hormones, lipids, neurotransmitters, aromatase, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured through enzyme-linked immunosorbent assays (ELISAs). The histological morphologies of the target organs after exposure to QEF were investigated by HE staining and immunohistochemical methods. The expression levels of estrogen pathway-related proteins and genes in the OVX rats were measured by Western blotting and real time quantitative PCR (RT-qPCR), respectively. The in vitro results showed that the QEF, Eucommia (EC) and Psoralea (PF) promoted the proliferation of MCF-7 cells and upregulated the expression of ERα, ERβ and pS2 genes in the MCF-7 cells. Notably, the QEF demonstrated the most active estrogen-like effects compared to the individual ingredients. The in vivo results showed that the QEF, EC, and PF increased the uterine coefficient, upregulated the expression of both ERs (ERα and ERβ) in the uterus, and increased blood serum hormone levels. QEF and its individual components ameliorated menopausal-derived lipid metabolism dysfunction, increased neurotransmitter production by stimulating the adrenal glands, enhanced the antioxidant activity in the serum by increasing the concentration of SOD, reversed ovariectomy-derived atrophy in the uterus, and reduced the weight gain associated with estrogen reduction in the OVX rats. The QEF also antagonize the loss of appetite of OVX animals caused by feeding Psoralea alone, which could explain the compatibility mechanism of Qing' E Formula with reducing toxicity and increasing efficiency. The estrogen-like effects of Eucommia and Psoralea were mainly mediated through activation of ERα and ERβ. The phytoestrogen components regulated hormone production and the expression of related proteins and genes, which indicated that these components exhibited estrogen-like therapeutic effects. However, the QEF showed the greatest estrogen-like effects compared to the individual components. Overall, this corroborated the therapeutic prowess of the QEF and clarified the pharmacodynamic interactions between the different components extracts in the QEF. [Display omitted] • The compatibility of the herbs in QEF was investigated and QEF is more effective than a single drug. • QEF, Psoraleae and Eucommia have significant estrogenic activities in vivo and vitro. • The function may be effected by classical ER pathway. [ABSTRACT FROM AUTHOR]