Marginal Zinc Deficiency in Pregnant Rats Impairs Bone Matrix Formation and Bone Mineralization in Their Neonates

Zinc (Zn) deficiency during pregnancy may result in a variety of defects in the offspring. We evaluated the influence of marginal Zn deficiency during pregnancy on neonatal bone status. Nine-week-old male Sprague-Dawley rats were divided into two groups and fed AIN-93G-based experimental diets containing 35 mg Zn/kg (Zn adequately supplied, N) or 7 mg Zn/kg (low level of Zn, L) from 14-day preconception to 20 days of gestation, that is, 1 day before normal delivery. Neonates were delivered by cesarean section. Litter size and neonate weight were not different between the two groups. However, in the L-diet-fed dam group, bone matrix formation in isolated neonatal calvaria culture was clearly impaired and was not recovered by the addition of Zn into the culture media. Additionally, serum concentration of osteocalcin, as a bone formation parameter, was lower in neonates from the L-diet-fed dam group. Impaired bone mineralization was observed with a significantly lower content of phosphorus in neonate femurs from L-diet-fed dams compared with those from N-diet-fed dams. Moreover, Zn content in the femur and calvaria of neonates from the L-diet group was lower than that of the N-diet-fed group. In the marginally Zn-deficient dams, femoral Zn content, serum concentrations of Zn, and osteocalcin were reduced when compared with control dams. We conclude that maternal Zn deficiency causes impairment of bone matrix formation and bone mineralization in neonates, implying the importance of Zn intake during pregnancy for proper bone development of offspring.     

2型糖尿病模型GK大鼠骨形态学和生物力学特点观察

目的观察2型糖尿病模型GK大鼠的骨代谢特点以及骨密度和骨生物力学特性的变化。方法采用雄性6月龄GK大鼠10只,以月龄、性别匹配的健康Wistar大鼠作为正常对照。颈静脉取血检测与骨代谢有关的生化指标。DXA法测定股骨和腰椎骨密度,并行股骨三点弯曲实验和腰椎压缩实验。甲基丙烯酸甲酯包埋胫骨干骺端以制备不脱钙骨切片。应用多媒体病理图像分析软件进行骨组织形态计量学分析。结果GK大鼠体重明显低于健康对照Wistar大鼠（P〈0.01）。与对照组相比,GK大鼠血清骨钙素水平明显降低[（4.97±0.49,6.75±0.71）μg/mL,P〈0.01],而抗酒石酸酸性磷酸酶活性明显升高[（17.92±5.23,8.31±2.69）U/L,P〈0.01],但血钙和血磷无明显变化（P〉0.05）;股骨和腰椎骨密度显著降低[（0.16±0.01,0.22±0.02;0.12±0.01,0.16±0.02）g/cm2,P〈0.01];骨强度和腰椎的弹性模量明显降低（P〈0.01）。骨形态学分析显示GK大鼠股骨长度和第五腰椎高度分别降低10.3%和9.5%（P〈0.01）,股骨和腰椎横截面积无明显变化（P〉0.05）。骨组织形态计量学分析显示,GK大鼠骨小梁体积、骨小梁厚度、类骨质表面和厚度明显降低[（15.72±1.18,19.13±1.13）%,（61.91±4.54,74.43±3.63）μm,（18.18±1.25,19.63±1.07）%,（3.68±0.48,4.34±0.35）μm,P〈0.01或0.05],动态参数如矿化表面、矿化沉积率和骨形成率也明显降低[（17.77±1.54,19.56±2.07）%,（1.07±0.22,1.35±0.16;0.20±0.03,0.26±0.04）μm/day,P〈0.05或0.01],而矿化延迟时间显著延长（2.66±0.56,2.12±0.35,P〈0.05）。结论非肥胖的GK大鼠表现有骨量减少和骨折危险性增加;2型糖尿病本身可干扰成骨细胞功能和活性而导致骨重建失衡。     

二甲双胍调控糖尿病大鼠骨髓间充质干细胞的增殖和分化

虽然二甲双胍广泛用于治疗2型糖尿病,但是其对骨骼的潜在影响知之甚少。因此,本研究评估了二甲双胍对培养的大鼠骨髓间充质干细胞(MSCs)和脂肪细胞两者的分化以及增殖的影响。首先随机组形成对照实验,其中对照组为在不经二甲双胍处理培养基中培养MSCs细胞21 d,而二甲双胍组则在用100μmol/L二甲双胍处理培养基中培养MSCs 21 d。结果表明,二甲双胍增强了大鼠MSCs的成骨细胞分化细胞中ALP的活性,抑制了培养中MSCs脂肪形成分化的过程,但是增强了MSCs细胞的增殖能力。     

Evaluation of the Anti‐Diabetic Activity of Polysaccharide from Cordyceps cicadae in Experimental Diabetic Rats

Cordyceps cicadae is a medicinal fungus used in treating night sweat, childhood convulsions, vision improvement and pain. This study was designed to evaluate the anti‐diabetic activity of the crude polysaccharide (SHF) from the mycelium and body portion of C. cicadae. Diabetes mellitus was induced in the rat with a single intravenous injection of alloxan monohydrate (150 mg/kg). In other to evaluate the anti‐diabetic effects of C. cicadae polysaccharide in alloxan‐induced diabetic rats, the crude polysaccharide (SHF at 100, 200 and 400 mg/kg body weight) and glibenclamide were administered orally to diabetic rats for 30 days. Blood glucose level, total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), creatinine (CREA), urea, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH) were determined. SHF showed significant reduction in blood glucose in diabetic rats. Treatment of diabetic rats also resulted an improvement in body weights, increased HDL, SOD and GSH, as well as decreased TC, TG, LDL, MDA, urea, CREA, ALT, AST and ALP. These results suggested that C. cicadae polysaccharide displayed anti‐hyperglycemic, anti‐hyperlipidemic and antioxidant activities and could be a promising therapeutic source in managing diabetes mellitus and its associated complications.     

Accelerating Bone Generation and Bone Mineralization in the Interparietal Sutures of Rats Using an rhBMP-2/ACS Composite after Rapid Expansion

This study aims to investigate the effects of rhBMP-2/ACS composite on bone regeneration and mineralization during expansion of the interparietal suture in rats. Forty 10-week-old Sprague-Dawley rats were divided into four groups (n=10). The first group (intact group) did not receive any intervention. The second group (expansion control group) received an expansion force of 60 g. The remaining two groups received an expansion force of 60 g and were implanted with an atelo-type I absorbable collagen sponge and rhBMP-2/ACS composite positioned on the suture beneath the periosteum. The relapse, relapse ratio, relevant bone remodelling, and calcium and osteocalcin contents were evaluated. Bone regeneration in the interparietal suture was estimated by the histological method. The osteocalcin content was measured by radioimmunoassay, and the calcium content was measured by atomic absorption spectrophotometry. Bone regeneration was more active in the suture after application of the expansion force compared with that of the suture without any intervention. Bone bridges formed in the rhBMP-2/collagen composite group. Both osteocalcin and calcium content were higher in the rhBMP-2/collagen composite group than in the other three groups (P<0.01). The relapse ratio in the rhBMP-2/collagen group was much lower than that in the other two expansion groups (P<0.01). RhBMP-2/ACS composite can promote bone regeneration and bone mineralization in the expanded suture and decrease the relapse ratio. Thus, the rhBMP-2/ACS composite may be therapeutically beneficial to the inhibition of relapse and shortening of the retention period during rapid expansion.     

An Efficient Multi-Scale Modelling Approach for ssDNA Motion in Fluid Flow

The paper presents a multi-scale modelling approach for simulating macromolecules in fluid flows. Macromolecule transport at low number densities is frequently encountered in biomedical devices, such as separators, detection and analysis systems. Accurate modelling of this process is challenging due to the wide range of physical scales involved. The continuum approach is not valid for low solute concentrations, but the large timescales of the fluid flow make purely molecular simulations prohibitively expensive. A promising multi-scale modelling strategy is provided by the meta-modelling approach considered in this paper. Meta-models are based on the coupled solution of fluid flow equations and equations of motion for a simplified mechanical model of macromolecules. The approach enables simulation of individual macromolecules at macroscopic time scales. Meta-models often rely on particle-corrector algorithms, which impose length constraints on the mechanical model. Lack of robustness of the particle-corrector algorithm employed can lead to slow convergence and numerical instability. A new FAst Linear COrrector （FALCO） algorithm is introduced in this paper, which significantly improves computational efficiency in comparison with the widely used SHAKE algorithm. Validation of the new particle corrector against a simple analytic solution is performed and improved convergence is demonstrated for ssDNA motion in a lid-driven micro-cavity.     

不同强度的体育运动对糖尿病大鼠骨密度及骨代谢的影响

目的:探讨运动强度对糖尿病大鼠骨密度及骨代谢的影响,为糖尿病骨质疏松的预防和治疗提供实验依据。方法:采用一次性腹腔注射链服佐菌素建立糖尿病大鼠模型,随机分为糖尿病对照组、小强度运动组(10 m/min)、中强度运动组(20 m/min)和高强度运动组(30 m/min)。分别于运动前后测定各组大鼠的血糖、骨密度、血清骨钙素(BGP)、碱性磷酸化酶(AKP)、血钙(S-Ca)及血磷(S-P)含量。结果:运动组大鼠血糖均低于训练前和对照组(P0.05)。小强度运动组和高强度运动组大鼠骨密度低于对照组,中强度运动组大鼠骨密度显著高于对照组、小强度运动组和高强度运动组(P0.05);小强度运动组与高强度运动组大鼠骨密度无显著性差异(P0.05)。运动组大鼠BGP和S-P显著升高,AKP下降,差异具有统计学意义(P0.05)。小强度运动组和高强度运动组大鼠S-Ca无显著变化(P0.05);中强度运动组大鼠S-Ca显著升高,且高于小强度运动组和高强度运动组(P0.05)。结论:运动强度对骨密度和骨代谢有一定影响,采取适当的体育运动可提高血清骨钙素含量,改善骨代谢状况,有利于糖尿病骨质疏松症的预防。     

Niaspan Attenuates the Adverse Effects of Bone Marrow Stromal Cell Treatment of Stroke in Type One Diabetic Rats

Aims

Our previous studies have found that bone-marrow-stromal cells (BMSC) therapy improves functional recovery after stroke in non-diabetic rats while increases brain hemorrhage and induces arteriosclerosis-like changes in type-one-diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats.

Methods

T1DM-rats induced by streptozotocin were subjected to 2 hours of middle-cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5×10⁶); 3) Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5×10⁶) +Niaspan (40 mg/kg, daily for 14 days) combination starting at 24 hours after MCAo. All rats were monitored for 14 days.

Results

Combination BMSC+Niaspan treatment of T1DM-MCAo rats did not increase brain hemorrhage, and significantly decreased BBB leakage and vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal-carotid-artery compared to non-treatment control and BMSC monotherapy animals.

Conclusions

Combination therapy using BMSC with Niaspan decreases BBB leakage and cerebral arteriosclerosis-like changes. These beneficial effects may be attributed to the decreased expression of Angiogenin, MMP9 and ED1.     

Curcumin Alleviates Diabetic Cardiomyopathy in Experimental Diabetic Rats

Objectives

Diabetic cardiomyopathy (DCM), characterized by myocardial structural and functional changes, is an independent cardiomyopathy that develops in diabetic individuals. The present study was sought to investigate the effect of curcumin on modulating DCM and the mechanisms involved.

Methods

An experimental diabetic rat model was induced by low dose of streptozoticin(STZ) combined with high energy intake on rats. Curcumin was orally administrated at a dose of 100 or 200 mg·kg⁻¹·d⁻¹, respectively. Cardiac function was evaluated by serial echocardiography. Myocardial ultrastructure, fibrosis area and apoptosis were assessed by histopathologic analyses. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. Inflammatory factors were detected by ELISA, and interrelated proteins were measured by western blot.

Results

Rats with DCM showed declined systolic myocardial performance associated with myocardial hypertrophy and fibrosis, which were accompanied with metabolism abnormalities, aberrant myocardial enzymes, increased AGEs (advanced glycation end products) accumulation and RAGE (receptor for AGEs) expression, elevated markers of oxidative stress (MDA, SOD, the ratio of NADP⁺/NADPH, Rac1 activity, NADPH oxidase subunits expression of gp91^phox and p47^phox ), raised inflammatory factor (TNF-α and IL-1β), enhanced apoptotic cell death (ratio of bax/bcl-2, caspase-3 activity and TUNEL), diminished Akt and GSK-3β phosphorylation. Remarkably, curcumin attenuated myocardial dysfunction, cardiac fibrosis, AGEs accumulation, oxidative stress, inflammation and apoptosis in the heart of diabetic rats. The inhibited phosphorylation of Akt and GSK-3β was also restored by curcumin treatment.

Conclusions

Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of DCM, and perhaps other cardiovascular disorders, by attenuating fibrosis, oxidative stress, inflammation and cell death. Furthermore, Akt/GSK-3β signaling pathway may be involved in mediating these effects.     

Evaluation of the Preventive Effect of Isoflavone Extract on Bone Loss in Ovariectomized Rats

To examine a potential role for soybean phytoestrogens in postmenopausal bone loss, twenty-four 12-week-old Sprague-Dawley rats were divided randomly into 4 groups and given controlled diets for 16 weeks. The treatment groups were as followed: sham operated, ovariectomized (OVX) control, OVX + isoflavone extract (6.25 g/kg), and OVX + 17β-estradiol (4 mg/kg). OVX treatments reduced femoral and fourth lumbar vertebral bone density and mineral content (p<0.01), decreased uterine weight (p<0.01), accelerated body weight increases (p<0.05), and increased the activities (p<0.01) of both serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP). Supplementation with isoflavone prevented the losses of bone density and mineral content caused by OVX (p<0.01). Although both isoflavone and 17β-estradiol exhibited similar bone-sparing ability on the OVX-induced bone loss, the effect of isoflavone was not the same as that of 17β-estradiol on the serum ALP and TRAP, body weight increase, and uterine weight change. We concluded that dietary supplementation with soybean isoflavone can prevent postmenopausal bone loss via a different mechanism of estrogen in OVX rats.     

Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function.     

Evaluation of Shear Wave Velocity and Human Bone Morphogenetic Protein-7 for the Diagnosis of Diabetic Kidney Disease

Purpose

The aim of this study was to determine the diagnostic values of kidney shear wave velocity (SWV) and bone morphogenetic protein-7 (BMP-7), and their correlation in the diagnosis of early diabetic kidney disease.

Methods

A total of 150 patients with type 2 diabetes mellitus were divided into three equal groups based on the urinary albumin-creatinine ratio (ACR): normal albuminuria (normo- group, ACR < 30 mg/g creatinine, n = 50), microalbuminuria (micro- group, 30 ≤ ACR < 300 mg/g creatinine, n = 50), and macroalbuminuria (macro- group, ACR ≥ 300 mg/g creatinine and estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m², n = 50). Fifty healthy volunteers were recruited to serve as controls (control group). The levels of serum BMP-7 were detected, and virtual touch tissue quantification was used to detect the renal SWV value in all study subjects. Correlations between groups as well as SWV and BMP-7 were analyzed.

Results

Serum BMP-7 and SWV were significantly and progressively decreased and increased, respectively, during the development of renal disease, from the normo- to the micro- and to the macro- groups (all P < 0.01 between each other for BMP-7 and SWV). Moreover, no significant differences between the normo- and control groups were observed for either BMP-7 or SWV (both P > 0.05). In addition, a significant correlation was found between SWV and BMP-7, with a coefficient of -0.569 (P < 0.05).

Conclusion

The determination of SWV together with serum BMP-7 may play an important role in the diagnosis of diabetic kidney disease.     

A Preliminary Approach to the Use of the Isotopic Ratio 13C/12C for the Evaluation of Mineralization in Aquatic Environments

¹²C/¹³C ratio is used as natural tracer for the estimation of the mineralizing activity of pelagic bacteria. Attention is particularly given to the variations of the isotopic ratio of the inorganic carbon produced by the microbial oxidation in comparison with the ratio of the dissolved organic matter.     

Evaluation of the Effects of Favipiravir Combined with Vitamin C on Alveolar Bone in Rats

Journal of Evolutionary Biochemistry and Physiology - Introduction: Favipiravir and Vitamin C (Vit C) were used together in the treatment of the COVID-19 pandemic. However, the effects of...     

Mineralization of Adult Mouse Bone Marrow In Vitro

Abstract. Murine adult bone marrow exhibits mineralizing capacity in vitro as is demonstrated by the new in vitro assay we report here. In less than 2 weeks after the onset of the cultures, mineralization is obtained in more than 80% of the marrow cultures. Moreover, morphological studies reveal that during incubation phenotypic changes related to osteogenic differentiation occur at the extracellular matrix as well within cell populations. Well banded collagen is synthesized. Matrix vesicles and needles of hydroxy-apatite crystals are observed via transmission electron microscopy. Osteoblast-like cells are present with membrane-associated alkaline phosphatase activity. the mineralization is specific for cultured bone marrow and is not observed in cultured spleen fragments as is shown via ⁸⁵Sr uptake, calcein uptake and histomorphology. No inducing agent is added to the tissue culture medium except for 10% fetal calf serum, beta-glycerophosphate (10⁻² M) and ascorbic acid. However, the prerequisite for obtaining mineralization is the three-dimensional structure of the marrow in culture. the in vitro organ culture we developed may provide the opportunity to identify which marrow cells have osteogenic potential and to investigate the mechanisms triggering differentiation towards osteogenesis.     

Paeoniflorin Prevents Diabetic Nephropathy in Rats

The aim of this study was to test the hypothesis that paeoniflorin prevents the progression of diabetic nephropathy by modulating the inflammatory process. Sprague–Dawley rats were divided into 5 groups: nondiabetic control rats; untreated diabetic model (DM) rats; and DM rats treated with 5, 10, or 20 mg/kg paeoniflorin in drinking water once daily. Rats received a single intravenous injection of streptozotocin to induce diabetes; 9 wk after injection, rats began the 8-wk daily paeoniflorin treatment regimen. Compared with that of nonDM controls, the urinary albumin:creatinine ratio was increased significantly in untreated DM rats; this ratio was decreased in DM rats treated with 5, 10, or 20 mg/kg paeoniflorin compared with that of untreated DM rats. In addition, paeoniflorin treatment effectively suppressed glomerular hypertrophy; blood glucose; the expression of transforming growth factor β, type IV collagen, and intercellular adhesion molecule 1; and renal infiltration of macrophages compared with levels in untreated DM rats. Furthermore, renal nuclear factor κB activity was increased in untreated but not paeoniflorin-treated DM rats. In conclusion, our data suggest that the preventive effects of paeoniflorin may be mediated by its antiinflammatory actions.Abbreviations: DM, diabetic model; ECM, extracellular matrix; ICAM1, intercellular adhesion molecule 1; MCP1, monocyte chemoattractant protein 1; NFκB, nuclear factor κB; TGFβ, transforming growth factor βDiabetic nephropathy is the most common cause of endstage renal disease and high mortality in humans. Adequate control of blood glucose may slow the rate of its progression, but it is still difficult to achieve strict glycemic control for diabetic patients in the longer term, due at least in part to the limitations of available therapeutic approaches.³ Recent studies have suggested the emerging role of inflammatory processes in the pathogenesis of diabetic nephropathy in addition to other well-known mechanisms.In human renal disease, transforming growth factor β (TGFβ) may mediate the buildup of tissue extracellular matrix (ECM) proteins.¹⁷ This cytokine reportedly stimulated ECM protein accumulation in diabetic tissues by upregulating the production of ECM proteins or by downregulating the production of ECM-degrading enzymes.²⁶ Renal levels of TGFβ1 increase in both experimental and human diabetes. In addition, TGFβ1 induces the synthesis of ECM components including collagen types I, III, and IV and fibronectin.^2,5Intercellular adhesion molecule 1 (ICAM1) is a key adhesion molecules. In addition, the ICAM1-dependent infiltration of macrophages into the kidney is very important in the pathogenesis of diabetic nephropathy.¹⁸ In addition, the expression of ICAM1 is rapidly induced and maintained for a long time in renal tissues after induction of diabetes in experimental type 1 diabetic rats.^14,20 Macrophage infiltration was blocked by antiICAM1 antibody, confirming that ICAM1 mediates macrophage infiltration into the diabetic kidney.⁶ Furthermore, ICAM1-deficient mice were protected from renal injury after the induction of diabetes, suggesting that the inflammatory process is a critical factor for the development of diabetic nephropathy.²¹Despite the availability of treatments that lower blood glucose and blood pressure, many diabetic patients are still prone to developing kidney failure, which no currently available therapies can reverse.²⁴ Therefore a search is needed for new therapeutic approaches—based on novel mechanisms of action—to the treatment of diabetic nephropathy. Paeoniflorin is a monoterpene glucoside and a component of the total glucoside extract obtained from the root of Paeonia lactiflora.²⁸ This extract was approved for marketing in China in 1998.²³ As a disease-modifying drug, the total glucoside extract of peony has both antiinflammatory and immune-regulatory effects and is used in the treatment of rheumatoid arthritis, hepatitis, systemic lupus erythematosus, and mesenteric hyperplastic nephritis.^8,9,27 The goal of this study is to address whether paeoniflorin might prevent the progression of diabetic nephropathy through the inhibition of the inflammatory processes including TGFβ, type IV collagens, and ICAM1 expression, monocyte chemoattractant protein 1 (MCP1), nuclear factor κB (NFκB) activation, and macrophage infiltration.     

NADPH Oxidase and Superoxide-Producing Associates in Cells of the Spinal Cord and Bone Marrow in Diabetic Rats with Spinal Cord Injury

Neurophysiology - For the first time, a method for isolation and purification of the total fraction of NOX isoforms (NOX1 + NOX2) and the total fraction of O2 – producing stable associates of...