Investigation of the temperature gradient control in the printing space for the material extrusion of medical biodegradable hydrogel.

Material extrusion has shown promise in the fabrication of biocompatible scaffolds for tissue engineering using medical biodegradable hydrogel materials. However, the uncontrollable shape of prepared 3D architecture decelerates the development of large-size complex hydrogel models for the fabrication of human-scale tissue or organs. A primary cause of the collapse as well as shrinkage of prepared architectures is the uncontrollable ambient temperature distribution during the extruding process for hydrogel materials. Therefore, there is a need to accurately control the temperature gradient in the printing space during the material extrusion. The study proposed a novel temperature-controlled substrate configuration with a multilayered enclosure, by which the temperature gradient in the printing space can be regulated by varying the height as well as the internal diameter of the enclosure. Subsequently, a finite element simulation model, as well as a self-developed temperature measuring device, was established to numerically and experimentally investigate the temperature distribution in the printing space. Furthermore, printing trials were implemented on the novel substrate. The collapse of 3D architectures was successfully avoided, and the height of scaffolds was improved obviously from 2.21 mm to 13.24 mm.

Label-free detection of vitamin B by two-step enhanced Raman technique using dynamic borohydride-reduced silver nanoparticles.

A creatively designed novel two-step enhancement technique is presented in which B vitamin molecules are dynamically adsorbed onto the surface of silver nanoparticles by sodium borohydride, followed by local plasmon resonance in the presence of cations (calcium ions), ultimately achieving synergistic chemical and physical enhancement on the same molecule and constructing a "surface hot spots" two-step enhancement platform for vitamin detection. The Raman signal of the promoted vitamin molecule is enhanced by nine orders of magnitude. In a subsequent study it was observed that the vitamin B2 molecules were in a near-vertical image on the surface of the silver nanoparticles, which may also contribute to the Raman signal enhancement. Combined with deep learning techniques, the method has been successfully applied to the detection of B vitamins in body fluids. As an accurate, rapid, reproducible, non-invasive, and versatile assay platform, it holds great promise for the intelligent identification of trace B molecules in food, pharmaceuticals, and the human body.

Computational investigation of a 3D-printed skin substitute with orthotropy in mechanical property.

As a promising treatment for third-degree burns, grafting with bioengineering skin substitutes shows a capability to overcome the deficiency of donor skin. Similar mechanical properties with human skin are required for employed skin substitutes to avoid secondary damage to patients. Given the representativeness of orthotropy in mechanical properties, there is a need for developing orthotropic skin substitutes. This paper presents computational investigation as well as structural design for the fabrication of orthotropic skin substitutes. A finite element method (FEM) based mechanics simulation model for analyzing the stress field in the skin substitute was developed, by which the stress distribution in mimetic structures of the epidermis and dermis can be acquired. Moreover, the equation of Young's modulus was deduced based on the simulation result, which expressed the mechanical property of designed skin substitutes. Furthermore, several structures of skin substitutes were proposed and their calculated Young's modulus ranged from 21.87 kPa to 213.32 kPa, which was similar to the human skin. Ultimately, uniaxial tensile tests were performed for three types of 3D-printed orthotropic skin substitutes, which validates the feasibility to regulate Young's modulus by regulating the structure of fabricated skin substitutes.

Association of LDL-C/HDL-C Ratio With Stroke Outcomes Within 1 Year After Onset: A Hospital-Based Follow-Up Study.

Stroke remains a leading cause of death and disability. The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C ratio) ratio has been confirmed to be a predictor of stroke. However, few studies have assessed the prognostic impact of the LDL-C/HDL-C ratio for stroke patients. We aimed to investigate the relationship between the LDL-C/HDL-C ratio and the prognosis following stroke in Chinese patients. A total of 3,410 patients who had experienced their first ischemic stroke was recruited to this study within 72 h of stroke onset. The patients were followed for at least 12 months. A multivariate regression analysis was used to assess the association between the LDL-C/HDL-C ratio and prognosis following stroke. We considered the LDL-C/HDL-C ratio as a continuous variable and stratified patients according to the LDL-C/HDL-C ratio quartile. A higher LDL-C/HDL-C ratio was associated with lower rates of death, recurrence, and moderate disability (defined as a modified Rankin scale score >2) at 3 months. Using group 1 as the reference group, the relative risk (RRs) at 3 months for death were 0.45 (95% confidence interval [CI]: 0.27, 0.77) for group 2, 0.58 (95% CI: 0.34, 0.98) for group 3, and 0.97 (95% CI: 0.60, 1.56) for group 4; for recurrence, the RRs were 0.75 (95% CI: 0.56, 0.99) for group 2, 0.65 (95% CI: 0.48, 0.89) for group 3, and 0.55 (95% CI: 0.39, 0.78) for group 4; and for moderate disability, the RRs were 0.74 (95% CI: 0.55, 0.99) for group 2, 0.65 (95% CI: 0.47, 0.89) for group 3, and 0.55 (95% CI: 0.39, 0.77) for group 4. At 12 months, patients in group 2 were the most protected against ischemic stroke death (RR: 0.57; 95% CI: 0.34, 0.95). However, there were no associations between the LDL-C/HDL-C ratio and stroke recurrence or moderate disability. A higher LDL-C/HDL-C ratio was found to protect against death, recurrence, and moderate disability at 3 months. However, there was no significant association between the LDL-C/HDL-C ratio and stroke recurrence or moderate disability at 12 months. These results nonetheless suggest that a higher LDL-C/HDL-C ratio was associated with short-term stroke prognosis.

Distribution characteristics of sweat gland nerve fibres in normal humans identified by acetylcholinesterase histochemical staining.

OBJECTIVE: To quantitatively analyze distribution characteristics of sweat gland nerve fibres (SGNF) in normal Chinese individuals for obtaining a reference for early diagnosis of peripheral neuropathy. PATIENTS AND METHODS: Skin biopsy samples were collected from 192 normal Chinese individuals and divided into six, four and two groups according to anatomic sites, age and gender, respectively. SGNF morphology was observed and SGNF density (SGNFD) was determined. RESULTS: There was a significant difference in SGNFD among different anatomic sites, age and gender. A degressive tendency was observed from proximal to distal anatomic sites. SGNFD was the lowest in subjects in the 21-40-year-old age group, but was the highest in subjects in the >61-year-old age group. Overall, SGNFD fluctuated with age. SGNFD in males was significantly higher than that in females. CONCLUSIONS: Distribution characteristics of SGNF in normal individuals may serve as a reference for early diagnosis of nerve fibre damage.

Role of gold nanoparticle from Cinnamomum verum against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mice model.

Parkinson's disease (PD) is a general neurodegenerative disorder which largely has an effect on the society of the aged populations. PD is distinguishedwith loss of dopaminergic (DA) neurons in the substantia nigra. The exceptional properties of gold nanoparticles (AuNPs) have fascinated great attention in biomedical applications. In this present study, we explored theprospective beneficial effects of AuNPs synthesized from Cinnamomum verum on PD. PD rat models were established through MPTP injection treatment and AuNPs was administered. Administration of AuNPs reduces effect of MPTP-induced oxidative stress and motor abnormalities observed in PD rats. In addition ELISA analysis demonstrated that AuNPs treatment significantly attenuates Tumor Necrosis Factor-α (TNF-α), Interleukin-1ß (IL-1ß) and Interleukin-6 (IL-6) expression levels. Consequently, we investigated TLR/NF-κB pathway to examine the function of AuNPs on MPTP- induced PD rats. We found that AuNPs suppressed the alterations in the pathway of TLR/NF-κB associated molecules in MPTP stimulated PD rats. Hence, our results suggest that AuNPs attenuates MPTP introduced motor disorders, oxidative stress, activated inflammatory cytokines and activated TLR/NF-κB signaling in PD rats. In conclusion, AuNPs ease PD symptoms by the inhibition of TLR/NF-κB signaling pathway and recommend promise approach in the treatment of neurodegenerative diseases such as PD.

Neuroprotective effect of biosynthesised gold nanoparticles synthesised from root extract of Paeonia moutan against Parkinson disease - In vitro &In vivo model.

Parkinson disease is one of the most common neurological movement disorders affecting geriatric population. Biosynthesized gold nanoparticles are the ideal alternatives spotlighted by many researchers to treat various diseases. In the present study we synthesized gold nanoparticles using the root extract of Paeonia mountan, woody trees which are used in traditional Chinese medicine to be prescribed for diverse diseases. The synthesis of gold nanoparticles was confirmed with UV-Vis spectroscopic analysis and characterized using FTIR, HR-TEM, EDAX and XRD analysis. The cytotoxicity property of synthesized gold nanoparticles was assessed using MTT assay in the murine microglial BV2 cells. The neuroprotective effect of synthesized gold nanoparticles in inflammatory agent lipopolysaccharides triggered murine microglial BV2 cells was evaluated using nitric oxide, prostaglandin E2 and inflammatory cytokines assays such as IL-6&IL-1ß. Further to confirm in vivo effect of synthesized nanoparticles, the nanoparticles were treated to Parkinson induced C57BL/6 mice. Behavioral, biochemical and molecular analysis were performed to estimate the potency of synthesized gold nanoparticles against the Parkinson induction in mice model. Our characterization results prove the gold nanoparticles synthesized using Paeonia mountan fulfills the requirement of ideal nanodrug and it potentially inhibited the inflammation in in vitro murine microglial BV2. The results of in vivo experiments authentically confirm gold nanoparticles synthesized using Paeonia mountan alleviates the neuroinflammation and improves the motor coordination in Parkinson induced mice.

Onjisaponin B (OB) is Neuroprotective During Cognitive Loss Through Immune-mediated and SIRT1 Pathways.

BACKGROUND: The purpose of the present study was to investigate the effects of Onjisaponin B (OB) in lipopolysaccharide (LPS)-induced cognitive deficits. METHODS: The rats were divided into four groups: sham group, LPS group (the model group), LPS + OB (1 mg/kg) group and LPS + OB (2 mg/kg) group. OB was treated three days before surgery and thereafter continuously for 7 days. Three days later, rats were intracerebroventricularly injected with LPS. The levels of inflammatory cytokines and the capability of free radical scavenging in serum and hippocampus were determined after the LPS challenge. PC12 cells were divided into control group, LPS group (the model group), LPS + OB (10 µM) group, LPS + OB (20 µM) group, LPS + OB (40 µM) group, LPS + OB (2 mg/kg) + nicotinamide group. The cell viability was measured by MTT assay. The protein expressions of Sirt1, p-AMPK, AMPK, Nrf-2, HO-1, Bcl-2, Bax, caspase-9, caspase-3, p-IκBα, IκBα, p-NF-κBp65 and NF-κBp65 were detected by western blot analysis. RESULTS: As a result, OB administration effectively relived the cognitive impairment, reduced the contents of IL-1ß, IL-6, TNF-α, MDA and restored SOD activities of SOD in serum and hippocampus of LPS-induced rats. Furthermore, OB treatment improved cell viability, ameliorated the alterations of IL-1ß, IL-6, TNF-α, MDA and SOD in the supernatant of LPS-induced PC12 cells. Of note, the expressions of Sirt1, Nrf-2, HO-1, Bcl-2 and p-AMPK were downregulated, while Bax, caspase-9, caspase-3 and the phosphorylations of IκBα and NF-κBp65 in the LPS-stimulated hippocampus and PC12 cells were increased attributed to the LPS stimulation. Nevertheless, the conditions were significantly attenuated by OB treatment. In the LPS-induced PC12 cell, nicotinamide, a SIRT1 inhibitor, abrogated the beneficial effects of OB, as indicated by the antioxidant, anti-inflammatory and anti-apoptosis signaling. CONCLUSION: Based on the above evidence, our results demonstrated that OB was a potential therapeutic candidate for LPS-induced cognitive deficits.

Quantitative and morphological study of intraepidermal nerve fibre in healthy individuals.

The study was aimed to observe the morphology of intraepidermal nerve fibre (IENF) and to explore the relationships between intraepidermal nerve fibre density (IENFD) and anatomic sites, age, genders and races. Intraepidermal nerve fibre was observed using immunohistochemistry. The relationships between IENFD and anatomic sites, ages, genders and races were analysed by quantitative analysis of IENFD. Five patterns of the IENFs were observed according to the morphological classification. A significant difference was observed in IENFD between different anatomic sites (P < 0.05). A linear negative correlation was observed between IENFD and age (r = - 0.2931, P < 0.01). No significant difference was found between IENFD and genders. Intraepidermal nerve fibre density at distal leg of Chinese (395.54 ± 166.92) was higher than that of Finnish (114.62 ± 32.32, P < 0.01). Skin biopsy may be an effective tool in quantitation of IENFD in healthy individuals. Intraepidermal nerve fibre density is independent of genders, and closely associated with anatomic sites, races and ages.

Deficiency of Trim27 protects dopaminergic neurons from apoptosis in the neurotoxin model of Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative movement disorder, characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The MPTP/MPP+ model is often used to investigate the signaling mechanisms of dopamine (DA) degeneration, both in vivo and in vitro. The identification of specific genetic and environmental factors responsible for PD has bolstered evidence for a shared pathway of neuronal death -apoptosis. Trim27 is reported to promote apoptosis. However, little evidence exists to indicate a linkage between Trim27 and PD. In this study, we found that compared to healthy individuals, Trim27 was significantly upregulated in patients with PD. We further showed that Trim27 expression was dramatically induced in PC12 cells and in the SNpc of the PD mouse model. RNAi-mediated knockdown of Trim27 in PC12 cells showed obvious suppression of apoptosis. There are reduced dopaminergic neuron loss and lower apoptotic protein expression levels in MPTP-treated Trim27-/- mice, compared with MPTP-treated WT mice. These data demonstrated that Trim27 deficiency decreases apoptosis and protects dopaminergic neurons in the neurotoxin model of PD, suggesting that Trim27 may be an effective potential target during the treatment of PD.

Intraepidermal nerve fiber density of healthy human.

OBJECTIVES: To analyze intraepidermal nerve fiber density (IEFND) by skin biopsy, evaluate the effect of age, anatomical sites, and ethnic origin on IEFND and develop a reference range of IENFD at the distal leg of healthy human. METHODS: Seventy skin biopsy specimens from surgical procedures involving 70 patients were analyzed. Specimens were fixed routinely in formalin and thereafter embedded in paraffin. Nerve fibers of 10-µm-thick sections were observed using immunoperoxidase staining with panaxonal antibody protein gene product 9·5 (PGP 9·5). The morphology of intraepidermal nerve fibers (IENFs) and the IENFD was determined using light microscope. The statistical analysis was performed with SPSS 16·0 software. RESULTS: No significant correlation was observed between IENFD and age (Pwrist  =  0·830, Pdistal leg  =  0·478). The significant correlation was observed between IENFD and anatomic site (P  =  0·001), the IENFD of upper arm and proximal thigh were significantly higher than that of wrist and distal leg. The reference range for IENFD of distal leg in normal Chinese humans was 40·55 fibers/mm(2). The IEFND of Chinese healthy human was significantly lower than that of Finnish (62·87 ± 15·25 vs 114·617 ± 32·322 fibers/mm(2), P < 0·05). DISCUSSION: Skin biopsy may be a useful tool in sensory neuropathies. IENFD is independent of age, but varies in different parts of the body. The proximal sites have a higher IENFD, but no significant difference is found between the wrist and distal leg.