Digital biomarkers for precision diagnosis and monitoring in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder with high prevalence among the elderly, primarily manifested by progressive decline in motor function. The aging global demographic and increased life expectancy have led to a rapid surge in PD cases, imposing a significant societal burden. PD along with other neurodegenerative diseases has garnered increasing attention from the scientific community. In PD, motor symptoms are recognized when approximately 60% of dopaminergic neurons have been damaged. The irreversible feature of PD and benefits of early intervention underscore the importance of disease onset prediction and prompt diagnosis. The advent of digital health technology in recent years has elevated the role of digital biomarkers in precisely and sensitively detecting early PD clinical symptoms, evaluating treatment effectiveness, and guiding clinical medication, focusing especially on motor function, responsiveness and sleep quality assessments. This review examines prevalent digital biomarkers for PD and highlights the latest advancements.

Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk.

INTRODUCTION: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. METHODS: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. RESULTS: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. CONCLUSION: In summary, we consider there to be a substantial correlation between anemia and increased PD risk.

Association between irritable bowel syndrome and Parkinson's disease by Cohort study and Mendelian randomization analysis.

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

Velocity vector imaging of longitudinal mechanical properties of upstream and downstream shoulders and fibrous cap tops of human carotid atherosclerotic plaque.

AIMS: Atherosclerotic plaque rupture is closely related to high regional mechanical stress in the plaque itself. We aimed to explore the longitudinal mechanical properties of upstream and downstream shoulders and fibrous cap tops of human atherosclerotic plaques in vivo by velocity vector imaging (VVI) combined with acoustic densitometry (AD) imaging. METHODS AND RESULTS: We included 135 patients with carotid atherosclerotic plaque. VVI and AD were used to examine 3 regions of carotid plaque along the longitudinal-axis view. A total of 405 regions were classified with low or high AD values by corrected averages image intensity (AIIc%) < or ≥50, respectively. Peak systolic strain, strain rate (SR), and velocity were significantly greater for upstream than downstream shoulders and fibrous cap tops of carotid plaque (P < 0.05 for both). AIIc% was significantly lower for upstream than downstream plaque shoulders (P < 0.05). Peak systolic SR of the plaque regions was negatively correlated with corresponding AIIc% (R(2) = 0.499, P < 0.05). CONCLUSIONS: The longitudinal strain of human carotid atherosclerotic plaques as derived by VVI is associated with its corresponding AD but also in part with the internal position of the strain, with values greater for upstream than downstream shoulders and fibrous cap tops.

Association between inflammatory bowel disease and Parkinson's disease: a prospective cohort study of 468,556 UK biobank participants.

Introduction: Inflammatory Bowel Disease (IBD) and Parkinson's disease (PD) are both chronic, progressive disorders. As such, given the inconclusive results of extensive research on the association between IBD and PD, our study intends to examine this relationship further using the UK Biobank database. Methods: We conducted a prospective cohort study using the Cox proportional hazards model, analyzing data from the UK Biobank to investigate the relationship between IBD and PD, following subjects until PD diagnosis, loss to follow up, death or study termination on 30 June, 2023. Results: The results show that IBD had no effect on the risk of PD (HR: 1.356, 95% CI: 0.941-1.955, p = 0.103), and the effect remained consistent in specific Crohn's disease, ulcerative colitis or unclassified IBD populations. In addition, after sensitivity analysis using propensity matching scores and excluding patients diagnosed with PD 5 or 10 years after baseline, IBD had no effect on the risk of PD. However, in the subgroup analysis, we found that in females (HR: 1.989, 95% CI: 1.032-3.835, p = 0.040), the polygenic risk score was highest (HR: 2.476, 95% CI: 1.401-4.374, p = 0.002), and having ulcerative colitis without hypertension (HR: 2.042, 95% CI: 1.128-3.697, p = 0.018) was associated with an increased risk of PD. Conclusion: In conclusion, over an average follow-up period of 13.93 years, we found no significant association between IBD and PD.

Characteristics and Treatment Strategy of Isolated Calf Deep Venous Thrombosis after Fractures: A Review of Recent Literature.

Isolated calf deep venous thrombosis (ICDVT) includes thrombosis located at the far end of the popliteal vein, such as the anterior tibial vein, posterior tibial vein, fibular vein, and intramuscular vein of the soleus and gastrocnemius. This type of thrombosis has the highest incidence, accounting for approximately half of all deep vein thrombosis (DVT) cases; however, there is no consistent recommendation for ICDVT treatment across countries, and there is also no optimal management strategy. In recent years, increasing evidence has shown that ICDVT can develop into proximal DVT, even causing pulmonary embolism (PE). Therefore, some experts suggest anticoagulant therapy for this type of DVT, while others hold an opposing attitude. Therefore, the treatment strategy for this type of DVT has become a hot and difficult research topic. The purpose of this review is to summarize the characteristics of ICDVT and the effects of different treatment strategies by analyzing recent and important classical works in the literature in an attempt to provide recommendations for the treatment of this most common type of DVT in orthopaedic clinics.

[Protective effects of puerarin on lens epithelial cells in rat diabetic cataract].

OBJECTIVE: The therapeutic effects of general and local applications of puerarin in the treatment of streptozotocin (STZ)-induced rat diabetic model were compared. METHODS: Experimental research. We equally divided normal Sprague-Dawley (SD) rats into a STZ group, a peritoneal injection group, a peribulbar injection group and a control group. STZ, peritoneal injection and peribulbar injection groups were first treated with STZ. Subsequently, the STZ group was injected with normal saline intraperitoneally, while in the later two groups puerarin was injected through peritoneal and peribular routes, respectively. Control group only received peritoneal injection of saline. The morphology of lens epithelial cells (LEC) and their subcellular structure were examined by bright-field microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) 20, 40 and 60 days after the injection. Nitrogen oxide (NO) and nitric oxide synthase (NOS) were measured by biochemistry methods. Finally, inducible nitric oxide synthase (iNOS) protein and mRNA levels were monitored by Western blot and RT-PCR, respectively. Data was processed with two factorial experiment analysis of variance. RESULTS: Twenty to sixty days after the injection, marked or complete lens opacities appeared in the STZ group, whereas only slight opacities appeared in the lens in peritoneal and peribulbar puerarin groups and the lens in the control group remained clear. At the 20th, 40th and 60th day after the injection, optical microscope detected pathological changes of LEC in the STZ group. The cell volume was decreased with a dense nucleus and many bubbles appeared around the equator area. Under TEM, enlargement of cell gap, vacuoles in the cytoplasm, swelling of mitochondria and unclear structure of rough endoplasmic reticulum appeared in the LEC of the STZ group. Part of the nucleus was in karyopyknosis and peripheral nucleus gap was enlargement. Under SEM, normal fiber conjunction structure of the lens disappeared, fibers were swelling, part of fiber membranes were discontinuous, detached, and accumulated in certain areas. Mild lens opacities detected by bright-field microscope were developed in peritoneal and peribulbar puerarin injection groups. Nucleus and fibers in the lens cells of both groups appeared to be normal, with minor swelling of mitochondria, minor enlargement of endoplasmic reticulum and slight increase of intracellular space. NO, NOS and iNOS protein and mRNA of the lens were increased and up-regulated in STZ group. In the other two groups only minor changes were present and the changes were significantly less than that of the STZ group but greater than that in the control group. CONCLUSION: Peritoneal and peribulbar injection of puerarin have similar therapeutic effects in the treatment of rat diabetic cataract.

Full-Endoscopic Approach Forchronic Low Back Pain from Baastrup's Disease: Interspinous Plasty.

The objective was to introduce a new endoscopic technique-interspinous plasty for low back pain from Baastrup's disease; based on clinical manifestations, imaging findings and diagnostic test, to discuss a detailed diagnostic procedure for Baastrup's disease; and to explore the mechanism of interspinous plasty in pain relief. To our knowledge, there is no report about the results of endoscopic lumbar technique for Baastrup's disease. This study described the successful full-endoscopic surgical treatment for Baastrup's disease, providing a brand-new therapeutic method for patients. Clinical manifestations, imaging findings, including X-ray, computed tomography (CT) and magnetic resonance imaging, and a "positive" diagnostic test with local anesthetic were used to confirm Baastrup's disease in the three included patients. The interspinous plasty procedure, which aimed to recover a physiological gap between the adjacent spinous processes, was performed by full-endoscopic resection of marginal osteophytes. The removal of local inflamed tissue and reducing inflammation via intraoperative saline irrigation also lead to pain relief. Clinical outcomes included visual analog scale (VAS) for low back pain and the Oswestry Disability Index (ODI). The distance between the adjacent spinous processes was measured from the preoperative and postoperative CT scan. We calculated and recorded the difference between preoperative and postoperative measurements. Technical procedures and advantages of interspinous plasty are introduced. The three patients showed improvement in terms of the postoperative VAS of low back pain (from 8 to 2, from 7 to 1 and from 8 to 2) and ODI (from 68.9% to 33.3%, from 77.8% to 28.9% and from 71.1% to 28.9%, respectively) at the 12-month follow-up. Compared postoperative ODI index, the ODI index increased from 26.7% to 33.3% and from 24.4% to 28.9% in two of the cases at the 12-month follow-up. At 1 week, CT confirmed an obvious reduction in the marginal osteophytes between the adjacent spinous processes. Compared with those on preoperative CT images, the distance between adjacent spinous processes on postoperative CT was enlarged from 1 to 4 mm, and a repeated CT scan 3 months later reconfirmed little recrudescent osteoproliferation. In selected cases, full-endoscopic surgical treatment for chronic mechanical back pain as part of the phenomena of Baastrup's disease may be beneficial. The operations in this study were performed under local anesthesia, with satisfactory early clinical outcomes and a low incidence of complications or adverse events. This may be a feasible therapeutic method or an alternative option for patients who cannot tolerate general anesthesia surgery.

miR-21 may Act as a Potential Mediator Between Inflammation and Abnormal Bone Formation in Ankylosing Spondylitis Based on TNF-α Concentration-Dependent Manner Through the JAK2/STAT3 Pathway.

OBJECTIVE: To explore the role of microRNA (miR-21) in new bone formation in ankylosing spondylitis (AS) as mediated by different concentration of tumor necrosis factor-α (TNF-α). METHODS: Fibroblasts isolated from the hips of patients with AS were induced to osteogenesis. These cells were then stimulated with varying concentrations of TNF-α. MicroRNA-21 expressions were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and osteogenesis was detected via Alizarin Red S (ARS) staining and measurement of alkaline phosphatase (ALP) activity. Relative expressions of p-STAT3, Nuclear STAT3, cytoplasm STAT3, Runx2, BMP2, osteopontin, osteocalcin, and LC3B in AS fibroblasts were measured after exposure to different concentrations of TNF-α. The STAT3-inhibiting small interfering RNA allowed further exploration on its impact on miR-21 and primary miR-21 expressions. A proteoglycan-induced arthritis (PGIA) Balb/c mouse model was established in order to monitor sacroiliac joint (SIJ) inflammation and subsequent damage through magnetic resonance image. Serum miR-21 and TNF-α expressions were evaluated using RT-PCR and enzyme-linked immunosorbent assay. At week 16, mice models were transfected intravenously with miR-21 overexpressing agomir and miR-21 inhibiting antagomir for 7 successive days. The rate of abnormal bone formation at SIJ was evaluated using microcomputed tomography and hematoxylin and eosin staining at week 24. Western blot analysis enabled quantification of STAT-3, JAK-2, and interleukin (IL)-17A expressions present in the SIJ. RESULTS: The in vitro miR-21 expression and osteogenesis activity were noted to be augmented in the setting of low TNF-α concentrations (0.01-0.1 ng/mL) while they were depressed in settings with higher TNF-α concentrations (1-10 ng/mL). Samples with the most distinct ARS manifestation and ALP activity as well as the highest miR-21 expressions were those who received 0.1 ng/mL of TNF-α. Primary miR-21 was found to be notable raised by Si-STAT3, while the converse effect was seen in mature miR-21 expressions. Intravenous injection of exogenous miR-21 contributed to new bone formation and significantly elevated expressions of STAT3, JAK2, and IL-17 in PGIA mice. CONCLUSIONS: The results revealed that miR-21 may act as a potential mediator between new bone formation and inflammation in AS.

Association between dopamine receptor D2 TaqIA polymorphism and Parkinson disease risk: a meta-analysis.

Although many publications have evaluated the correlation between dopamine receptor D2 (DRD2) TaqIA polymorphism and Parkinson disease (PD), the results remain inconclusive. In order to further address the association between DRD2 TaqIA polymorphism and PD risk, we performed a meta-analysis of all eligible studies from more databases. Related studies were identified from six databases involving PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) through Octorber 2018. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 13 studies including 3558 PD patients and 10186 controls were involved in this meta-analysis. Overall, no significant association was found between DRD2 TaqIA polymorphism and PD risk in the total population. A further subgroup study by ethnicity showed a significant association between DRD2 TaqIA polymorphism and PD in Caucasians (for A1 vs. A2: P=0.02, OR=1.14, 95% CI: 1.02-1.27; for (A1A1 + A1A2) vs. A2A2: P=0.03, OR=1.16, 95% CI: 1.02-1.33). No significant results were observed in Asians. In conclusion, this meta-analysis provides evidence that DRD2 TaqIA polymorphism may contribute to the PD development in Caucasians, and large-scale well-designed studies are required in future to confirm this conclusion.

Middle cerebral artery thrombus susceptibility-weighted imaging mapping predicts prognosis.

BACKGROUND: Susceptibility weighted imaging and mapping (SWIM) of magnetic resonance imaging (MRI) is used to evaluate cerebral arterial thrombosis. The aim of this research was to assess susceptibility, length, and clot burden score (CBS) of thrombus in the middle cerebral artery (MCA) and their relationship with cerebral infarction and early clinical prognosis in patients with acute or subacute cerebral infarction. METHODS: In total, 56 patients with acute or subacute cerebral infarction (with the time from onset to admission less than 72 h) and only unilateral MCA occlusion were included in the current study. All the patients had the corresponding susceptibility vessel sign (SVS) on susceptibility-weighted imaging (SWI). Parameters including susceptibility, length, and CBS of thrombus were obtained from SWI and SWIM. The differences in susceptibility of different portions of the thrombus were compared with each other by one-way ANOVA test. The relationship between susceptibility and stroke onset time was further analyzed by Spearman correlation analysis, in addition to the relationships between susceptibility, length, CBS, diffusion-weighted imaging-Alberta stroke program early CT score (DWI-ASPECTS), and admission and discharge National Institutes of Health Stroke Scale (NIHSS). RESULTS: The susceptibility among different portions and different segments of thrombus showed no statistical difference. The susceptibility and length were weakly yet negatively correlated with DWI-ASPECTS (rs=-0.382, -0.457; P=0.004, 0.000). The susceptibility was weakly yet positively correlated with admission NIHSS and discharged NIHSS (rs=0.403, 0.430; P=0.002, 0.001). CBS was weakly yet positively correlated with DWI-ASPECTS (rs=0.349; P=0.008) and weakly yet negatively correlated with admission and discharged NIHSS (rs=-0.375, -0.335; P=0.004, 0.012). CONCLUSIONS: The susceptibility remained consistent regardless of location, length, and onset time, which indicates that the thrombus composition was similar when detected on SWI less than 72 h from the onset. Susceptibility and CBS may help to predict clinical severity and short-term clinical prognosis to some extent.

The anatomical study of transoral atlantoaxial reduction plate internal fixation.

OBJECTIVE: To study relevant anatomical features of the structures involved in transoral atlanto-axial reduction plate (TARP) internal fixation through transoral approach for treating irreducible atlanto-axial dislocation and providing anatomical basis for the clinical application of TARP. METHODS: Ten fresh craniocervical specimens were microsurgically dissected layer by layer through transoral approach. The stratification of the posterior pharyngeal wall, the course of the vertebral artery, anatomical relationships of the adjacent structures of the atlas and axis, and the closely relevant anatomical parameters for TARP internal fixation were measured. RESULTS: The posterior pharyngeal wall consisted of two layers and two interspaces: the mucosa, prevertebral fascia, retropharyngeal space, and prevertebral space. The range from the anterior edge of the foramen magnum to C(3) could be exposed by this approach. The thickness of the posterior pharyngeal wall was (3.6+/-0.3) mm (ranging 2.9-4.3 mm) at the anterior tubercle of C1, (6.1+/-0.4) mm (ranging 5.2-7.1 mm) at the lateral mass of C(1) and (5.5+/-0.4) mm (ranging 4.3-6.5 mm) at the central part of C(2), respectively. The distance from the incisor tooth to the anterior tubercle of C(1), C(1) screw entry point, and C(2)screw entry point was (82.5+/-7.8) mm (ranging 71.4-96.2 mm), (90.1+/-3.8) mm (ranging 82.2-96.3 mm), and (89.0+/-4.1) mm (ranging 81.3-95.3 mm), respectively. The distance between the vertebral artery at the atlas and the midline was (25.2+/- 2.3) mm (ranging 20.4-29.7 mm) and that between the vertebral artery at the axis and the midline was (18.4+/- 2.6) mm (ranging 13.1-23.0 mm). The allowed width of the atlas and axis for exposure was (39.4+/-2.2) mm (ranging 36.2-42.7 mm) and (39.0+/-2.1) mm (ranging 35.8-42.3 mm), respectively. The distance (a) between the two atlas screw insertion points (center of anterior aspect of C(1) lateral mass) was (31.4+/-3.3) mm (ranging 25.4-36.6 mm). The vertical distance (b) between the line connecting the two C(1) screw entry points and that connecting the two C(2) screw entry points (at the central part of the vertebrae, namely 3-4 mm lateral to the midline of C(2) vertebrae) was (21.3+/-2.7) mm (ranging 19.4-24.3 mm), with an a/b ratio of 1.3-1.5. The screws of TARP had a lateral tilt of 12.2 degrees+/-0.4 degrees(ranging 10.2 degrees-14.6 degrees) at C(1) and a medial tilt of 7.3 degrees+/-0.3 degrees (ranging 5.1 degrees-9.4 degrees) at C(2) relative to the coronal plane. CONCLUSIONS: An atlanto-axial surgery through transoral approach is safe and feasible. This approach is suitable for an anterior TARP internal fixation, and the design of the internal fixation system should be based on the above anatomical data.

[Studies of increasing the forward-mutation rate of UV irradiated Streptomyces sp. AP 19-1, an antibiotics producing strain].

UV irradiated spores of Streptomyces sp. AP 19-1 strain that can produce antibiotics were incubated at 27 degrees C, and 33 degrees C which is close to inhibiting growth temperature, respectively. The results showed that there were much more forward mutants, whose level of producing antibiotics is higher than that of original strain, among the offspring of UV irradiated spores grown at 33 degrees C, compared to that grown at 27 degrees C. The percentage of the forward mutants was 25.8 % at 27 degrees C and 58.1% at 33 degrees C. The progeny strains and the original strain were tested by RAPD using total DNA with 17 primers. It was demonstrated that more variations occurred in the chromosomal DNA of the progeny strains grown at 33 degrees C than in that at 27 degrees C. This method facilitates increasing the efficiency of induced mutagenesis in breeding and provides a new way to study the mechanisms of mutation formation in UV irradiated Streptomyces sp. cells.

[Surgical anatomy of transoral atlantoaxial reduction plate internal fixation].

OBJECTIVE: To provide anatomical data for transoral atlantoaxial reduction plate internal fixation. METHOD: Microsurgical dissecting was performed on 10 fresh craniocervical specimens layer by layer according to transoral approach. Stratification of posterior pharyngeal wall, course of vertebral artery, adjacent relationships of atlas and axis and correlative anatomical parameters of internal fixation to atlantoaxial joint were observed. RESULT: (1) Posterior pharyngeal wall consisted of 2 layers and 2 interspace: mucosa, anterior fascia of vertebrae, posterior interspace of pharynx and anterior interspace of vertebrae. (2) The range from anterior rim of foramen magnum to C3 could be exposed by this approach. (3) The distance between the vertebral artery at atlas and midline was (25.2 +/- 2.3) mm and that between the vertebral artery at axis and midline was (18.4 +/- 2.6) mm. (4) The width of atlas and that of axis could be exposed respectively to (39.4 +/- 2.2) mm and (39.0 +/- 2.1) mm. The distance (a) between 2 atlas screw inserting points (center of anterior aspect of C-1 lateral mass) was (31.4 +/- 3.3) mm. The vertical distance (b) between the connecting line of 2 atlas screw inserting points and that of 2 axis screw inserting points (at the central part of the vertebrae which was 3 - 4 mm lateral to the midline of C-2 vertebrae) was (18.7 +/- 2.7) mm. The odds of a/b was 1.5 approximately 1.7. CONCLUSIONS: Anterior atlantoaxial plate internal fixation through transoral approach is suitable and feasible. The design of the plate should be based on the above data.

Designing a binding interface for control of cancer cell adhesion via 3D topography and metabolic oligosaccharide engineering.

This study combines metabolic oligosaccharide engineering (MOE), a technology where the glycocalyx of living cells is endowed with chemical features not normally found in sugars, with custom-designed three-dimensional biomaterial substrates to enhance the adhesion of cancer cells and control their morphology and gene expression. Specifically, Ac(5)ManNTGc, a thiol-bearing analog of N-acetyl-d-mannosamine (ManNAc) was used to introduce thiolated sialic acids into the glycocalyx of human Jurkat T-lymphoma derived cells. In parallel 2D films and 3D electrospun nanofibrous scaffolds were prepared from polyethersulfone (PES) and (as controls) left unmodified or aminated. Alternately, the materials were malemided or gold-coated to provide bio-orthogonal binding partners for the thiol groups newly expressed on the cell surface. Cell attachment was modulated by both the topography of the substrate surface and by the chemical compatibility of the binding interface between the cell and the substrate; a substantial increase in binding for normally non-adhesive Jurkat line for 3D scaffold compared to 2D surfaces with an added degree of adhesion resulting from chemoselective binding to malemidede-derivatived or gold-coated surfaces. In addition, the morphology of the cells attached to the 3D scaffolds via MOE-mediated adhesion was dramatically altered and the expression of genes involved in cell adhesion changed in a time-dependent manner. This study showed that cell adhesion could be enhanced, gene expression modulated, and cell fate controlled by introducing the 3D topograhical cues into the growth substrate and by creating a glycoengineered binding interface where the chemistry of both the cell surface and biomaterials scaffold was controlled to facilitate a new mode of carbohydrate-mediated adhesion.

Inducible nitric oxide synthase and Fas/FasL with C3 expression of mouse retinal pigment epithelial cells in response to stimulation by peroxynitrite and antagonism of puerarin.

BACKGROUND: Retinal pigment epithelial (RPE) cell is a monolayer of multifunctional cells between the retina and the choroid. Peroxynitrite (ONOO(-)) is known to induce toxicity on RPE cells. This study aimed to evaluate ONOO(-) induced expression of inducible nitric oxide synthase (iNOS) and complement 3 (C3) via Fas/FasL pathway in RPE cells and the values of puerarin as a therapeutic target for inhibiting the apoptosis of RPE cells. METHODS: RPE cells were obtained from eyes of C57BL/6 mice. RPE cells were divided into control, ONOO(-) and puerarin groups. Control group was treated with saline, ONOO(-) group was treated with ONOO(-), and puerarin group was treated with puerarin after added with ONOO(-). All changes were observered at 6, 12 and 24 hours after treatment. Western blotting analysis was used to determine the expression of nitrotyrosine (NT, the foot print of ONOO(-)) and C3; flow cytometry was used to determine the apoptosis of RPE cells. Immunohistochemistry and Western blotting were used to determine Fas/FasL signal transduction. Gene array analysis, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to determine the expression of iNOS mRNA and iNOS protein in RPE cells. RESULTS: There were minor expression of NT, C3, Fas/FasL and iNOS mRNA in control group, and strong expression of NT and C3 in ONOO(-) group, while in puerarin group weak expressions of NT and C3 were detected as time passed by (P < 0.001). Apoptosis of RPE cells occured and reached a higher level at 6 and 24 hours after addition of ONOO(-) respectively in ONOO(-) group, but delayed apoptosis in puerarin group (P < 0.05). Compared to control group, the expression of Fas/FasL was up-regulated in ONOO(-) group, but was down-regulated in puerarin group (P < 0.001). Similarly, the expressions of iNOS mRNA and iNOS protein in ONOO(-)group were up-regulated in ONOO(-) group, but down-regulated in puerarin group (P < 0.001). CONCLUSIONS: ONOO(-) expresseion in RPE cells may constitute the new way of oxidant stress. Fas/FasL signal transduction pathway and C3 may affect and reinforce apoptosis mediated by ONOO(-). Puerarin could reverse ONOO(-) damage on RPE cells. The antagonizing mechanism of puerarin may be related to its inhibitory to the expression of iNOS mRNA, and therefore decrease ONOO(-) formation as well as directly antagonize the effect of ONOO(-). Furthermore, puerarin may be an useful therapeutic agent against apoptosis of RPE cells.

Toxicity of endogenous peroxynitrite and effects of puerarin on transplanted retinal pigment epithelial sheets in the subretinal space in mice.

AIM: To evaluate the toxicity of endogeneous peroxynitrite on transplanted retinal pigment epithelial (RPE) sheets and the effect of puerarin on their survival in the C57BL/6 mice after RPE sheets have been transplanted into SD rats' subretinal space . METHODS: C57BL/6 mice eyes were used to culture RPE cells. Ninety-six SD rats were involved in the experiment. They were divided into control (block control), streptozotocin (STZ, negative control), untransplanted RPE (positive control) and transplanted RPE groups respectively. Diabetes was induced in SD rats by intra-peritoneal STZ injection in the latter three groups. Saline was injected into the subretinal space of 24 SD rats in the untransplanted RPE group and primary RPE sheets were injected into the subretinal space of 24 SD rats in the transplanted RPE group. Puerarin (45mg/kg) was administrated into both untransplanted RPE and transplanted RPE groups of diabetic rats through intra-peritoneal injection route after RPE sheets transplantation. At 20, 40, 60 days after surgery, Western blotting analysis, DNA ladder and RT-PCR were used for determining the differences in expression of nitrotyrosine (NT, the foot print of peroxynitrite ), apoptosis and iNOS mRNA in the control, STZ, untransplanted RPE and transplanted RPE groups respectively. HE staining was used for determining the RPE survival in the subretinal space of the transplanted RPE group. RESULTS: Apoptosis and expression of NT and iNOS mRNA were observed in STZ, untransplanted RPE and transplanted RPE groups, but were delayed in untransplanted RPE and transplanted RPE groups in a time-dependent manner compared with control and STZ groups (P<0.01). There were no differences between the two groups (P>0.01). NT, DNA ladder, iNOS mRNA were down-regulated, which were associated with the decrease of expression of peroxynitrite. Numerous pigmented cells emerged and increased in number in the subretinal space during the 60-day observation period after transplantation. On day 20, heavily pigmented cells were visible at the transplant site; On day 40, monolayer and multilayered transplant was visible in the subretinal space; On day 60, heavily pigmented monolayer and multilayered transplants with round apical profile were present along Bruch's membrane. CONCLUSION: Puerarin increased the 60-day survival of C57BL/6 mice RPE xenografts in the SD rats' subretinal space, which may be related to its direct inhibition of apoptosis of RPE cells and antagnism of damage of peroxynitrite to RPE cells.

Effect of puerarin on retinal pigment epithelial cells apoptosis induced partly by peroxynitrite via Fas/FasL pathway.

AIM: To evaluate the peroxynitrite (ONOO(-)) of puerarin on retinal pigment epithelial (RPE) cells apoptosis induced partly by peroxynitrite via Fas/FasL. METHODS: RPE cells from C57BL/6 mice eyes were cultured. Diabetes was induced in Sprague-Dawley (SD) rats by streptozotocin (STZ) intraperitoneal injection. Puerarin was administrated to cultured RPE cells and diabetic rats. Western blotting analysis, DNA ladder, RT-PCR, immunohistochemistry were used for determining the expression of nitrotyrosine (NT, the foot print of ONOO(-)), complement 3 (C3); apoptosis and inducible nitric oxide synthase (iNOS) mRNA as well as Fas/FasL signal transduction in RPE cells. RESULTS: Both RPE cells in ONOO(-) and puerarin group developed apoptosis and expressed NT, C3, iNOS mRNA and Fas/FasL. But latter delayed the all changes in a time-dependent manner compared with control and STZ group (P<0.001). iNOS, C3 and Fas/FasL were up-regulated and associated with an increase of expression of ONOO(-)in vivo and in vitro. CONCLUSION: Puerarin decreases RPE cells apoptosis partly induced by ONOO(-) for diabetic retinopathy.

Effect of atorvastatin versus rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia.

PURPOSE: To compare the short-term effect of treatment with atorvastatin and rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. METHODS: Sixty-nine patients with hypercholesterolemia were randomly assigned to receive 10 mg/day of atorvastatin or rosuvastatin for 12 weeks. Inflammatory biomarkers, including highsensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, matrix metalloproteinase-9 (MMP-9), and endothelin (ET-1), plasminogen activator inhibitor type 1 (PAI-1) and plasma tissue plasminogen activator (tPA), adiponectin, and lipid profiles were measured before and after statin therapy. RESULTS: Atorvastatin and rosuvastatin both lowered levels of hs-CRP, MMP-9, PAI-1, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) from baseline values, with rosuvastatin lowering TC and LDL-C to a greater extent than atorvastatin (P < 0.05). Adiponectin level increase was 15% higher than that at baseline with atorvastatin (P > 0.05) but 67% higher with rosuvastatin (P < 0.05). CONCLUSIONS: Therapy with both statins not only significantly improved lipid profiles but also decreased levels of vascular biomarkers hs-CRP, MMP-9, and PAI-1; however, only rosuvastatin increased serum adiponectin levels significantly in patients with hypercholesterolemia, which could imply a beneficial effect in coronary artery disease.