SIRT4 promotes neuronal apoptosis in models of Alzheimer's disease via the STAT2-SIRT4-mTOR pathway.

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study used APP/PS1 mice as an animal model of AD and amyloid-ß (Aß)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aß deposition in mice and apoptosis, respectively. Protein expression was assessed by Western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of Sirt4. Subsequently, the binding of transcription factors to Sirt4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aß-treated HT-22 cells compared with their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aß deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD.NEW & NOTEWORTHY The study reveals that in Alzheimer's disease models, SIRT4 expression increases, contributing to neuronal apoptosis and amyloid-ß deposition. Reducing SIRT4 lessens apoptosis and amyloid-ß accumulation, improving memory in mice. This process involves the mTOR pathway, regulated by STAT2 transcription factor. These findings suggest targeting the STAT2-SIRT4-mTOR axis as a potential Alzheimer's treatment strategy.

Enhanced Outcomes in Femoral Subtrochanteric Fractures Using Long INTERTAN Nails with Titanium Cable Cerclage: A Retrospective Analysis.

BACKGROUND The evidence on use of supplementary titanium cable cerclage (TCC) in treating femoral subtrochanteric fractures (FSF) remains scarce. Therefore, this study aimed to investigate the potential therapeutic effects for FSF patients using TCC. MATERIAL AND METHODS A retrospective study of 68 FSF patients treated by a long intramedullary (IM) nailing with (Observation group, n=41) or without (Control group, n=27) TCC was conducted from January 2020 to December 2021. The primary outcome measure was time to postoperative full weight-bearing. Secondary outcome measures were operation time, intraoperative blood loss, number of blood transfusions needed, varus angle loss, excellent and good rate of fracture reduction, Harris score, and survival rate. RESULTS Patients were followed up for 13 to 36 months. The excellent and good rate of fracture reduction was 100% in the Observation group versus 92.6% in the Control group (P=0.013), and the varus angle loss and time to postoperative full weight-bearing in the Observation group were significantly less than in the Control group (P<0.05). The intraoperative blood loss in the Observation group was significantly higher than in the Control group (P<0.001). No differences were noted between groups for Harris scores and survival rates at last follow-up. CONCLUSIONS TCC fixation combined with IM nailing can improve the excellent and good rate of fracture reduction and reduce varus angle loss, as well as shorten the time to full weight-bearing and promote early functional exercise, which offers an effective treatment option for FSF patients who have failed closed reduction.

Clinical application of instant 3D printed cast versus polymer orthosis in the treatment of colles fracture: a randomized controlled trial.

BACKGROUND: The shortcomings of plaster in water resistance, air permeability, skin comfort, fixed stability and weight of wearing are still to be solved. 3D printed cast can overcome the above shortcomings. At present, there is a relative lack of data on the clinical application of 3D printed cast, probably due to its complexity, relatively long operating time, and high price. We aimed to compare and evaluate the short-term effectiveness, safety and advantages of 3D printed wrist cast versus polymer orthosis in the treatment of Colles fracture. METHODS: Forty patients with Colles fracture in our hospital from June to December 2022 were selected and divided into an observation group (20 patients, treated with instant 3D printed cast) and a control group (20 cases, treated with polymer orthosis). Both groups treated with manual reduction and external fixation. The visual analogue scale (VAS), immobilization effectiveness and satisfaction scores, Disability of the Arm, Shoulder and Hand (DASH) score, complications and imaging data were collected and compared before immobilization and at 2, 6 and 12 weeks after the fracture. RESULTS: VAS at 2 weeks after the fracture was significantly lower in the observation group than in the control group ( P < 0.05). The immobilization effectiveness and satisfaction scores at 6 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). The DASH scores at 2 and 6 weeks after the fracture were significantly lower in the observation group than in the control group (all P < 0.05). There wasn't rupture of the printed cast or orthosis in both groups. There were 2 cases of skin irritation in the control group, and no skin irritation occurred in the observation group. The palmar tilt angle and ulnar inclination angle at 2 weeks and 12 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). CONCLUSIONS: Both instant 3D printed cast and polymer orthosis are effective in the treatment of Colles fracture. But instant 3D printed cast is better than polymer orthosis in areas of good clinical and imaging performance, and high patient satisfaction and comfort.

Research on the spatiotemporal evolution and influencing factors of urbanization and carbon emission efficiency coupling coordination: From the perspective of global countries.

Strategic coordination between urbanization and carbon emission efficiency (CEE) is vital for promoting low-carbon urbanization and sustainable urban planning. In order to assess the coupled coordination degree (CCD) of urbanization and CEE and investigate the factors influencing the CCD, this research employs the Super slacks-based measure (SBM) model, the coupled coordination degree model (CCDM), and the Tobit model. Four key findings emerge from the analysis of the temporal and spatial evolution traits of the CCD based on data from 106 nations worldwide between 2005 and 2020. (1) The global CEE shows a significant downward trend, and the spatial disparity is unambiguous. high CEE countries hang in the north and west of Europe, while those in Asia, Africa and the east of Europe have lower CEE. (2) The combined urbanization level and demographic, economic and social urbanization are all on an upward trend. Singapore has the greatest degree of urbanization overall globally. (3) The CCD of urbanization and CEE shows a fluctuating upward trend, with particularly strong changes in 2018-2020. 2017 and 2018 are the years with better global coupling coordination status. During the study period, the CCD results of countries are mostly uncoordinated and low coordination, and the CCD of the United States, China, India and Japan is in the front. (4) The effect of urban electrification rate on the CCD is positive; the effect of foreign trade and net inflow of foreign direct investment is negative; while energy structure and industrial structure have no significant effect. A number of policy proposals are put forth in light of the outcomes of the research to enhance the coordination.

Predicting haemorrhagic transformation through serum biochemical indices for patients after endovascular treatment: a retrospective study.

INTRODUCTION: The aim of this study was to determine the serum biochemical markers that can predict the risk of haemorrhagic transformation (HT) before and after endovascular treatment (EVT). MATERIAL AND METHODS: This study included patients with anterior circulation large vessel occlusion (ACLVO) who underwent EVT within six hours of symptom onset between September 2017 and September 2022. These patients were retrospectively categorised into two groups: an HT group and a No-HT group. RESULTS: A total of 180 patients were included in the study, of whom 55 (30.6%) had HT. The monocyte count before EVT (p = = 0.005, OR = 0.694, 95% CI 0.536-0.898), the activated partial thromboplastin time before EVT (p = 0.009, OR = 0.186, 95% CI 0.699-0.952), and the eosinophil count after EVT (p = 0.038, OR = 0.001, 95% CI 0.000-0.018) were all found to be independent predictors of HT, with warning values of 6.65%, 22.95 seconds, and 0.035*10^9/L, respectively. When compared to prediction using only demographic data [AUC = 0.662,95% CI (0.545, 0.780)], adding biochemical indices before EVT [AUC = 0.719,95% CI (0.617, 0.821)], adding biochemical indices after EVT [AUC = 0.670,95% CI (0.566, 0.773)], and adding both [AUC = 0.778,95% CI (0.686, 0.870)], the prediction efficiency of HT was improved among all three combinations, with no statistical significance. CONCLUSIONS: The levels of serum biochemical markers were found to show significant changes before and after EVT in ACLVO patients. A combination of demographic data and serum biochemical markers proved to be effective in predicting the occurrence of HT in patients with ACLVO who underwent EVT.

What were the spatiotemporal evolution characteristics and the influencing factors of urban land green use efficiency? A case study of the Yangtze River Economic Belt.

China's rapid urbanization has had a tremendous impact on the country's limited land resources, and one of the major issues of green development is how to utilize the limited land resources to maximize social, economic, and environmental advantages. From 2005 to 2019, the super epsilon-based measure model (EBM) was employed to assess the green land use efficiency of 108 prefecture-level and above cities in the Yangtze River Economic Belt (YREB), as well as investigate its spatial and temporal evolution and influential factors. The findings demonstrate that overall, urban land green use efficiency (ULGUE) in the YREB has been ineffective; in terms of city scale, megacities have the highest efficiency, followed by large cities and small and medium-sized cities; and at the regional level, downstream efficiency does have the greatest average value, followed by upstream efficiency and middle efficiency. The results of temporal and spatial evolution reveal that the number of cities with a high ULGUE is increasing in general but that their spatial characteristics are relatively dispersed. Population density, environmental regulation, industrial structure, technology input, and the intensity of urban land investment all have major beneficial effects on ULGUE, whereas urban economic development level and urban land use scale clearly have inhibitory effects. In light of the previous conclusions, some recommendations are made to continuously improve ULGUE.

Parathyroid Hormone (1-34) Attenuates Cartilage Degradation and Preserves Subchondral Bone Micro-architecture in Rats with Patella Baja-Induced-Patellofemoral Joint Osteoarthritis.

Several studies have revealed that PTH1-34 may possess the potential for treating osteoarthritis (OA) and osteoporosis. However, no study has yet determined whether PTH1-34 can be used for the treatment of patella baja-induced patellofemoral joint OA (PFJOA). Thus, this study sought to assess the efficacy of PTH1-34 for the treatment of PFJOA in a rat model. Patella baja was induced in 3-month-old female Sprague-Dawley (SD) rats by patellar ligament shortening (PLS), after which the rats were randomly divided into three groups (n = 12): Sham, PLS, and PTH group (PTH + PLS, PTH1-34, 30 µg/kg/d, 5 days per week for 10 weeks). Thereafter, radiographic imaging, macroscopic and microscopic analyses, immunohistochemistry, and microcomputed tomography (CT) analysis were performed. The appearance of PLS-induced PFJOA promoted obvious changes in the patellar position and structure in the PLS group, which were characterized by cartilage degeneration, subchondral bone microstructure deterioration, patella baja, and increasing patella length. However, these negative characteristics were markedly ameliorated by PTH1-34, which not only inhibited cartilage catabolism by decreasing MMP-13 and ADAMTS-4 but also enhanced anabolism by increasing Col-II and Aggrecan. Furthermore, the micro-CT results showed a marked improvement in subchondral bone microarchitecture. The findings presented herein demonstrated that early treatment with PTH1-34 could improve cartilage metabolism and subchondral bone health in this PFJOA model.

The efficacy of dynamic compression locking system vs. dynamic hip screw in the treatment of femoral neck fractures: a comparative study.

BACKGROUND: There is still a lack of consensus on which internal fixation method can better maintain the stability of femoral neck fractures (FNF), promote fracture healing, and reduce postoperative complications such as femoral head necrosis and nonunion. Therefore, the purpose of this study was to evaluate the clinical efficacy of the novel dynamic compression locking system (DCLS) versus dynamic hip screw (DHS) in the treatment of FNF. METHODS: Fifty cases of FNF from July 2018 to February 2020 were retrospectively analyzed. According to different treatment methods, they were divided into DCLS group (26 cases) and DHS group (24 cases). Baseline data, intraoperative and postoperative clinical data, reoperation rate, and Harris score were collected to evaluate the clinical efficacy. RESULTS: All patients were followed up for 24 months. All "fractures" were caused by fall. The baseline data of the two groups were comparable (P > 0.05). There weren't significant differences in the length of hospital stay and mobility after two years postoperatively between the two groups (P > 0.05). The operation time, blood loss, incision length, fluoroscopy times and the degree of femoral neck shortening after two years postoperatively in the DCLS group were significantly less than those in the DHS group (all P < 0.05). Harris score after two years postoperatively in the DCLS group was significantly higher than that in the DHS group (P < 0.05). Although the reoperation rate in the DHS group was slightly higher than that in the DCLS group, it wasn't statistical significance (P > 0.05). CONCLUSIONS: Compared with DHS, DCLS in the treatment of FNF had less surgical trauma, shorter incision length, shorter operation time, lower radiation dose and higher Harris scores. Although the reoperation rate in the DHS group was slightly higher than that in the DCLS group, it wasn't statistical difference. Further research is needed.

Biocatalytic Depletion of Tumorigenic Energy Sources Driven by Cascade Reactions for Efficient Antitumor Therapy.

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2 O2 ) generation. Meanwhile, CAT catalyzes H2 O2 into O2 , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.

Analysis of the effect of percutaneous vertebroplasty in the treatment of thoracolumbar Kümmell's disease with or without bone cement leakage.

BACKGROUND: Bone cement leakage is a major complication in the treatment of percutaneous vertebroplasty for Kümmell's disease, and the focus of close attention during the surgery. The purpose of this article was to investigate the clinical outcomes of Kümmell's disease treated by percutaneous vertebroplasty with or without bone cement leakage. METHODS: A total of 64 patients with Kümmell's disease from December 2016 to February 2018 treated by percutaneous vertebroplasty were included in the study. After the treatment, 32 cases were respectively divided into two groups according to X-ray examination of bone cement leakage: leakage group and non-leakage group. Preoperative course, age, sex, bone mineral density, damaged segment, anterior vertebral height, vertebral compression rate, Cobb angle, visual analogue scale and Oswestry dysfunction index were compared between the two groups. After surgery, the amount of bone cement injected, operation time, adjacent vertebral refracture rate, visual analogue scale, Oswestry dysfunction index, the recovery value of vertebral anterior height and the improvement value of Cobb angle were compared between the two groups. RESULTS: The course, age and Cobb angle of the leakage group were significantly greater than those of the non-leakage group (P< 0.05, respectively). The height of anterior vertebral margin and bone mineral density in the leakage group were significantly lower than those in the non-leakage group (P< 0.05, respectively). The two groups were followed up for at least 24 months. The amount of bone cement injected was significantly greater in the leakage group than in the non-leakage group (P=0.000). Visual analogue scale and Oswestry dysfunction index of the two groups on the second day after surgery and at the last follow-up were significantly lower than these before surgery (P< 0.05, respectively), but there was no significant difference between the two groups. In the leakage group, the recovery value of the anterior edge height of the injured vertebra and the improvement value of the Cobb angle on the second day after surgery and at the last follow-up were significantly improved compared with the non-leakage group (P< 0.05, respectively). CONCLUSION: Percutaneous vertebroplasty is an effective and minimally invasive treatment for Kümmell's disease. The leakage group had longer course, older age, more serious kyphotic deformity, vertebral compression and osteoporosis, and higher amount of bone cement injected than these of the non-leakage group. However, there were not significant differences in the rate of adjacent vertebral refractures, visual analogue scale and Oswestry dysfunction index between the two groups. Therefore, the bone cement leakage does not affect the surgical effect.

Lenticulostriate arteries appearance before thrombectomy predicts good outcome in acute middle cerebral artery occlusion.

BACKGROUND: Endovascular therapy is widely used in acute large vessel occlusion. This study investigated whether imaging of lateral lenticulostriate arteries (LSAs) before thrombectomy would potentially be helpful for predicting prognosis of patients with acute M1 segment of middle cerebral artery occlusion (MCAO). METHODS: 59 consecutive patients with acute M1 segment of MCAO treated with mechanical thrombectomy at two comprehensive stroke centers were analyzed. Patients were categorized into LSA+ (appearing of lateral LSAs) and LSA- (sparing of lateral LSAs) group according to preprocedural digital substraction angiography (DSA). Baseline data and clinical outcomes were compared. A good clinical outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The association between clinical and imaging parameters and functional outcome was evaluated with logistic regression analysis. RESULTS: LSA+ was shown in 36 patients (61%). LSA+ group had a significantly higher proportion of good outcome (72.2% vs. 8.7%, OR 27.3,95% CI 5.38-138.4, P < 0.001), lower risk of symptomatic intracranial haemorrhages (sICH) (8.3% vs. 47.8%,OR 0.10,95% CI 0.02-0.42, P = 0.001) and lower mortality in hospital (5.6% vs. 34.8%, OR 0.11,95% CI 0.02-0.58, P < 0.004) compared with LSA- group. Patients in LSA+ group had lower baseline NIHSS score(P < 0.01) and NIHSS score at 14 days(P < 0.01) and smaller infarct core volume (P = 0.016) on computed tomography perfusion imaging (CTP) compared to the LSA- group. Multivariate logistic regression analysis showed that a small infarct core volume (OR 6.74,95% CI 1.148-39.569, P = 0.035) and LSA+(OR 22.114,95% CI 3.339-146.470, P = 0.001) were associated with a good clinical outcome. CONCLUSIONS: Our data suggest that appearance of lateral LSAs before mechanical thrombectomy would be potentially helpful for predicting favorable prognosis of patients with acute M1 segment of MCAO.

Efficacy and experience of arthroscopic lateral patella retinaculum releasing through/outside synovial membrane for the treatment of lateral patellar compression syndrome.

BACKGROUND: Arthroscopic closure release includes arthroscopic lateral patella retinaculum releasing (LPRR) either outside synovial membrane (OSM) or through synovial membrane (TSM). At present, there is no research to compare the clinical efficacy of the above two methods for the treatment of lateral patellar compression syndrome (LPCS). So, the goal of this study was to investigate the method and overcome of arthroscopic LPRR either OSM or TSM for the treatment of LPCS. METHODS: From September 2014 to December 2017, 125 patients of LPCS underwent arthroscopic LPRR either OSM or TSM combined with joint debridement. In the OSM group, knee joint was cleaned first. The surface of lateral patella retinaculum (LPR) was created the chamber for arthroscopic operation to release LPR. Synovial membrane was retained. In the TSM group, knee joint was cleaned first. Then synovial membrane, joint capsule and LPR, and superficial fascia were gradually incised from the joint cavity to subcutaneous tissue. The synovial membrane was cut open. Before and after surgery, Lysholm score, patella medial shift, Kujala score, VAS score and surgical complications were collected for evaluating clinical overcomes. RESULTS: All patients were followed up for 1.5-5 years. All patients had significant reduction in knee pain and improved function after 1 month and 1 year. The Lysholm score, the distance of patella medial shift, Kujala score, and VAS score in the OSM group and the TSM group were significantly improved in the final follow-up compared with before surgery (All P < 0.001), but these observed targets before surgery and at the last follow-up were compared between the OSM group and the TSM group with no statistical differences. However, the number of occurrences of joint hematoma and adhesion was significantly higher in the TSM group than the OSM group (P = 0.024). CONCLUSIONS: Arthroscopic closing LPRR for the treatment of LPCS can effectively improve the function and symptoms of patellofemoral joint with the advantages of small trauma, rapid recovery and less complications. But, the number of occurrences of hemarthrosis and joint adhesion were significantly higher in the TSM group than in the OSM group. TRIAL REGISTRATION: The trial registration number (IRCT): IRCT20200205046378N1 and date of registration: February 10, 2020 (retrospectively registered).

Comparison of the clinical outcomes of percutaneous vertebroplasty vs. kyphoplasty for the treatment of osteoporotic Kümmell's disease:a prospective cohort study.

BACKGROUND: Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are widely used in the treatment of Kümmell's disease. The purpose of this article is to investigate the clinical efficacy of PVP and PKP for Kümmell's disease. METHODS: The clinical data that 56 cases of Kümmell's disease treated with either PVP (28 cases) or PKP (28 cases) from December 2015 to December 2017 were prospectively analyzed. Gender, age, course of disease, injury segment, bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI), imaging measurement indexes before surgery between the two groups showed no significant difference (all P > 0.05). The bone cement leakage rate, bone cement injection amount, operation time, VAS, ODI, the rate of vertebral compression, correction rate of kyphosis and refracture rate of adjacent vertebra in 2 years were compared between the two groups to calculate clinical efficacy. RESULTS: The two groups were followed up for 24-48 months. There was no significant difference in the follow-up time, amount of bone cement injected, incidence of bone cement leakage and refracture rate of adjacent vertebrae between the two groups (all P > 0.05). The operation time, intraoperative blood loss and fluoroscopy times of the PVP group were significantly lower than those of the PKP group (all P = 0.000). VAS score and ODI of the two groups were significantly lower at 1 day, 1 year and 2 years after surgery than before surgery (all P < 0.05), but there was not statistically significant difference between the two groups at each time point after surgery (all P > 0.05). The rate of vertebral compression and kyphosis correction in the two groups were significantly corrected (P < 0.05, respectively) and decreased significantly with time (all P < 0.05), But there was not significant difference between the two groups at any time point (all P > 0.05). CONCLUSION: Both PVP and PKP can achieve similar effects in the treatment of Kümmell's disease. Because the cost, operation time, blood loss, radiation exposure and surgical procedure of PVP are less than those of PKP, PVP has more clinical priority value.

Dynamic compression locking system versus multiple cannulated compression screw for the treatment of femoral neck fractures: a comparative study.

BACKGROUND: Femoral neck fractures are one of the problems in clinical treatment. The prognosis is uncertain. Currently, No internal fixation method is superior to other internal fixation methods in the treatment of femoral neck fractures. Therefore, the internal fixation system needs to be further explored. The aim of this study was to compare clinical outcomes of femoral neck dynamic compression locking system (DCLS) and multiple cannulated compression screws(MCCS) in the treatment of femoral neck fractures. METHODS: A prospective analysis of 54 cases of femoral neck fractures treated with either a DCLS (n = 28) or MCCS (n = 26) was conducted between December 2015 and November 2017 in authors' hospitals. The perioperative and postoperative parameters of the two groups were recorded and evaluated. RESULTS: Fifty-four patients were followed up for 24-47 months. The etiology was caused by a fall. There was no significant difference in follow-up time, operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the two groups (all P > 0.05). The Harris score, fracture healing time, femoral neck shortening, partial weight-bearing time and complete weight-bearing time were significantly better in the DCLS group than in the MCCS group (all P < 0.05). The fracture healing rate in the DCLS group was higher than that in the MCCS group. CONCLUSIONS: The DCLS and MCCS might be equally effective in terms of operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the treatment of femoral neck fractures. However, the DCLS is superior to the MCCS in Harris score, fracture healing time, femoral neck shortening, weight-bearing time and fracture healing rate. So, DCLS deserves further study.

Amino Acid-Linked Low Molecular Weight Polyethylenimine for Improved Gene Delivery and Biocompatibility.

The construction of efficient and low toxic non-viral gene delivery vectors is of great significance for gene therapy. Herein, two novel polycations were constructed via Michael addition from low molecular weight polyethylenimine (PEI) 600 Da and amino acid-containing linkages. Lysine and histidine were introduced for the purpose of improved DNA binding and pH buffering capacity, respectively. The ester bonds afforded the polymer biodegradability, which was confirmed by the gel permeation chromatography (GPC) measurement. The polymers could well condense DNA into nanoparticles and protect DNA from degradation by nuclease. Compared with PEI 25 kDa, these polymers showed higher transfection efficiency, lower toxicity, and better serum tolerance. Study of this mechanism revealed that the polyplexes enter the cells mainly through caveolae-mediated endocytosis pathway; this, together with their biodegradability, facilitates the internalization of polyplexes and the release of DNA. The results reveal that the amino acid-linked low molecular weight PEI polymers could serve as promising candidates for non-viral gene delivery.

A Novel Rat Model of Patellofemoral Osteoarthritis Due to Patella Baja, or Low-Lying Patella.

BACKGROUND Patella baja, or patella infera, consists of a low-lying patella that results in a limited range of motion, joint pain, and crepitations. Patellofemoral joint osteoarthritis (PFJOA) is a subtype OA of the knee. This study aimed to develop a reproducible and reliable rat model of PFJOA. MATERIAL AND METHODS Three-month-old female Sprague-Dawley rats (n=24) included a baseline group (n=8) that were euthanized at the beginning of the study. The sham group (n=8), and the patella ligament shortening (PLS) group (n=8) were euthanized and evaluated at ten weeks. The PLS model group (n=8) underwent insertion of a Kirschner wire under the patella tendon to induce patella baja. At ten weeks, the sham group and the PLS group were compared using X-ray imaging, macroscopic appearance, histology, immunohistochemistry, TUNEL staining for apoptosis, and micro-computed tomography (micro-CT). The patella height was determined using the modified Insall-Salvati (MIS) ratio. RESULTS The establishment of the rat model of patella baja in the PLS group at ten weeks was confirmed by X-ray. In the PLS group, patella volume, sagittal length, and cross-sectional area were significantly increased compared with the sham group. The PFJ showed typical lesions of OA, confirmed macroscopically and histologically. Compared with the sham group, in the rat model of PFJOA, there was increased cell apoptosis, and immunohistochemistry showed increased expression of biomarkers of osteoarthritis, compared with the sham group. CONCLUSIONS A rat model of PFJOA was developed that was confirmed by changes in cartilage and subchondral bone.

[Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ß-catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ß-catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ß-catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.

Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis.

BACKGROUND: Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartilage, subchondral bone mass and subchondral trabecular bone structure in medial meniscectomized (MNX) guinea pigs. METHOD: Thirty-six 3-month-old male Dunkin Hartley albino guinea pigs received either sham or medial meniscectomy operations. One week after the procedure, meniscectomized animals began 12 weeks of SR (625 mg/kg, daily) treatment by oral gavage for MNX + SR group, or normal saline for MNX + V group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. RESULTS: Both OARSI scores (P = 0.523 for marcoscopic scores, P = 0.297 for histological scores) and Cartilage thickness (P = 0.335) in MNX + SR group were comparable to MNX + V group. However, osteophyte sizes were larger in MNX + SR group (P = 0.014), and collapsed osteophytes in MNX + SR group (7 by 12) were significantly more than in MNX + V group (1 by 12) (P = 0.027), while immunohistochemistry indicates catabolic changes in osteophyte/plateau junction. Micro-CT analysis showed bone mineral density (BMD) (P = 0.001), bone volume fraction (BV/TV) (P = 0.008), trabecular spacing (Tb.Sp) (P = 0.020), trabecular thickness (Tb.Th) (P = 0.012) and structure model index (SMI) (P = 0.005) levels to be significantly higher in the MNX + SR group than in the MNX + V group. CONCLUSIONS: SR (625 mg/kg/day) did not protect cartilage from degeneration in MNX guinea pigs but subchondral bone was significantly enhanced. In early phase OA, SR administration causes osteophyte overgrowth, which may be related to incorporation into mineralizing osteophytes. This adverse effect is important for future studies of SR in OA.

Characteristics, composition, and antioxidant activities in vitro and in vivo of Gynostemma pentaphyllum (Thunb.) Makino seed oil.

BACKGROUND: In order to further develop and utilise Gynostemma pentaphyllum (Thunb.) Makino seeds, a detailed analysis of the characteristics of G. pentaphyllum seed oil (GPSO), including its physico-chemical parameters, fatty acid composition and unsaponifiable matter constituents, has been investigated in this study. The antioxidant potential of GPSO was evaluated by radical-scavenging activity and ferric-reducing antioxidant power assay in vitro, and the antioxidant activity in vivo was examined by using an aged mice model. RESULTS: The main components of the seeds are lipids (485.54 g kg-1 ) and proteins (203.26 g kg-1 ). The GPSO obtained by supercritical CO2 fluid extraction was rich in polyunsaturated fatty acids (92.85%), especially conjugated linolenic acid (88.17%); and various useful compounds (squalene, tocopherol and phytosterols) were identified in the unsaponifiable matter. The overall antioxidant capacity of GPSO in vitro was shown to be comparable to that of Camellia seed oil as a positive control. GPSO could provide protection to the aged mice against oxidative stress and minimised the impact of ageing. CONCLUSION: All the results suggest that GPSO has direct and potent antioxidant activities; it could be utilised as a functional food to supplement or replace some conventional oils. © 2016 Society of Chemical Industry.

Fruit Extract from Pyropolyporus fomentarius (L. ex Fr.) Teng Induces Mitochondria-Dependent Apoptosis in Leukemia Cells but Enhances Immunomodulatory Activities of Splenic Lymphocytes.

Pyropolyporus fomentarius (L. ex Fr.) Teng is a unique woody mushroom due to its medicinal value with numerous pharmacological activities. This study presented the potential antitumor and immunomodulatory properties of ethanol extract of P. fomentarius. The results showed that P. fomentarius extract inhibited the viability of murine leukemia L1210 cells in a dose-dependent manner with IC50 value of 69.35 µg/ml. Flow cytometry analysis demonstrated that the extract induced apoptosis in L1210 cells. Additionally, the decline of mitochondrial membrane potential was observed as well as the changes of caspase-3, caspase-9, Bcl-2, and Bax, suggesting that proapoptosis effect of the extract involved mitochondria-related pathway. Simultaneously, the P. fomentarius extract significantly enhanced the proliferation and activation of splenic lymphocytes in a dose-dependent manner. This P. fomentarius extract has potential applications as a natural antitumor agent with immunomodulatory activity.