ß-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture.

The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the ß-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-ßAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy.

Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.

Targeting aging with the healthy skeletal system: The endocrine role of bone.

Aging is an inevitable biological process, and longevity may be related to bone health. Maintaining strong bone health can extend one's lifespan, but the exact mechanism is unclear. Bone and extraosseous organs, including the heart and brain, have complex and precise communication mechanisms. In addition to its load bearing capacity, the skeletal system secretes cytokines, which play a role in bone regulation of extraosseous organs. FGF23, OCN, and LCN2 are three representative bone-derived cytokines involved in energy metabolism, endocrine homeostasis and systemic chronic inflammation levels. Today, advanced research methods provide new understandings of bone as a crucial endocrine organ. For example, gene editing technology enables bone-specific conditional gene knockout models, which allows the study of bone-derived cytokines to be more precise. We systematically evaluated the various effects of bone-derived cytokines on extraosseous organs and their possible antiaging mechanism. Targeting aging with the current knowledge of the healthy skeletal system is a potential therapeutic strategy. Therefore, we present a comprehensive review that summarizes the current knowledge and provides insights for futures studies.

DJ-1-mediated p62 degradation delays intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is the most important pathological basis of degenerative spinal diseases, for which effective interventions are still lacking. Oxidative stress is considered to be one of the leading pathological mechanisms contributing to IDD. However, the exact role of DJ-1 as an essential member of the antioxidant defense system in IDD is still unclear. Therefore, the aim of this study was to investigate the role played by DJ-1 in IDD and to reveal its potential molecular mechanisms. Western blot and immunohistochemical staining assays were performed to detect the expression of DJ-1 in degenerative nucleus pulposus cells (NPCs). After overexpression of DJ-1 in NPCs by lentiviral transfection, DCFH-DA and MitoSOX fluorescent probes were used to evaluate the levels of reactive oxygen species (ROS); while western blot, TUNEL staining, and Caspase-3 activity were used to assess apoptosis. Immunofluorescence staining was used to demonstrate the relationship between DJ-1 and p62. After inhibition of lysosomal degradation function with chloroquine, p62 degradation and apoptosis in DJ-1 overexpressing NPCs were further examined. In vivo, we assessed the therapeutic effect of upregulated DJ-1 on IDD by X-ray, MRI and Safranin O-Fast green staining. The protein expression of DJ-1 was significantly decreased in degenerated NPCs, accompanied by increased apoptosis. However, overexpression of DJ-1 significantly inhibited the elevated ROS levels and apoptosis in NPCs under oxidative stress. Mechanistically, our results showed that upregulation of DJ-1 promoted p62 degradation via the autophagic lysosomal pathway and that the protective effect of DJ-1 on NPCs under oxidative stress was partially mediated by promoting lysosomal pathway degradation of p62. Moreover, intradiscal injection of adeno-associated virus for overexpression of DJ-1 mitigated the progression of IDD in rats. This study reveals that DJ-1 maintains the homeostasis of NPCs by promoting the degradation of p62 through the autophagic lysosomal pathway, suggesting that DJ-1 is a promising new target for IDD intervention.

Incidence and cost of vertebral fracture in urban China: a 5-year population-based cohort study.

BACKGROUND: Osteoporotic vertebral fractures cause pain and disability, which result in a heavy socioeconomic burden. However, the incidence and cost of vertebral fractures in China are unknown. We aimed to assess the incidence and cost of clinically recognized vertebral fractures among people aged 50 years and older in China from 2013 to 2017. MATERIALS AND METHODS: This population-based cohort study was conducted by using Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) data in China from 2013 to 2017, which covered more than 95% of the Chinese population in urban areas. Vertebral fractures were identified by the primary diagnosis (i.e. International Classification of Diseases code or text of diagnosis) in UEBMI and URBMI. The incidence and medical cost of these clinically recognized vertebral fractures in urban China were calculated. RESULTS: A total of 271 981 vertebral fractures (186 428, 68.5% females and 85 553, 31.5% males) were identified, with a mean age of 70.26 years. The incidence of vertebral fractures among patients aged 50 years and over in China increased ~1.79-fold during the 5 years, from 85.21 per 100 000 person-years in 2013 to 152.13 per 100 000 person-years in 2017. Medical costs for vertebral fractures increased from US$92.74 million in 2013 to US$505.3 million in 2017. Annual costs per vertebral fracture case increased from US$3.54 thousand in 2013 to US$5.35 thousand in 2017. CONCLUSION: The dramatic increase in the incidence and cost of clinically recognized vertebral fractures among patients aged 50 and over in urban China implies that more attention should be given to the management of osteoporosis to prevent osteoporotic fractures.

Association between weather and hip fracture in adults: a nationwide study in China 198 cities.

Hip fractures represent a significant public health issue due to high incidence in aging society. Our study further proved that increased risk for hip fractures in adults is associated with weather conditions. PURPOSE: Hip fractures represent a significant public health issue due to high incidence in aging society. Evidence of the short-term effects of weather on the risk of hip fracture is limited and inconsistent. We aimed to examine the associations between weather conditions and daily hospital admissions for hip fracture in adults in China. METHODS: A national time-series analysis between 2014 and 2017 was conducted. Data on daily hospital admissions for hip fracture were obtained from the database of Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI). Weather conditions were acquired from the China Meteorological Data Sharing Service Center. Based on a time-stratified case-crossover design, conditional Poisson regression was used to estimate the impact on relative risk (RR) of weather conditions on hospital admissions for hip fracture. RESULTS: During the study period, a total of 137,504 hospital admissions for hip fractures were identified. All analyzed weather conditions showed consistent significant associations at lag 0 day for each 10 mm increase in precipitation, 10 m/s in wind speed, and 10°C in temperature, with the RR value being 1.079 (95% CI, 1.074-1.083) for precipitation, 1.404 (95% CI, 1.346-1.465) for wind speed, and 1.558 (95% CI, 1.546-1.570) for temperature. Women were more vulnerable to be affected by precipitation and temperature. CONCLUSION: In conclusion, increased risk for hip fractures in adults is associated with weather conditions. The improved understanding of the relationship between weather conditions and hip fractures hospital admission can be useful for resource allocation and provider preparedness.

Simvastatin-hydroxyapatite coatings prevent biofilm formation and improve bone formation in implant-associated infections.

Implant-associated infections (IAIs) caused by biofilm formation are the most devastating complications of orthopedic surgery. Statins have been commonly and safely used drugs for hypercholesterolemia for many years. Here, we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated infections. The antibacterial properties of simvastatin against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro was confirmed by crystal violet staining and live-dead bacterial staining. We developed a simvastatin-and hydroxyapatite (Sim-HA)-coated titanium alloy via electrochemical deposition. Sim-HA coatings inhibited Staphylococcus aureus biofilm formation and improved the biocompatibility of the titanium alloy. Sim-HA coatings effectively prevented Staphylococcus aureus IAI in rat femurs, as confirmed by radiological assessment and histological examination. The antibacterial effects of the Sim-HA coatings were attributed to their inhibitory effects on biofilm formation, as verified by scanning electron microscopic observations and bacterial spread plate analysis. In addition, the Sim-HA coatings enhanced osteogenesis and osteointegration, as verified by micro-CT, histological evaluation, and biomechanical pull-out tests. In summary, Sim-HA coatings are promising implant materials for protection against biofilm-associated infections.

Pathophysiological mechanism of acute bone loss after fracture.

BACKGROUND: Acute bone loss after fracture is associated with various effects on the complete recovery process and a risk of secondary fractures among patients. Studies have reported similarities in pathophysiological mechanisms involved in acute bone loss after fractures and osteoporosis. However, given the silence nature of bone loss and bone metabolism complexities, the actual underlying pathophysiological mechanisms have yet to be fully elucidated. AIM OF REVIEW: To elaborate the latest findings in basic research with a focus on acute bone loss after fracture. To briefly highlight potential therapeutic targets and current representative drugs. To arouse researchers' attention and discussion on acute bone loss after fracture. KEY SCIENTIFIC CONCEPTS OF REVIEW: Bone loss after fracture is associated with immobilization, mechanical unloading, blood supply damage, sympathetic nerve regulation, and crosstalk between musculoskeletals among other factors. Current treatment strategies rely on regulation of osteoblasts and osteoclasts, therefore, there is a need to elucidate on the underlying mechanisms of acute bone loss after fractures to inform the development of efficacious and safe drugs. In addition, attention should be paid towards ensuring long-term skeletal health.

Neurophysiological mechanisms of cancer-induced bone pain.

Background: Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific research suggest that neuropathic pain is a representative component of CIBP. However, given the variability of cancer conditions and the complexity of neuropathic pain, related mechanisms have been continuously supplemented but have not been perfected. Aim of Review: Therefore, the current review highlights the latest progress in basic research on the field and proposes potential therapeutic targets, representative drugs and upcoming therapies. Key Scientific Concepts of Review: Notably, factors such as central sensitization, neuroinflammation, glial cell activation and an acidic environment are considered to be related to neuropathic pain in CIBP. Nonetheless, further research is needed to ascertain the mechanism of CIBP in order to develop highly effective drugs. Moreover, more attention needs to be paid to the care of patients with advanced cancer.

Nonspherical Metal-Based Nanoarchitectures: Synthesis and Impact of Size, Shape, and Composition on Their Biological Activity.

Metal-based nanoentities, apart from being indispensable research tools, have found extensive use in the industrial and biomedical arena. Because their biological impacts are governed by factors such as size, shape, and composition, such issues must be taken into account when these materials are incorporated into multi-component ensembles for clinical applications. The size and shape (rods, wires, sheets, tubes, and cages) of metallic nanostructures influence cell viability by virtue of their varied geometry and physicochemical interactions with mammalian cell membranes. The anisotropic properties of nonspherical metal-based nanoarchitectures render them exciting candidates for biomedical applications. Here, the size-, shape-, and composition-dependent properties of nonspherical metal-based nanoarchitectures are reviewed in the context of their potential applications in cancer diagnostics and therapeutics, as well as, in regenerative medicine. Strategies for the synthesis of nonspherical metal-based nanoarchitectures and their cytotoxicity and immunological profiles are also comprehensively appraised.

Inhibition of LRRK2 restores parkin-mediated mitophagy and attenuates intervertebral disc degeneration.

OBJECTIVE: To elucidate the role of LRRK2 in intervertebral disc degeneration (IDD) as well as its mitophagy regulation mechanism. METHODS: The expression of LRRK2 in human degenerative nucleus pulposus tissues as well as in oxidative stress-induced rat nucleus pulposus cells (NPCs) was detected by western blot. LRRK2 was knocked down in NPCs by lentivirus (LV)-shLRRK2 transfection; apoptosis and mitophagy were assessed by western blot, TUNEL assay, immunofluorescence staining and mitophagy detection assay in LRRK2-deficient NPCs under oxidative stress. After knockdown of Parkin in NPCs with siRNA transfection, apoptosis and mitophagy were further assessed. In puncture-induced rat IDD model, X-ray, MRI, hematoxylin-eosin (HE) and Safranin O-Fast green (SO) staining were performed to evaluate the therapeutic effects of LV-shLRRK2 on IDD. RESULTS: We found that the expression of LRRK2 was increased in degenerative NPCs both in vivo and in vitro. LRRK2 deficiency significantly suppressed oxidative stress-induced mitochondria-dependent apoptosis in NPCs; meanwhile, mitophagy was promoted. However, these effects were abolished by the mitophagy inhibitor, suggesting the effect of LRRK2 on apoptosis in NPCs is mitophagy-dependent. Furthermore, Parkin knockdown study showed that LRRK2 deficiency activated mitophagy by recruiting Parkin. In vivo study demonstrated that LRRK2 inhibition ameliorated IDD in rats. CONCLUSIONS: The results revealed that LRRK2 is involved in the pathogenesis of IDD, while knockdown of LRRK2 inhibits oxidative stress-induced apoptosis through mitophagy. Thus, inhibition of LRRK2 may be a promising therapeutic strategy for IDD.

Controlled release of baricitinib from a thermos-responsive hydrogel system inhibits inflammation by suppressing JAK2/STAT3 pathway in acute spinal cord injury.

Aggressive inflammation is an important pathological process of secondary injury in acute spinal cord injury (SCI). However, traditional treatments of secondary injury in acute SCI have achieved little success. Novel biomaterials combined with small molecule drugs are considered as a potential treatment for SCI. Baricitinib, a highly selective JAK1/JAK2 inhibitor, can effectively inhibit the JAK2/STAT3 pathway involved in the modulation of inflammation. However, to evaluate Baricitinib's therapeutic effect on SCI remains to be confirmed. In this study, we designed an injectable PLGA-PEG-PLGA thermos-sensitive hydrogel with baricitinib (Bari-P hydrogel) and measured its efficacy, physical and biological properties in vitro. In the SCI rat, Bari-P hydrogel was injected into the injured spinal cord. Neuronal regeneration was evaluated at 3 days and 4 weeks after surgery by determining the inflammatory cytokine levels, behavioral tests, and histological analysis. The hydrogel can gel in the body, disintegrate almost within 72 h and achieve drug release. Baricitinib can effectively inhibit the JAK2/STAT3 pathway of microglia in vitro; while in vivo experiments show that Bari-P hydrogel treatment can inhibit the phosphorylation of JAK2, STAT3 and suppress the production of inflammatory cytokines, and reduces neuronal apoptosis. Histopathological analysis and behavioral tests showed that Bari-P hydrogel reduced neuronal apoptosis in the early stage of injury and later promoted functional recovery. In summary, Bari-P hydrogel reduced neuronal apoptosis and promoted functional recovery in spinal cord injured rats by inhibiting the JAK2-STAT3 pathway and controlling the expression of inflammatory cytokines in the early stages of injury.

The endocrine role of bone: Novel functions of bone-derived cytokines.

Bone-derived cytokines refer to various proteins and peptides that are released from the skeleton and can distribute in organisms to regulate homeostasis by targeting many organs, such as the pancreas, brain, testicles, and kidneys. In addition to providing support and movement, many studies have disclosed the novel endocrine function of bone, and bone can modulate glucose and energy metabolism as well as phosphate metabolism by versatile bone-derived cytokines. However, this specific exoskeletonfunction of bone-derived cytokines in the regulation of homeostasis and the pathological response caused by skeletal dysfunction are still not very clear, and elucidation of the above mechanisms is of great significance for understanding the pathological processes of metabolic disorders and in the search for novel therapeutic measures for maintaining organ stability and physical fitness.

Prognostic Nomograms to Predict Overall Survival and Cancer-specific Survival in Sacrum/Pelvic Chondrosarcoma (SC) Patients: A Population-based Propensity Score-matched Study.

STUDY DESIGN: A longitudinal cohort study. OBJECTIVE: The objective of this study was to evaluate the prognostic factors and determine the difference between different surgery scopes. Nomograms were constructed and validated to predict overall survival (OS) and cancer-specific survival (CSS) of sacrum/pelvic chondrosarcoma (SC) patients. SUMMARY OF BACKGROUND DATA: Chondrosarcoma is a bone malignancy which is reported to be resistant to both chemotherapy and radiotherapy. Therefore, surgery is the most preferred treatment method. However, this remains a great challenge due to the complex anatomy of the area. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database of patients with conventional SC between 1998 and 2016 was retrieved for analysis. Cox analysis was used to estimate the mortality hazards ratios among patients. Propensity score matching was used to compare different surgery scope. Nomograms were constructed to predict the OS and CSS of patients with SC. RESULTS: A total of 377 patients were included in this study. The cutoff value for tumor size was considered to be 118 mm. The concordance indices (C-index) value for nomogram predictions of CSS were 0.871. Following propensity score matching, 158 patients were selected for the second time and its result showed no significant difference between the scope of surgery. CONCLUSIONS: Tumor size was considered to be closely related to the outcome of SC. There is no significant difference in the scope of surgery and limb salvage can be considered. The nomograms can precisely predict OS and CSS in patients with SC. These could help clinicians to perform survival assessments and identify patients at high risk. LEVEL OF EVIDENCE: Level IV.

Can Acupuncture Improve Chronic Spinal Pain? A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To investigate the effect and safety of acupuncture for the treatment of chronic spinal pain. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, the WHO Clinical Trial Registry, and the US National Library of Medicine clinical trial registry were searched from January 1, 2000, to November 1, 2019. Randomized controlled trials (RCTs) involving patients with chronic spinal pain treated by acupuncture versus sham acupuncture, no treatment, or another treatment were included. RESULTS: Data was extracted from 22 RCTs including 2588 patients. Pooled analysis revealed that acupuncture can reduce chronic spinal pain compared to sham acupuncture (weighted mean difference [WMD] -12.05, 95% confidence interval [CI] -15.86 to -8.24), mediation control (WMD -18.27, 95% CI -28.18 to -8.37), usual care control (WMD -9.57, 95% CI -13.48 to -9.44), and no treatment control (WMD -17.10, 95% CI -24.83 to -9.37). In terms of functional disability, acupuncture can improve physical function at immediate-term follow-up (standardized mean difference [SMD] -1.74, 95% CI -2.04 to -1.44), short-term follow-up (SMD -0.89, 95% CI -1.15 to -0.62), and long-term follow-up (SMD -1.25, 95% CI -1.48 to -1.03). CONCLUSION: In summary, compared to no treatment, sham acupuncture, or conventional therapy such as medication, massage, and physical exercise, acupuncture has a significantly superior effect on the reduction in chronic spinal pain and function improvement. Acupuncture might be an effective treatment for patients with chronic spinal pain and it is a safe therapy.

The Characteristics and Mortality of Osteoporosis, Osteomyelitis, or Rheumatoid Arthritis in the Diabetes Population: A Retrospective Study.

BACKGROUND: Patients with diabetes mellitus are prone to develop osteoporosis, osteomyelitis, or rheumatoid arthritis (RA). Furthermore, the presence of these complications in those with diabetes may lead to higher mortality. The aim of our study was to assess characteristics and mortality of osteoporosis, osteomyelitis, or rheumatoid arthritis in individuals with diabetes. METHODS: We analyzed osteoporosis, osteomyelitis, and RA deaths associated with diabetes from 1999-2017 using the CDC WONDER system (CDC WONDER; https://wonder.cdc.gov). We used ICD-10 codes to categorize the underlying and contributing causes of death. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 1,000,000 person-years were calculated. RESULTS: The AAMR for osteoporosis in the population with diabetes was significantly higher in females (AAMR: 4.17, 95% CI: 4.10-4.24) than in males (AAMR: 1.12, 95% CI: 1.07-1.16). Deaths due to osteoporosis increased gradually from 1999, peaked in 2003 (AAMR: 3.78, 95% CI: 3.55-4.00), and reached a nadir in 2016 (AAMR: 2.32, 95% CI: 2.15-2.48). The AAMR for RA associated with diabetes was slightly higher in females (AAMR: 4.04, 95% CI: 3.98-4.11) than in males (AAMR: 2.45, 95% CI: 2.39-2.51). The mortality rate due to RA increased slightly from 1999 (AAMR: 3.18, 95% CI: 2.97-3.39) to 2017 (AAMR: 3.20, 95% CI: 3.02-3.38). The AAMR for osteomyelitis associated with diabetes was higher in males (AAMR: 4.36, 95% CI: 4.28-4.44) than in females (AAMR: 2.31, 95% CI: 2.26-2.36). From 1999 to 2017, the AAMR from osteomyelitis in this population was 2.63 (95% CI: 2.44-2.82) per 1,000,000 person-years in 1999 and 4.25 (95% CI: 4.05-4.46) per 1,000,000 person-years in 2017. CONCLUSIONS: We found an increase in the age-adjusted mortality rates of RA and osteomyelitis and a decrease of osteoporosis associated with diabetes from 1999 to 2017. We suggest that increased attention should therefore be given to these diseases in the population with diabetes, especially in efforts to develop preventative and treatment strategies.

Association between Bone Mineral Density and Severity of Chronic Kidney Disease.

OBJECTIVE: We sought to evaluate the association between femoral neck (FN) and lumbar spine (LS) bone mineral densities (BMDs) with severity of chronic kidney disease (CKD) and prevalence of osteopenia or osteoporosis (OP) among the CKD group. METHODS: Cross-sectional data from 11050 participants aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) were analyzed. Specifically, Pearson correlation was applied to analyze the relationship between BMD and estimated glomerular filtration rate (eGFR). General linear models (GLMs) were adjusted for potential confounders and used to analyze mean BMD, based on CKD and CKD stages. RESULTS: FN BMD was positively correlated with the eGFR in the total and male CKD, but not in the female CKD population. LS BMD was not significantly associated with eGFR. After controlling for partial correlations, FN T-score was positively correlated with the eGFR in the total at-risk population. According to FN BMD, OP prevalence was positively associated with CKD stage. However, according to LS BMD, there was no significant association between OP and CKD stage. CONCLUSION: Our results may explain the higher prevalence of hip fracture, relative to that of the spine, among CKD patients and generate meaningful insights to guide care, prevention, and treatment regimens for CKD patients. However, the fact that this was a cross-sectional study may limit the possibility of drawing concrete conclusions. Nevertheless, these findings open up a new frontier for further studies to uncover the higher decrease of FN BMD compared to LS BMD among CKD cases.

Sinapic Acid Inhibits IL-1ß-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration.

BACKGROUND: Low back pain (LBP) is a very common condition and leads to serious pain, disability, and price tag all over the world. Intervertebral disk degeneration (IDD) is one of the major reasons that contributed to LBP. The levels of interleukin 1 beta (IL-1ß) increase significantly in degenerative disks. IL-1ß also accelerates IDD. Sinapic acid (SA) has the effect of anti-inflammatory, antioxidant and antimicrobial. However, the effect of SA on IDD has never been studied. Therefore, the aim of this study was to figure out whether SA has protective effect on nucleus pulposus (NP) cells and further explore the possible underlying mechanism. METHODS: The nucleus pulposus (NP) tissues of rats were collected and cultured into NP cells. The NP cells were stimulated by IL-1ß and treated with SA. In vitro treatment effects were evaluated by ELISA, Western blot assay, immunofluorescence, TUNEL method and real-time PCR. We conducted percutaneous needle puncture in the rat tail to build intervertebral disk degeneration model and treated rats with SA. In vivo treatment effects were evaluated by hematoxylin and eosin (HE) and safranin O (SO) staining and magnetic resonance imaging (MRI) method. RESULTS: Our results showed that SA not only inhibited apoptosis but also suppressed inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in IL-1ß-stimulated NP cells. As to extracellular matrix (ECM), SA could increase collagen II and aggrecan levels and reduce the expression of MMP13 and ADAMTS5 during the stimulation of IL-1ß. Furthermore, SA could activate nuclear factor-erythroid 2-related factor-2 (Nrf2) to inhibit nuclear factor κB (NF-κB) induced by IL-1ß. Nrf2 knockdown partly reduced the protective effect of SA on NP cells. Correspondingly, SA ameliorated IDD by promoting Nrf2 expression. In vivo results also showed that SA could delay the progression of IDD. CONCLUSION: In conclusion, we demonstrated that SA could protect the degeneration of NP cells and revealed the underlying mechanism of SA on Nrf2 activation in NP cells.

Hydroxysafflor yellow A promotes multiterritory perforating flap survival: an experimental study.

The use of perforator flaps is a common surgical technique in wound repair. However, the area surrounding the multiterritory perforating flap often becomes necrotic due to ischemia. Hydroxysafflor yellow A (HSYA), a traditional Chinese medicine extracted from edible safflower, can be used medicinally to promote angiogenesis, inhibit apoptosis, and alleviate oxidative stress and other biological activities. Here, we investigated the effect of HSYA on perforator flap survival and its potential mechanism. Our results demonstrate that HSYA significantly improves the survival area of perforator flaps, increases blood supply, reduces tissue edema, and increases mean vascular density. HSYA treatment promotes angiogenesis and inhibits oxidative stress, apoptosis, and autophagy in perforator flaps, suggesting many potential mechanisms for flap survival.