ABSTRACT
BACKGROUND: Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD). METHODS: All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured. RESULTS: Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively. CONCLUSION: Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.
Subject(s)
Cobalt , Pulmonary Disease, Chronic Obstructive , Uteroglobin , Humans , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Male , Uteroglobin/blood , Female , Cobalt/blood , Aged , Middle Aged , Cross-Sectional Studies , Lung/drug effects , Lung/physiopathology , Lung/metabolism , Forced Expiratory Volume/physiology , Respiratory Function Tests/methods , Biomarkers/blood , Vital Capacity/physiologyABSTRACT
BACKGROUND: As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. METHODS: This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. RESULTS: Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. CONCLUSION: Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.
Subject(s)
Biomarkers , C-Reactive Protein , Disease Progression , Interleukin-6 , Mucin-1 , Pulmonary Disease, Chronic Obstructive , Severity of Illness Index , Humans , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/physiopathology , Mucin-1/blood , Male , Female , Aged , Biomarkers/blood , Prognosis , Prospective Studies , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Middle Aged , Interleukin-6/blood , Case-Control Studies , Uric Acid/blood , L-Lactate Dehydrogenase/blood , Leukocyte Count , Aged, 80 and overABSTRACT
Glucocorticoid-induced osteoporosis (GIOP) commonly accelerates bone loss, increasing the risk of fractures and osteonecrosis more significantly than traditional menopausal osteoporosis. The extracellular environment influenced by glucocorticoids heightens fracture and osteonecrosis risks. Fraxin (Fra), a key component of the traditional Chinese herbal remedy Cortex Fraxini, is known for its wide-ranging pharmacological effects, but its impact on GIOP remains unexplored. This investigation aims to delineate the effects and underlying mechanisms of Fra in combating dexamethasone (Dex)-induced ferroptosis and GIOP. We established a mouse model of GIOP via intraperitoneal injections of Dex and cultured osteoblasts with Dex treatment for in vitro analysis. We evaluated the impact of Fra on Dex-treated osteoblasts through assays such as C11-BODIPY and FerroOrange staining, mitochondrial functionality tests, and protein expression analyses via Western blot and immunofluorescence. The influence of Fra on bone microarchitecture of GIOP in mice was assessed using microcomputerized tomography, hematoxylin and eosin staining, double-labeling with Calcein-Alizarin Red S, and immunohistochemistry at imaging and histological levels. Based on our data, Fra prevented Dex-induced ferroptosis and bone loss. In vitro, glutathione levels increased and malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species decreased. Fra treatment also increases nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and COL1A1 expression and promotes bone formation. To delve deeper into the mechanism, the findings revealed that Fra triggered the activation of Nrf2/GPX4 signaling. Moreover, the use of siRNA-Nrf2 blocked the beneficial effect of Fra in osteoblasts cultivated with Dex. Fra effectively combats GIOP by activating the Nrf2/GPX4 signaling pathway to inhibit ferroptosis.
ABSTRACT
Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1-2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)2D3 inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)2D3 reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.
Subject(s)
Inflammation/immunology , Pulmonary Disease, Chronic Obstructive/immunology , Receptors, Calcitriol/metabolism , Vitamin D Deficiency/immunology , Vitamin D/blood , A549 Cells , Aged , Case-Control Studies , Female , Humans , Inflammation/metabolism , Male , Middle Aged , NF-kappa B/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Signal Transduction , Transcription Factor AP-1/metabolism , Vitamin D Deficiency/metabolismABSTRACT
The human heat shock protein plays a critical role in various diseases and is an important target for pharmacological modulation. Simulation of conformational changes and free energy profiles of the human heat shock protein derived by the ligand-leaving process is a challenging issue. In this work, steered molecular dynamics simulation was adopted to simulate the ligand-leaving process. Two composite systems of heat shock protein NHSP90 and small molecules 6FJ and 6G7 are selected as research objects. The free energy during the leaving of ligand small molecules is calculated using conventional molecular dynamics simulation, steered molecular dynamics simulation (SMD), and the umbrella sampling method. We found that the a slower pulling velocity (0.001 nm ns-1) will result in 2.19 kcal mol-1, and the umbrella sampling method gives a value of 3.26 kcal mol-1 for the free energy difference for the two systems, which reasonably agrees with experimental results. A faster-pulling velocity (0.01 nm ns-1) leads to a large overestimation of free energy. At the same time, the conformational analysis indicated that the faster pulling velocity may lead to the conformational change of NHSP90, which was proved to be false by the slower pulling velocity and the umbrella sampling method.
Subject(s)
Heat-Shock Proteins , Molecular Dynamics Simulation , Humans , Ligands , ThermodynamicsABSTRACT
Objective: This study evaluated the efficacy and safety of bionic tiger bone powder (Jintiange) in comparison to placebo in treating knee osteoarthritis osteoporosis. Methods: A total of 248 patients were randomly allocated to a Jintiange group or a placebo group, undergoing 48 weeks of double-blind treatment. The Lequesne index, clinical symptoms, safety index (adverse events), and Patient's Global Impression of Change score were recorded at pre-determined time intervals. All P values ≤ .05 were deemed statistically significant. Results: Both groups showed a decreasing trend in the Lequesne index, with the Jintiange group's reduction significantly larger from the 12th week (P ≤ .01). Similarly, the effective rate of Lequesne score in the Jintiange group was significantly higher (P < .001). After 48 weeks, clinical symptom score differences between the Jintiange group (2.46 ± 1.74) and the placebo group (1.51 ± 1.73) were statistically significant (P < .05), as were differences in the Patient's Global Impression of Change score (P < .05). Adverse drug reactions were minimal with no significant difference between the groups (P > .05). Conclusion: Jintiange demonstrated superior efficacy over placebo in treating knee osteoporosis, with comparable safety profiles. Findings warrant further comprehensive real-world studies.
Subject(s)
Osteoarthritis, Knee , Osteoporosis , Humans , Double-Blind Method , Osteoarthritis, Knee/drug therapy , Powders/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. METHODS: The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru - T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. RESULTS: After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference (p < 0.05). CONCLUSION: Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.
Subject(s)
Aortic Diseases , Arterial Occlusive Diseases , Spinal Cord Ischemia , Rats , Animals , Spinal Cord Ischemia/etiology , Ischemia , Spinal Cord/blood supply , Spinal Cord/pathology , Spinal Cord/physiology , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aorta, Thoracic/pathology , Aortic Diseases/pathology , Necrosis/pathologyABSTRACT
BACKGROUND: Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients. METHODS: All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (<0.77 µg/L, L), medium (0.77-1.01 µg/L, M), and high (1.01 µg/L, H). Logistic regression analysis found that serum cadmium was inversely correlated with pulmonary function before and after adjusted confounding variables. When stratified by gender, serum cadmium was still negatively correlated with pulmonary function in COPD patients. Moreover, higher serum cadmium elevated CAT (COPD Assessment Test) score before and after adjusted confounding variables. Though a non-linear association between serum cadmium and inflammatory cytokines, serum cadmium was positively associated with inflammatory cytokines (TNF-α and MCP-1). TNF-α and MCP-1 exerted a partial mediator in the association between cadmium exposure and pulmonary function decline in COPD patients. CONCLUSIONS: Serum cadmium concentration is inversely correlated with pulmonary function among COPD patients. Inflammatory cytokines may be important mediators for cadmium-induced pulmonary function decline in COPD patients.
Subject(s)
Cytokines , Pulmonary Disease, Chronic Obstructive , Cadmium , Case-Control Studies , Humans , Lung , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Due to the complexity of the anatomical structure and the difficulty of exposing the surgical area, the surgery for spinal tuberculosis in the upper thoracic vertebra (above T6-T7) is complicated and the prognosis is not good. This study aimed to investigate the clinical effects of posterolateral costotransversectomy using an extrapleural approach in patients with upper thoracic spinal tuberculosis. METHODS: This was a retrospective analysis of 132 patients (including 78 males and 54 females) with upper thoracic spinal tuberculosis who underwent one-stage internal fixation and debridement followed by combined interbody and posterior fusion via posterolateral costotransversectomy using an extrapleural approach. The age ranged from 23 to 82 years (54.5 ± 13.2 years). Lesion segments were distributed from T2 to T7. According to Frankel's spinal cord function evaluation, there were 2 cases of grade A, 6 of grade B, 6 of grade C, 12 of grade D, and 106 of grade E. The preoperative Cobb angle was 16-40° (29.1° ± 6.5°). Operation time, bleeding volume, incision healing, bone graft fusion, deformity correction, and improvement of nerve function were analyzed. RESULTS: The operation time ranged from 2.8 to 4.1 h (3.4 ± 0.3 h), and blood loss ranged from 350 to 550 mL (460 ± 47 mL). All incisions healed in the first stage. The bone graft fusion time was 3-6 months (median of 4 months). There was no loosening or broken of the internal fixation. The C-reactive protein and erythrocyte sedimentation rate were significantly improved at the end of follow-up in comparison with before surgery. The Cobb angle of the fusion segment was corrected and ranged from 5° to 17° (average of 10.7° ± 3.3°) at the end of follow-up. The nerve function of all patients improved at different degrees by the time of the last follow-up. In the last follow-up, the Frankel grade distribution was 1 case in B grade, 2 cases in grade C, 6 cases in grade D, and 123 cases in grade E. CONCLUSION: Posterolateral costotransversectomy using an extrapleural approach is a safe and effective surgical method that can expose the upper thoracic spine lesions and reduce trauma.
Subject(s)
Spinal Fusion , Tuberculosis, Spinal , Adult , Aged , Aged, 80 and over , Bone Transplantation/methods , Debridement/methods , Female , Fracture Fixation, Internal/methods , Humans , Lumbar Vertebrae , Male , Middle Aged , Retrospective Studies , Spinal Fusion/methods , Thoracic Vertebrae/surgery , Treatment Outcome , Tuberculosis, Spinal/surgery , Young AdultABSTRACT
Periprosthetic joint infection (PJI) is the most difficult complication following total joint arthroplasty. Most of the etiological strains, accounting for over 98% of PJI, are bacterial species, with Staphylococcusaureus and Coagulase-negative staphylococci present in between 50% and 60% of all PJIs. Fungi, though rare, can also cause PJI in 1%-2% of cases and can be challenging to manage. The management of this uncommon but complex condition is challenging due to the absence of a consistent algorithm. Diagnosis of fungal PJI is difficult as isolation of the organisms by traditional culture may take a long time, and some of the culture-negative PJI can be caused by fungal organisms. In recent years, the introduction of next-generation sequencing has provided opportunity for isolation of the infective organisms in culture-negative PJI cases. The suggested treatment is based on consensus and includes operative and non-operative measures. Two-stage revision surgery is the most reliable surgical option for chronic PJI caused by fungi. Pharmacological therapy with antifungal agents is required for a long period of time with antibiotics and included to cover superinfections with bacterial species. The aim of this review article is to report the most up-to-date information on the diagnosis and treatment of fungal PJI with the intention of providing clear guidance to clinicians, researchers and surgeons.
Subject(s)
Arthritis, Infectious , Arthroplasty, Replacement, Knee , Prosthesis-Related Infections , Arthritis, Infectious/etiology , Arthroplasty, Replacement, Knee/adverse effects , Fungi , Humans , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/therapy , Retrospective StudiesABSTRACT
INTRODUCTION: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure. MATERIALS AND METHODS: All 154 patients with COVID-19 were recruited from the Second People's Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study. RESULTS: There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge. CONCLUSION: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.
Subject(s)
COVID-19/complications , COVID-19/physiopathology , Kidney Diseases/complications , Kidney/physiopathology , Adult , Age Factors , Aged , China , Creatinine/blood , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Hypertension/complications , Kidney Function Tests , Male , Middle Aged , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study. METHODS: A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured. RESULTS: Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients. CONCLUSION: Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.
Subject(s)
Calgranulin B/blood , Community-Acquired Infections/blood , Pneumonia/blood , Aged , Biomarkers/blood , Cohort Studies , Community-Acquired Infections/diagnosis , Female , Humans , Male , Middle Aged , Patient Acuity , Pneumonia/diagnosis , Prognosis , Prospective StudiesABSTRACT
Vitamin D deficiency is correlated with the increased morbidity of chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying these effects have largely remained elusive. This study analyzed the correlations among COPD, vitamin D concentration, and epithelial-mesenchymal transition (EMT). Ninety-five patients with newly diagnosed COPD and 190 age- and sex-matched healthy subjects were recruited for this research. Serum 25(OH)D levels were detected, and pulmonary EMT biomarkers and TGF-ß/Smad signaling were evaluated. Serum 25(OH)D level was remarkably decreased in COPD patients compared with that in control subjects. Furthermore, serum 25(OH)D concentration gradually decreased in COPD patients ranging from grade 1-2 to 4. However, reduced expression of the epithelial biomarker E-cadherin and increased expression of the mesenchymal biomarkers vimentin and α-SMA were found in COPD patients. Mechanistic analysis showed that pulmonary nuclear vitamin D receptor (VDR) was decreased in patients with COPD. In contrast, TGF-ß/Smad signaling was obviously activated in COPD patients. Furthermore, the level of serum TGF-ß in COPD patients increased in parallel with COPD severity. Serum 25(OH)D concentration was inversely associated with TGF-ß levels in COPD patients. In vitro experiments showed that active vitamin D3 inhibits TGF-ß-induced Smad2/3 phosphorylation in MRC-5 cells. Furthermore, vitamin D concentration was inversely correlated with TGF-ß/Smad signaling and EMT in COPD patients, suggesting EMT as a vital mediator of COPD development in patients with low vitamin D concentrations.
Subject(s)
Epithelial-Mesenchymal Transition/physiology , Pulmonary Disease, Chronic Obstructive/metabolism , Vitamin D/metabolism , Aged , Biomarkers/blood , Biomarkers/metabolism , Cadherins/metabolism , Calcifediol/blood , Female , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/blood , Receptors, Calcitriol/metabolism , Signal Transduction/physiology , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta/metabolism , Vimentin/metabolismABSTRACT
To be faced with an infected bone defect and the need to accelerate bone union while controlling infection is a welcome challenge for orthopedists. Platelet-rich plasma (PRP) has been applied in tissue defects given their composition of growth factors however the weak antibacterial effects have limited the use of PRP in the clinical setting. Therefore, the aim of this study was to explore the feasibility of using PRP in a local antibiotic delivery system (PADS) with the characteristics of promoting wound healing of bone infection. PADS was prepared with the addition of antibiotics or no antibiotics as control after PRP was prepared by a two-step centrifugation procedure. Antibacterial tests showed zones of inhibition produced by antibiotics were not significantly different with antibiotics combined with PRP. HPLC analysis demonstrated that about 60% of the total vancomycin (VAN) and ceftazidime (CAZ) dose were released within 10 min, then the release rate gradually decreased. However, 90% clindamycin was released within 10 min. Interestingly, above 10 times the minimum inhibitory concentration was presented after 72 h. Additionally, ELISA and morphology studies of PADS indicated that loaded antibiotics could reduce the PRP-released growth factor concentration and disturb the structure of platelet-fibrin beams and fibrin network in a dose-dependent manner. Fortunately, the lower dose of antibiotics maintained their anti-microbial effect, meanwhile growth factors released from PADS, the structure of platelet-fibrin beams, fibrin network remained unaffected. In addition, a patient experiencing infected bone defect receiving this PADS treatment achieved union within the 15-month follow-up. Therefore, this novel PADS approach might represent a potential therapy for patients who have sustained infected bone defects.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Platelet-Rich Plasma/drug effects , Wound Healing/drug effects , Adult , Anti-Bacterial Agents/pharmacology , Humans , MaleABSTRACT
AIM: To investigate paediatric outpatients' nutritional status using bioelectrical impedance analysis and anthropometric z-scores. METHODS: A retrospective data analysis of tertiary paediatric hospital outpatients from 2017 to 2019 was conducted. Patients were categorised into three groups (non-illness, illness and simple obesity) according to clinical diagnoses. The nutritional status was evaluated using anthropometric and bioelectrical impedance analysis. In addition, body composition measurements of patients in three subgroups of the illness group and age- and gender-matched healthy controls were compared. RESULTS: A total of 2015 paediatric outpatients were enrolled. According to body mass index z-scores, undernutrition prevalence among participants was 14.0% (non-illness group, 21.3%; illness group, 11.4%). Body composition measurements indicated that 41.6% of participants had a low fat-free mass index, and the proportions of participants with a low fat-free mass index in the non-illness, illness and simple obesity groups were 48.4, 47.0 and 10.7%, respectively. Compared with healthy controls, the haematology and oncology subgroup had a significantly lower fat-free mass index and fat mass index; the nephrology and rheumatology subgroup had significantly lower height-for-age z-scores but higher fat mass index; and the gastroenterology subgroups had lower fat mass index, fat-free mass index and body mass index z-scores. CONCLUSIONS: The results suggested the low fat-free mass index prevalence was greater than the low body mass index z-score prevalence among paediatric outpatients, and body composition parameters varied across different illnesses. Body composition analysis is recommended in nutrition clinics for accurate paediatric outpatient nutritional assessment, thereby providing timely individualised nutritional interventions.
Subject(s)
Nutritional Status , Outpatients , Anthropometry , Body Composition , Body Mass Index , Child , Electric Impedance , Humans , Retrospective StudiesABSTRACT
Environmental cadmium (Cd) exposure can cause several pulmonary diseases. Epithelial-mesenchymal transition (EMT) involved in the process of chronic obstructive pulmonary disease (COPD). However, the association between environmental Cd exposure and EMT was unclear in COPD patients. This study aimed to analyze the associations among circulatory Cd, EMT and COPD based on case-control study. Four hundred COPD patients and 400 control subjects were recruited. Circulatory Cd was detected using atomic adsorption spectrometer. MicroRNA-30 (miR-30) was measured by RT-PCR and the markers of pulmonary EMT were evaluated through western blotting. Circulatory Cd concentration was increased and serum miR-30 was decreased in COPD patients. Circulatory Cd was inversely associated with pulmonary function in COPD patients. Moreover, serum miR-30 was gradually decreased in parallel with FEV1 in COPD patients. Meanwhile, there was a negative association between serum miR-30 and circulatory Cd in COPD patients. Further analysis found that E-cadherin, one of epithelial biomarkers, was reduced in lung tissues of COPD patients with higher circulatory Cd. On the contrary, pulmonary N-cadherin, Vimentin and α-SMA, three of mesenchymal biomarkers, were increased in COPD patients with higher circulatory Cd. In vitro experiments revealed that Cd exposure repressed miR-30 levels and promoted EMT in BEAS-2B cells. Our results provide evidence that miR-30 reduction contributing to pulmonary EMT may involve in the process of Cd-induced COPD.
Subject(s)
Cadmium/blood , Environmental Exposure/statistics & numerical data , Environmental Pollutants/blood , Pulmonary Disease, Chronic Obstructive/blood , Antigens, CD , Cadherins , Case-Control Studies , Epithelial-Mesenchymal Transition , Female , Humans , Lung/physiopathology , Male , MicroRNAs , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , VimentinABSTRACT
Skeletal homeostasis is closely effectuated by the regulation of bone formation and bone resorption. Osteoclasts are multinuclear giant cells responsible for bone resorption. Overactivated osteoclasts and excessive bone resorption result in various lytic bone diseases, such as osteoporosis, osteoarthritis, periprosthetic infection, and inflammatory aseptic loosening of orthopedic implants. In consideration of the severe side effects caused by the currently available drugs, exploitation of novel drugs has gradually attracted attention. Because of its anti-inflammatory, antioxidant, and antitumor capacities, diallyl disulfide (DADS), a major oil-soluble organosulfur ingredient compound derived from garlic, has been widely researched. However, the effects of DADS on osteoclasts and lytic bone diseases are still unknown. In this study, we investigated the effects of DADS on receptor activator of NF-κB ligand (RANKL)- and LPS-mediated osteoclastogenesis, LPS-stimulated proinflammatory cytokines related to osteoclasts, and LPS-induced inflammatory osteolysis. The results showed that DADS significantly inhibited RANKL-mediated osteoclast formation, fusion, and bone resorption in a dose-dependent manner via inhibiting the NF-κB and signal transducer and activator of transcription 3 signaling and restraining the interaction of NF-κB p65 with nuclear factor of activated T cells cytoplasmic 1. Furthermore, DADS also markedly suppressed LPS-induced osteoclastogenesis and reduced the production of proinflammatory cytokines with LPS stimulation to indirectly mediate osteoclast formation. Consistent with the in vitro results, DADS prevented the LPS-induced severe bone loss by blocking the osteoclastogenesis. All of the results indicate that DADS may be a potential and exploitable drug used for preventing and impeding osteolytic lesions.-Yang, J., Tang, R., Yi, J., Chen, Y., Li, X., Yu, T., Fei, J. Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF-κB-NFATc1 signal pathway.
Subject(s)
Allyl Compounds/pharmacology , Anti-Inflammatory Agents/pharmacology , Disulfides/pharmacology , NF-kappa B/physiology , Osteoclasts/drug effects , Osteolysis/drug therapy , Signal Transduction/drug effects , Allyl Compounds/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Bone Resorption/drug therapy , Cell Differentiation/drug effects , Disulfides/therapeutic use , Endotoxemia/complications , Female , Inflammation , Lipopolysaccharides/toxicity , Macrophage Colony-Stimulating Factor/pharmacology , Macrophages/cytology , Macrophages/drug effects , Mice , Mice, Inbred C57BL , Osteoclasts/pathology , Osteolysis/etiology , RANK Ligand/antagonists & inhibitors , RANK Ligand/pharmacology , RAW 264.7 Cells , Random Allocation , Recombinant Proteins/pharmacology , STAT3 Transcription Factor/antagonists & inhibitors , STAT3 Transcription Factor/physiology , Signal Transduction/physiologyABSTRACT
BACKGROUND: Many studies have indicated that S100A8 and S100A9 may be involved in the development and progression of chronic obstructive pulmonary disease (COPD). However, there has been no clinical study analyzing the role of the serum S100A8/S100A9 heterodimer in COPD patients. The aim of this study was to analyze the correlation of the serum S100A8/S100A9 heterodimer with pulmonary function in COPD patients during acute exacerbation (AE-COPD) based on a cross-sectional study. METHODS: A total of 131 AE-COPD patients and matched healthy subjects were recruited. Pulmonary function, arterial blood gas values, and serum inflammatory cytokines were measured. RESULTS: Serum S100A8/S100A9 was increased in AE-COPD patients. AE-COPD patients were ranked into different grades based on FEV1%. Serum S100A8/S100A9 was higher in Grade 4 than in Grade 1-2 and Grade 3 patients with AE-COPD. Univariate regression analysis found that serum S100A8/S100A9 was negatively correlated with FEV1% in AE-COPD patients. Furthermore, serum S100A8/S100A9 was positively associated with MCP-1 in AE-COPD patients. Further stratified analysis revealed that serum S100A8/S100A9 was negatively associated with FEV1/FVC in Grade 3 (OR 0.629, P < 0.05) and in Grade 4 (OR 0.347, P < 0.05). In addition, there was a positive relationship between serum S100A8/S100A9 and PaCO2 in Grade 3 (OR 1.532, P < 0.05) and Grade 4 (OR 1.925, P < 0.01). CONCLUSION: S100A8/S100A9 was negatively associated with pulmonary function in AE-COPD patients, indicating that the serum S100A8/S100A9 heterodimer may be involved in the progression of AE-COPD, and may be a relevant serum biomarker in the diagnosis for AE-COPD.
Subject(s)
Leukocyte L1 Antigen Complex/blood , Pulmonary Disease, Chronic Obstructive/blood , Aged , Blood Gas Analysis , Calgranulin A , Calgranulin B , Chemokine CCL2/blood , Disease Progression , Female , Forced Expiratory Volume , Humans , Interleukin-1beta/blood , Interleukin-6/blood , Male , Protein Multimerization , Pulmonary Disease, Chronic Obstructive/physiopathology , Tumor Necrosis Factor-alpha/blood , Vital CapacityABSTRACT
In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.
Subject(s)
Bone and Bones/injuries , Bone and Bones/metabolism , Immune System/immunology , Osteitis/metabolism , Osteitis/microbiology , Staphylococcal Infections , Anti-Bacterial Agents/administration & dosage , Bone and Bones/immunology , Cellular Microenvironment , Humans , Lymphocyte Subsets/immunology , Osteitis/drug therapy , Osteitis/immunology , Osteoblasts/physiology , Osteoclasts/physiologyABSTRACT
Excessive osteoclast formation is one of the important pathological features of inflammatory bone destruction. Interleukin-37 (IL-37) is an anti-inflammatory agent that is present throughout the body, but it displays low physiological retention. In our study, high levels of the IL-37 protein were detected in clinical specimens from patients with bone infections. However, the impact of IL-37 on osteoclast formation remains unclear. Next, IL-37 alleviated the inflammatory bone destruction in the mouse in vivo. We used receptor activator of nuclear factor-κB ligand and lipopolysaccharide to trigger osteoclastogenesis under physiological and pathological conditions to observe the role of IL-37 in this process and explore the potential mechanism of this phenomenon. In both induction models, IL-37 exerted inhibitory effects on osteoclast differentiation and bone resorption. Furthermore, IL-37 decreased the phosphorylation of inhibitor of κBα and p65 and the expression of nuclear factor of activated T cells c1, while the dimerization inhibitor of myeloid differentiation factor 88 reversed the effects. These data provide evidence that IL-37 modulates osteoclastogenesis and a theoretical basis for the clinical application of IL-37 as a treatment for bone loss-related diseases.