The role of extracellular vesicles in iron homeostasis and ferroptosis: Focus on musculoskeletal diseases.

Iron homeostasis is crucial for maintaining proper cellular function, and its disruption is considered one of the pathogenic mechanisms underlying musculoskeletal diseases. Under conditions of oxidative stress, the accumulation of cellular iron overload and lipid peroxidation can lead to ferroptosis. Extracellular vesicles (EVs), serving as mediators in the cell-to-cell communication, play an important role in regulating the outcome of cell ferroptosis. Growing evidence has proven that EV biogenesis and secretion are tightly associated with cellular iron export. Furthermore, different sources of EVs deliver diverse cargoes to bring about phenotypic changes in the recipient cells, either activating or inhibiting ferroptosis. Thus, delivering therapies targeting ferroptosis through EVs may hold significant potential for treating musculoskeletal diseases. This review aims to summarize current knowledge on the role of EVs in iron homeostasis and ferroptosis, as well as their therapeutic applications in musculoskeletal diseases, and thereby provide valuable insights for both research and clinical practice.

Indole-3-acetic acid regulating the initial adhesion of microalgae in biofilm formation.

Regulating the microalgal initial adhesion in biofilm formation is a key approach to address the challenges of attached microalgae cultivation. As a type of phytohormone, Indole-3-acetic acid (IAA) can promote the growth and metabolism of microalgae. However, limited knowledge has been acquired of how IAA can change the initial adhesion of microalgae in biofilm formation. This study focused on investigating the initial adhesion of microalgae under different IAA concentrations exposure in biofilm formation. The results showed that IAA showed obvious hormesis-like effects on the initial adhesion ability of microalgae biofilm. Under exposure to the low concentration (0.1 mg/L) of IAA, the initial adhesion quantity of microalgae on the surface of the carrier reached the highest value of 7.2 g/m2. However, exposure to the excessively high concentration (10 mg/L) of IAA led to a decrease in the initial adhesion capability of microalgal biofilms. The enhanced adhesion of microalgal biofilms due to IAA was attributed to the upregulation of genes related to the Calvin Cycle, which promoted the synthesis of hydrophobic amino acids, leading to increased protein secretion and altering the surface electron donor characteristics of microalgal biofilms. This, in turn, reduced the energy barrier between the carriers and microalgae. The research findings would provide crucial support for the application of IAA in regulating the operation of microalgal biofilm systems.

Risk factors for osteonecrosis of the humeral head after internal fixation of proximal humeral fractures: a systematic review and meta-analysis.

BACKGROUND: Osteonecrosis of the humeral head (ONHH) is a severe complication after the internal fixation of proximal humeral fractures (IFPHF). The risk factors remain controversial though many studies have reported. In this research, meta-analysis was used to evaluate which surgeon-level factors can be modified to lower the risk and we hope to provide evidence-based support for preventing ONHH. METHODS: Literature was retrieved from PubMed, Cochrane Library, Embase, Web of Science, and Scopus for eligible studies published up to January 2023. The pooled odds ratios (ORs) were calculated with their corresponding 95% confidence intervals (CIs) to evaluate. STATA 15.1 software was applied for data synthesis, sensitivity synthesis, and publication bias. RESULTS: 45 articles were published between 2000 and 2022, and 2482 patients were finally included. All articles were observational research, with 7 case-control studies and 38 cohort studies, and the Newcastle Ottawa Scale (NOS) score ranged from 7 to 9. The pooled results suggested that age (OR 0.32, 95% CI 0.14-0.74, P = 0.01), reduction quality (OR 0.08, 95% CI 0.01-0.44, P = 0.00), fracture type (OR 0.44, 95% CI 0.25-0.78, P = 0.01), surgical approach (OR: 4.06, 95% CI 1.21-13.61, P = 0.02) and fixation implant (OR = 0.68, 95% CI = 0.34-1.33, P = 0.02) were risk factors for ONHH after IFPHF. According to sensitivity analysis, Begg (P = 0.42) and Egger (P = 0.68) tests, the results were stable and exhibited no publication bias. CONCLUSIONS: The study showed that age, reduction quality, fracture type, surgical approach and fixation implant were risk factors for ONHH after IFPHF, while gender, varus or valgus, timely operation, injured side, and the existence of medial support have little influence on ONHH, as they could not be considered risk factors and still need further investigations.

N-acyl homoserine lactone mediating initial adhesion of microalgal biofilm formation.

While pioneering methods have demonstrated that bacterial N-acyl homoserine lactone (AHL) signaling molecules can influence the growth and self-aggregation of suspended microalgae, whether AHLs can affect the initial adhesion to a carrier has remained an open question. Here we revealed that the microalgae exhibited different adhesion potential under AHL mediation, where the performance was affiliated to both AHL types and concentrations. The result can be well explained by the interaction energy theory, where the energy barrier between the carriers and the cells varied due to AHL mediation. Depth analyses revealed that AHL acted through modifying the properties of the surface electron donor of the cells, which were dependent upon three major components, i.e., extracellular protein (PN) secretion, the PN secondary structure, and the PN amino acid composition. These findings expand the known diversity of AHLs mediation on microalgal initial adhesion and metabolisms, which may interface with other major cycles and become helpful to theoretically guide the application of AHLs in microalgal culture and harvesting.

[Association of phthalate and polycyclic aromatic hydrocarbon exposure during early pregnancy with premature delivery: A cohort study].

OBJECTIVE: To explore the relationship of the exposure to phthalate esters (PAE) and polycyclic aromatic hydrocarbons (PAH) with clinical premature delivery during early pregnancy. METHODS: We conducted a baseline questionnaire survey among 821 pregnant women undergoing prenatal examination in Hubei Provincial Maternal and Child Health Care Hospital, collected their morning urine samples and followed them up to the outcomes of pregnancy. We quantitatively analyzed 10 PAE and 10 PAH metabolites in the urine samples, followed by Mann-Whitney U test, chi-square test, and logistic regression analysis. RESULTS: The detection rate of the 5 factors exposed to was >80% while that of phthalic acid monobenzyl ester (MBzP) was <50% in PAEs; that of the 5 factors exposed to was >80%, that of 3-hydroxyphene (3-OHPHE) was 86.91% while that of 4-hydroxyphene (4-OHPHE) was <50% in PAHs. Logistic regression analysis showed that the risk of premature delivery was higher in the high MBzP- than in the low MBzP-exposure group (aOR = 2.26, 95% CI: 1.17－4.39). CONCLUSION: High MBzP-exposure may be a risk factor for premature delivery.

Minimally Invasive Percutaneous Leverage Reduction in the Treatment of Pediatric Salter-Harris IV and V Distal Femoral Physeal Fractures.

OBJECTIVE: Distal femoral physeal fractures (DFPF) are rare but severe injuries in children, and there is no consensus on treatments for Salter-Harris (S-H) IV and V type of DFPF yet. This study aimed to introduce a minimally invasive technique using percutaneous leverage reduction combined with Kirschner wires fixation in treating pediatric DFPF with S-H IV and V type of injury and evaluate the clinical results. METHODS: From July 2008 to June 2018, the authors' institute (Union Hospital, Tongji Medical College) retrospectively reviewed all patients diagnosed with pediatric DFPF. They were divided into two groups according to received treatment: children in the minimally invasive technique group were treated with a minimally invasive percutaneous leverage reduction technique, and the traditional technique group included the other children who received the conventional open reduction with internal fixation (ORIF). The surgical and clinical results of the two groups were collected and analyzed. The independent sample t-test analysis and the chi-square test were applied to compare continuous and categorical variables. RESULTS: A total of 14 pediatric patients were recruited, including five females and nine males with DFEF. All eight patients in the minimally invasive technique group and four of the six patients in the ORIF group were treated successfully. One patient in the minimally invasive technique group opted for conservative treatment due to his good functional recovery, while the other two patients in the ORIF group needed further surgery because of the limb length discrepancy. There was a difference in surgery duration (p < 0.001), intraoperative fluoroscopy numbers (p = 0.006), intraoperative blood loss (p < 0.001), radiological union time (p = 0.003) and knee flexion angle (p < 0.001) between two groups. Patients in the minimally invasive technique group all received total knee society (KSS) scores, while the average scores in the ORIF group were lower (100.00 vs. 97.67). CONCLUSION: The minimally invasive technique is better than conventional ORIF in terms of surgery duration, intraoperative blood loss, radiological union time, knee flexion angle and average KSS score. This percutaneous leverage reduction technique might be a good alternative for treating S-H IV and V DFPF in children.

Engineered extracellular vesicles as therapeutics of degenerative orthopedic diseases.

Degenerative orthopedic diseases, as a global public health problem, have made serious negative impact on patients' quality of life and socio-economic burden. Traditional treatments, including chemical drugs and surgical treatments, have obvious side effects and unsatisfactory efficacy. Therefore, biological therapy has become the focus of researches on degenerative orthopedic diseases. Extracellular vesicles (EVs), with superior properties of immunoregulatory, growth support, and drug delivery capabilities, have emerged as a new cell-free strategy for the treatment of many diseases, including degenerative orthopedic diseases. An increasing number of studies have shown that EVs can be engineered through cargo loading, surface modification, and chemical synthesis to improve efficiency, specificity, and safety. Herein, a comprehensive overview of recent advances in engineering strategies and applications of engineered EVs as well as related researches in degenerative orthopedic diseases, including osteoarthritis (OA), osteoporosis (OP), intervertebral disc degeneration (IDD) and osteonecrosis of the femoral head (ONFH), is provided. In addition, we analyze the potential and challenges of applying engineered EVs to clinical practice.

Minimally invasive technique combined with external fixator in the treatment of pediatric flexion-type humeral supracondylar fractures.

Flexion-type pediatric humeral supracondylar fractures are rare, and the reduction technique remains contradictory. A minimally invasive technique using percutaneous leverage reduction combined with an external fixator was described to achieve satisfactory reduction and avoid the open reduction in this study. The operation and clinical results of patients treated with this technique were retrospectively compared with traditional closed reduction. From January 2013 to January 2018, children diagnosed with displaced flexion-type humeral supracondylar fractures were included in this study. Patients were treated with closed reduction (Group A) or minimally invasive reduction technique (Group B). The external fixator fixation was then applied. The demographic information, as well as the clinical and functional results of the operation, were retrospectively reviewed and evaluated. There were twenty-two patients, ten in Group A and twelve in Group B. The mean duration of the operation in Group A was more prolonged than Group B (59 min versus 46 min, p < 0.001). No infection, nonunion, myositis ossificans, neurovascular injury or other complications related to the operation were observed by the time the fractures healed. During an average 36 months follow-up time, almost all children achieved good to excellent results except for one fair in Group A according to the MEPS and the Flynn criteria. This study introduced a safe and efficient minimally invasive technique for displaced flexion-type supracondylar humerus fractures. With the assistance of mosquito forceps, this leverage technique might achieve similar satisfactory clinical outcomes as traditional closed reduction but with a shorter surgical duration.

Small incision reduction and external fixation for the treatment of delayed over fourteen days supracondylar humeral fractures in children.

Background: Supracondylar humeral fractures (SHF) are the most common type of fracture occurring at the distal humerus in children. In patients with delayed presentation of SHF, closed reduction is challenging to achieve with traditional reduction maneuvers. This study aimed to report the clinical results of pediatric SHF delayed over 14 days treated by closed reduction with a minimally invasive technique and external fixation and evaluate the efficacy of this technique. Methods: Between October 2010 and September 2018, children with delayed presentation of SHF over 14 days were retrospectively included in this study. The patients received closed reduction with a minimally invasive technique followed by external fixation. The demographics and radiographic data were collected. The Mayo Elbow Performance Score (MEPS) and the Flynn criteria were used to evaluate the clinical outcomes of treatments. Results: A total of 11 children (aged 4-13 years) with delayed presentation (range, 14-22 days) were recruited. They received surgery using closed reduction with a minimally invasive technique followed by external fixation. None of the surgery was done with the open method. After surgery, the patients' carrying angle returned to normal. The radiological union was evident in 8 to 12 weeks in all fractures without complications. Every patient had a good to excellent score on the MEPS and the Flynn criteria. Conclusions: The results of this series indicated a satisfactory outcome in children with delayed more than 14 days of supracondylar humeral fractures. The closed reduction with a minimally invasive technique followed by external fixation is an alternative treatment for such injury.

Cadmium exposure and the risk of GDM: evidence emerging from the systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) has become a global concern for its severe adverse effects on both mother and fetus. Recent epidemiological studies reported inconsistent results of the association between cadmium (Cd) exposure and GDM. Therefore, a systematic review and meta- analysis were performed. PubMed, Web of Science, Scopus, Embase, and SpringerLink were searched up to July 2021. Observational studies containing the adjusted relative risks between Cd exposure and GDM were included in the quantitative synthesis. The retrieval comprised 218 articles out of which 11 met our criteria and 9 were included in the meta-analysis, representing a total of 32,392 subjects (2881 GDM). In total, Cd exposure might increase the risk of GDM in some extent (OR = 1.21, 95% CI [0.89, 1.64]), even without statistical significance in high heterogeneity (Q = 28.45, p < 0.05, I2 = 71.9%). Filtering two outliers indicated by Galbraith plot yielded a similar risk (OR = 1.19, 95% CI [1.02, 1.39]) with statistical significance. However, the heterogeneity among studies was obviously reduced (Q = 11.75, p = 0.068, I2 = 48.9%). Additionally, biological specimen, study design, and diagnostic criteria contributed to the high heterogeneity according to the subgroup analysis. Since some important results do not deny that Cd exposure increases the risk of GDM, high-quality multi-centered large cohort studies are required in the future.

Induction of cardiotoxicity in zebrafish embryos by 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene through the JAK-STAT and NOTCH signaling pathways.

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is the primary molecular metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), a pesticide used to control the spread of dengue and Zika viruses, and can be detected in the majority of human blood samples. However, whether p,p'-DDE affects embryonic cardiac development remains unknown. This study aimed to explore the cardiotoxicity of p,p'-DDE and its potential mechanisms of action in zebrafish embryos. We demonstrated for the first time that zebrafish embryos exposed to p,p'-DDE exhibited cardiac development abnormalities, including morphological and functional abnormalities, such as pericardial edema, thinning of the ventricular wall, reduced erythrocyte intensity, and increased heart rate. The results of Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes and qRT-PCR showed that JAK-STAT-related genes (il17d, socs3a, and bcl2b) and Notch-related genes (notch1a, notch1b, bmp10, efnb2a, tbx2b, and tbx5a) were altered after p,p'-DDE treatment, leading to reduced proliferation and increased apoptosis of cardiomyocytes and irregular formation of ventricular and abnormal atrioventricular junctions. These results were verified using acridine orange staining, 5-ethynyl-2'-deoxyuridine assays, and whole-mount in situ hybridization. Our research suggests that p,p'-DDE affects cardiac development in zebrafish embryos and that its cardiotoxicity may be associated with the JAK-STAT and Notch signaling pathways. Our findings may provide the basis for future population-based cohort studies.

The Effect and Mechanism of Exercise Training on Rats with Poststroke Depression Based on the Intestinal Flora.

Depression of poststroke depression (PSD) is the most common neuropsychiatric complication after stroke. Patients with PSD had higher mortality, more cognitive disorder, lower quality of life, and higher suicidal tendency. The pathogenesis of PSD mainly involves neurotransmitter inflammatory factors, HPA and BDNF. Enteral dysfunction and intestinal flora disorders caused by stroke can participate in the pathogenesis of PSD through various ways, such as immune, endocrine, and nervous system. In this experiment, we used exercise training as an intervention means to explore the curative effect and possible mechanism by observing the changes of behavior, inflammatory factors, and intestinal flora in rats. The results show that the mechanism of exercise training to improve the depressive behavior of rats may be related to inhibiting the expression of proinflammatory factors and increasing the number of lactic acid bacteria in the intestine.