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Frontiers in Pharmacology 2024Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The...
Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.
PubMed: 38799163
DOI: 10.3389/fphar.2024.1391511 -
Knee Surgery, Sports Traumatology,... May 2024Instability of the glenohumeral joint remains a complex clinical issue with high rates of surgical failure and significant morbidity. Advances in specific radiologic...
PURPOSE
Instability of the glenohumeral joint remains a complex clinical issue with high rates of surgical failure and significant morbidity. Advances in specific radiologic measurements involving the glenoid and the humerus have provided insight into glenohumeral pathology, which can be corrected surgically towards improving patient outcomes. The contributions of capsular pathology to ongoing instability remain unclear. The purpose of this study is to provide a systematic review of existing glenohumeral capsular measurement techniques published in the last 15 years.
METHODS
A systematic review of multiple databases was performed following PRISMA guidelines for all primary research articles between 2008 and 2023 with quantitative measurements of the glenohumeral capsule in patients with instability, including anterior, posterior and multi-directional instability.
RESULTS
There were a total of 14 articles meeting the inclusion criteria. High variability in measurement methodology across studies was observed, including variable amounts of intra-articular contrast, heterogeneity among magnetic resonance sequence acquisitions, differences in measurements performed and the specific approach taken to compute each measurement.
CONCLUSION
There is a need for standardization of methods in the measurement of glenohumeral capsular pathology in the setting of glenohumeral instability to allow for cross-study analysis.
LEVEL OF EVIDENCE
Level III.
PubMed: 38796731
DOI: 10.1002/ksa.12236 -
Anatomical Record (Hoboken, N.J. : 2007) May 2024The temporomandibular joint (TMJ) is a complex structure that plays a vital role in the movement of the jaw. Some anatomy and dental textbooks show that, at the medial...
The temporomandibular joint (TMJ) is a complex structure that plays a vital role in the movement of the jaw. Some anatomy and dental textbooks show that, at the medial margin, the TMJ capsule attaches to a suture between the sphenoid ala major and the temporal bone squamosa. In near-term fetuses, the ala major extends posterolaterally to approach the TMJ. In this study, we aimed to investigate the contribution of the sphenoid ala major to the socket of the TMJ in near-term fetuses. We examined histological sections from 22 human fetuses (approximately 15-40 weeks). At midterm, the lateral and superior walls of the TMJ cavity were formed by the temporal bone squamosa, whereas the ala major was distant from the joint. However, at near-term, the ala major formed the medial wall of almost the entire part of the joint cavity. The top of the TMJ was attached to both the squamosa and ala major, with the condylar head consistently separated from the sphenoid by the joint disk. We observed a significant descent of the middle cranial fossa in near-term fetuses, which brought the ala major close to the TMJ. This transient position of the TMJ near the sphenoid is likely due to brain enlargement and posterolateral growth of the ala major. After birth, occlusion causes the anterior growth of the mandibular fossa of the squamosa, which moves the ala major away from the TMJ. Similarly, the lateral growth of the sphenoid toward the squamosa suture may also stop in children.
PubMed: 38794819
DOI: 10.1002/ar.25507 -
Medicina (Kaunas, Lithuania) Apr 2024(1) : Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial...
(1) : Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial myofibroblasts, implicated in synovial fibrosis and OA-related pain, offer a potential explanation for these sex differences. Additionally, interleukin-24 (IL24), known for its role in autoimmune disorders and potential myofibroblast production, adds complexity to understanding sex-specific variations in OA. We investigate its role in OA and its contribution to observed sex differences. (2) : To assess gender-specific variations, we analyzed myofibroblast marker expression and levels in synovial tissue samples from propensity-matched male and female OA patients (each = 34). Gene expression was quantified using quantitative polymerase chain reaction (qPCR). The association between expression levels and pain severity, measured by a visual analog scale (VAS), was examined to understand the link between and OA pain. Synovial fibroblast subsets, including CD45-CD31-CD39- (fibroblast) and CD45-CD31-CD39+ (myofibroblast), were magnetically isolated from female patients ( = 5), and expression was compared between these subsets. (3) : Females exhibited significantly higher expression of myofibroblast markers (MYH11, ET1, ENTPD2) and compared to males. expression positively correlated with pain severity in females, while no correlation was observed in males. Further exploration revealed that the myofibroblast fraction highly expressed compared to the fibroblast fraction in both male and female samples. There was no difference in the myofibroblast fraction between males and females. (4) : Our study highlights the gender-specific role of myofibroblasts and IL24 in OA pathogenesis. Elevated IL24 levels in females, correlating with pain severity, suggest its involvement in OA pain experiences. The potential therapeutic implications of IL24, demonstrated in autoimmune disorders, open avenues for targeted interventions. Notwithstanding the limitations of the study, our findings contribute to understanding OA's multifaceted nature and advocate for future research exploring mechanistic underpinnings and clinical applications of IL24 in synovial myofibroblasts. Additionally, future research directions should focus on elucidating the precise mechanisms by which IL24 contributes to OA pathology and exploring its potential as a therapeutic target for personalized medicine approaches.
Topics: Humans; Female; Male; Myofibroblasts; Interleukins; Synovial Membrane; Osteoarthritis; Middle Aged; Aged; Propensity Score; Sex Factors; Pain
PubMed: 38792924
DOI: 10.3390/medicina60050741 -
Medicina (Kaunas, Lithuania) Apr 2024: The number of hip arthroscopy procedures is on the rise worldwide, and awareness regarding proper management of the hip capsule has increased. No capsulotomy shape is...
: The number of hip arthroscopy procedures is on the rise worldwide, and awareness regarding proper management of the hip capsule has increased. No capsulotomy shape is agreed upon as a standard approach, with literature supporting both isolated interportal and T-shaped capsulotomies. The aim of this retrospective cohort study is to report the clinical results of a standardized extended interportal capsulotomy (EIPC) during hip arthroscopy. : Patients operated on between 2017 and 2020 with a hip arthroscopy were eligible. The inclusion criteria were ages 18-60 years, failed non-operative treatment, and at least a 2-year follow-up. Exclusion criteria were bilateral femoroacetabular impingement syndrome (FAS) cases or labral lesions, ipsilateral knee injury, history of ipsilateral hip surgery, and significant spine lesions. Data regarding demographic characteristics such as age, gender, operation date, BMI, but also Beighton score, presence of postoperative pudendal nerve damage, and revision for any reason were gathered from patients' records. All patients were evaluated preoperatively with a visual analog scale (VAS), the Hip Disability and Osteoarthritis Outcome Score (HOOS), and the modified Harris Hip Score (mHHS). : Of the 97 patients operated on with a hip arthroscopy between the defined dates, only 90 patients were included. The mean age was 37.9 ± 9.8, and 58.9% of patients were male. The most frequent surgical indication was an isolated FAS lesion (73.3%), followed by FAS associated with a labral tear (12.2%), an isolated labrum tear (10.0%), synovitis (3.3%), and a loose body (1.1%). The mean follow-up for the study cohort was 39.3 months. The majority of the patients had uneventful surgeries (76.7%), while there were three cases of sciatic nerve neuropraxia and 12 cases of pudendal nerve neuropraxia. Two patients underwent revision surgery during the study period. Comparison between preoperative and postoperative clinical scores showed a significant improvement with a final mHHS mean value of 67.7 ± 18.2, an HOOS value of 74.1 ± 13.2, and a low VAS score of 1.3 ± 1.2. : A hip arthroscopy procedure with a standardized and unrepaired, extended interportal capsulotomy is a safe procedure with satisfactory mid-term results and high overall patient satisfaction. At a minimum of 2 years and a mean of 39.2 months, patients showed improved clinical scores and a low revision rate.
Topics: Humans; Adult; Male; Female; Retrospective Studies; Middle Aged; Arthroscopy; Hip Joint; Adolescent; Joint Capsule; Treatment Outcome; Cohort Studies; Young Adult; Femoracetabular Impingement
PubMed: 38792921
DOI: 10.3390/medicina60050738 -
Medicina (Kaunas, Lithuania) Apr 2024: The interspace between the popliteal artery and the posterior capsule of the knee (iPACK) block has been widely used in perioperative settings to control posterior...
Investigation of Optimal Needle Position for Radiofrequency Ablation-Based Blockade of Interspace between the Popliteal Artery and the Posterior Capsule of the Knee: A Cadaveric Study.
: The interspace between the popliteal artery and the posterior capsule of the knee (iPACK) block has been widely used in perioperative settings to control posterior knee pain and can additionally be used for chronic knee pain. In this cadaveric study, we aimed to investigate the needle tip position and its proximity to the articular branch of the tibial nerve (ABTN) during an iPACK-targeted radiofrequency procedure. : An ultrasound-guided iPACK block was performed on 20 knees of 10 cadavers. We injected 0.1 mL each of blue and green gelatinous dye near the tibial artery (point A) and posterior knee capsule (point B), respectively, and evaluated the spread of both around the ABTN. For a hypothetical conventional radiofrequency ablation (RFA) lesion (diameter, 2.95 mm) and cooled RFA lesion (diameter, 4.9 mm), we counted the number of specimens in which the ABTNs would be captured. : The percentage of specimens in which the ABTN would be captured by a cooled RFA lesion was 64.71% at point A and 43.75% at point B ( = 0.334). Meanwhile, the percentage of specimens in which the ABTN would be captured by a conventional RFA lesion was 58.82% from point A and 25% from point B ( = 0.065). : When performing an RFA-based iPACK block, the needle tip may be positioned either lateral to the tibial artery or in the space between the posterior knee capsule and the tibial artery. However, more studies with larger samples are needed to verify these results before the clinical use of this procedure can be recommended.
Topics: Humans; Cadaver; Popliteal Artery; Radiofrequency Ablation; Female; Male; Nerve Block; Needles; Aged; Knee Joint; Aged, 80 and over; Tibial Nerve; Ultrasonography, Interventional
PubMed: 38792872
DOI: 10.3390/medicina60050689 -
Orthopaedic Journal of Sports Medicine May 2024The labral suction seal has been shown to provide the majority of resistance in the initial phase of hip distraction. However, the effect of an unrepaired interportal...
BACKGROUND
The labral suction seal has been shown to provide the majority of resistance in the initial phase of hip distraction. However, the effect of an unrepaired interportal capsulotomy and capsular repair on the initial phase of hip distractive stability in vivo is not well understood.
PURPOSE
To investigate the effect of capsular repair on the initial phase of distractive stability of hip joints in patients with femoroacetabular impingement (FAI) syndrome.
STUDY DESIGN
Controlled laboratory study.
METHODS
Patients undergoing primary hip arthroscopy for FAI between March and August 2020 were prospectively enrolled. Total joint space was measured on fluoroscopic images at the medial and lateral edges of the sourcil at 12.5-lb (5.7-kg) axial traction intervals (up to 100 lb [45.4 kg]) in 3 capsular states: (1) native capsule, (2) interportal capsulotomy, and (3) capsular repair. Distraction on anteroposterior radiographs was calculated as the difference between total joint space at each traction interval and baseline joint space at 0 lb, normalized to millimeters. The native, capsulotomy, and capsular repair states were compared using Wilcoxon signed-rank and McNemar tests.
RESULTS
Included were 36 hips in 35 patients. The median force required to distract ≥3 mm was 75 lb (34.0 kg; 95% CI, 70-80 lb [31.8-36.3 kg]) in both the native and capsular repair states ( = .629), which was significantly greater than the median force required to distract ≥3 mm in the capsulotomy state (50 lb [22.7 kg]; 95% CI, 45-55 lb [20.4-24.9 kg]) ( < .001). The most rapid rates of change in joint space were observed at the traction interval at which hips first achieved ≥3 mm of distraction (n = 33 hips; 92%).
CONCLUSION
The traction force at which hips distracted ≥3 mm was 75 lb (34.0 kg) in both the native capsular and capsular repair states. Significantly less traction force (50 lb [22.7 kg]) distracted hips ≥3 mm in the capsulotomy state. Complete capsular closure after interportal capsulotomy resulted in restoration of initial distractive stability relative to the unrepaired capsulotomy state at time zero after primary hip arthroscopy.
CLINICAL RELEVANCE
This study provides surgeons with an improved understanding of the additional stability to the hip joint from capsular repair after hip arthroscopy for FAI syndrome.
PubMed: 38784788
DOI: 10.1177/23259671241249719 -
Analytica Chimica Acta Nov 2023Total joint arthroplasty (TJA) has significantly improved the quality of life for millions suffering from end-stage arthritis. However, periprosthetic joint infections...
BACKGROUND
Total joint arthroplasty (TJA) has significantly improved the quality of life for millions suffering from end-stage arthritis. However, periprosthetic joint infections (PJI) remain a serious complication, necessitating extensive interventions and prolonged antimicrobial treatments. The aging population is expected to lead to a rise in TJA cases, subsequently increasing the incidence of PJI, particularly in the elderly who face higher mortality rates. Current diagnostic methods for suspected PJI, such as radiographs and biochemical markers like CRP and ESR, exhibit limited sensitivity. Therefore, there is a critical need for a specific synovial fluid biomarker assay to enhance PJI diagnosis using specific SF-based assay.
RESULTS
This study introduces a novel microfluidic chip with a paper-based aptamer-sandwich assay for the quantitative detection of HNP 1, a crucial PJI biomarker, in synovial fluid. The assay leverages the advantages of aptamers over antibodies, demonstrating high selectivity and affinity for target molecules. The integration of a nitrocellulose (NC) membrane onto the microfluidic platform represents a significant advancement, reducing background signals and simplifying the assay procedure without intricate procedure and pre-treatment. The NC membrane-based microfluidic device offers rapid, cost-effective, and highly sensitive detection of HNP 1, with a limit of detection of 0.5 mg L. The microfluidic device demonstrates exceptional performance, detecting up to four clinical samples in approximately 42 min on a single chip with 100 % accuracy, as confirmed by analysis of 12 clinical samples and comparison with "gold-standard". Moreover, the assay exhibits a wide dynamic range of 0.5-100 mg L-1, underscoring its potential as a powerful tool for PJI diagnosis in clinical settings.
SIGNIFICANCE
This work introduces a paper-based microfluidic system tailored for rapid HNP 1 detection using synovial fluid near joint region (and not serum via blood) for better diagnosis. The innovative paper-based aptamer-sandwich assay yields results within 42-min. Significantly, it boasts a wide dynamic range, detecting levels from an impressive 0.5 mg L-1, crucial in the 2.6 mg L-1 threshold region. This heightened sensitivity and expansive detection capability establish our assay as a leader in PJI diagnostics, promising unmatched precision and efficiency in clinical applications.
Topics: Humans; Aptamers, Nucleotide; Biomarkers; Lab-On-A-Chip Devices; Limit of Detection; Microfluidic Analytical Techniques; Paper; Prosthesis-Related Infections; Synovial Fluid; alpha-Defensins
PubMed: 38783735
DOI: 10.1016/j.aca.2023.341879 -
Journal of Cataract and Refractive... May 2024To explore the severity of posterior capsule opacification (PCO) using objective detection techniques and its relationship with visual acuity.
PURPOSE
To explore the severity of posterior capsule opacification (PCO) using objective detection techniques and its relationship with visual acuity.
SETTING
The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
DESIGN
Prospective cohort study.
METHODS
All patients underwent slit-lamp examination, intraocular pressure measurement (IOP), best-corrected visual acuity (BCVA) before neodymium: yttrium aluminium garnet (Nd:YAG) laser capsulotomy, followed by examination after fully dilated, including IOLMaster 700, optical coherence tomography (OCT), Sirius anterior segment analysis system (Sirius), color fundus photography (CFP). Conducting BCVA and IOP post-treatment again. Recording the thickness and density of posterior capsule, color fundus photography quality (CFPQ) and OCT Signal Strength (OCTSS). Analysis using Spearman correlation analysis, heatmaps, and ROC curves.
RESULTS
A total of 83 eyes in 78 patients were included in this study. Spearman correlation analysis revealed correlations between pre-treatment BCVA and IOLMaster 700 PCO thickness (MT), IOLMaster 700 cumulative effect (MCE), Sirius PCO thickness (ST), Sirius maximum density (SMD), Sirius cumulative effect (SCE), OCTSS, and CFPQ (correlation coefficients were 0.500, 0.484, 0.465, -0.256, 0.317, -0.442, -0.412, all P<0.05). The improvement of Vision Acuity (ImpVA) showed correlations with MT, MCE, ST, SCE, OCTSS, and CFPQ (correlation coefficients were -0.452, -0.471, -0.346, -0.278, 0.320, 0.381, all P<0.05). For ImpVA, the predictive ability of IOLMaster 700 was superior to Sirius, and the joint model was significantly better than single factors.
CONCLUSIONS
Posterior capsule thickness and cumulative effect were reliable indicators for evaluating PCO. Compared to Sirius, IOLMaster 700 demonstrates superior predictive ability and higher correlation.
PubMed: 38783488
DOI: 10.1097/j.jcrs.0000000000001494 -
Arthritis Research & Therapy May 2024Fibroblast-like synoviocytes (FLSs) play a central role in RA pathogenesis and are the main cellular component in the inflamed synovium of patients with rheumatoid... (Review)
Review
Fibroblast-like synoviocytes (FLSs) play a central role in RA pathogenesis and are the main cellular component in the inflamed synovium of patients with rheumatoid arthritis (RA). FLSs are emerging as promising new therapeutic targets in RA. However, fibroblasts perform many essential functions that are required for sustaining tissue homeostasis. Direct targeting of general fibroblast markers on FLSs is challenging because fibroblasts in other tissues might be altered and side effects such as reduced wound healing or fibrosis can occur. To date, no FLS-specific targeted therapies have been applied in the clinical management of RA. With the help of high-throughput technologies such as scRNA-seq in recent years, several specific pathogenic FLS subsets in RA have been identified. Understanding the characteristics of these pathogenic FLS clusters and the mechanisms that drive their differentiation can provide new insights into the development of novel FLS-targeting strategies for RA. Here, we discuss the pathogenic FLS subsets in RA that have been elucidated in recent years and potential strategies for targeting pathogenic FLSs.
Topics: Arthritis, Rheumatoid; Humans; Fibroblasts; Synoviocytes; Synovial Membrane; Animals; Cell Differentiation
PubMed: 38783357
DOI: 10.1186/s13075-024-03343-4