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Cellular Signalling Jun 2024Silicosis, one of the occupational health illnesses is caused by inhalation of crystalline silica. Deposition of extracellular matrix and fibroblast proliferation in...
BACKGROUND AND OBJECTIVES
Silicosis, one of the occupational health illnesses is caused by inhalation of crystalline silica. Deposition of extracellular matrix and fibroblast proliferation in lungs are linked to silicosis development. Mitochondrial dysfunction plays critical role in some diseases, but how these processes progress and regulated in silicosis, remains limited. Detailed study of silica induced pulmonary fibrosis in mouse model, its progression and severity may be helpful in designing future therapeutic strategies.
METHODS
In present study, mice model of silicosis has been developed after repeated silica exposures which may closely resemble clinical symptoms of silicosis in human. In addition to efficiently mimicking the acute/chronic transformation processes of silicosis, this is practical and efficient in terms of time and output, which avoids mechanical injury to the upper respiratory tract due to surgical interventions. Sonicated sterile silica suspension (120 mg/kg) was administered through intranasal route thrice a week at regular intervals (21, 28 and 35 days).
RESULTS
Presence of minute to larger silicotic nodules in H&E-stained lung sections were observed in all silica induced model groups. Enhanced ECM deposition was noted in MT stained lung sections of silica exposure groups as compared to control which were confirmed by significantly higher MMP9 expression levels and hydroxyproline content in silica 35 days group. Increase in Reactive oxygen species (ROS), inflammatory cell recruitment mainly, neutrophils and macrophage were observed in all three silica exposure groups. Transmission electron microscopic analysis has confirmed presence of many aberrant shaped mitochondria (swollen, round shape) in 35 days model where autophagosomes were minimum. Western blot analysis of mitophagy and autophagy markers such as Pink1, Parkin, Cytochrome c, SQSTM1/p62, the ratio of light chain LC3B II/LC3B I was found higher in 21 and 28 days which were significantly reduced in 35 days silica model.
CONCLUSIONS
Higher MMP9 activity and MMP9 /TIMP1 ratio demonstrate excessive extracellular matrix damage and deposition in 35 days model. Significantly reduced expressions of autophagy and mitophagy markers have also confirmed progression in fibrosis severity and its association with repeated silica exposures in 35 days model group.
PubMed: 38944258
DOI: 10.1016/j.cellsig.2024.111272 -
International Journal of Pharmaceutics Jun 2024Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of...
Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.
PubMed: 38944168
DOI: 10.1016/j.ijpharm.2024.124396 -
International Journal of Biological... Jun 2024Lignin, renowned for its renewable, biocompatible, and environmentally benign characteristics, holds immense potential as a sustainable feedstock for agrochemical...
Lignin, renowned for its renewable, biocompatible, and environmentally benign characteristics, holds immense potential as a sustainable feedstock for agrochemical formulations. In this study, raw dealkaline lignin (DAL) underwent a purification process involving two sequential solvent extractions. Subsequently, an enzyme-responsive nanodelivery system (Pyr@DAL-NPs), was fabricated through the solvent self-assembly method, with pyraclostrobin (Pyr) loaded into lignin nanoparticles. The Pyr@DAL-NPs shown an average particle size of 250.4 nm, demonstrating a remarkable loading capacity of up to 54.70 % and an encapsulation efficiency of 86.15 %. Notably, in the presence of cellulase and pectinase at a concentration of 2 mg/mL, the release of Pyr from the Pyr@DAL-NPs reached 92.66 % within 120 h. Furthermore, the photostability of Pyr@DAL-NPs was significantly improved, revealing a 2.92-fold enhancement compared to the commercially available fungicide suspension (Pyr SC). Bioassay results exhibited that the Pyr@DAL-NPs revealed superior fungicidal activity against Botrytis cinerea over Pyr SC, with an EC value of 0.951 mg/L. Additionally, biosafety assessments indicated that the Pyr@DAL-NPs effectively declined the acute toxicity of Pyr towards zebrafish and posed no negative effects on the healthy growth of strawberry plants. In conclusion, this study presents a viable and promising strategy for developing environmentally friendly controlled-release systems for pesticides, offering the unique properties of lignin.
PubMed: 38944092
DOI: 10.1016/j.ijbiomac.2024.133488 -
International Journal of Surgery Case... Jun 2024A right side diaphragmatic injury was linked to serious trauma to the abdomen, pelvis, and chest. The most significant type of injury was blunt abdominal trauma...
INTRODUCTION
A right side diaphragmatic injury was linked to serious trauma to the abdomen, pelvis, and chest. The most significant type of injury was blunt abdominal trauma sustained in a car collision. The left side was more likely than the right to experience herniation. The stomach and colon were the most often herniated abdominal viscera. In the same location as the diaphragm rupture, there were rib fractures, hemothorax, and liver damage. Delayed diaphragmatic rupture with diaphragmatic hernia is rare and has a mysterious nature.
CASE PRESENTATION
A 68 years old female patient who has repeated history of shortness of breath, for which she treated as lung infection presented with sudden exacerbation of shortness of breath, she witnessed history of blunt trauma 20 years back and up on investigation bowel herniation to the chest cavity diagnosed. Posteriolateral thoracotomy done, the herniated bowel reduced and the diaphragmatic defect repaired. The patient significantly improved and discharged from the hospital smoothly on 4th postoperative day.
DISCUSSION
Careful recording of past history and physical examination are the best approaches in diagnosing delayed presentation of traumatic diaphragmatic rupture. CT scan with reconstruction of the diaphragm is helpful in both diagnosis and differential diagnosis. Surgical therapy after diagnosis is the best treatment.
CONCLUSION
Delayed right side diaphragmatic hernia is a rare entity resulting in grave consequences, In a patient with history of trauma there should be a high index of suspension and patients should undergo imaging and surgical management is the best treatment.
PubMed: 38943935
DOI: 10.1016/j.ijscr.2024.109973 -
Journal of Burn Care & Research :... Jun 2024Autologous skin cell suspension (ASCS) is an adjunct to conventional split-thickness skin grafts (STSG) for acute burns, enhancing healing and reducing donor site...
Autologous skin cell suspension (ASCS) is an adjunct to conventional split-thickness skin grafts (STSG) for acute burns, enhancing healing and reducing donor site requirements. This study validates ASCS's predictive benefits in hospital stay reduction and cost savings by analyzing outcomes and real-world charges post-ASCS implementation at a single institution. A retrospective study (2018-2022) included burn patients with ≥10% TBSA. The study population comprised two groups: burns treated either with a combination of ASCS ± STSG or with STSG alone. Outcomes included LOS, surgeries, infection, complications, days on antibiotics, and adjusted charge per TBSA. The ASCS ± STSG group demonstrated significantly shorter LOS (Mdn: 16.0 days, IQR: 10-26) than the STSG group (Mdn: 20.0 days, IQR: 14-36; P = 0.017), and fewer surgeries (Mdn: 1.0, IQR: 1-2) versus the STSG group (Mdn: 1.0, IQR: 1-4; P = 0.020). Postoperative complications were significantly lower in ASCS ± STSG (11% vs. 36%; P < 0.001). The STSG group had a longer distribution of antibiotic days (IQR: 0-7.0, min-max: 0-76) than the ASCS ± STSG group (IQR: 0-0, min-max: 0-37; P = 0.014). Wound infection incidence did not differ (P = 0.843). ASCS ± STSG showed a lower distribution of adjusted charge per TBSA (IQR: $10,788.5 - $28,332.6) compared to the STSG group (IQR: $12,336.8 - $29,507.3; P = 0.602) with a lower mean adjusted charge per TBSA ($20,995.0 vs. $24,882.3), although this was not statistically significant. ASCS ± STSG utilization demonstrated significant reductions in LOS, surgeries, postoperative complications, antibiotics, and potential cost savings. These findings underscore the practicality of integrating ASCS in burn management, offering substantial benefits to patients and healthcare institutions.
PubMed: 38943671
DOI: 10.1093/jbcr/irae133 -
Regulatory Toxicology and Pharmacology... Jun 2024Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable... (Review)
Review
Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable nonclinical efficacy tests. Two common tests used in nonclinical efficacy studies of antidepressants-the forced swim test (FST) and tail suspension test (TST)-have come under criticism in recent years for their inconsistency and lack of validity, yet they continue to be used in the pharmaceutical industry. In this review, we provide a rationale for why international pharmaceutical regulatory and guidance agencies should begin issuing direction on methods for non-clinical efficacy testing that traditionally use the FST and TST, particularly considering that some regulators, such as those in the U.S. and E.U., allow the authorization of clinical trials to proceed without requiring tests in animals. The area of antidepressant drug discovery represents an important opportunity for reducing the attrition of psychiatric drugs, harmonizing regulatory requirements, and reducing animal use. Specific recommendations for the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) have been provided.
PubMed: 38942190
DOI: 10.1016/j.yrtph.2024.105666 -
Behavioural Brain Research Jun 2024Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the...
Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.
PubMed: 38942086
DOI: 10.1016/j.bbr.2024.115122 -
European Journal of Dentistry Jun 2024This study aims to investigate DSM 17938's antibiofilm effects on and , common causes of alveolar osteitis. It seeks topical alternatives to prevent this condition...
OBJECTIVES
This study aims to investigate DSM 17938's antibiofilm effects on and , common causes of alveolar osteitis. It seeks topical alternatives to prevent this condition posttooth extraction. The secondary objective is to assess these effects under different pH conditions (pH 4.5 and pH 7), mimicking oral cavity saliva pH dynamics.
MATERIALS AND METHODS
Ethical approval was secured for the saliva collection process involving five healthy adult participants who had undergone wisdom tooth extraction. Saliva samples were diligently collected on the 7th day post-surgery. The unstimulated saliva underwent a series of treatments, including the addition of phenylmethylsulfonyl fluoride (PMSF), pH adjustments, centrifugation, and filtration. The pH levels were re-measured, and subsequent adjustments were made to achieve pH values of 4.5 or 7. DSM 17938, with a concentration of 1×10 colony-forming units (CFU) per 5 drops, was utilized in the study. Biofilm testing involved incubating saliva samples with varying pH (4.5 or 7) alongside bacterial suspensions (, or a mixed species). The Interlac suspension was introduced, and plates were anaerobically incubated for 24 hours. Biofilm results were obtained using a spectrometer. The test is conducted in triplicate.
STATISTICAL ANALYSIS
To scrutinize the impact of pH on biofilm development, the acquired data underwent a two-way ANOVA test in SPSS as part of the statistical analysis. A significance level of <0.05 was used to determine statistical significance.
RESULTS
DSM 17938 significantly reduced biofilm formation across bacterial strains ( = 0.000). Statistical analysis indicated a significant impact of pH on biofilm development ( = 0.000) compared to no saliva samples, with higher formation observed under acidic conditions (pH 4.5). However, the pH levels of 4.5 and 7 did not result in significantly different bacterial biofilm formation ( = 0.529).
CONCLUSION
This research highlights DSM 17938's potency in inhibiting biofilm formation of and . Salivary pH variations significantly influence biofilm development, emphasizing the need to consider pH when assessing probiotic effectiveness. Despite limitations in saliva sample sterilization, this study provides valuable insights into alternative approaches for preventing alveolar osteitis. Further research should explore clinical applications and refine sterilization methods for more accurate results.
PubMed: 38942052
DOI: 10.1055/s-0044-1786846 -
Medicine Jun 2024This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind...
BACKGROUND
This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind patellar tunnel during medial patellofemoral ligament (MPFL) reconstruction.
METHODS
This study included 52 patients (25 men, 27 women) who underwent MPFL reconstruction using a semitendinosus tendon graft. The graft was fixed to the ellipsoidal single blind tunnel opened on the medial side of the patella with an endobutton and was fixed to the femoral tunnel by using bioabsorbable screw. Clinical scores (Kujala score, Lysholm score, Tegner activity score and the visual analog scale [VAS] score) were evaluated preoperatively and at the end-follow up. Preoperative and postoperative radiological measurements (trochlea depth, sulcus angle, patellar height, patellar congruence angle, patellar tilt angle and lateral patellofemoral angle) were evaluated with X-ray (Merchant X-ray, anteroposterior and lateral radiography) and computed tomography (CT) of the knee.
RESULTS
Postoperative patellar redislocation or subluxation was not observed in any patient. Patellar congruence angle, patellar tilt angle and lateral patellofemoral angle mean values were found to return to normal values in the postoperative period and the results were statistically significant. Also statistically significant improvement in all clinical scores postoperatively. According to the Insall-Salvati index (ISI) and Caton-Deschamps index (CDI) on lateral radiography of the knee at 30° flexion, patellar height decreased in the postoperative period statistically significant. The CDI was above 1.3 in 17 (%32) of our patients. Thirteen of these values decreased to normal values. No radiological progression of patellofemoral osteoarthritis was observed in all patients at the final follow-up evaluation.
CONCLUSION
In cases of patellofemoral instability, fixation of the tendon graft in blind ellipsoid tunnel using the Toggleloc suspension system provides satisfactory patellar graft fixation strength, significant functional improvement and a low failure rate.
Topics: Humans; Female; Male; Adult; Patellofemoral Joint; Follow-Up Studies; Patella; Plastic Surgery Procedures; Young Adult; Ligaments, Articular; Treatment Outcome; Adolescent
PubMed: 38941440
DOI: 10.1097/MD.0000000000038379 -
Macromolecular Rapid Communications Jun 2024Creating bionic intelligent robotic systems that emulate human-like skin perception presents a considerable scientific challenge. This study introduces a multifunctional...
Creating bionic intelligent robotic systems that emulate human-like skin perception presents a considerable scientific challenge. This study introduces a multifunctional bionic electronic skin (e-skin) made from polyacrylic acid ionogel (PAIG), designed to detect human motion signals and transmit them to robotic systems for recognition and classification. The PAIG was synthesized using a suspension of liquid metal and graphene oxide nanosheets as initiators and cross-linkers. The resulting PAIGs demonstrate excellent mechanical properties, resistance to freezing and drying, and self-healing capabilities. Functionally, the PAIG effectively captures human motion signals through electromechanical sensing. Furthermore, we developed a bionic intelligent sorting robot system by integrating the PAIG-based e-skin with a robotic manipulator. This system leverages its ability to detect frictional electrical signals, enabling precise identification and sorting of materials. The innovations presented in this study hold significant potential for applications in artificial intelligence, rehabilitation training, and intelligent classification systems. This article is protected by copyright. All rights reserved.
PubMed: 38940242
DOI: 10.1002/marc.202400379