Tissue Changes Research Articles

Establishment of a Mouse Model of Mycoplasma pneumoniae-Induced Plastic Bronchitis.

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15-20 min) and intratracheal administration (6-50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.

Histopathological changes of mice tissues in course of the envenomation by the Macrovipera lebetina obtusa venom and the neutralizing effect of the ovine-derived experimental antivenom

Viper bites pose a significant public health issue in Armenia, even within urban areas, often resulting in clotting disorders, hypofibrinogenemia, and tissue necrosis in humans. This study investigates histopathological changes in various tissues during mice envenomation by West-Asian blunt-nosed viper (Macrovipera lebetina obtusa) venom, as well as the recovery process aided by experimental antivenom derived from sheep. The high venom dose caused substantial damage to the heart, lungs, liver, and kidneys in mice, indicating systemic harm. While antivenom administration can prevent mortality in mice envenomation, it may not fully mitigate histological damage in affected organs. Additionally, the study highlights the importance of timing antivenom administration, as the severity of tissue alterations can vary depending on the duration of envenomation. These findings shed light on antivenom's effects on viper envenomation and stress the need for further research to optimize its timing and dosage for minimizing histological damage and enhancing clinical outcomes.

Study on the pharmacodynamics and related mechanism of Tangningtongluo tablet on prediabetes mice based on the theory of “liver controlling dispersion”

Background and aimPrediabetes is an unavoidable process and a high risk factor for developing of type 2 diabetes. Tangningtongluo (TNTL) tablet is a kind of pure plant preparation in hospital and used for the diabetes (消渴病, xiāo kě bìng) caused by deficiency of both Qi and Yin (气阴两虚，qì yīn liǎng xū). However, the effect of TNTL tablet on prediabetes has not been reported for now. This study was aimed to investigate the effect and related mechanism of TNTL tablet on prediabetes. Experimental procedurePrediabetic mice induced by a high-sugar and high-fat diet combined with streptozotocin were treated with TNTL tablet, and the pharmacodynamics and related mechanism were studied. Results and conclusionOur results showed that TNTL tablet reduced body weight and regulated the disorder of glucose and lipid metabolism in prediabetic mice. The function and the pathological changes of liver and islet tissue were improved after TNTL tablet treated prediabetic mice. Additionally, TNTL tablet decreased the levels of MDA, TNF-α, IL-1β and IL-6 in serum, increased the contents of SOD and GSH-px, up-regulated the expression of p-PI3K and p-AKT protein, and down-regulated the expression of p-IKK and p-NF-κB p65 protein in liver tissue. This study revealed that TNTL tablet could improve insulin sensitivity and insulin resistance in prediabetic mice, and delay the procession of prediabetes to diabetes, which might be related to inhibiting IKK/NF-κB signaling pathway, exerting anti-inflammatory and antioxidant effects, and activating PI3K/AKT signaling pathway.

THE STUDY THE EFFECT OF COMPLEX TREATMENT OF PATIENTS WITH EARLY CLINICAL MANIFESTATIONS OF INCREASED TOOTH ABRASION ON THE QUALITY OF LIFE

To date, an increase in the number of dental erosions is one of the most common dental diseases. The most important factor in the correction of CAN is to compensate for the loss of hard tooth tissues. We propose a minimally invasive restoration technique for restoring dental defects with increased erosion, developed on the basis of experimental data studying morphostructural changes in hard tooth tissues. Combined treatment of cases of increased dental erosion resulted in a fourfold improvement in QOL due to dental health, according to the integral index.

Exploring the effect of Gouqi Nuzhen Liuhe decoction on the PI3K/mTOR signaling pathway for premature ovarian insufficiency based on system pharmacology

ObjectiveTo explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. MethodsFirst, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. ResultsThe results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). ConclusionGNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.

Soft-Tissue Augmentation Around Dental Implants by a New Laser-Aided Pouch Roll Technique: Volumetric and Clinical Evaluation After 1 Year.

The ultimate goal in implantology is to restore the whole tooth-gingival complex in a fashion that cannot be distinguished from the rest of the natural dentition. This study assesses the volumetric and clinical changes in vestibular gingival soft tissues, crucial for satisfactory engraftment and esthetic results, upon treatment with laser-aided pouch roll augmentation in second-stage surgery for dental implant uncovering. Twelve patients with mild ridge deficiencies in 16 edentulous sites, including distal elements, were enrolled and reevaluated for up to 1 year. Digital impressions, taken with an intraoral laser scanner and software, were analyzed before (day 0) and after (month 12) treatment. The digital STL files were superimposed to assess volumetric and linear dimensional variations in selected peri-implant regions of interest by 3D analysis software. Clinical periodontal parameters (probing depth [PD], bleeding on probing [BoP], plaque index [PI]) and subjective patient-reported outcomes were also evaluated. In all patients, the applied technique induced a substantial increase in the volume of the vestibular peri-implant gingiva at 12-month follow-up (range, 24%-69%, mean 40.4%) with respect to day 0. The gingival mucosa appeared normal at both inspection and evaluation of the periodontal parameters (PD 2.7 ± 1 mm; BoP 0.11 ± 0.2 seconds; PI 0.19 ± 0). Patients' satisfaction with perceived pain/discomfort and esthetic outcome was high. These findings indicate that laser-aided pouch roll flap is a safe, patient-liked procedure whose long-term effectiveness has been objectively demonstrated by volumetric and clinical assessment.

Toxicological impact of copper and zinc exposure on liver and gill tissues of Oreochromis mossambicus

Abstract Copper and zinc are needed as essential nutrients for plants, animals, and human’s daily basic activity, however, at high concentrations and prolonged exposure they bring harmful effect to life creature and the environment. Thus, this study aimed at finding out the toxicological impact of copper and zinc on liver and gill tissues of Oreochromis mossambicus. This study used 21 male tilapia (60-100 grams), which grouped into 7 treatment groups, K1 was negative control; K2, K3, and K4 were exposed to 1, 2.5, and 5 mg/L CuSO4; K5, K6, and K7 were exposed to 2.5, 5, and 7.5 mg/L ZnCl2, respectively, for 15 days. Fish liver and gill were collected for histopathological procedure using hematoxylin-eosin. The results showed similar figure of tissues damages between treatment groups, including melanomacrophage center, vacuolar degeneration, cell necrosis, and hemorrhage. The spreading of MMCs in the liver tissue of tilapia fish exposed to copper was higher than in zinc exposure. In gills tissue, several minor, moderate, and severe changes were observed, revealed that the higher the concentration of CuSO4 and ZnCl2 exposure the more severe the tissue damage observed. In conclusion, both CuSO4 and ZnCl2 exposure changes the histopathology of liver and gill of tilapia fish.

Screening of Oxidative Stress Biomarkers and Inflammatory Cytokines in the Pathogenesis of Diabetic Neuropathy

Diabetic neuropathy is a neurological syndrome characterized by severe pain and significant mortality caused primarily by somatosensory nerve system damage. In DN patients, the structural and functional damages of neurons are caused by variety of factors. Among these factors, the production of free radicals serves as significant contributors to DN. In addition, hyperglycemia causes chronic inflammation and metabolic changes in neuronal tissues by producing variety of proinflammatory cytokines which serve a significant role in the pathophysiology of DN. Hence, the present study aimed to determine the levels of oxidative stress indicators like SOD, CAT, GR and GPX, as well as proinflammatory cytokines like IL-2, IL-4 and IL-6 in patients with DN in comparison to healthy subjects. The results demonstrated that the mean glucose levels in DN patients range from 142.6±7.2 to 168.1±8.2 mg/dl. The Hb levels exhibited negative correlation in both the DN patients and healthy controls with age. In DN patients, enzymatic antioxidants including SOD, CAT, GR and GPX exhibited significantly decreased activity than the healthy individuals and they exhibited strong negative correlations such as r = -0.943, r = -0.819, r = -0.969 and r = -0.973 respectively. The mean TAS levels in DN patients range from 0.93±0.1 to 0.37±0.02 mM FE with increasing age. Additionally, proinflammatory cytokines such as IL-2, IL-4 and IL-6 levels in DN patients were observed in the ranges of 2.48±1.2 to 3.97±1.5, 41.15±3.7 to 56.43±4.3, 7.61±2.1 to 10.24±1.8 pg/ml respectively with increasing age. The present study concluded that patients with high inflammatory marker levels had elevated oxidative stress, demonstrating that oxidative stress and inflammation are important pathophysiological factors in DN.

3D extraoral morphometric changes after implant surgery: an exploratory pilot study using stereophotogrammetry.

This pilot study aimed to evaluate, for the first time, the changes in facial tissues following the placement of a single dental implant. Patients were scanned with a 3D facial scanner (3dMD) before implant surgery, immediately after surgery (T1), at 7 days postoperatively (T2), and at the impression stage (T3). Acquired images were processed using the 3dMDvultus (3dMD) software program and volume differences and linear depth measurements were calculated to determine the morphometric changes over time. A total of 11 patients were included in the analyses. Descriptive statistics were employed to analyze the data. The volumetric changes and maximum depth differences indicated an initial increase, followed by a progressive decrease in tissue volume after implant placement in the area of the surgery. The volume change values ranged between 2.5 and 3.9 cm3 for T1, whereas for T2, the volume change decreased to a range of 0.8 to 1.8 cm3. Maximum depth differences ranged between 2.06 and 2.80 mm in the soft tissues immediately after the implant surgery and reduced to around 2.01 to 0.55 mm at the impression stage. The amount of painkiller used was not related to the magnitude of linear depth measurements at any assessed time point. There was a longitudinal decrease in soft tissue volume and depth difference in extraoral soft tissues in the region of implant placement after surgery up to 6 weeks. The use of a facial scanner is a promising noninvasive method to monitor 3D morphometric changes after implant surgery.

Postnatal overfeeding in mice induces early lipidic changes in heart tissue and impacts cardiomyocyte proliferation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): French Federation of Cardiology Foundation of France Background Shortly after birth, cardiomyocytes lose their ability to proliferate to switch towards a hypertrophic growth and this ability is known to be influenced by nutritional factors. Postnatal overfeeding (PNOF) induced by litter size reduction in rodents reproduces the impact of childhood overnutrition. While PNOF was shown to induce major cardiac and metabolic alterations in adulthood, little is known about its impact during the first days of life. Purpose The objective of this project was to investigate the early changes induced by PNOF induced in heart tissue in terms of lipid profile and cardiomyocyte proliferation. Methods Two days after birth, C57BL/6 male pups were randomly distributed in litters adjusted to either 9 or 3 pups to form normally fed (NF) or postnatally overfed (PNOF) group, respectively. At 7, 10 and 24 postnatal days (D7, D10 and D24, respectively), hearts were harvested for immunostaining of the proliferation marker Ki67. Cardiac and plasma lipid composition of NF and PNOF was evaluated using liquid chromatography coupled to mass spectrometry technique. Finally, cardiomyocytes from D24 hearts were isolated and counted on Malassez counting chamber. Results At D7, D10 and D24, body weight and cardiac mass of PNOF pups were significantly higher than these of NF controls. Interestingly, at D7, lipid composition of PNOF hearts was decreased in cardiolipins, fatty acids and cholesterol derivatives. Moreover, plasma triglyceride levels were lower in D10 PNOF pups. These modifications were associated with a significant reduction of cardiomyocytes’ proliferation rate and an increased hypertrophy in PNOF hearts at D7, resulting in the reduction of cardiomyocyte number at D24 in PNOF mice. Conclusion Only five days after litter size reduction, PNOF induced major lipidic changes both in the cardiac tissue and in the plasma. In parallel, PNOF shortened the cardiomyocyte proliferative window and induced earlier cardiomyocyte maturation. Given the importance of fatty acid metabolism in cardiac development and function, these early changes could be linked to the long-term cardiometabolic alterations observed later in life.

Synergistic effect of chrysin and kaempferol in ameliorating Cerebral Ischemic Reperfusion injury in rat by controlling expression of proinflammatory mediators NF-κB and STAT3

ABSTRACT Objectives The two flavonoids kaempferol and chrysin are known to possess anti-inflammatory and antioxidant activities. In addition, these two flavonoids were reported to display synergistic effects against inflammation. The present study aims to provide an analysis of the combined effects of kaempferol and chrysin on ischemic rat brain induced by endothelin-1. Methods The neurological deficit score and infarct area of the brain were determined post drug treatment. Histopathological sections displayed the morphological changes in the brain tissue. The brain tissues were processed for assessing the antioxidant and anti-inflammatory activity by measuring superoxide dismutase activity, catalase activity, level of reduced glutathione, brain malondialdehyde, and amount of calcium. The expression level of inflammatory molecules was analyzed by western blotting and immunohistochemistry. Results The infarct area, neurological score and NF-κB and STAT3 expression levels were significantly reduced. Discussion The analysis of neuroprotective synergistic activity of kaempferol and chrysin indicated the therapeutic potential of the combination in alleviating cerebral ischemia by controlling expression of proinflammatory mediators.

MiR-21-Mediated Endothelial Senescence and Dysfunction Are Involved in Cigarette Smoke-Induced Pulmonary Hypertension through Activation of PI3K/AKT/mTOR Signaling.

Smoking is a pathogenic factor for pulmonary hypertension (PH). Our previous study showed that serum miR-21 levels are elevated in smokers. miR-21 is considered as engaged in the PH process; however, its mechanisms remain unclear. In this investigation, we found that in the lung tissue of smoking-induced PH patients, the levels of miR-21 and aging markers (p21 and p16) were upregulated, and the function of pulmonary vascular endothelial cells was also impaired. Exposure of mice to cigarette smoke (CS) for four months caused similar changes in lung tissues and increased pulmonary arterial pressure, which were attenuated by knockout of miR-21. Further, human umbilical vein endothelial cells (HUVECs) exposed to cigarette smoke extract (CSE) revealed upregulation of miR-21 levels, depression of PTEN, activation of PI3K/AKT/mTOR signaling, an increase in senescence indexes, and enhanced dysfunction. Inhibiting miR-21 overexpression reversed the PTEN-mTOR signaling pathway and prevented senescence and dysfunction of HUVECs. In sum, our data indicate that miR-21-mediated endothelial senescence and dysfunction are involved in CS-induced PH through the activation of PI3K/AKT/mTOR signaling, which suggests that selective miR-21 inhibition offers the potential to attenuate PH.

Tissue changes around dental implants installed in alveolar ridge preservation sites: A 1-year follow-up randomized controlled clinical trial.

This study aimed to assess radiographic marginal bone changes 22 months post extraction, which is 1 year after implant loading in alveolar ridge preservation (ARP) sites grafted with a combination of collagen-embedded xenogenic bone substitute (DBBM-C) and collagen matrix (CMX), comparing them with implants placed in naturally healed sites. This randomized controlled clinical trial was conducted over 22 months. Patients who needed a single tooth extraction and subsequent implant placement in nonmolar areas were enrolled. The test group received deproteinized bovine bone mineral with 10% collagen covered by a procaine collagen membrane, while the control group allowed spontaneous healing. Radiographic bone level changes were documented using periapical radiographs at implant placement and follow-up visits (6, 10, and 22 months postextraction). Early implant soft tissue exposure, clinical parameters, and patient-reported outcomes were recorded. Twenty-two out of 28 participants completed a 22-month follow-up, 9 in the test group and 13 in the control group. At 10-month postextraction follow-up, the mean MBL was 1.01 ± 1.04 mm in the treatment group and 0.81 ± 0.93 mm in the control group (p = 0.804). At 22 months, the mean MBL was 2.09 ± 1.03 mm in the treatment group and 1.58 ± 0.73 mm in the control group (p = 0.339). No statistically significant differences in probing depth (PD) and bleeding on probing (BOP) were found at the 22 -month follow-up as well. Soft tissue mean recession was observed in the control group (0.36 ± 0.84 mm), while no recession was found in the test group (p = 0.2). Early implant soft tissue exposure occurred in 33% of test group participants, while none was observed in the control group (p = 0.047). One year after implant loading, no significant differences in marginal bone resorption were found between implants placed in ARP-treated and naturally healed sites. However, ARP-treated sites exhibited early implant soft-tissue exposure, suggesting a possible impairment in soft tissue healing.

Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice.

The aim of this study is to observe the changes in autophagy activities in lung tissues of mice with different degrees of pulmonary fibrosis (PF), and explore the association between PF and autophagy activity. The PF model was established by bleomycin (BLM, 25 and 35 mg/kg) atomization inhalation in C57BL/6 mice, samples were collected on the 7, 14, and 28 days after BLM administration. Hematoxylin-eosin staining was used to observe the pathological changes in lung tissues. Masson staining was utilized to assess areas of blue collagen fiber deposition in lung tissues. Quantitative real time polymerase chain reaction was used to detect the mRNA expressions of autophagy-related genes, including Atg5, Atg7, and Atg10 in lung tissues. Western blot was used to detect the protein expressions of autophagy-related genes, including p62 and LC3II/LC3I in lung tissues. Compared with control group, BLM dose-dependently decreased PaO2, mRNA expressions of Atg5, Atg7, Atg10, and LC3II/LC3I, while increased lung wet weight, lung coefficient, PF score, the blue area of collagen fibers, and p62 protein on the 7th, 14th, and 28th days. In conclusion, the more severe the PF induced by BLM, the lower the autophagy activity.

Nasal profile changes after LeFort I osteotomy (maxillary advancement) with and without ANS reduction in class III skeletal patients: a study protocol for a randomized clinical trial

BackgroundDentofacial malformation is a common condition that affects a significant portion of the population, resulting in functional and aesthetic defects. Orthognathic surgeries, such as LeFort I osteotomy, are performed to correct these abnormalities. However, the impact of these surgeries on nasal profile changes remains unclear. Additionally, the role of anterior nasal spine (ANS) reduction in maxillary advancement surgeries of 3–5 mm range is yet to be determined. This study aims to investigate the effect of ANS reduction on soft tissue profile changes following LeFort I osteotomy with a maxillary advancement range of 3–5 mm in class III skeletal patients. The hypothesis is that the changes in nasolabial angle and upper lip length will not significantly differ between patients who undergo LeFort I osteotomy with and without ANS reduction.Method and designThis study is designed as a randomized controlled trial. A total of 26 class III skeletal patients with maxillofacial abnormalities will be recruited from the maxillofacial clinic of Bu-Ali and Farahikhtegan Hospitals in Tehran, Iran. Patients meeting the inclusion criteria will be randomly assigned to two groups: one group will undergo LeFort I osteotomy with ANS reduction, and the other group will undergo LeFort I osteotomy without ANS reduction. The soft tissue profile changes, specifically the nasolabial angle and upper lip length, will be evaluated and compared between the two groups.DiscussionAchieving facial harmony through orthognathic surgery requires careful planning and consideration of the impact on surrounding soft tissue. The primary objective is to predict and plan for the effects on the nasolabial region. LeFort I osteotomy is a common procedure used to correct dentofacial deformities, particularly in class III patients. Maxillary advancement during this surgery can lead to changes in nasal tip position, width, and rotation, potentially due to repositioning of the anterior nasal spine and soft tissue dissection. In this study, soft tissue changes will be assessed in non-growing class III patients using cephalometric radiographs. The impact of reducing the anterior nasal spine (ANS) on nasal profile changes will be investigated for maxillary advancements of 3–5 mm. Objective measurements and patient-reported outcomes will be evaluated to gain insights into the aesthetic outcomes of orthognathic surgery. The findings will provide valuable guidance for treatment decisions and alternative options based on expected nasal profile changes.Trial registrationThis project was registered at The Iranian Registry of Clinical Trials (Identifier No. IRCT20210928052625N1, Website: https://www.irct.ir/trial/59171) and Open Science Framework (OSF) (Registration https://doi.org/10.17605/OSF.IO/X3HD4). 2021-06-09.

Genetic Background Strongly Influences the Impact of Carrying the Thr92Ala-DIO2 Polymorphism in the Male Mouse.

About half of the world population carries at least one allele of the Ala92-DIO2, which slows down the activity of the type 2 deiodinase (D2), the enzyme that activates T4 to T3. Carrying the Ala92-DIO2 allele has been associated with increased body mass index and insulin resistance, but this has not been reproduced in all populations. To test if the genetic background affects the impact of this polymorphism, here we studied the genetically distant C57Bl/6J (B6) and FVB/N (FVB) mice carrying the Ala92-Dio2 allele as compared to control mice carrying the Thr92-Dio2 allele. Whereas B6-Ala92-Dio2 and B6-Thr92-Dio2 mice-fed chow or high-fat diet-behaved metabolically similar in studies using indirect calorimetry, glucose- and insulin tolerance tests, and measuring white adipose tissue (WAT) weight and liver steatosis, major differences were observed between FVB-Ala92-Dio2 and FVB-Thr92-Dio2 mice: carrying the Ala92-Dio2 allele (on a chow diet) resulted in hypercholesterolemia, smaller WAT pads, hepatomegaly, steatosis, and transcriptome changes in the interscapular brown adipose tissue (iBAT) typical of ER stress and apoptosis. Acclimatization at thermoneutrality (30 °C) eliminated most of the metabolic phenotype, indicating that impaired adaptive (BAT) thermogenesis can be involved. In conclusion, the metabolic impact of carrying the Ala92-Dio2 allele depends greatly on the genetic background of the mouse, varying from no phenotype in B6 mice to a major phenotype in FVB mice. These results will help the planning of future clinical trials studying the Thr92Ala-DIO2 polymorphism and may explain why some clinical studies performed in different populations across the globe have obtained inconsistent results.

Chitosan-modified manganese oxide-conjugated methotrexate nanoparticles delivering 5-aminolevulinic acid as a dual-modal T1-T2* MRI contrast agent in U87MG cell detection.

Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans. The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images. The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1-T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect. This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma.

Da-yuan-yin decoction alleviates ulcerative colitis by inhibiting complement activation, LPS-TLR4/NF-κB signaling pathway and NET formation

Ethnopharmacological relevanceDa-yuan-yin decoction (DYY) is a classical traditional Chinese medicine prescription for ulcerative colitis (UC). Aim of studyThis study explored the protective effects and mechanisms of DYY on UC. Materials and methodsThe mice were fed 2.5% dextran sulfate sodium (DSS) for 7 days to establish UC. On the second day, DYY (0.4 g/kg, 0.8 g/kg, 1.6 g/kg) was orally administered daily for 7 consecutive days. The colon tissues and serum were measured by histopathological examination and biochemical analysis. ResultsDYY significantly reduced the disease activity index (DAI) and severity of colon shortening and alleviated pathological changes in the colon tissue. DYY restored the protein expression of intestinal tight junction (TJ) protein (ZO-1, occludin and claudin-3). DYY remarkably decreased the level of lipopolysaccharide (LPS), Lactic acid (LA), circulating free DNA (cfDNA), complement (C3, C3a, C3c, C3aR1, C5a and C5aR1) and regulated the levels of inflammatory cytokines in serum. DYY significantly inhibited the expressions of nuclear factor kappa-B p65 (NF-κB p65) and Toll-like receptor 4 (TLR4), citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), reactive oxygen species (ROS) peptidylarginine deiminase 4 (PAD4) and CD 11b, the mRNA levels of PADI4, MPO and ELANE in colon tissues. ConclusionsDYY significantly attenuated DSS-induced UC, which was related with regulating the inflammatory response by the inhibition of complement activation, the LPS-TLR4/NF-κB signaling pathway and neutrophil extracellular traps (NETs) formation. DYY is a potential therapeutic agent for UC.

Oral health in systemic sclerosis: A scoping review

Background: Limited research on oral health in systematic sclerosis poses a significant challenge for people with systematic sclerosis and health care professionals. We conducted a scoping review to map existing research on oral health–related quality of life in systematic sclerosis across domains including (1) oral manifestations or symptoms, (2) functional consequences, (3) psychosocial aspects, (4) associated patient factors and (5) self-care and management considerations. Methods: We searched MEDLINE, EMBASE, SCOPUS and CINAHL databases to 10 March 2023 for studies on oral health in people with systematic sclerosis. Study data were mapped into pre-specified domains of oral health–related quality of life, subtopics and types of research and reported in tabular form. Results: Of 1460 unique studies reviewed, 91 were eligible and included in the scoping review; of these, 69 (76%) were published as full-text versions, 72 (79%) were from Europe or North America, and 63 (69%) included ⩽50 participants. Only 1 study had &gt;200 participants (N = 382). By domains, 85 (93%) studies reported aspects of oral manifestations or symptoms, with the most common subtopics being oral opening and mandibular function, sicca, periodontitis and soft tissue changes and pathology; 36 (40%) studies provided information on associated patient factors, 23 (25%) on self-care and management, 19 (21%) on psychosocial aspects and 6 (7%) on functional consequences. No studies related to interventions included &gt;50 participants. Conclusion: Most studies on oral health in systematic sclerosis report on manifestations or symptoms, and there are relatively few studies on other important domains. Most studies have been conducted with small samples. Updated systematic reviews should evaluate the quality of existing evidence in domains where enough studies have been done. Large, well-conducted primary studies are needed to address knowledge gaps across domains, including studies that test approaches for supporting oral self-care, improving routine professional care and addressing major disability-causing manifestations.

Evaluation of left atrial function and tissue after pulmonary vein isolation - initial results of The EVALUATE-PVI STUDY

Abstract Background Pulmonary vein (PV) isolation (PVI) by catheter ablation is a well-established treatment for atrial fibrillation (AF). Currently, the direct and long-term impact of ablation injury on left atrial (LA) function and tissue is poorly understood. Purpose The aim of this study is to evaluate the acute and long-term impact of radiofrequency (RF) PVI ablation on LA function and corresponding tissue changes as assessed with cardiac magnetic resonance imaging (CMR). Methods Seventeen patients (76.5% male, 60.8±9.7 years) with AF who underwent primo RF PVI as part of the EVALUATE-PVI STUDY underwent three sequential CMR scans prior to PVI, and &amp;lt;72 hours and 3 months after PVI ablation. T2-weighted turbo spin echo imaging was applied to assess post-ablation edema. High-resolution three-dimensional (3D) late gadolinium-enhancement (LGE) images were acquired to study acute LA wall injury and chronic fibrosis formation. LA volume and function were derived from two-chamber and four-chamber SSFP cine images. Maximum and minimal LA volume was indexed to body surface area to compute LAVimax and LAVimin. Longitudinal LA strain was calculated using feature tracking, and subdivided into reservoir, conduit, and contractile strain. Results Acutely post-PVI, T2w images showed increased signal intensity and thickening throughout the entire LA wall. LGE images showed diffuse increased signal intensity, without distinct focal high signal intensity areas (Fig. 1). Functional assessment at this stage showed significantly reduced LA emptying fraction (EF), LA reservoir, and contractile strain compared to pre-PVI (54.8±11.1% vs. 48.5±7.9%, p=0.01; 18.6±5.6% vs. 14.6±2.0%, p&amp;lt;0.01; 8.5±3.5% vs. 5.2±1.8%, p&amp;lt;0.001, respectively), while LA conduit strain, LAVimin, and LAVimax did not differ significantly (Fig. 2). The LGE images acquired at 3 months, displayed clear, focal, high signal intensity areas surrounding the PVs. At this stage post-PVI, a significant increase in LA strain was observed (LA reservoir strain 14.6±2.0% vs. 16.9±3.5%, p&amp;lt;0.01; and contractile strain 5.2±1.8% vs. 6.7±2.9%, p&amp;lt;0.01; respectively). LAVimax was significantly reduced at 3 months compared to acutely post-PVI (Fig. 2). LAVimin and LA conduit strain did not differ between the pre- and post-PVI stages. Conclusion PVI ablation resulted in temporary reduced LA function acutely post-PVI, likely due to edema and thickening of the LA wall. At three months, LGE images revealed clearly visible increased signal intensity in the ablated segments. At this stage, LA function improved, though full recovery did not occur as evidenced by the persistent slightly reduced contractile strain, possibly due to the ablation-induced loss of LA myocardium and formation of fibrosis. The decrease in LAVimax indicates reverse remodeling as a result of the ablation.