Tissue Changes Research Articles

Multiphysics simulations reveal haemodynamic impacts of patient‐derived fibrosis‐related changes in left atrial tissue mechanics

AbstractStroke is a leading cause of death and disability worldwide. Atrial myopathy, including fibrosis, is associated with an increased risk of ischaemic stroke, but the mechanisms underlying this association are poorly understood. Fibrosis modifies myocardial structure, impairing electrical propagation and tissue biomechanics, and creating stagnant flow regions where clots could form. Fibrosis can be mapped non‐invasively using late gadolinium enhancement magnetic resonance imaging (LGE‐MRI). However, fibrosis maps are not currently incorporated into stroke risk calculations or computational electro‐mechano‐fluidic models. We present multiphysics simulations of left atrial (LA) myocardial motion and haemodynamics using patient‐specific anatomies and fibrotic maps from LGE‐MRI. We modify tissue stiffness and active tension generation in fibrotic regions and investigate how these changes affect LA flow for different fibrotic burdens. We find that fibrotic regions and, to a lesser extent, non‐fibrotic regions experience reduced myocardial strain, resulting in decreased LA emptying fraction consistent with clinical observations. Both fibrotic tissue stiffening and hypocontractility independently reduce LA function, but, together, these two alterations cause more pronounced effects than either one alone. Fibrosis significantly alters flow patterns throughout the atrial chamber, and particularly, the filling and emptying jets of the left atrial appendage (LAA). The effects of fibrosis in LA flow are largely captured by the concomitant changes in LA emptying fraction except inside the LAA, where a multifactorial behaviour is observed. This work illustrates how high‐fidelity, multiphysics models can be used to study thrombogenesis mechanisms in patient‐specific anatomies, shedding light onto the links between atrial fibrosis and ischaemic stroke. imageKey points Left atrial (LA) fibrosis is associated with arrhythmogenesis and increased risk of ischaemic stroke; its extent and pattern can be quantified on a patient‐specific basis using late gadolinium enhancement magnetic resonance imaging. Current stroke risk prediction tools have limited personalization, and their accuracy could be improved by incorporating patient‐specific information such as fibrotic maps and haemodynamic patterns. We present the first electro‐mechano‐fluidic multiphysics computational simulations of LA flow, including fibrosis and anatomies from medical imaging. Mechanical changes in fibrotic tissue impair global LA motion, decreasing LA and left atrial appendage (LAA) emptying fractions, especially in subjects with higher fibrosis burdens. Fibrotic‐mediated LA motion impairment alters LA and LAA flow near the endocardium and the whole cavity, ultimately leading to more stagnant blood regions in the LAA.

Manifestations of toxic pulmonary edema during respiratory support in an experiment

BACKGROUND: Currently, respiratory support is successfully used to treat pulmonary edema of non-toxic origin. The manifestations of pulmonary edema of non-toxic origin and toxic pulmonary edema have similar features, so respiratory support can be effective in treating the latter. AIM: To describe the manifestations of toxic pulmonary edema in rabbits and demonstrate the effectiveness of artificial pulmonary ventilation with support of positive end-expiratory pressure (PEEP) in case of severe intoxication with thermal destruction products of fluoroplastic-4. MATERIALS AND METHODS: Three rabbits were used in the study: rabbit N 1 (control), rabbit N 2 (intoxication) and rabbit N 3 (treatment). Rabbits N 2 and 3 were subjected to severe intoxication with thermal destruction products of fluoroplastic-4 (1,5 HLC50, 15 min). For treatment, rabbit N 3 (treatment), an hour after exposure, underwent mechanical ventilation with PEEP (pressure-controlled mode; oxygen fraction — 0,3; starting PEEP — 5 cm H2O, tidal volume — 20–25 ml). At various times, chest radiography was performed, oxygenation index, hemoglobin saturation (SaO2), and partial pressure of carbon dioxide in exhaled air (PetCO2) were determined. Posthumously, pathological changes in lung tissue, pulmonary coefficient were determined, and histological examination was performed. RESULTS: Exposure of rabbit N 2 (intoxication) to the thermal destruction products of fluoroplastic-4 led to the sequential formation of the interstitial and alveolar phases of toxic pulmonary edema, which contributed to its death 13 hours after exposure. As SaO2 decreased and PetCO2 increased (3 and 5 hours after exposure), in rabbit N 3 (treatment), during respiratory support, PEEP was increased twice by 2 cm H2O (maintaining a given respiratory volume), which led to the normalization of the studied parameters. On the 7th day after exposure, the condition of rabbit N 3 (treatment) did not differ from the condition of rabbit N 1 (control); no pathological changes in the respiratory system were detected. CONCLUSION: Carrying out mechanical ventilation with PEEP, started an hour after exposure (with a stepwise increase in PEEP as the condition worsens), is effective for correcting toxic pulmonary edema in rabbits caused by severe intoxication with the thermal destruction products of fluoroplastic-4.

The Impact of Changes in Paraspinal Muscle Tissue on Lumbar Percutaneous Intradiscal Radiofrequency Therapy

Background/Objectives: This study aimed to assess whether fatty changes in paraspinal muscle tissue negatively affect pain relief and functional outcomes, measured by the Oswestry Disability Index (ODI), in patients undergoing intradiscal bipolar radiofrequency thermocoagulation for lumbar degenerative disc (LDD) disease. Fatty changes in paraspinal muscles, often associated with sarcopenia, are known to negatively influence treatment outcomes. However, there is limited research on how these changes affect pain and functional capacity following intradiscal procedures. Methods: In this study, data from 59 patients treated for LDD were analyzed. Pain severity was measured using the Numerical Rating Scale (NRS), and the ODI was recorded before the procedure and at 1, 3, and 6 months post-procedure. Fatty changes in the paraspinal muscle tissue were evaluated using the Goutallier classification based on pre-procedure T2-weighted MRI scans, while disc degeneration was assessed using the Pfirrmann classification. Results: The results showed significant positive correlations between the Goutallier and Pfirrmann classifications and pain levels at all time points post-procedure (p < 0.05). Notably, the relationship between NRS scores and Goutallier classification was stronger than that with Pfirrmann classification (p < 0.05). ODI scores were also significantly correlated with both Goutallier and Pfirrmann classifications at each time point, with a stronger association observed between ODI and Goutallier classification than with NRS (p < 0.05). Conclusions: These findings suggest that fatty changes in the paraspinal muscle tissue may significantly influence treatment outcomes and should be considered during pre-treatment evaluations. Further research is needed to explore this relationship more comprehensively.

Assessing and managing lower limb oedema: a clinical review.

Lower limb oedema is a common condition in clinical practice, frequently affecting the distal lower limbs. Whereas benign causes such as prolonged sitting or standing are typical, oedema can also indicate serious systemic diseases such as cardiac failure, liver disease, or renal impairment. Identifying the cause is crucial to prevent irreversible skin and tissue changes. This clinical review aims to increase the knowledge of advanced clinical practitioners (ACPs) and generalist practitioners, including practice and community nurses, by providing an overview of how to approach patients with lower limb oedema, encompassing history-taking, examinations, investigations, and management plans. The main focus is on lymphoedema, which can be primary or secondary. Primary lymphoedema results from genetic abnormalities, while secondary lymphoedema arises from acquired defects due to factors such as obesity, infections, neoplasms, and trauma. Effective management includes addressing the underlying cause, ensuring proper skin care, recommending appropriate exercises, and the use of compression garments. Referral to a lymphoedema specialist is recommended for patient education on managing and treating the condition when required. Additionally, the article discusses the importance of regular skin inspections, minor injury management, environmental considerations, and the critical role of compression garments in lymphoedema management. This comprehensive approach aims to enhance patient outcomes and provide a thorough strategy for ACPs and generalist practitioners.

Alanyl-Glutamine Inhibits the Epithelial-Mesenchymal Transition of Airway Epithelial Cells in Asthmatic Mice via DPP4-SIRT1 Pathway

Introduction: Alanyl-glutamine (Ala-Gln) is a compound known for its protective effects in various tissue injuries. However, its role in asthma-related lung injuries remains underexplored. This study investigates the mechanisms by which Ala-Gln modulates sDPP4-induced airway epithelial-mesenchymal transition and ovalbumin (OVA)-induced asthma in a mouse model. Methods: An asthma model was established in female C57BL/6 J mice by using OVA. CD4+ T cells and bronchial epithelial cells (BECs) were isolated from the spleen and bronchi of the mice, respectively. Interventions included recombinant sCD26/sDPP4 protein, Ala-Gln, and EX527 (a SIRT1 inhibitor). Flow cytometry was used to assess Th17 and Treg cell populations. Mice were treated with Ala-Gln, EX527, and budesonide (BUD). Histopathological changes in lung tissues were evaluated using hematoxylin-eosin and Masson staining. White blood cell counts were measured with a hematology analyzer. The expression levels of DPP4, IL-17, SIRT1, SMAD2/3, N-cadherin, E-cadherin, MMP9, and α-SMA proteins were analyzed. Results: Treatment with recombinant sCD26/sDPP4 resulted in decreased E-cadherin expression in BECs and increased levels of α-SMA, MMP9, and N-cadherin, effects that were mitigated by Ala-Gln. Ala-Gln also prevented the reduction in SIRT1 expression in BECs and the increase in Th17 cell differentiation induced by recombinant sCD26/sDPP4. EX527 administration alongside Ala-Gln reversed these changes and enhanced the phosphorylation of SMAD2/3 through SIRT1 signaling. BUD alone reduced inflammation and fibrosis in bronchial tissue and lowered the Th17/Treg ratio in peribronchial lymph nodes. The therapeutic effect of BUD was further improved with concurrent Ala-Gln treatment. Conclusion: Ala-Gln can inhibit BEC fibrosis and Th17 cell differentiation mediated by recombinant sCD26/sDPP4 through the SIRT1 pathway. Combined with BUD, Ala-Gln enhanced therapeutic efficacy in OVA-induced asthma in mice, which could offer improved outcomes for asthmatic patients with elevated DPP4 levels.

CORRELATION OF Trichomonas vaginalis INFECTION AND PROSTATE CANCER: A SYSTEMATIC REVIEW

Introduction: The presence of T. vaginalis in men should be investigated in terms of its ability to trigger inflammatory reactions and tissue changes capable of damaging the prostatic tissue. Objective: To assess whether there is a correlation between T. vaginalis infection and the risk of developing prostate cancer through systematic investigation. Methodology: To obtain the original studies, crosses were made between the descriptors in Health Sciences and Free Terms, in English and Portuguese, in the databases without limitation for the year of publication. Result: Of the nine articles used, four indicate the association of T. vaginalis infection with developing a malignant prostatic tumor. However, we emphasize the lack of studies with larger population groups and more specific and sensitive methodologies. Conclusion: We emphasize that seven articles were conducted with men residing in the United States, therefore, studies with the male population of other countries are fundamental for a better understanding of the association of T. vaginalis infection with the development of prostate cancer.

Morphofunctional Features of Glomeruli and Nephrons After Exposure to Electrons at Different Doses: Oxidative Stress, Inflammation, Apoptosis

Kidney disease has emerged as a significant global health issue, projected to become the fifth-leading cause of years of life lost by 2040. The kidneys, being highly radiosensitive, are vulnerable to damage from various forms of radiation, including gamma (γ) and X-rays. However, the effects of electron radiation on renal tissues remain poorly understood. Given the localized energy deposition of electron beams, this study seeks to investigate the dose-dependent morphological and molecular changes in the kidneys following electron irradiation, aiming to address the gap in knowledge regarding its impact on renal structures. The primary aim of this study is to conduct a detailed morphological and molecular analysis of the kidneys following localized electron irradiation at different doses, to better understand the dose-dependent effects on renal tissue structure and function in an experimental model. Male Wistar rats (n = 75) were divided into five groups, including a control group and four experimental groups receiving 2, 4, 6, or 8 Gray (Gy) of localized electron irradiation to the kidneys. Biochemical markers of inflammation (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF-α]) and oxidative stress (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) were measured, and morphological changes were assessed using histological and immunohistochemical techniques (TUNEL assay, caspase-3). The study revealed a significant dose-dependent increase in oxidative stress, inflammation, and renal tissue damage. Higher doses of irradiation resulted in increased apoptosis, early stages of fibrosis (at high doses), and morphological changes in renal tissue. This study highlights the dose-dependent effects of electrons on renal structures, emphasizing the need for careful consideration of the dosage in clinical use to minimize adverse effects on renal function.

Muscle Tissue Response to Vipera berus berus and Vipera berus nikolskii Venoms: A Study on Matrix Metalloproteinases and Cytokine Modulation

Vipera berus, also known as the common adder, is a snake species widely distributed in Europe and parts of Asia. Its venom is a mix of enzymatic and non-enzymatic components causing both local and systemic effects including edema, hemorrhage, myonecrosis, gastrointestinal disorders, and rarely – rhabdomyolysis, coagulopathy and hypovolemic shock. Matrix metalloproteinases (MMPs) and cytokines, being inflammatory mediators, participate both in the development of these reactions and in tissue regeneration after acute damage. The current study was aimed at analyzing the concentrations of important mediators of tissue damage, inflammation and regeneration, namely, MMP-1, -2, -3, -8, -10, TIMP-1 (a tissue inhibitor of MMPs), and pro- and anti-inflammatory cytokines, in rat muscle after intraperitoneal injection of venoms from two subspecies of adders – V. berus berus and V. berus nikolskii — to clarify their role in the local response of skeletal muscle to the studied venoms. Changes in muscle tissue were revealed, namely, significant increase in almost all MMPs including MMP-2, as well as TIMP-1, IFN-γ and anti-inflammatory IL-4 and IL-10 content. Moreover, a tendency for some pro-inflammatory cytokines levels to decline 24 h after venom administration was observed, which may be a sign of inflammation suppression and the beginning of reparative processes associated with extracellular matrix remodeling and formation of an optimal environment for muscle regeneration. However, to establish the exact mechanisms of the changes we found, further studies are needed. The ability of V. berus nikolskii venom to induce more pronounced changes was also shown. Our results may be useful for the development of differentiated and more effective treatment strategies for the consequences of bites by these snakes, which include myonecrosis

Distinct brain and neurocognitive transformations after bariatric surgery: a pilot study

BackgroundObese patients have worse outcomes after surgery and are at increased risk for perioperative neurocognitive disorders (PND). Our aim was to detail the cognitive trajectories of patients undergoing bariatric surgery (BS) and map distinct structural brain changes using magnetic resonance imaging (MRI) to better understand the association between the vulnerable brain, surgery, and the arc of PND.MethodsProspective pilot study with longitudinal comprehensive cognitive assessments and MRI were performed on obese patients scheduled for BS. We analyzed baseline cognitive function and high-resolution T1-/T2-weighted brain images on 19 obese patients [age, 54 (9) years, BMI, 40 (36, 42) kg m−2] and compared with 50 healthy control subjects [age, 52 (6) years; BMI, 25 (24, 27) kg m−2]. Patients were evaluated within five days of BS (baseline), immediately after (within 48h), and follow up at six months.ResultsAt baseline, obese patients had significant brain tissue changes seen in MRI and decreased cognitive scores compared to controls (MoCA 26 vs 28, P = 0.017). Surgery induced further gray matter volume and brain tissue changes along with reduced cognitive scores within the immediate postoperative period (MoCA 26 vs 24, P < 0.001). At six months, we observed reversal of brain alterations for most patients and a concomitant rebound of cognitive scores to patient’s baseline status.ConclusionsBariatric surgery resulted in worsening of preexisting brain structural integrity and lower cognitive function for obese patients compared to baseline. These distinct brain lesions are consistent with specific domains of cognition. Most of these changes reverted to patient’s baseline condition within six months after surgery.

Impact of Cardiac Surgery Scar on Heart Rupture Following a Fall from Height

Death from falls accounts for a significant number of injuries and fatalities globally, often linked to suicides, workplace accidents, or substance abuse, and rarely to homicidal causes. Injuries from falls vary based on height, impact point, and surface struck, with severe trauma often seen, including visceral ruptures, organ lacerations, and complex fractures. Even minimal external injuries can mask severe internal damage, such as multiple organ ruptures, organ tears, and large vessel lacerations. Blunt cardiac injuries, which occur in 5% to 50% of falls, are significant, especially in falls over 6 m. In 70% of the cases, cardiac rupture is observed at the level of the posterior wall of the heart and occurs due to a contusive action on the heart during the diastolic filling phase. We report a case of a 29-year-old man (weight 95 kg) who died from an 11-meter fall. He had a history of cardiac surgery for the transposition of the great vessels, and an autopsy revealed extensive cardiac rupture, likely worsened by fibrotic adhesions anchoring the heart to the pericardium. Toxicological investigations on peripheral blood showed BAC > 2.58 g/L. Heart scars, macro- and microscopically as a deposit of fibrous tissue, due to previous surgery, may have contributed to the extent of the lesion, suggesting the need for further study on post-operative tissue changes and their effects on trauma from falls.

Changes in anthropometry, adiposity, and inflammation in Black and White women engaged in intentional weight loss.

We examined associations among changes in anthropometry, regional adiposity, and inflammatory markers in Black and White women participating in intentional weight loss. A total of 104 women with BMI ≥ 25 kg/m2 self-selected bariatric surgery (n = 66) or a diet and exercise program (n = 38). Anthropometric, dual-energy x-ray absorptiometry-quantified regional adiposity, and inflammatory markers (C-reactive protein [CRP], tumor necrosis factor α [TNF-α], soluble TNF receptor I [sTNFRI], sTNFRII, interleukin [IL]-6, and soluble IL-1 receptor antagonist) were measured at baseline and 6 months. Weight, BMI, visceral adipose tissue, and regional (android and gynoid) adiposity declined in the bariatric surgery group. Among bariatric surgery participants, Black women experienced declines of lesser magnitude in terms of weight and BMI than White women, but changes in regional adiposity and visceral adipose tissue did not differ. In the bariatric surgery group, decreases in weight and BMI were associated with decreases in CRP and IL-6 among White women, but not Black women. Decreases in weight, BMI, and android fat were associated with increases in TNF-α, sTNFRI, and sTNFRII among Black women, but not White women. Decreases in anthropometry and adiposity were observed among Black and White bariatric surgery participants; however, associations among changes in adiposity, anthropometry, and inflammation differed by race.

A review of artificial intelligence in wound care

Our aging population, diabetes, and obesity have fueled the growth of chronic wounds seen throughout the world. Often, wounds are a marker of poor health that leads to increased mortality rates. However, the diagnosis and treatment of these wounds are challenging. Incorrectly differentiating between chronic wounds and other complex conditions can lead to adverse events. Artificial intelligence (AI) has been shown to offer some early benefits, and we hypothesized that it may enhance wound care but also carry some notable risks. We performed a detailed search using PubMed, Scopus, Cumulated Index in Nursing and Allied Health Literature, and Web of Science for AI applications in wound care. AI was found to be applied to wound diagnosis and characterization, wound monitoring for tissue change, daily therapy, and prevention and prognostics. AI made for more efficient and accurate wound assessments, less painful assessments of chronic wounds, more personalized treatment, and improved prognostic prediction capabilities. AI also allowed for more precise at-home observation and care, facilitating earlier wound treatment as needed. Challenges associated with AI included how to best allocate AI-assisted technologies equitably, how to safely maintain patient data, and how to diversify datasets for algorithm training. Because the algorithms are not transparent, validating findings may be challenging. AI presents a powerful tool in several aspects of advanced wound care and has the potential to improve diagnoses, accelerate healing, reduce pain, and improve the cost-effectiveness of wound care. More research needs to be done into how to best incorporate AI into daily clinical practice while keeping clinicians aware of the potential risks of using these evolving technologies.

Perindopril Ameliorates Sodium Valproate-Induced Rat Model of Autism: Involvement of Sirtuin-1, JAK2/STAT3 Axis, PI3K/Akt/GSK-3β Pathway, and PPAR-Gamma Signaling

Background and Objectives: Autism is a developmental disability characterized by impairment of motor functions and social communication together with the development of repetitive or stereotyped behaviors. Neither the exact etiology or the curative treatment of autism are yet completely explored. The goals of this study were to evaluate the possible effects of perindopril on a rat model of autism and to elucidate the possible molecular mechanisms that may contribute to these effects. Materials and Methods: In a rat model of sodium valproate (VPA)-induced autism, the effect of postnatal administration of different doses of perindopril on growth and motor development, social and repetitive behaviors, sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling in the hippocampal tissues were investigated. The histopathological and electron microscopic changes elicited by administration of the different treatments were also investigated. Results: Perindopril dose-dependently combatted the effects of prenatal exposure to VPA on growth and maturation, motor development, and social and repetitive behaviors. In addition, the different doses of perindopril ameliorated the effects of prenatal exposure to VPA on sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling. These effects had a mitigating impact on VPA-induced histopathological and electron microscopic changes in the hippocampal tissues. Conclusions: Perindopril may emerge as a promising agent for amelioration of the pathologic changes of autism spectrum disorders.

Hypoxic Responses in Periodontal Tissues: Influence of Smoking and Periodontitis.

This study aimed to investigate the hypoxic changes in periodontal tissues resulting from smoking and periodontitis by assessing levels of hypoxia-inducible factors (HIF-1α, HIF-2α, HIF-3α) and vascular endothelial growth factor (VEGF) in gingival crevicular fluid (GCF). The study comprised 22 periodontally healthy non-smokers (Group H), 22 periodontally healthy smokers (Group HS), 22 non-smokers with periodontitis (Group P) and 22 smokers with periodontitis (Group PS). Clinical periodontal parameters were documented, and GCF samples were collected and analysed using enzyme-linked immunosorbent assay (ELISA). Significantly elevated levels of HIF-1α, HIF-3α and VEGF were observed in Groups HS, P and PS compared to Group H (p < 0.05). Moreover, higher HIF-2α levels were detected in the Groups HS and P compared to Group H (p < 0.05). Significant correlations were detected between all evaluated hypoxia biomarkers in the Group P (p < 0.05) except HIF-2α and HIF-3α. However, in the PS group, significant correlation appeared only between HIF-1α and HIF-2α (p < 0.05). Our findings indicate that smoking and periodontitis induce comparable hypoxic effects in periodontal tissues, as evidenced by the evaluated biomarkers. Further research is warranted to gain a deeper understanding of the mechanisms underlying hypoxia in periodontal tissues.

Digital assessment of soft and hard tissue alterations after anterior maxillary tooth extraction

Objectives: This study aimed to assess dimensional alterations in soft and hard tissues 12 weeks post-extraction using novel computerized methods. Secondary objectives included exploring potential correlations between soft tissue changes and underlying bone variations, as well as investigating relationships between soft and hard tissue alterations and various contributing factors. Methods: For all patients, preoperative and postoperative CBCT scans and intra-oral scans were obtained. Soft and hard tissue dimensions before extraction and at 12 weeks post-extraction were measured using 3D-slicer software. Both DICOM and STL files were superimposed, and measurements were taken at 2mm and 4mm from the facial crestal level. Results: At twelve weeks, soft tissue thickness increased by 73.5% at 2mm and 51.2% at 4mm from the facial crestal bone. In contrast, there was a 42.5% and 33% bone resorption at 2mm and 4mm, respectively. Furthermore, the study found that smokers had a higher rate of soft tissue thickening and hard tissue resorption compared to non-smokers. The female group exhibited greater soft tissue thickening and bone resorption than the male group. Finally, the central incisor showed the highest bone loss rate, followed by the canine and the lateral incisor. Conclusions: Three months following tooth extraction, a physiological thickening of the facial soft tissue occurs concurrently with significant bone loss beneath it. Clinical Significance: This article’s novel digital assessment methods for evaluating soft and hard tissue alterations offer the potential to optimize treatment planning, enhancing patient outcomes and minimizing complications. By providing a comprehensive understanding of post-extraction tissue changes, it empowers clinicians to tailor treatments for individual patients, improving predictability and personalized care.

Comparison Change of Pre and Post-Treatment in Vermilion Height and Lip Area in Adult Class II Division I Malocclusion Treated with Premolar Extraction

Aim: This study aimed to evaluate the alterations in vermilion height and lip area before and after fixed orthodontic treatment in adult patients with Class II Division I malocclusion who underwent premolar extractions. Assessments were conducted using frontal photographs and measurements from lateral cephalograms focusing on dentoalveolar and soft tissue parameters. Methods: Twenty-three adult patients with Class II skeletal malocclusion were selected from the records of the Department of Orthodontics and Dentofacial Orthopedics at AJ Institute of Dental Sciences, Mangalore. Pre-treatment and post-treatment lateral cephalograms and frontal photographs were obtained. Cephalograms were captured using a standardized KODAK 8000c digital cephalostat (69 kVp, 12 mA, 2 s), ensuring accurate patient positioning. The same investigator manually traced the cephalograms to minimize observer variability. Measurements were computed both manually and digitally for comparison purposes. Results: The study found a significant increase in the thickness from the cervical portion of the upper incisors to the upper lip after treatment (mean post-treatment: 15.77±2.28 mm; pre-treatment: 14.95±1.90 mm; P=0.006). Conversely, the thickness from the lower incisors to the upper lip decreased significantly post-treatment (mean post-treatment: 15.46±2.72 mm; pre-treatment: 17.26±2.19 mm; P&lt;0.001). Additionally, there was a significant increase in vermilion height (St-Me) and lower facial height (N-Me) after treatment, with mean differences of 3.58 mm (P&lt;0.001) and 1.18 mm (P=0.04), respectively. Conclusion: Orthodontic treatment involving premolar extractions in Class II Division I malocclusion patients led to significant soft tissue changes, particularly in lip thickness and vermilion height. Other parameters did not exhibit statistically significant differences.

Cyclanoline Reverses Cisplatin Resistance in Bladder Cancer Cells by Inhibiting the JAK2/STAT3 Pathway.

Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin resistance presents a significant clinical challenge. This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin resistance. Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3. T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence (IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. In vivo, subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed via WB and IHC. Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and induced apoptosis and cell cycle arrest in the G0/G1 phase in vitro. In vivo, tumor growth was significantly suppressed, with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in combination. Cyc reverses cisplatin resistance via JAK/STAT3 inhibition in bladder cancer, offering a potential clinical strategy to enhance cisplatin efficacy in treating bladder cancer.

Hemin attenuates bleomycin-induced lung fibrosis in mice by regulating the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/NF-κB pathways.

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model. The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA. Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.

Diallyl trisulfide alleviates dextran sulphate sodium-induced colitis in mice by inhibiting NLRP3 inflammasome activation via ROS/Trx-1 pathway.

Diallyl trisulfide (DATS), a sulphur-containing compound isolated from the medicinal food plant garlic, has been previously reported to attenuate experimental colitis induced by either dextran sodium sulphate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice; however, the underlying mechanism remains to be identified. In this study, we deciphered the key mechanism by which DATS alleviates ulcerative colitis (UC). We showed that oral administration of DATS for 10 consecutive days greatly restrained the infiltration of macrophages and the pathological changes in colonic tissues of mice with DSS-induced colitis. DATS treatment notably dampened the content of IL-1β and IL-18 and suppressed NLRP3 inflammasome activation in colon. Mechanistically, DATS effectively diminished the generation of ROS in macrophages. The suppressive effect of DATS on the activation of NLRP3 inflammasome and downregulation of IL-18 and IL-1β levels was blunted by xanthine oxidase. Further studies revealed that DATS inhibited NF-κB pathway activation by suppressing the expression of Trx-1, thereby inhibiting NLRP3 inflammasome activation. Trx-1 overexpression and interference in macrophages promoted and diminished NLRP3 inflammasome activation, respectively. In summary, garlic and its main active ingredient DATS have potentials to prevent and treat UC, and DATS functions by inhibiting NLRP3 inflammasome activation via Trx-1/ROS pathway.

The essential oils from Asarum sieboldii Miq. alleviate allergic rhinitis by regulating tight junction and inflammation; Network analysis and preclinical validation

Ethnopharmacological relevanceEssential oils from herbs, including those from Asarum sieboldii Miq., are readily absorbed through mucous membranes, explaining their widespread use in inhalation formulations. Asarum sieboldii Miq. has a long history of traditional use for various medicinal purposes, attributed to its anti-inflammatory, antiallergic, and antioxidant properties. Despite research on Asarum sieboldii Miq. for allergic inflammation in respiratory diseases, detailed mechanistic studies are still lacking. Aim of the studyWe utilized bioinformatics and network pharmacology to identify the effectiveness of Asarum sieboldii Miq. in treating allergic rhinitis (AR). Our aim is to elucidate the potential therapeutic effects of essential oil derived from Asarum sieboldii Miq. (ASO), which is recognized for its diverse pharmacological properties, on AR. Materials and methodsCommon genes associated with the active compounds of ASO and AR were utilized to construct a related network and predict their mode of action. AR was induced in BALB/c mice by exposing them to ovalbumin (OVA) and particulate matter 10 (PM10; airborne particles <10 μm). With induction, aerosolized ASO (0.0002% and 0.02%) were administered via nebulizer for 5 minutes per day, three times a week for 7 weeks. Mice were examined for histopathological changes in the nasal tissue, nasal epithelial inflammation, the production of allergen-specific cytokine response in vitro and in vivo. ResultsThe common genes of ASO and AR were predicted to include 'Tight junction', 'Apoptosis', and 'TGF-beta signaling', which are the main pathways of pathogenesis in AR. Consistent with network prediction, nebulized ASO treatment effectively improved the expression of tight junction-related factors, zonula occludens-1, claudin-1, occludin and junction adhesion molecule A, in OVA+PM10 induced mice. Additionally, it reduced hyperplasia of nasal epithelial thickness, goblet cell counts, and inflammatory cell infiltration (eosinophils, neutrophils, macrophages, and lymphocytes) in nasal lavage fluid, while also alleviating allergic symptoms such as sneezing, rubbing, and serum IgE level when compared to the AR-induced group. The levels of mRNA and protein expression related to tight junctions were restored to normal levels by ASO, as confirmed in immunofluorescence analysis in nasal epithelial cells RPMI2650. Furthermore, treatment of ASO on PM10-treated nasal epithelial cells significantly reduced ROS production, recovered mitochondria membrane potential, and inhibition of the production of proinflammatory cytokines (TNF-α, IL-4, and IL-13) and inflammatory mediators linked to the MAPK/NF-κB signaling pathways. ConclusionIntranasal nebulization of ASO improves TJs and alleviates allergic nasal inflammation in AR. It supports the potential pharmaceutical application of ASO treatment for AR.