Tissue Lesions Research Articles

Terminally differentiated cytotoxic CD4+ T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

Accumulating evidence supports the involvement of adaptive immunity in the development of radiation-induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8+ T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4+ T cells (CD4+ CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context. Utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 3934 CD4+ T cells from the brain lesions of four RIBI patients and identified six subclusters within this population. A notable subset, the cytotoxic CD4+ T cells (CD4+ CTLs), was marked with high expression of cytotoxicity-related genes (NKG7, GZMH, GNLY, FGFBP2, and GZMB) and several chemokine and chemokine receptors (CCL5, CX3CR1, and CCL4L2). Through in-depth pseudotime analysis, which simulates the development of CD4+ T cells, we observed that the CD4+ CTLs exhibited signatures of terminal differentiation. Their functions were enriched in protein serine/threonine kinase activity, GTPase regulator activity, phosphoprotein phosphatase activity, and cysteine-type endopeptidase activity involved in the apoptotic signaling pathway. Correspondingly, mice subjected to gamma knife irradiation on the brain showed a time-dependent infiltration of CD4+ T cells, an increase of MHCII+ cells, and the existence of CD4+ CTLs in lesions, along with an elevation of apoptotic-related proteins. Finally, and most crucially, single-cell T-cell receptor sequencing (scTCR-seq) analysis at the patient level determined a large clonal expansion of CD4+ CTLs in lesion tissues of RIBI. Transcriptional factor-encoding genes TBX21, RORB, and EOMES showed positive correlations with the cytotoxic functions of CD4+ T cells, suggesting their potential to distinguish RIBI-related CD4+ CTLs from other subsets. The present study enrichesthe understanding of the transcriptional landscape of adaptive immune cells in RIBI patients. It provides the first description of a clonally expanded CD4+ CTL subset in RIBI lesions, which may illuminate new mechanisms in the development of RIBI and offer potential biomarkers or therapeutic targets for the disease.

Current Insights into Tissue Injury of Giant Cell Arteritis: From Acute Inflammatory Responses towards Inappropriate Tissue Remodeling.

Giant cell arteritis (GCA) is an autoimmune disease affecting large vessels in patients over 50 years old. It is an exemplary model of a classic inflammatory disorder with IL-6 playing the leading role. The main comorbidities that may appear acutely or chronically are vascular occlusion leading to blindness and thoracic aorta aneurysm formation, respectively. The tissue inflammatory bulk is expressed as acute or chronic delayed-type hypersensitivity reactions, the latter being apparent by giant cell formation. The activated monocytes/macrophages are associated with pronounced Th1 and Th17 responses. B-cells and neutrophils also participate in the inflammatory lesion. However, the exact order of appearance and mechanistic interactions between cells are hindered by the lack of cellular and molecular information from early disease stages and accurate experimental models. Recently, senescent cells and neutrophil extracellular traps have been described in tissue lesions. These structures can remain in tissues for a prolonged period, potentially favoring inflammatory responses and tissue remodeling. In this review, current advances in GCA pathogenesis are discussed in different inflammatory phases. Through the description of these-often overlapping-phases, cells, molecules, and small lipid mediators with pathogenetic potential are described.

Dental Care for Cancer Patients in the Prevention of Complications of Chemotherapy and Head and Neck Radiation Therapy

Oncological diseases occupy one of the first places in the structure of disability and mortality of the population. The main methods of treating patients with malignant tumors in the maxillofacial area are surgical method, radiation therapy and chemotherapy. Treatment with only one of the listed methods It is rarely performed, mainly at the stage of cancer in situ or stage I of the disease. The treatment depends on the clinical and morphological characteristics of the tumor and requires the use of all methods simultaneously or in a certain sequence. Radiation and chemotherapy treatments not only have systemic side effects, but also side effects in the treatment area. Against the background of antitumor treatment, there is an exacerbation of concomitant chronic diseases, including odontogenic ones. Pathological changes appear on the mucous membrane oral cavity, on the skin, in the subcutaneous tissue, in the salivary glands and in the bone marrow of the jaw bones. The degree of damage to these structures during tumor treatment depends on their initial condition. At the same time, the initial condition of the oral cavity affects the quality of antitumor treatment. Poor oral hygiene and chronic odontogenic lesions can cause the development of episodic fevers and other general complications. All this requires stopping or changes in the tactics of antitumor treatment, which reduces its radicalism. It becomes obvious that sanitation of the oral cavity, carried out before treatment by an oncologist, will avoid or reduce the frequency complications in the maxillofacial area, improve the quality of life of an oncology patient. Dental care for such a patient has features and requires an individual approach. The purpose of this study was to review the literature on the main oral tissue complications arising from chemotherapy and radiation therapy in the head and neck region. In Google Scholar, Medline, Scopus, Web of Sciences, PubMed a systematic review was conducted. Search keywords terms included head and neck cancer, dental care, prevention of complications of cancer, oral tissue lesions manifestationin, chemotherapy, head and neck radiation therapy. Conducted a preliminary search and reviewed 132 titles and abstracts in this literary review included 48 article. This article analyzes the main complications of oral tissues resulting from chemotherapy and radiation therapy in the head and neck area and provides practical recommendations for the management and prevention of complications in this category of patients.

Ретроспективний аналіз каріозного ураження твердих тканин зубів у дітей з радіаційно забруднених унаслідок аварії на Чорнобильській АЕС територій України

The relevance of the study is due to the presence of significant carious lesions of the hard tissues of the teeth in children from radiation-contaminated territories as a result of the accident at the Chornobyl nuclear power plant (ChNPP). Purpose - to conduct a retrospective analysis of the intensity of dental caries in children of Ukraine, residents of radiation-contaminated territories, taking into account the general state of health at different times after the accident at the ChNPP (1993-1996, 2001-2003, 2016-2018) as a basis for the further development of a complex of therapeutic and preventive measures for this pathology. Materials and methods. The object of the study: 1852 children aged 7-15 - residents of territories contaminated with radionuclides. Assessment of caries intensity of permanent teeth in accordance with WHO recommendations (2013) included determination of caries prevalence and index assessment of caries intensity of permanent teeth (PT): «decayed, missing, filled permanent teeth» (DMFT) and «decayed, missing, filled permanent teeth surfaces» (DMFS). Statistical processing of data was carried out using methods of variational statistics (statistical package «IBM SPSS Statistics 20.0.0»). Results. In 1993-1996 irradiated children from the III zone had a very high intensity of dental caries (DMFT - 7.25±0.77, DMFS - 10.92±1.77), twice as high compared to residents of the IV zone. In children from III and IV zones in 2001-2003 the intensity of dental caries was higher in the presence of somatic pathology. In 2016-2018 compared to the period 2001-2003 there was a significant (p<0.05) decrease in both indices of carious lesions, probably due to a decrease in the degree of exposure of children to radionuclides. Conclusions. During the period 1993-1996 the highest rates of dental caries intensity were determined in 15-year-old children from zone III compared to residents of zone IV. The intensity of dental caries during the periods of 2001-2003 and 2016-2018 decreased, although it remained at a high level, which requires the further development of a complex of treatment and prevention measures for this pathology. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the children's parents was obtained for the research. The authors declare no conflict of interests.

Surgeon-Generated Reconstructed Three-Dimensional Tomography Images Improve Surgical Outcomes on Deep Soft Tissue Lesions

Background: Recent advances in three-dimensional (3D) reconstruction of tomographic imaging have rarely been applied to wound management and soft tissue-related diseases due to the nature of imaging modality hindering automatic segmentation of the region of interest (ROI). The authors created 3D images of soft tissue lesions using open-source software and evaluated their usefulness through four clinical cases.Methods: Patients with wounds or soft tissue lesions underwent enhanced tomography. The surgeon manually segmented the ROIs and reconstructed them using 3D Slicer. The reconstructed images were overlaid on an anatomy plate or clinical pictures for clinical application. The authors conducted hands-on training and surveyed the participants before and after the course to evaluate clinical applicability and efficacy.Results: Nine plastic surgeons were enrolled. After training, their perception of applying 3D imaging on deep pus pocket drainage, foreign body removal, and deep-located lesion biopsy remained unchanged. However, their response significantly changed from likely to very likely in whether 3D reconstruction imaging of deep soft tissue lesions would help improve the surgical outcome. They answered positively in their recommendation of 3D reconstruction and its application to clinical practice. However, they responded neutrally to whether it was easy to learn. This method was found most useful for deep lesion excision planning, followed by drainage of deep concealed pus pockets, foreign body removal, and biopsies of lesions difficult to localize.Conclusion: Surgeon-generated 3D reconstruction of wounds and soft tissue lesions using open-source software can aid clinical practice, significantly improving surgical outcomes in deep soft tissue lesions.

Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models

Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22–23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVaxTM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.

Magnetic Resonance Imaging Monitoring of Thermal Lesions Produced by Focused Ultrasound

Abstract Background: The main goal of the study was to find the magnetic resonance imaging (MRI) parameters that optimize contrast between tissue and thermal lesions produced by focused ultrasound (FUS) using T1-weighted (T1-W) and T2-weighted (T2-W) fast spin echo (FSE) sequences. Methods: FUS sonications were performed in ex vivo porcine tissue using a single-element FUS transducer of 2.6 MHz in 1.5 and 3 T MRI scanners. The difference in relaxation times as well as the impact of critical MRI parameters on the resultant contrast-to-noise ratio (CNR) between coagulated and normal tissues were assessed. Discrete and overlapping lesions were inflicted in tissue with simultaneous acquisition of T2-W FSE images. Results: FUS lesions are characterized by lower relaxation times than intact porcine tissue. CNR values above 80 were sufficient for proper lesion visualization. For T1-W imaging, repetition time values close to 1500 ms were considered optimum for obtaining sufficiently high CNR at the minimum time cost. Echo time values close to 50 ms offered the maximum lesion contrast in T2-W FSE imaging. Monitoring of acute FUS lesions during grid sonications was performed successfully. Lesions appeared as hypointense spots with excellent contrast from surrounding tissue. Conclusion: MRI monitoring of signal intensity changes during FUS sonication in grid patterns using optimized sequence parameters can provide useful information about lesion progression and the success of ablation. This preliminary study demonstrated the feasibility of the proposed monitoring method in ex vivo porcine tissue and should be supported by in vivo studies to assess its clinical potential.

Safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer

Purpose To evaluate the safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer. Materials and methods A total of 27 patients with 40 liver lesions underwent fluorescence-assisted laparoscopic ablation between January 2020 to March 2023. The sensitivity of indocyanine green (ICG)-fluorescence imaging, technique effectiveness rate and complications of fluorescence-assisted laparoscopic thermal ablation were evaluated. Results In total, 33 out of the 40 lesions were identified by ICG-fluorescence imaging technique, with the sensitivity of 82.5%. The sensitivity of ICG-fluorescence imaging of tumor detection in liver surface of parenchyma was significantly higher than that in the deeply located hepatic parenchyma (96.8% vs 33.3%, p = 0.002). ICG-fluorescence imaging procedures detected 4 lesions that cannot be seen on intraoperative ultrasound. It provides clear demarcation lines on the hepatic surface. Technical success is achieved if the necrotic zone had at least a 5 mm ablative margin around the outer edge of the ICG-fluorescence image. Technical success of fluorescence laparoscopic radiofrequency ablation (FLRFA) and fluorescence laparoscopic microwave ablation (FLMWA) was 100% (27/27). Technical effectiveness is defined by the complete necrotic lesions of the local tumor tissue during follow-up. According to the CT/MRI one month after FLRFA or FLMWA, the technical efficacy rate was 92.5% (37/40) and local tumor progression occurred in 7.5% (3/40) of the enrolled lesions. During the follow-up period, no major complications were observed. Conclusion ICG-fluorescence imaging guided laparoscopic thermal ablation was feasible, safe and effective.

Pulmonary cryptococcoma in a Friesian horse in the Netherlands

AbstractA 6‐year‐old female Friesian horse was admitted with pyrexia, dullness, weight loss, watery faeces and mild bilateral mucoid nasal discharge. Radiographic and ultrasonographic examination of the thorax indicated a large mid‐thoracic soft tissue mass, and the horse was euthanased because of a poor prognosis. At postmortem examination, it was found that the lung tissue was partly replaced by multiple to coalescing soft tissue lesions with a yellow gelatinous aspect, varying in size up to 15 × 15 × 20 cm. Histologically, the mass showed mild pyogranulomatous inflammation associated with large numbers of globular encapsulated 10–20 μm yeasts with or without narrow‐based budding, consistent with multiple coalescing cryptococcomas. Quantitative PCR testing of formalin‐fixed paraffin‐embedded tissue led to the identification of Cryptococcus gattii species complex. To the authors’ knowledge, this is the first case reported in the Netherlands of pulmonary cryptococcomas due to C. gattii sensu lato in a horse that had never travelled abroad.

Role of Wisteria floribunda agglutinin binding glycans in carcinogenesis and metastasis of cholangiocarcinoma.

Aberrant glycosylation is an important factor in facilitating tumor progression and therapeutic resistance. In this study, using Wisteria floribunda agglutinin (WFA), we examined the expression of WFA-binding glycans (WFAG) in cholangiocarcinoma (CCA). The results showed that WFAG was highly detected in precancerous and cancerous lesions of human CCA tissues, although it was rarely detected in normal bile ducts. The positive signal of WFAG in the cancerous lesion accounted for 96.2% (50/52) of the cases. Overexpression of WFAG was significantly associated with lymph node and distant metastasis (P < 0.05). The study using the CCA hamster model showed that WFAG is elevated in preneoplastic and neoplastic bile ducts as early as 1month after being infected with liver fluke and exposed to N-nitrosodimethylamine. Functional analysis was performed to reveal the role of WFAG in CCA. The CCA cell lines KKU-213A and KKU-213B were treated with WFA, followed by migration assay. Our data suggested that WFAG facilitates the migration of CCA cells via the activation of the Akt and ERK signaling pathways. In conclusion, we have demonstrated the association of WFAG with carcinogenesis and metastasis of CCA, suggesting its potential as a target for the treatment of the disease.

Approach to Nonmass Lesions on Breast Ultrasound

AbstractNonmass lesions in breast ultrasound (US) are areas of altered echogenicity without definite margins or mass effect. However, these lesions may show calcifications, associated architectural distortion, or shadowing just like masses. They vary in their echogenicity, distribution, ductal or nonductal appearance and the associated features that can be seen in variety of benign and malignant pathologies. With no uniform definition or classification system, there is no standardized approach in further risk categorization and management strategies of these lesions. Malignant nonmass lesions are not uncommon and few sonographic features can help in differentiating benign and malignant pathologies. US-guided tissue sampling or lesion localization can be preferred in the nonmass lesions identified on second look US after magnetic resonance imaging or mammography. This article aims to describe various imaging patterns and attempts to provide an algorithmic approach to nonmass findings on breast US.

Orbital pseudolymphoma: a benign condition mimicking malignancy

Orbital lymphomas are not a rare condition that causes systemic and ocular morbidity, in which vision loss often occurs due to compressive optic neuropathy, and whose treatment is complex, involving chemotherapy and radiotherapy. We report a 54-year-old male with protrusion of the right eye associated with mild diminution of vision for one year, limitation of extraocular movements, and a relative afferent pupillary defect with optic disc edema. Imaging revealed a well-defined soft tissue lesion filling the retro-orbital intraconal space, suggestive of orbital lymphoma. Incisional biopsy and fine needle aspiration cytology revealed the lesion to be a reactive lymphoid hyperplasia. Following the administration of oral steroids, the patient showed significant improvement. To our knowledge, a benign lesion with an aggressive presentation is rare, and histopathology plays an important role in diagnosis and management.

Effects of Different Types of Periodontitis on CBCT Morphology of Dental Tissue in Two Ethnic Groups

For the periodontitis patients who came to our hospital from October 2021 till now, the influence of different types of periodontitis on the CBCT morphology of dental tissue of different nationalities was analyzed. To measure the distance between the enamel dentin boundary and root fork of the mandibular first molar, the thickness of the crown hard tissue above the mesial pulp Angle, the thickness of the crown hard tissue above the distal pulp Angle, the height of the pulp chamber, the volume and surface area of the pulp, so as to provide a certain basis for the possibility of future dental tissue lesions.

Free Fibula Flap for Congenital Pseudarthrosis of the Tibia: Indications and Challenges

BackgroundCongenital pseudoarthrosis of the tibia (CPT) is a rare pathological disease associated with neurofibromatosis type 1 (NF1). It presents with tibial bowing and can progress into a nonhealing fracture. Treatment options include conservative approaches such as serial bracing or various surgical options.Surgically, the aims are to achieve long-term bone union, prevent limb length discrepancies (LLDs), and avoid mechanical axis deviation, soft tissue lesions, nearby joint stiffness, and pathological fracture.The purpose of our study is to highlight our experience with both the conservative approach and the use of vascularized free fibula reconstruction of these deformities, including the challenges encountered with a long-term follow-up until skeletal maturity. MethodsWe present a retrospective analysis of a total of nine (9) patients consisting of three (3) girls and six (6) boys. Six (6) children were treated with a vascularized fibula flap, and the other three (3) were treated conservatively. Outcomes measured included fractures, LLD, ankle valgus deformity, donor site morbidity, and number of surgical corrections. ResultsAll patients had flap survival. Three (3) of six children had a previous failed surgery with intramedullary nail and bone graft prior to performing a vascularized free fibula reconstruction. The follow-up period ranged from 8 months to 200 months. The complications included stress fractures (50%), LLD (66.6%), and ankle valgus (33.3%). During growth phases, these children required multiple corrective surgeries. ConclusionsFibula free flap is a good treatment option for CPT even in patients with prior surgical failures with variable results.Level of Evidence - Level 4 - Case series Therapeutic Studies—Investigating the Results of Treatment.

Fibrosis Management Algorithm in Secondary Liposculpture.

Liposuction is considered one of the most common procedures in plastic surgery. However, major postoperative complications such as visceral injury, fluid overload, and necrotizing fasciitis still occur. Likewise, minor complications such as ecchymosis, seromas, infections, and contour irregularities that do not threaten the life of the patient do generate significant dissatisfaction. Current evidence regarding the management of fibrosis after previous liposuction remains limited. The objective of this article is to standardize a management algorithm based on the extensive experience and successful results of the primary author (G.M.). Patients who underwent secondary liposculpture between August 2022 and May 2023 were evaluated prospectively. Inclusion criteria comprised females between 18 and 60 years old, nonsmokers, with a BMI < 35 kg/m2 and a history of previous body contouring surgeries. Identification of the patient's skin condition and subcutaneous lesions in the adipose tissue were obtained in detail. Statistical analysis of preoperative and postoperative medical photographs was also performed with the Fiji Biological image analyzer. Photographic analysis of preoperative and postoperative photographs showed a statistically significant difference between the areas affected by fibrosis (P < .001). The most frequent clinical findings were depressions in 99% of the females (74), followed by soft nodules in 95% (70), hard nodules in 81% (61), adhesions in 47% (35), and finally cutaneous bursas in 4%. Our classification system and management algorithm for fibrosis and contour irregularities is a safe and reliable tool. Results were objectively verified, yielding statistically significant outcomes.

SDMS CME Credit – Case Series: Multiple Soft Tissue Lesions Demonstrated by Sonography and MRI Correlation

SDMS CME Credit – Case Series: Multiple Soft Tissue Lesions Demonstrated by Sonography and MRI Correlation

Oral Tissue Lesions Manifestation in Cancer Patients Following Chemotherapy and Head and Neck Radiation Therapy

Background: As is known, cancer therapy includes a complex of therapeutic measures: chemotherapy, radiotherapy and radical. The purpose of this study was to review the literature on the main oral tissue complications arising from chemotherapy and radiation therapy in the head and neck region. Methods: In Google Scholar, Medline, Scopus, Web of Sciences, PubMed a systematic review was conducted. Search keywords terms included: Cancer patients, oral tissue lesions, head and neck, chemotherapy, radiation therapy. Conducted a preliminary search and reviewed 134 titles and abstracts in this literary review included 58. Cancer patients in the oral cavity exhibit a variety of oral tissue lesions during and shortly after radiation therapy to the head and neck. Results: Our search showed that cancer patients following chemotherapy and head and neck radiation therapy often experience oral manifestations. Among these lesions, increased susceptibility to dental caries, periodontal disease, oral mucositis, tissue fibrosis, salivary gland dysfunction, o pportunistic infections of the mucous membranes, and neurosensory disorders are often encountered. These manifestations represent a serious problem for patients and require special strategies from treating physicians to mitigate the harmful effects of radiation therapy on vital functions and improve the quality of life of these patients. Complications in the oral cavity, chemotherapy and head and neck radiation therapy creates many social problems and difficulties for cancer patients. Arguments for an interdisciplinary approach to the management of these patients are recommended in many studies. Conclusion: This review will help dental practitioners manage the risks of dental interventions and prevent potential complications in patients with cancer requiring dental care. Prevention, supportive care, and symptom management by health care providers are important for patients with oral problems related to cancer treatment and can help the patient cope with cancer and its complications.

Managing Periorbital Necrotizing Fasciitis: How Invasive Should We Go?

Introduction : Periorbital necrotizing fasciitis (PNF) is rapidly progressive and severe infection that may result in vision loss, serious facial disfigurement, and death. Primary management includes surgical debridement; however, here we report a case in which conservative approach resulted in favorable resolution.&#x0D; Case Illustration : A 24-year-old male presented with swollen right upper eyelid, with watery eye, pain, and blurry vision since 1 week prior. No history of trauma or known systemic diseases was reported. Restricted movement of the right eye (RE), slight nonaxial proptosis, and skin defect along the right superior palpebra with pus, blood, necrotic and granulation tissues were found. Visual acuity (VA) of RE decreased to 6/40 with normal intraocular pressure. No abnormalities on the left eye, fever, and other signs of systemic involvement were present. Contrast orbital computed tomography (CT) scan revealed right preseptal and postseptal tissue lesions, suggesting orbital cellulitis. Initial blood work showed leukocytosis, elevated neutrophil and lymphocyte counts, and high liver function markers. The diagnosis of right orbital cellulitis with PNF was established. Skin swabs and blood cultures were taken, while intravenous ampicillin-sulbactam, bedside wound debridement, and chloramphenicol ointment application were initiated. The swab culture later showed Acinetobactersp. The infection improved, VA was restored to 6/6, and wound closure was achieved without any surgery.&#x0D; Discussion : Management of necrotizing fasciitis localized in periorbita in an otherwise healthy patient may be successfully accomplished with a less invasive approach.&#x0D; Conclusion : Timely diagnosis and correct antibiotic therapy are mandatory to decrease morbidity and mortality related to PNF.

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats.

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.

Morphological and biomechanical characterization of long bones and peri-implant bone repair in type 2 diabetic rats treated with resveratrol

Type 2 diabetes interferes with bone remodeling mechanisms, requiring studies to reverse this damage, and resveratrol is a polyphenol with rich properties. This study aimed to characterize the long bone morphology and peri-implant biomechanics of normoglycemic and type 2 diabetic animals treated with resveratrol. Thirty-two male Wistar rats were used and divided into normoglycemic and diabetic with or without treatment. They had the installation of implants in the tibia and treatment with oral resveratrol within 45 days. Resveratrol was responsible for weight homeostasis and decreased glycemic levels in rats with type 2 diabetes. The three-point bending testing, resveratrol showed positive effects on the biomechanics of long bones, corroborating a more resistant bone in comparison to untreated diabetics. Micro-ct revealed how bone metabolism is affected by systemic disease, decreasing bone quality. The counter-torque of normoglycemic animals showed superior osseointegration to diabetes, with no differences in the administration of the polyphenol, showing the sovereignty of the deleterious effects of the disease when there is a tissue lesion and an inflammatory picture installed. Overall, resveratrol acted positively in the etiopathogenesis of type 2 diabetes and revealed positive effects on the strength of long bones.