Search Results (147)

Kidney diseases in patients with SLE include glomerulonephritis (GN), tubulointerstitial nephritis (TIN) and vasculitis alone or in combination. Immune complex (IC) deposition with complement activation in renal glomeruli causes lupus GN. However, IC deposition can also occur in the tubular basement membrane, renal interstitium, peritubular capillaries and arteries/arterioles to elicit inflammatory responses. TIN is usually associated with more severe GN with inflammation induced by IC. Immunopathologically, the aberrant presentation of T cell subpopulations, T_h1, T_h2, T_h9, T_h17, Treg and follicular T helper cells (T_fh), is closely implicated in TIN in SLE. In addition, M₁/M₂ macrophages and more specific dendritic cells (DCs) contribute to the inflammatory reactions of SLE-TIN. TIN may also present alone (isolated TIN) in apparently normal glomeruli or class I GN. It is intriguing that lupus nephritis constitutes two different pathological predilections, i.e., GN and tubulointerstitial inflammation. Alternatively, these two types may represent a continuous spectrum of inflammatory renal damages. In the present review, we will discuss in detail the pathology/immunopathogenesis, likely specific biomarkers/predictors and novel therapeutic designs for SLE-tubulointerstitial inflammation. In addition, we also raise several plausible investigation methods in SLE-tubulointerstitial inflammation that may help further elucidate this setting of perplexing renal diseases with rheumatic characteristics. Full article

Highly selective inhibitors of the members of the cAMP-selective cyclic nucleotide phosphodiesterases, or PDE4 family, have shown clinically meaningful activity in two different classes of lung disease: roflumilast in obstructive lung disease, specifically chronic obstructive pulmonary disease (COPD), and nerandomilast in restrictive lung diseases characterized by inflammation/fibrosis of the alveolar interstitium, including idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). The beneficial therapeutic benefit of these agents in both of these disorders suggests that they share a common mechanism that underlies their effects on different pulmonary cells and tissues. This review outlines the biochemical, pharmacologic and cellular effects of PDE4-selective inhibitors, emphasizing their role in signal transduction pathways common to many pulmonary cell types. It then compares and contrasts the myriad cellular effects of these agents and their effects in pre-clinical animal models of these disorders. The emerging data are compatible with PDE4-selective inhibitors having targets of action in a large number of pulmonary cell types, only a subset of which is dysregulated in either COPD or IPF. This suggests that differences between the benefits observed with these individual agents in their various clinical indications reflect differences in disease pathogenesis, rather than proven differences in the enzyme-inhibitory effects of the various PDE4 inhibitors that have been studied to date. Full article

Myocardial infarction (MI) and its sequelae continue to be the leading cause of mortality globally. Following MI, a series of structural pathophysiological changes occur in the myocardium, including sympathetic remodeling. Tyrosine hydroxylase (TH), protein gene product 9.5 (PGP9.5), and synaptophysin (SYN) are recognized as key markers of sympathetic nerves. However, the expression patterns of these biomarkers during sympathetic remodeling, particularly their temporal profiles, remain insufficiently characterized. A cohort of 60 healthy adult male C57BL/6 mice was randomly divided into a control group (n = 12) and four MI groups with postoperative intervals of 2, 5, 7, and 10 days (n = 12/group). MI was induced via permanent ligation of the left anterior descending coronary artery (LAD). Cardiac tissues were subjected to histological analyses (HE and Masson’s trichrome staining), immunohistochemical profiling, and quantitative reverse-transcriptase PCR (qRT-PCR) (TH, PGP9.5, and SYN). Immunohistochemical staining revealed that TH-, PGP9.5-, and SYN-immunopositive sympathetic nerves were present in the epicardium, myocardial interstitium, and the periphery of small blood vessels in normal mice. Normal cardiomyocytes were negative for TH but exhibited focal expression of PGP9.5 and SYN. In the myocardial infarction tissue, TH-positive staining indicated sympathetic nerve proliferation in the epicardium, myocardial infarction border zone, and infarct zone, with peak expression occurring at 7 days post-MI. In contrast to TH, PGP9.5 exhibited prominent immunoreactivity, specifically localized to the infarct core and peri-infarct zone cardiomyocytes, while SYN was primarily located in fibroblast-like cells within the same region. qRT-PCR analyses revealed that the time-dependent trends of TH, PGP9.5, and SYN mRNAs exhibited similarities, peaking between 5 and 7 days post-MI. TH demonstrates higher specificity than PGP9.5 and SYN in sympathetic nerve identification, solidifying its role as the optimal biomarker for post-MI sympathetic remodeling. The ectopic expression of PGP9.5 and SYN in non-neuronal cells within myocardial infarction tissue remains speculative and requires further mechanistic studies for validation. Full article

Interstitial pneumonia is a general term for diseases in which inflammation occurs mainly in the interstitium of the lung. It is also pointed out that interstitial pneumonia reduces alveolar function and makes it difficult to take in oxygen through inspiration, causing symptoms such as dyspnea and coughing, which may eventually lead to respiratory failure. At present, there is no effective treatment, and only conservative treatment exists. This time, we report that the therapeutic effect was confirmed in patients with interstitial pneumonia who took platinum palladium. In this case, improvement tendencies were observed in patients with Idiopathic pulmonary fibrosis (IPF), but improvement tendencies were also observed in many other lung diseases. In order to explore the mechanism, AMPK was measured at the in vitro level, and blood KL-6 and hydrogen peroxide levels in the patient were measured at the in vivo level. AMPK values were significantly elevated by more than 800%, and KL-6 and hydrogen peroxide levels were also significantly decreased by drinking platinum palladium. Platinum palladium exhibits a strong antioxidant effect and is the only substance in the world that can approach all four types of active oxygen. In addition, when it was actually administered to patients, there were cases of dramatic improvement, and it was confirmed that KL-6, a parameter of lung function, decreased in 16 out of 32 patients, and furthermore, oxygen inhalation was completed. Patients were also seen. It was suggested that increasing the number of cases in the future may help improve interstitial pneumonia. Full article

Background: Pneumoconiosis is a group of lung diseases characterized by the deposition and accumulation of dust or mineral fibers in the lung interstitium, primarily caused by occupational exposure. Methods: The aim of this study was to identify cases of pneumoconiosis induced by occupational exposure in patients living on the island of Sicily (South Italy), through the retrospective analysis of pneumoconiosis cases registered by the Reference Center for the Prevention, Diagnosis and Treatment of Interstitial Lung Diseases and Rare Lung Diseases (RCLD) of University of Catania, during the decade 2012–2022. Furthermore, the results of a screening conducted in the same 10-year period (2012–2022) on cohorts of workers potentially exposed to RCS generated by Etna’s volcanic dust are reported. Results: From the consultation of the RCLD database, there does not appear to be any correlation between pulmonary fibrosis and exposure to dust of basaltic origin. Conclusions: These data seem to be confirmed by the data of the health monitoring conducted over 10 years on 200 workers involved in different processes of working with lava stone. Full article

The presence of hemoglobin beta mRNA and protein in the female gonad suggests that hemoglobin beta may be present in the male gonad as well. The frequent occurrence of hemoglobin beta in nonerythroid tissues with hypoxic environments further underscores a potential role for hemoglobin beta in the testis to facilitate the regulation of oxygen availability for the developing germ cells and Sertoli cells since they are separated from the blood supply by multiple tissues. The presence of mRNA and protein were evaluated by qPCR and immunohistochemistry, respectively. The mRNA and protein for hemoglobin were detected in juvenile and postpuberal porcine testes. The most intense immunolabelling for the protein was present in testicular interstitial cells, in contrast to previously reported ovarian labelling in close proximity to the gamete and observed in porcine ovaries in the current study. The observed decrease in mRNA expression of hemoglobin beta with age is probably due to the change in testicular composition (increase in seminiferous tubule compartment) with age. The localization of hemoglobin beta in the testis will contribute to future understanding of its potential function in facilitating oxygen availability to seminiferous tubules or reducing oxidative damage. Full article

Interstitial lung diseases (ILD) represent a diverse group of disorders that primarily affect the pulmonary interstitium and, less commonly, involve the alveolar and vascular epithelium. Overlapping clinical, radiological and histopathological features make proper classification difficult, requiring multiple complementary methodologies, including flow cytometry of bronchoalveolar lavages (BAL). This retrospective study analyzed BAL flow cytometry data from 1074 real-life patients, quantifying alveolar macrophages, CD4/CD8 lymphocytes, neutrophils, eosinophils, and CD1a+ Langerhans cells, with the aim of evaluating its diagnostic utility in ILD and pulmonary infection. Clustering and logistic regression analyses identified seven distinct leukocyte profiles: lymphocytic (associated with hypersensitivity pneumonitis, cryptogenic organizing pneumonia, and lymphocytic interstitial pneumonia), sarcoidosis, macrophagic (including nonspecific interstitial pneumonia, desquamative interstitial pneumonitis, pneumoconiosis, and unclassifiable ILD), neutrophilic (including usual interstitial pneumonia, respiratory bronchiolitis ILD, and acute interstitial pneumonia), infectious diseases, eosinophilic ILD, and Langerhans cell histiocytosis. The estimated leukocyte profiles were associated with different overall survival (OS) outcomes. Neutrophilic profiles, both infectious and non-infectious, correlated with poorer OS, particularly in patients without pulmonary fibrosis. Furthermore, corticosteroids and other immunosuppressive therapies did not show significant OS differences across leukocyte profiles. Although the gold standard in BAL cytology continues to be cytopathology, these results support BAL flow cytometry as a rapid and reliable complementary tool to aid in the classification of interstitial lung diseases based on immune cell profiles, providing valuable predictive information and contributing to personalized therapeutic approaches. Full article

The long-term reduction of the Aral Sea area has led to an ecological catastrophe and a deterioration in the health of the population. The progressing demographic crisis necessitates research on factors that negatively impact the fertility of the population in the Aral region. To investigate the influence of Aral Sea dust–salt aerosols on rat testicular tissues, we exposed male rats to the inhalation of dust–salt aerosols for 7, 24, 30, 48 and 72 days. The results of the morphometric analysis of the rat testes tissues indicate that aerosols containing salts from the Aral Sea have a detrimental effect on the seminiferous epithelium, causing a depletion of the spermatogenic layer and reduction of seminiferous tubules lumen. The morphological signs of testicular damage in the experimental animal groups included low cellularity of seminiferous tubules, vacuolization of Sertoli cells, and a decrease in the number of Leydig cells in the interstitium. The smallest thickness of the spermatogenic layer and the lowest number of Leydig cells were observed in rats after the longest inhalation exposure to the dust–salt aerosols. Full article

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that can cause fibrosis of the lung interstitium, resulting in respiratory failure and death. Patients with an ILD, particularly idiopathic pulmonary fibrosis (IPF) or connective tissue disease-associated ILDs (CTD-ILDs), are prone to develop chronic pulmonary infections such as tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD). Methods: This case series examines the management of three ILD patients with a usual interstitial pneumonia (UIP) pattern and concomitant NTM-PD or TB at National Institute for Infectious Diseases “Lazzaro Spallanzani” in Rome, Italy, over three years (2019–2022). Results and Conclusions: Multi-disciplinary discussion (MDD) was crucial to define the therapeutic approach due to the increased risk of side effects and drug interactions. Our work underscored how a comprehensive diagnostic evaluation, enriched by MDD, is useful for optimizing the management and reducing drug-related adverse effects and interactions in ILD patients with cavitary lesions. Full article

Collagen is the main protein found in skin, bone, cartilage, ligaments, tendons and connective tissue, and it can exhibit properties ranging from compliant to rigid or form gradients between these states. The collagen family comprises 28 members, each containing at least one triple-helical domain. These proteins play critical roles in maintaining mechanical characteristics, tissue organization, and structural integrity. Collagens regulate cellular processes such as proliferation, migration, and differentiation through interactions with cell surface receptors. Fibrillar collagens, the most abundant extracellular matrix (ECM) proteins, provide organs and tissues with structural stability and connectivity. In the mammalian myocardial interstitium, types I and III collagens are predominant: collagen I is found in organs, tendons, and bones; collagen II is found in cartilage; collagen III is found in reticular fibers; collagen IV is found in basement membranes; and collagen V is found in nails and hair. Recombinant human collagens, particularly in sponge-like porous formats combined with bone morphogenetic proteins, serve as effective scaffolds for bone repair. Due to their biocompatibility and low immunogenicity, collagens are pivotal in tissue engineering applications for skin, bone, and wound regeneration. Recombinant technology enables the production of triple-helical collagens with amino acid sequences identical to human tissue-derived collagens. This review summarizes recent advances in the molecular functions and recombinant expression of human collagens, with a focus on their biomedical applications. Full article

ARDS is a challenging syndrome in which the hallmark is alveolar epithelium damage, with the consequent extravasation of fluids into the interstitium and alveolar space. Patients with severe ARDS almost always require mechanical ventilation and aggressive fluid resuscitation, at least in the initial phases. The increased intrathoracic pressure during positive pressure ventilation reduces cardiac output, worsening the circulatory status of these patients even more. In this pathological context, fluid therapies serve as a means to restore intravascular volume but can simultaneously play a detrimental role, increasing the amount of liquid in the lungs and worsening gas exchange and lung mechanics. Indeed, clinical research suggests that fluid overload leads to worsening outcomes, mostly in terms of gas exchange, days of mechanical ventilation, and ICU stay duration. For these reasons, this review aims to provide basic information about ARDS pathophysiology and heart–lung interactions, the understanding of which is essential to guide fluid therapy, together with the close monitoring of hemodynamics and fluid responsiveness. Full article

The cryopreservation of testicular tissues meets the demands for the germplasm preservation of humans and animals. Previously, we reported on the cryopreservation of bovine testicular tissues. To further evaluate the viability of these tissues, subcutaneous xenotransplantation of the frozen–thawed calf testicular tissues was performed with castrated nude mice as the recipients. After 28 days (D28), the survival and development of the grafts were examined. The grafts from 1-day-old (D1) calf testes were recovered and angiogenesis around the grafts was observed. Histologically, the seminiferous cords in the grafts were well maintained and capillaries in the interstitium were observed. Quantitative real-time PCR (qRT-PCR) analysis showed that the grafts expressed germline genes Gfrα-1, C-kit, and Sycp3 and somatic genes Sox9, Acta2, and Star. The expressions of C-kit, Sox9, Acta2, and Star were higher in 28D grafts than those in 1D and 30-day-old (30D) calf testicular controls. Together, we initially demonstrate that cryopreserved calf testicular tissues retain their viability and developmental capacity after xenotransplantation. Full article

Primary and post-primary TB are distinct entities. Primary TB occurs when the patient is infected with Mycobacterium tuberculosis (MTB) for the first time without prior immunity, and post-primary TB occurs when the patient has developed immunity against the primary infection. Post-primary TB occurs only in humans. It accounts for 80% of all clinical cases and nearly 100% of transmissions of infection. Early lesions of post-primary TB are reversible, and studying it using modern immunological tools holds the key to developing preventive or treatment strategies. Human lung tissue from untreated TB patients was acquired from pathology archives stored at the Gades Institute of Pathology, Haukeland University Hospital, Bergen, Norway, from 1931 to 1947. Manual immunohistochemistry was performed for macrophage (CD68, CD64 and CD163), T cells (CD3 and CD8), matrix metalloproteinases (MMP-9), and markers for programmed death-pathway PD/PDL-1. Digital quantification was performed using Qupath software. In early lesions of post-primary TB, macrophages showed mixed-phenotype M1 and M2, expressed PDL-1, and were compartmentalized in the alveolar space. T-cells expressed PD-1 and were compartmentalized in the interstitial wall surrounding early lesions. MTB antigens and MMP-9 were also found in early lesions. As the lesion progressed towards necrosis, macrophages showed predominant M1 morphology, and expressions of PDL-1, PD-1, CD8⁺ cells, and MTB antigens increased. In the early lesions of post-primary TB, the compartmentalization of macrophages in the alveoli and T cells in the interstitium was shown. The PDL-PD1 pathway probably facilitated the mycobacterial growth by evading host immunity. Full article

The morphophysiology of intratesticular sperm pathways in mammals, including humans, is poorly understood. The seminiferous tubule is continuous with the straight tubule; however, its final portion—the terminal segment (TS)—has a different tissue composition. This paper reviews the most important histological results from mammal studies from the last decades of the 20th century, including the different nomenclatures given to the TS. The TS presents a loss of spermatogenesis and is lined mainly with modified Sertoli cells. There is no unanimity among authors when it comes to naming and defining TS. In the last ten years, studies on rats and mice have highlighted the importance of this testicular zone, proposing that there is a high proliferation of modified Sertoli cells with an undifferentiated cellular profile associated with stem spermatogonia. In hamsters, an immunohistochemical study showed the existence of heterogeneity between these cells, and the surrounding interstitium presents numerous Leydig cells that are ultrastructurally different from those of the rest of the testis rest. In conclusion, we have only just begun to understand the tissue biology of TS. Emerging research is very promising; it can potentially modify our current knowledge of testicular biology and be very useful in promoting the advancement of male fertility restoration therapies in andrology. Full article

Interstitial lung diseases (ILDs) are pathologies affecting the pulmonary interstitium and, less frequently, the alveolar and vascular epithelia. Bronchoalveolar lavage (BAL) is commonly used in ILD evaluation since it allows the sampling of the lower respiratory tract. The prognostic value of BAL cell counts in ILD is unknown. Flow cytometry quantification of lymphocytes and neutrophils in BAL of 1074 real-life consecutive patients were retrospectively correlated with clinical, radiological, anatomopathological, functional/spirometry, and evolutionary data. Cut-offs with predictive value were established at 7% and 5% for lymphocytes and neutrophils, respectively. Three risk stratification groups (Risk-LN) were established: FAVORABLE (lymphocytes > 7% and neutrophils < 5%), INTERMEDIATE (rest of patients), and UNFAVORABLE (lymphocytes < 7% and neutrophils > 5%), showing 75th percentile overall survival (OS) of 10.0 ± 1.4, 5.8 ± 0.6, and 3.0 ± 0.3 years (p < 0.001), respectively. A scoring model combining Risk-LN and the age of the patients with great predictive capacity for OS on fibrotic and non-fibrotic ILDs is proposed. This score is an independent predictive factor (HR = 1.859, p = 0.002) complementary to the fibrosis status (HR = 2.081, p < 0.001) and the type of treatment. Flow cytometry of BAL provides rapid and accurate quantification of lymphocytes and neutrophils, allowing the establishment of a risk score model that is useful in the clinical management of fibrotic and non-fibrotic ILDs from the time of diagnosis. Full article