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Histophilus somni is an important causative agent of bovine respiratory disease complex. Here, we report the complete genome sequence of a Histophilus somni strain 91, which was isolated from a pneumonic lung tissue sample collected from a beef calf.

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Micro-scale models of lung tissue have been employed by researchers to investigate alveolar mechanics; however, they have been limited by the lack of biofidelic material properties for the alveolar wall. To address this challenge, a finite element model of an alveolar cluster was developed comprising a tetrakaidecahedron array with the nominal characteristics of human alveolar structure. Lung expansion was simulated in the model by prescribing a pressure and monitoring the volume, to produce a pressure-volume (PV) response that could be compared to experimental PV data. The alveolar wall properties in the model were optimized to match experimental PV response of lungs filled with saline, to eliminate surface tension effects and isolate the alveolar wall tissue response. When simulated in uniaxial tension, the model was in agreement with reported experimental properties of uniaxial tension on excised lung tissue. The work presented herein was able to link micro-scale alveolar response to two disparate macroscopic experimental datasets (stress-stretch and PV response of lung) and presents hyperelastic properties of the alveolar wall for use in alveolar scale finite element models and multi-scale models. Future research will incorporate surface tension effects, and investigate alveolar injury mechanisms.

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Elasticidad , Análisis de Elementos Finitos , Presión , Alveolos Pulmonares , Estrés Mecánico , Alveolos Pulmonares/fisiología , Humanos , Modelos Biológicos , Fenómenos Biomecánicos

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The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2- to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

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Vacunas contra el Adenovirus , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Ratones Endogámicos BALB C , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Ratones , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas contra el Adenovirus/inmunología , Vacunas contra el Adenovirus/administración & dosificación , Femenino , Humanos , Inmunogenicidad Vacunal , Vacunación , Adenoviridae/genética , Adenoviridae/inmunología

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Haematitum is a commonly used mineral medicine. It is toxic, as recorded in the second volume of Chinese Materia Medica. Therefore, it should not be taken for a long time. In this study, the effects of Haematitum and calcined Haematitum on multiple organ injuries in mice were investigated, and the mechanism of the toxicity of the related organs was explored by metabolomics. The mice were randomly divided into the control group, Haematitum low-dose group(ZS-L group), Haematitum high-dose group(ZS-H group), and calcined Haematitum high-dose group(DZS-H group), with 12 mice in each group. Haematitum decoction was given by continuous intragastric administration for 10 days. Then the life situation was observed, and samples were taken to detect various indicators. The results showed that the ZS-H group showed obvious toxicity, with different degrees of toxicity damage in the intestinal tract,liver, spleen, and lung. ZS-L group had no toxic reaction. The toxicity of the DZS-H group was significantly reduced, and only the lung was damaged. Metabolomics technology was used to detect the lung tissue of mice in the control group and the ZS-H group, and a total of 15 kinds of significant difference metabolites were detected, mainly involved in choline metabolism in cancer, sphingolipid metabolism, and glycerophospholipid metabolism. Immunohistochemical results showed that the INSIG1 protein expression level in the lung tissue of mice in the ZS-H group was significantly higher than that in the control group. In summary, large doses and long-time use of Haematitum decoction will cause a variety of organ damage, and the same dose of calcined Haematitum is less toxic than Haematitum. In addition, a low dose of Haematitum has no obvious toxic effect. The dysfunction of lipid metabolic pathways such as sphingolipid and glycerophospholipid metabolism may be an important factor in Haematitum-induced pulmonary toxicity. This study provides a reference for further research on the mechanism of Haematitum pulmonary toxicity.

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Medicamentos Herbarios Chinos , Pulmón , Animales , Ratones , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Bazo/efectos de los fármacos , Bazo/metabolismo , Insuficiencia Multiorgánica/metabolismo , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/inducido químicamente , Femenino , Metabolómica , Humanos

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3D printing can revolutionize personalized medicine by allowing cost-effective, customized tissue-engineering constructs. However, the limited availability and diversity of biopolymeric hydrogels restrict the variety and applications of bioinks. In this study, we introduce a composite bioink for 3D bioprinting, combining a photo-cross-linkable derivative of Mucin (Mu) called Methacrylated Mucin (MuMA) and Hyaluronic acid (HA). The less explored Mucin is responsible for the hydrogel nature of mucus and holds the potential to be used as a bioink material because of its plethora of features. HA, a crucial extracellular matrix component, is mucoadhesive and enhances ink viscosity and printability. Photo-cross-linking with 405 nm light stabilizes the printed scaffolds without damaging cells. Rheological tests reveal shear-thinning behavior, aiding cell protection during printing and improved MuMA bioink viscosity by adding HA. The printed structures exhibited porous behavior conducive to nutrient transport and cell migration. After 4 weeks in phosphate-buffered saline, the scaffolds retain 70% of their mass, highlighting stability. Biocompatibility tests with lung epithelial cells (L-132) confirm cell attachment and growth, suggesting suitability for lung tissue engineering. It is envisioned that the versatility of bioink could lead to significant advancements in lung tissue engineering and various other biomedical applications.

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Materiales Biocompatibles , Bioimpresión , Ácido Hialurónico , Ensayo de Materiales , Mucinas , Impresión Tridimensional , Ingeniería de Tejidos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Humanos , Mucinas/química , Mucinas/metabolismo , Tinta , Luz , Pulmón/citología , Tamaño de la Partícula , Andamios del Tejido/química , Hidrogeles/química , Hidrogeles/farmacología

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Background and Objectives: In this study, we aimed to investigate the effects of bosentan, an endothelin receptor antagonist, on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), and tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB), and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in an experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Materials and Methods: Thirty-seven male Sprague-Dawley rats were divided into five groups. C: The control group (n = 6) consisted of unprocessed and untreated rats. PC3 (n = 8) underwent 3 days of PC. PC-B3 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 3 days. The PC7 group (n = 7) underwent 7 days of PC, and PC-B7 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 7 days. Results: ET-1, NF-κB, TNF-α, HIF-1α, and PAB levels were higher, while TAC activity was lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-α levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05), while NF-κB, HIF-1α, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan decreased ET-1, NF-κB, TNF-α, HIF-1α, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: Bosentan decreased the severity of oxidative stress in the lungs and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation, and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, and oxidative stress in some diseases that may be accompanied by ischemia.

Asunto(s)

Bosentán , Modelos Animales de Enfermedad , Inflamación , Estrés Oxidativo , Ratas Sprague-Dawley , Sulfonamidas , Traumatismos Torácicos , Heridas no Penetrantes , Animales , Bosentán/uso terapéutico , Bosentán/farmacología , Estrés Oxidativo/efectos de los fármacos , Masculino , Ratas , Traumatismos Torácicos/complicaciones , Traumatismos Torácicos/tratamiento farmacológico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Inflamación/tratamiento farmacológico , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/análisis , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , FN-kappa B/metabolismo , Endotelina-1/análisis , Antagonistas de los Receptores de Endotelina/uso terapéutico , Antagonistas de los Receptores de Endotelina/farmacología

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The study aimed to ascertain the prevalence and frequency of relapses of respiratory tuberculosis (TB) and examine the characteristics of its clinical progression in members of the Kazakh population based on the alleles of the HLA-DRB1 gene. Methods of clinical and genetic research, statistical processing and analysis of the obtained data were used to achieve this goal. The research led to an analysis of the statistical processing of clinical and genetic investigations that found out how often TB in the respiratory tract is found and how different HLA-DRB1 gene alleles affect the disease's progression. To find out how exposure to certain HLA-DRB1 gene alleles affects the chance of relapse, the number of times they were found was compared between people who had relapsed and people who had just been diagnosed with TB. The impact of these alleles on the progression of the disease was assessed based on their frequency of detection of different clinical forms of TB (infiltrative, fibro-cavernous, generalised, disseminated), unilateral and bilateral lung damage, lung tissue deterioration, and the presence of bacterial secretions. The highest detection rate for all comparisons had gene alleles HLA-DRB1*01 (9.5%), *08 (4.2%), *15 (3.9%), *09 (1.6%), *12 (1.3%), *13 (0.9%), *11 (0.2%). The study found that Kazakhs with the HLA-DRB1*01, *08, and 15 gene alleles are more likely to develop recurrent respiratory TB. The study's practical value lies in its potential to utilise its findings for the prompt identification and eradication of genetic variables contributing to the recurrence of TB.

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The human lung is a complex organ comprised of diverse populations of epithelial, mesenchymal, vascular and immune cells, which gains even greater complexity during disease states. To effectively study the lung at a single cell level, a dissociation protocol that achieves the highest yield of viable cells of interest with minimal dissociation-associated protein or transcription changes key. Here, we detail a rapid collagenase-based dissociation protocol (Col-Short), which provides a high-yield single cell suspension suitable for a variety of downstream applications. Diseased human lung explants were obtained and dissociated through the Col-Short protocol and compared to four other dissociation protocols. Resulting single cell suspensions were then assessed with flow cytometry, differential staining, and quantitative real-time PCR to identify major hematopoietic and non-hematopoietic cell populations, as well as their activation states. We observed that the Col-Short protocol provides the greatest number of cells per gram of lung tissue with no reduction in viability when compared to previously described dissociation protocols. Col-Short had no observable surface protein marker cleavage as well as lower expression of protein activation markers and stress-related transcripts compared to four other protocols. The Col-Short dissociation protocol can be used as a rapid strategy to generate single cells for respiratory cell biology research.

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Adult rats exposed to hyperoxia (>95% O2) die from respiratory failure in 60-72 h. However, rats preconditioned with >95% O2 for 48 h followed by 24 h in room air acquire tolerance of hyperoxia (H-T), whereas rats preconditioned with 60% O2 for 7 days become more susceptible (H-S). Our objective was to evaluate lung tissue mitochondrial bioenergetics in H-T and H-S rats. Bioenergetics was assessed in mitochondria isolated from lung tissue of H-T, H-S, and control rats. Expressions of complexes involved in oxidative phosphorylation (OxPhos) were measured in lung tissue homogenate. Pulmonary endothelial filtration coefficient (Kf) and tissue mitochondrial membrane potential (Δψm) were evaluated in isolated perfused lungs (IPLs). Results show that ADP-induced state 3 OxPhos capacity (Vmax) decreased in H-S mitochondria but increased in H-T. Δψm repolarization time following ADP-stimulated depolarization increased in H-S mitochondria. Complex I expression decreased in H-T (38%) and H-S (43%) lung homogenate, whereas complex V expression increased (70%) in H-T lung homogenate. Δψm is unchanged in H-S and H-T lungs, but complex II has a larger contribution to Δψm in H-S than H-T lungs. Kf increased in H-S, but not in H-T lungs. For H-T, increased complex V expression and Vmax counter the effect of the decrease in complex I expression on Δψm. A larger complex II contribution to Δψm along with decreased Vmax and increased Kf could make H-S rats more hyperoxia susceptible. Results are clinically relevant since ventilation with ≥60% O2 is often required for extended periods in patients with acute respiratory distress syndrome (ARDS).NEW & NOTEWORTHY We assessed lung tissue mitochondrial bioenergetics in rats with tolerance (H-T) or susceptibility (H-S) to hyperoxia-induced ARDS. Results from studies in isolated mitochondria, tissue homogenate, and isolated perfused lungs show that mitochondrial bioenergetics are differentially altered in H-T and H-S lungs suggesting a potential role for mitochondrial bioenergetics in hyperoxia-induced ARDS. Results are clinically relevant since hyperoxia exposure is a primary therapy for patients with ARDS, and differential sensitivity to hyperoxia surely occurs in humans.

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Lesión Pulmonar Aguda , Hiperoxia , Pulmón , Mitocondrias , Fosforilación Oxidativa , Ratas Sprague-Dawley , Animales , Hiperoxia/metabolismo , Hiperoxia/fisiopatología , Hiperoxia/complicaciones , Pulmón/metabolismo , Pulmón/fisiopatología , Ratas , Mitocondrias/metabolismo , Masculino , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/fisiopatología , Potencial de la Membrana Mitocondrial/fisiología , Metabolismo Energético

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This paper investigates the variation of lung tissue dielectric properties with tidal volume under in vivo conditions to provide reliable and valid a priori information for techniques such as microwave imaging. In this study, the dielectric properties of the lung tissue of 30 rabbits were measured in vivo using the open-end coaxial probe method in the frequency band of 100 MHz to 1 GHz, and 6 different sets of tidal volumes (30, 40, 50, 60, 70, 80 mL) were set up to study the trends of the dielectric properties, and the data at 2 specific frequency points (433 and 915 MHz) were analyzed statistically. It was found that the dielectric coefficient and conductivity of lung tissue tended to decrease with increasing tidal volume in the frequency range of 100 MHz to 1 GHz, and the differences in the dielectric properties of lung tissue for the 6 groups of tidal volumes at 2 specific frequency points were statistically significant. This paper showed that the dielectric properties of lung tissue tend to vary non-linearly with increasing tidal volume. Based on this, more accurate biological tissue parameters can be provided for bioelectromagnetic imaging techniques such as microwave imaging, which could provide a scientific basis and experimental data support for the improvement of diagnostic methods and equipment for lung diseases.

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Pulmón , Volumen de Ventilación Pulmonar , Animales , Conejos , Pulmón/fisiología , Pulmón/diagnóstico por imagen , Impedancia Eléctrica , Conductividad Eléctrica , Imágenes de Microonda , Microondas

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Introduction: Current vaccines against COVID-19 administered via parenteral route have limited ability to induce mucosal immunity. There is a need for an effective mucosal vaccine to combat SARS-CoV-2 virus replication in the respiratory mucosa. Moreover, sex differences are known to affect systemic antibody responses against vaccines. However, their role in mucosal cellular responses against a vaccine remains unclear and is underappreciated. Methods: We evaluated the mucosal immunogenicity of a booster vaccine regimen that is recombinant protein-based and administered intranasally in mice to explore sex differences in mucosal humoral and cellular responses. Results: Our results showed that vaccinated mice elicited strong systemic antibody (Ab), nasal, and bronchiole alveolar lavage (BAL) IgA responses, and local T cell immune responses in the lung in a sex-biased manner irrespective of mouse genetic background. Monocytes, alveolar macrophages, and CD103+ resident dendritic cells (DCs) in the lungs are correlated with robust mucosal Ab and T cell responses induced by the mucosal vaccine. Discussion: Our findings provide novel insights into optimizing next-generation booster vaccines against SARS-CoV-2 by inducing spike-specific lung T cell responses, as well as optimizing mucosal immunity for other respiratory infections, and a rationale for considering sex differences in future vaccine research and vaccination practice.

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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Mucosa , Inmunogenicidad Vacunal , SARS-CoV-2 , Vacunas de Subunidad , Animales , Femenino , Ratones , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Masculino , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Pulmón/inmunología , Pulmón/virología , Linfocitos T/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Ratones Endogámicos C57BL , Administración Intranasal , Factores Sexuales , Inmunoglobulina A/inmunología , Células Dendríticas/inmunología , Inmunización Secundaria , Inmunidad Humoral

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This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S-acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO-NPs. This observation suggests that the toxicity of CuO-NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu-NPs.

Asunto(s)

Supervivencia Celular , Cobre , Lisosomas , Macrólidos , Nanopartículas del Metal , Mitocondrias , Cobre/toxicidad , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Animales , Humanos , Nanopartículas del Metal/toxicidad , Macrólidos/toxicidad , Ratones , Supervivencia Celular/efectos de los fármacos , Línea Celular , Masculino

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Purpose: Semantic segmentation in high-resolution, histopathology whole slide images (WSIs) is an important fundamental task in various pathology applications. Convolutional neural networks (CNN) are the state-of-the-art approach for image segmentation. A patch-based CNN approach is often employed because of the large size of WSIs; however, segmentation performance is sensitive to the field-of-view and resolution of the input patches, and balancing the trade-offs is challenging when there are drastic size variations in the segmented structures. We propose a multiresolution semantic segmentation approach, which is capable of addressing the threefold trade-off between field-of-view, computational efficiency, and spatial resolution in histopathology WSIs. Approach: We propose a two-stage multiresolution approach for semantic segmentation of histopathology WSIs of mouse lung tissue and human placenta. In the first stage, we use four different CNNs to extract the contextual information from input patches at four different resolutions. In the second stage, we use another CNN to aggregate the extracted information in the first stage and generate the final segmentation masks. Results: The proposed method reported 95.6%, 92.5%, and 97.1% in our single-class placenta dataset and 97.1%, 87.3%, and 83.3% in our multiclass lung dataset for pixel-wise accuracy, mean Dice similarity coefficient, and mean positive predictive value, respectively. Conclusions: The proposed multiresolution approach demonstrated high accuracy and consistency in the semantic segmentation of biological structures of different sizes in our single-class placenta and multiclass lung histopathology WSI datasets. Our study can potentially be used in automated analysis of biological structures, facilitating the clinical research in histopathology applications.

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Solitary respiratory papilloma is a rare epithelial tumour that can be categorized into multiple subtypes. The glandular type (Glandular papilloma, GP) is the rarest. Most GP occurs in the proximal airways and is only rarely found in the lung parenchyma. In this article, we reported a case of GP in lung parenchyma.

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OBJECTIVE: The timing and dosing of antimicrobial therapy are key in the treatment of pneumonia in critically ill patients. It is uncertain whether the presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. The effects of lung inflammation and injury on tissue penetration of two antimicrobial drugs commonly used for pneumonia were determined in an established model of unilateral lung injury. METHODS: Unilateral lung injury was induced in the left lung of 13 healthy pigs through cyclic rinsing; the right healthy lung served as control. Infusions of meropenem and vancomycin were administered and concentrations of these drugs in lung tissue, blood, and epithelial lining fluid (ELF) were compared over a period of 6 h. RESULTS: Median vancomycin lung tissue concentrations and penetration ratio were higher in inflamed and injured lungs compared with uninflamed and uninjured lungs (AUC0-6h: P = 0.003 and AUCdialysate/AUCplasma ratio: P = 0.003), resulting in higher AUC0-24/MIC. Median meropenem lung tissue concentrations and penetration ratio in inflamed and injured lungs did not differ from that in uninflamed and uninjured lungs (AUC0-6: P = 0.094 and AUCdialysate/AUCplasma ratio: P = 0.173). The penetration ratio for both vancomycin and meropenem into ELF was similar in injured and uninjured lungs. CONCLUSION: Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not identify the impact of inflammation and injury.

Asunto(s)

Antibacterianos , Modelos Animales de Enfermedad , Lesión Pulmonar , Pulmón , Meropenem , Vancomicina , Animales , Meropenem/farmacocinética , Meropenem/administración & dosificación , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Porcinos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Pulmón/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Femenino , Pruebas de Sensibilidad Microbiana

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Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

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Sulfuro de Hidrógeno , Exposición por Inhalación , Pulmón , Animales , Sulfuro de Hidrógeno/toxicidad , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/inmunología , Ratas , Exposición por Inhalación/efectos adversos , Masculino , Inflamación/inducido químicamente , Inflamación/patología , Ratas Sprague-Dawley , Metaloproteinasa 9 de la Matriz/metabolismo , Contaminantes Atmosféricos/toxicidad

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OBJECTIVE: To determine morphological alterations in lung tissues in the case of novel coronavirus infection (COVID-19) in the aspect of process staging with consideration to disease duration. MATERIAL AND METHODS: The number of COVID-19-related deaths of patients aged 55-65 years equal 17 were investigated. Serial cuts of lung tissue stained with hematoxylin and eosin, obtained from several lung fragments of each corpse, were analyzed. Morphological features previously described in literature sources were taken into account. RESULTS AND CONCLUSION: It has been established, that processes in lungs have a phasic character, furthermore they are not clearly delimited in time. In addition, there were no morphological features specific to COVID-19. Obtained results may allow forensic medical experts-histologists to predict the COVID-19 duration.

Asunto(s)

COVID-19 , Humanos , COVID-19/complicaciones , Pulmón , SARS-CoV-2 , Persona de Mediana Edad , Anciano

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This study aimed to investigate the effects of combined exposure to noise (85 dB(A)) and inhaled Toluene (300 ± 10 ppm) on rat lung health. It also aimed to assess the potential therapeutic effects of Olea europaea L. leaves extract (OLE) (40 mg/kg/day) using biochemical, histopathological, and immunohistochemical (IHC) analyses, as well as determination of pro-inflammatory cytokines (TNF-α and IL-1ß), and in silico Docking studies. The experiment involved forty-two male Wistar rats divided into seven groups, each exposed to a 6-week/6-hour/day regimen of noise and Toluene. The groups included a control group, rats co-exposed to noise and Toluene, and rats co-exposed to noise and Toluene treated with OLE for different durations. The results indicated that noise and Toluene exposure led to structural damage in lung tissue, oxidative harm, and increased levels of pro-inflammatory cytokines (TNF-α and IL-1ß). However, the administration of OLE extract demonstrated positive effects in mitigating these adverse outcomes. OLE treatment reduced lipid peroxidation and enhanced the activities of catalase and superoxide dismutase, indicating its anti-oxidant properties. Furthermore, OLE significantly decreased the levels of pro-inflammatory cytokines compared to the groups exposed to noise and Toluene without OLE treatment. Moreover, the in silico investigation substantiated a robust affinity between COX-2 and OLE components, affirming the anti-inflammatory activity. Overall, our findings suggest that OLE possesses anti-inflammatory and anti-oxidative properties that mitigate the adverse effects of concurrent exposure to noise and Toluene.

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Rationale: Recent efforts in bioengineering and embryonic stem cell (ESC) technology allowed the generation of ESC-derived mouse lung tissues in transgenic mice that were missing critical morphogenetic genes. Epithelial cell lineages were efficiently generated from ESC, but other cell types were mosaic. A complete contribution of donor ESCs to lung tissue has never been achieved. The mouse lung has never been generated in a rat. Objective: We sought to generate the mouse lung in a rat. Methods: Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome editing was used to disrupt the Nkx2-1 gene in rat one-cell zygotes. Interspecies mouse-rat chimeras were produced by injection of wild-type mouse ESCs into Nkx2-1-deficient rat embryos with lung agenesis. The contribution of mouse ESCs to the lung tissue was examined by immunostaining, flow cytometry, and single-cell RNA sequencing. Measurements and Main Results: Peripheral pulmonary and thyroid tissues were absent in rat embryos after CRISPR-Cas9-mediated disruption of the Nkx2-1 gene. Complementation of rat Nkx2-1-/- blastocysts with mouse ESCs restored pulmonary and thyroid structures in mouse-rat chimeras, leading to a near-99% contribution of ESCs to all respiratory cell lineages. Epithelial, endothelial, hematopoietic, and stromal cells in ESC-derived lungs were highly differentiated and exhibited lineage-specific gene signatures similar to those of respiratory cells from the normal mouse lung. Analysis of receptor-ligand interactions revealed normal signaling networks between mouse ESC-derived respiratory cells differentiated in a rat. Conclusions: A combination of CRISPR-Cas9 genome editing and blastocyst complementation was used to produce mouse lungs in rats, making an important step toward future generations of human lungs using large animals as "bioreactors."

Asunto(s)

Sistemas CRISPR-Cas , Edición Génica , Pulmón , Animales , Ratas , Edición Génica/métodos , Pulmón/embriología , Ratones , Factor Nuclear Tiroideo 1/genética , Células Madre Embrionarias

RESUMEN

BACKGROUND: Human lung tissue, as an interface with the environment, is susceptible to various environmental pollutants, including trace metals. However, quantitative data on trace metals in human lung tissues remain poorly described. METHODS: This study aimed to characterize the elemental composition of histologically healthy, unaffected parts of human lung tissues, associated with non-infective, non-infiltrative, and non-malignant diseases (n = 60) for essential (Cr, Mn, Fe, Co, Cu, Zn, and Se) and toxic trace elements (Sr, Ni, As, Cd, and Pb). Additionally, we investigated the influence of personal factors (sex, age, and smoking habits) on the examined trace element profiles, as well as between the trace elements correlations in the healthy human lungs. RESULTS: Among the analyzed trace elements, Fe was the most prevalent, while As was the least prevalent in healthy lung tissues. Stratifying by age revealed significantly higher Cr and Co (less Sr, Ni, and Pb) and lower Se levels in older individuals (above 65 years) compared to their younger counterparts. Sex-based differences were also notable, with Cu and Co 1.2- and 2.3-fold higher levels in females than in males. Exploring the impact of smoking habits revealed a striking 10-fold increase in Cd levels in the lung tissues of smokers compared to non-smokers. Correlation analyses showed significant positive associations between concentrations of certain toxic and essential trace elements in healthy lung tissues. CONCLUSIONS: This study could contribute to the establishment of baseline intervals for essential and toxic trace elements, valuable for toxicological and clinical assessment, in healthy, unaffected human lungs, and indicates the influence of sex, age, and smoking. However, further larger-scale studies are needed to make more stable conclusions.

Asunto(s)

Pulmón , Oligoelementos , Humanos , Oligoelementos/análisis , Masculino , Femenino , Pulmón/metabolismo , Pulmón/química , Persona de Mediana Edad , Anciano , Adulto , Fumar/metabolismo