Lung Tissue Inflammation Research Articles

Celastrol reduces lung inflammation induced by multiwalled carbon nanotubes in mice via NF-κb-signaling pathway

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50−/−). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.

Epigallocatechin-3-Gallate attenuates lipopolysacharide-induced pneumonia via modification of inflammation, oxidative stress, apoptosis, and autophagy

BackgroundPneumonia, the acute inflammation of lung tissue, is multi-factorial in etiology. Hence, continuous studies are conducted to determine the mechanisms involved in the progression of the disease and subsequently suggest effective treatment. The present study attempted to evaluate the effects of Epigallocatechin-3-Gallate (EGCG), an herbal antioxidant, on inflammation, oxidative stress, apoptosis, and autophagy in a rat pneumonia model.MethodsForty male Wistar rats, 5 months old and 250–290 g were divided into four groups including control, EGCG, experimental pneumonia (i/p LPS injection, 1 mg/kg), and experimental pneumonia treated with EGCG (i/p, 15 mg/kg, 1 h before and 3 h after LPS instillation). Total cell number in the bronchoalveolar lavage fluid, inflammation (TNF-a, Il-6, IL-1β, and NO), oxidative stress (Nrf2, HO-1, SOD, CAT, GSH, GPX, MDA, and TAC), apoptosis (BCL-2, BAX, CASP-3 and CASP-9), and autophagy (mTOR, LC3, BECN1) were evaluated.ResultsThe findings demonstrated that EGCG suppresses the LPS-induced activation of inflammatory pathways by a significant reduction of inflammatory markers (p-value < 0.001). In addition, the upregulation of BCL-2 and downregulation of BAX and caspases revealed that EGCG suppressed LPS-induced apoptosis. Furthermore, ECGC suppressed oxidative injury while promoting autophagy in rats with pneumonia (p-value < 0.05).ConclusionThe current study revealed that EGCG could suppress inflammation, oxidative stress, apoptosis, and promote autophagy in experimental pneumonia models of rats suggesting promising therapeutical properties of this compound to be used in pneumonia management.

Cell-in-cell-mediated intercellular communication exacerbates the pro-inflammatory progression in asthma.

Cell-in-cell (CIC) structures have been suggested to mediate intracellular substance transport between cells and have been found widely in inflammatory lung tissue of asthma. The aim of this study was to investigate the significance of CIC structures in inflammatory progress of asthma. CIC structures and related inflammatory pathways were analyzed in asthmatic lung tissue and normal lung tissue of mouse model. In vitro, the activation of inflammatory pathways by CIC-mediated intercellular communication was analyzed by RNA-Seq and verified by Western blotting and immunofluorescence. Results showed that CIC structures of lymphocytes and alveolar epithelial cells in asthmatic lung tissue mediated intercellular substance (such as mitochondria) transfer and promoted pro-inflammation in two phases. At early phase, internal lymphocytes triggered inflammasome-dependent pro-inflammation and cell death of itself. Then, degraded lymphocytes released cellular contents such as mitochondria inside alveolar epithelial cells, further activated multi-pattern-recognition receptors and NF-kappa B signaling pathways of alveolar epithelial cells, and thereby amplified pro-inflammatory response in asthma. Our work supplements the mechanism of asthma pro-inflammation progression from the perspective of CIC structure of lymphocytes and alveolar epithelial cells, and provides a new idea for anti-inflammatory therapy of asthma.

Yemazhui () ameliorates lipopolysaccharide-induced acute lung injury modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flora in rats.

To investigate the impact of Yemazhui (Herba Eupatorii Lindleyani, HEL) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its underlying mechanism in vivo. The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method. Then, HEL was found to suppress LPS-induced ALI in vivo. Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups: control, LPS, Dexamethasone (Dex), HEL low dose 6 g/kg (HEL-L), HEL medium dose 18 g/kg (HEL-M) and HEL high dose 54 g/kg (HEL-H) groups. The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model. Leukocyte counts, lung wet/dry weight ratio, as well as myeloperoxidase (MPO) activity were determined followed by the detection with hematoxylin and eosin staining, enzyme linked immunosorbent assay, quantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence. Besides, to explore the effect of HEL on ALI-mediated intestinal flora, we performed 16s rRNA sequencing analysis of intestinal contents. HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance. Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats, inhibited leukocytes exudation and MPO activity, and improved the pathological injury of lung tissue. In addition, HEL reduced the expression of tumor necrosis factor-alpha, interleukin-1beta (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid and serum, and inhibited nuclear displacement of nuclear factor kappa-B p65 (NF-κBp65). And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88, NF-κBp65, phosphorylated inhibitor kappa B alpha (phospho-IκBα), nod-like receptor family pyrin domain-containing 3 protein (NLRP3), IL-1β, and interleukin-18 (IL-18) in lung tissue, and regulated intestinal flora disturbance. In summary, our findings revealed that HEL has a protective effect on LPS-induced ALI in rats, and its mechanism may be related to inhibiting TLR4/ NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.

Associations of Inflammation, Oxidative Stress and Prognosis with IL-37 Expression in Sepsis Rats with Lung Injury

This study aimed to investigate the role of interleukin-37 (IL-37) expression in lung tissues of sepsis-induced acute lung injury (ALI) rats and its impact on ALI, along with the underlying mechanisms. Sprague-Dawley (SD) rats were categorized into three groups: Control, sepsis-induced ALI (via cecal ligation and puncture, CLP), and sepsis-induced ALI with antibiotics (CLP+An). ALI models were established, and lung tissue injuries were assessed through hematoxylineosin staining. mRNA levels of IL-1α, IL-1β, IL-37, and tumor necrosis factor-α (TNF-α) were measured via RT-PCR, while IL-37 protein levels in lung tissues were determined using Western blotting. Additionally, bronchoalveolar lavage fluid (BALF) and blood samples were collected to assess inflammatory factors through ELISA. In the CLP group, there was an increase in pro-inflammatory factors (IL-1α, IL-1β, and TNF-α) in lung tissues and serum. However, in the CLP+An group, these factors decreased, IL-37 expression increased, and oxidative stress levels decreased. IL-37 demonstrated an inhibitory effect on the release of pro-inflammatory factors (IL-1α, IL-1β, and TNF-α) in sepsis rats, leading to a reduction in lung tissue inflammation. Furthermore, IL-37 exhibited a protective role by reducing oxidative stress in sepsis-induced lung tissues. These findings highlight IL-37 as a potential therapeutic target for mitigating ALI in sepsis.

Cepharanthine inhibits influenza A virus replication by impairing viral polymerase activity and regulating influenza-induced immune response

BackgroundCepharanthine (CEP), a natural bis-benzylisoquinoline alkaloid extracted from the plant Stephania cephalantha Hayata, has been widely used to treat several acute and chronic diseases. However, its antiviral potential against influenza A virus (IAV) infection remains unknown. PurposeThe study aims to assess the antiviral and immunomodulatory effects of CEP in vivo and in vitro and investigate its underlying antiviral mechanisms. MethodsAntiviral and anti-inflammatory activities of CEP were assessed in MDCK, A549 and RAW264.7 cells infected with influenza virus. Proinflammatory cytokine levels were measured by qRT-PCR and ELISA. The anti-influenza effect and underlying antiviral mechanism of CEP were mainly determined by MTT assay, plaque reduction assay, time-of-addition and mini-replicon assay. The inhibition of CEP on IAV-induced activation of innate immune signaling was detected by western blotting. Furthermore, BALB/c mice were infected intranasally with A/PR/8/34 (H1N1) virus and treated with CEP (60, 30, 15 mg/kg/d) or oseltamivir (60 mg/kg/d). The changes in body weight, survival rates, viral titers, proinflammatory cytokine levels and pathological parameters were detected. ResultsCEP exhibited antiviral effects against multiple IAV strains, while also demonstrating anti-inflammatory effects in influenza virus-infected RAW264.7 and A549 cells. The results of the mechanism study indicated that CEP effectively suppressed IAV replication by limiting viral polymerase activity. On the other hand, CEP could modulate pro-inflammatory responses via inhibition of janus kinase/signal transducer and activator of transcription/ nuclear factor kappa B (JAK/STAT/NF‑κB) signaling pathways involved in influenza virus pathogenesis. Treatment of mice with CEP improved the survival rate and body weight of influenza virus-infected mice, reduced viral titers and alleviated influenza virus-induced pathological damage and inflammation in mouse lung tissue. ConclusionCollectively, the anti-influenza virus property of CEP was a result of inhibiting viral polymerase activity and preventing virus-induced excessive inflammation, highlighting it might be an oral medication for the treatment of IAV infection.

Abstract 1464: Smoking carcinogen-induced inflammation promotes lung carcinogenesis via IRAK4 activation

Abstract Lung cancer is globally the most common cancer, and most cases are associated with smoking. Smoking exposes respiratory epithelial tissues to various carcinogens. Evaluating the effects of these carcinogens administered intratracheally in mouse models would allow us to study lung carcinogenesis in a relevant manner and determine therapeutically targetable pathways. Cigarette smoking exposure was mimicked in vivo using a smoke machine and the condensate was subjected to chemical analysis. In addition to nicotine, cigarette smoking condensate included significant levels of the carcinogens, Nicotine-derived nitrosamine ketone (NNK) and Benzo(α)pyrene (BP). Next, a mouse model of cigarette smoking-induced carcinogenesis was developed by exposing ICR mice to intratracheal exposure to NNK and BP three times a week for 18 months. Mice chronically exposed to NNK and BP developed epithelial dysplasia at 4 months of exposure and lung cancers at 8-12 mo. of exposure at significantly increased rates relative to controls. Histology revealed myeloid inflammation in murine lung tissues. Exposure of lung epithelial cells to cigarette smoking condensate led to increased production of pro-inflammatory IL-1β. Downstream mediator of IL-1β signaling, Interleukin 1 receptor associated kinase-4 (IRAK4), was overexpressed in murine lung tissues exposed to carcinogens in vivo. Two-thirds of human tissue sections obtained from archived lung cancers also exhibited overactivated IRAK4 expression. In lung cancer cell lines, IRAK4 immunofluorescence revealed a microtubule like pattern of expression in lung cancer cells. Immunoblotting confirmed IRAK4 colocalization within purified microtubules. Using mass spectrometry on isolated microtubules, we observed that phosphorylation decreased in various tubular proteins after IRAK4 inhibition. Inhibition of IRAK4 using small molecule specific inhibitors resulted in decreased invasion in lung cancer cell lines. These data show that chronic intratracheal exposure of smoking associated carcinogens leads to dysplasia and malignancies in mouse models. This exposure also leads to myeloid inflammation and activation of IRAK4 in lung tissues. Therapeutic targeting of IRAK4 can have potentially beneficial effects in lung cancer models. Citation Format: Ritesh K. Aggarwal, Simone Sidoli, Srabani Sahu, Srinivas Aluri, Charan Vegivinti, Divij Verma, Shanisha Gordon-Mitchell, Beamon Agarwal, Tanya Verma, Daniel T. Starczynowski, Ulrich G. Steidl, Balazs Halmos, Lindsay M. LaFave, Haiying Cheng, Amit Verma, Yiyu Zou. Smoking carcinogen-induced inflammation promotes lung carcinogenesis via IRAK4 activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1464.

SP-8356 inhibits acute lung injury by suppressing inflammatory cytokine production and immune cell infiltration

This study investigated the anti-inflammatory and protective properties of SP-8356, a synthetic derivative of (1S)-(-)-verbenone, in a mouse model of LPS-induced acute lung injury (ALI). By targeting intracellular signaling pathways and inflammatory responses, SP-8356 demonstrated a potent ability to attenuate deleterious effects of proinflammatory stimuli. Specifically, SP-8356 effectively inhibited the activation of crucial signaling molecules such as NF-κB and Akt, and subsequently dampened the expression of inflammatory cytokines in various lung cellular components. Intervention with SP-8356 treatment also preserved the structural integrity of the epithelial and endothelial barriers. By reducing immune cell infiltration into inflamed lung tissue, SP-8356 exerted a broad protective effect against ALI. These findings position SP-8356 as a promising therapeutic candidate for pulmonary inflammatory diseases that cause ALI.

Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation

BackgroundMacrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity.MethodsHuman lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5–24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192.ResultsIn obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge.ConclusionsOur study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.Graphical

Bone Marrow-Derived C-Kit+ Cells Improved Inflammatory IL-33/ST-2/ILC2 Axis in the Lung Tissue of Type 2 Diabetic Rats.

Inflammation is an essential factor in pulmonary complications of diabetes. Bone marrow (BM)-derived C-kit+ cells have immunomodulatory properties and their transplantation is suggested as a promising strategy for ameliorating diabetes complications. This study evaluated the effect of BM-derived C-kit+ cells on the inflammation signaling pathway in lung tissue of type 2 diabetic male rats. Ten rats were used to extract C-kit cells, and 48 male Wistar rats weighing 180 ± 20 g were randomly divided into four equal groups: (1) Control (Cont), (2) Diabetic (D), (3) Diabetic + C-kit+ cells (D + C-kit pos) intravenously injected 50-µl phosphate buffer saline (PBS) containing 300,000C-kit+ cells, and (4) Diabetic + C-kit- cells (D + C-kit neg), intravenously injected C-kit- cells. Diabetes induction increased IL-33, ST-2, CD127, and IL-2 levels and decreased IL-10. C-kit+ cell therapy significantly decreased IL-33 and CD127 and increased IL-10. In addition, lung histopathological changes significantly improved in the C-kit+ group compared to the diabetic group. These findings suggest that C-kit+ cells may have a potential therapeutic role in mitigating diabetes-induced respiratory complications via ameliorating the inflammation and histopathological changes in lung tissue.

Polyphyllin B inhibited STAT3/NCOA4 pathway and restored gut microbiota to ameliorate lung tissue injury in cigarette smoke-induced mice

ObjectiveSmoking was a major risk factor for chronic obstructive pulmonary disease (COPD). This study plan to explore the mechanism of Polyphyllin B in lung injury induced by cigarette smoke (CSE) in COPD.MethodsNetwork pharmacology and molecular docking were applied to analyze the potential binding targets for Polyphyllin B and COPD. Commercial unfiltered CSE and LPS were used to construct BEAS-2B cell injury in vitro and COPD mouse models in vivo, respectively, which were treated with Polyphyllin B or fecal microbiota transplantation (FMT). CCK8, LDH and calcein-AM were used to detect the cell proliferation, LDH level and labile iron pool. Lung histopathology, Fe3+ deposition and mitochondrial morphology were observed by hematoxylin–eosin, Prussian blue staining and transmission electron microscope, respectively. ELISA was used to measure inflammation and oxidative stress levels in cells and lung tissues. Immunohistochemistry and immunofluorescence were applied to analyze the 4-HNE, LC3 and Ferritin expression. RT-qPCR was used to detect the expression of FcRn, pIgR, STAT3 and NCOA4. Western blot was used to detect the expression of Ferritin, p-STAT3/STAT3, NCOA4, GPX4, TLR2, TLR4 and P65 proteins. 16S rRNA gene sequencing was applied to detect the gut microbiota.ResultsPolyphyllin B had a good binding affinity with STAT3 protein, which as a target gene in COPD. Polyphyllin B inhibited CS-induced oxidative stress, inflammation, mitochondrial damage, and ferritinophagy in COPD mice. 16S rRNA sequencing and FMT confirmed that Akkermansia and Escherichia_Shigella might be the potential microbiota for Polyphyllin B and FMT to improve CSE and LPS-induced COPD, which were exhausted by the antibiotics in C + L and C + L + P mice. CSE and LPS induced the decrease of cell viability and the ferritin and LC3 expression, and the increase of NCOA4 and p-STAT3 expression in BEAS-2B cells, which were inhibited by Polyphyllin B. Polyphyllin B promoted ferritin and LC3II/I expression, and inhibited p-STAT3 and NCOA4 expression in CSE + LPS-induced BEAS-2B cells.ConclusionPolyphyllin B improved gut microbiota disorder and inhibited STAT3/NCOA4 pathway to ameliorate lung tissue injury in CSE and LPS-induced mice.

The Role of Rosmarinic Acid in the Protection Against Inflammatory Factors in Rats Model With Monocrotaline-Induced Pulmonary Hypertension: Investigating the Signaling Pathway of NFκB, OPG, Runx2, and P-Selectin in Heart.

Shortness of breath and syncope are common symptoms of right ventricular failure caused by pulmonary arterial hypertension (PAH), which is the result of blockage and increased pressure in the pulmonary arteries. There is a significant amount of evidence supporting the idea that inflammation and vascular calcification (VC) are important factors in PAH pathogenesis. Therefore, we aimed to investigate the features of the inflammatory process and gene expression involved in VC in monocrotaline (MCT)-induced PAH rats. MCT (60 mg/kg, i.p.) was used to induce PAH. Animals were given normal saline or rosmarinic acid (RA) (10, 15, and 30 mg/kg, gavage) for 21 days. An increase in right ventricular systolic pressure was evaluated as confirming PAH. To determine the level of inflammation in lung tissue, pulmonary edema and the total and differential white blood cell counts in the bronchoalveolar lavage fluid were measured. Also, the expression of NFκB, OPG, Runx2, and P-selectin genes was investigated to evaluate the level of VC in the heart. Our experiment showed that RA significantly decreased right ventricular hypertrophy, inflammatory factors, NFκB, Runx2, and P-selectin gene expression, pulmonary edema, total and differential white blood cell count, and increased OPG gene expression. Therefore, our research showed that RA protects against MCT-induced PAH by reducing inflammation and VC in rats.

Effect of hydrogen inhalation on cardiovascular and interstitial components of pulmonary hypertension in rats

Hydrogen is known to have selective antioxidant properties. It binds highly reactive hydroxyl radicals. The pathogenesis of the monocrotaline animal model of pulmonary hypertension is associated with oxidative stress and leads to all the symptoms of pulmonary hypertension (PH) and interstitial lung disease (ILD) associated with hypertension.The aim of this work was to study the effect of 4% hydrogen inhalations on the symptoms of PH and ILD in rats.Methods. To model monocrotaline-induced pulmonary hypertension (MCT-PH), two groups of animals received a single subcutaneous injection of monocrotaline (MCT) on day 1. The control group was injected subcutaneously with MCT solvent only. The animals receiving MCT were further divided into 2 subgroups. Subgroup 1 rats breathed room air and subgroup 2 rats breathed a mixture of room air and 4% hydrogen. The regular inhalations continued until day 21. On day 21, hemodynamic parameters were measured under urethane anesthesia, the heart and its components and the lungs were weighed, and lung tissue was preserved for morphological study.Results. The inhalation had no effect on the main cardiovascular symptoms of PH, but a positive effect on the state of the connective tissue of the lungs affected by PH was shown. The mast cell response was reduced both quantitatively and functionally. There was a decrease in tryptase expression by mast cells, with predominance of the forms without signs of degranulation. TGF-β secretion was also significantly reduced and visualized by immunopositive cells in alveolar cellular structures and vessel walls.Conclusion. Inhalation of 4% hydrogen reduces inflammation and fibrosis of lung tissue during the development of MCT-PH.

Assessing the acceptability and feasibility of remote spirometric monitoring for rural patients with interstitial lung disease: a multimethod approach

IntroductionInterstitial lung disease encompasses a group of rare lung conditions causing inflammation and scarring of lung tissue. The typical method of monitoring disease activity is through pulmonary function tests performed in a hospital setting. However, accessing care can be difficult for rural patients due to numerous barriers. This study assesses the feasibility and acceptability of home spirometry telemonitoring using MIR-Spirometers and the patientMpower home-monitoring platform for rural patients with interstitial lung disease.MethodsUnblinded, uncontrolled, prospective, multiple-methods study of the feasibility and utility of remote monitoring of 20 rural subjects with interstitial lung disease. Study assessments include adherence to twice weekly spirometry for 3 months in addition to mMRC dyspnea and EQ-5D-5L health-related quality of life questionnaires with each spirometry maneuver. Upon completion, subjects were encouraged to complete an 11-question satisfaction survey and participate in semi-structured qualitative interviews to further explore expectations and perceptions of rural patients to telehealth and remote patient monitoring.Results19 subjects completed the 3-month study period. Adherence to twice weekly spirometry was mean 53% ± 38%, with participants on average performing 2.26 ± 1.69 maneuvers per week. The median (Range) number of maneuvers per week was 2.0 (0.0, 7.0). The majority of participants responded favorably to the patient satisfaction survey questions. Themes regarding barriers to access included: lack of local specialty care, distance to center with expertise, and time, distance, and high cost associated with travel. Remote monitoring was well perceived amongst subjects as a way to improve access and overcome barriers.ConclusionsRemote spirometry monitoring through web-based telehealth is acceptable and feasible for rural patients. Perceived benefits include overcoming access barriers like time, distance, and travel costs. However, cost, reimbursement, and internet access must be addressed before implementing it widely. Future studies are needed to ensure long-term feasibility and to compare outcomes with usual care.

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human β-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

Farnesoid X Receptor Protects Murine Lung against IL-6-promoted Ferroptosis Induced by Polyriboinosinic-Polyribocytidylic Acid.

Various infections trigger a storm of proinflammatory cytokines in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid [poly(I:C)] activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal models of RNA virus-infected lung injury. In this study, intratracheal instillation of poly(I:C) with or without an IL-6-neutralizing antibody model was combined with metabonomics, transcriptomics, and so forth to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury. We found that poly(I:C) increased the IL-6 concentration, and the upregulated IL-6 further induced lung ferroptosis, especially in alveolar epithelial type II cells. Meanwhile, lung regeneration was impaired. Mechanistically, metabolomic analysis showed that poly(I:C) significantly decreased glycolytic metabolites and increased bile acid intermediate metabolites that inhibited the bile acid nuclear receptor farnesoid X receptor (FXR), which could be reversed by IL-6-neutralizing antibody. In the ferroptosis microenvironment, IL-6 receptor monoclonal antibody tocilizumab increased FXR expression and subsequently increased the Yes-associated protein (YAP) concentration by enhancing PKM2 in A549 cells. FXR agonist GW4064 and liquiritin, a potential natural herbal ingredient as an FXR regulator, significantly attenuated lung tissue inflammation and ferroptosis while promoting pulmonary regeneration. Together, the findings of the present study provide the evidence that IL-6 promotes ferroptosis and impairs regeneration of alveolar epithelial type II cells during poly(I:C)-induced murine lung injury by regulating the FXR-PKM2-YAP axis. Targeting FXR represents a promising therapeutic strategy for IL-6-associated inflammatory lung injury.

Tobacco introduced Perilla frutescens and Ocimum basilicum genes attenuates neutrophilic inflammation in lung tissues of COPD rats

The new-type tobacco varieties “Zisu” and “Luole” were obtained by distant hybridization between N. tabacum L. var. HHY and Perilla frutescens and Ocimum basilicum, with obviously different chemical composition. Smoking is the major risk factor for COPD, characterized by neutrophil-dominant inflammation. In the present study, rat COPD model was established by cigarette exposure, and the health hazard of three varieties was compared by general condition observation, pathological and morphological evaluation, total and differential cell numeration, and characterization of major inflammatory mediators and MAPK/NF-κB pathway, etc. Rats in “HHY” group developed obvious symptoms such as cough, dyspnea, mental fatigue, etc., but these symptoms were obviously mitigated in “Zisu” and “Luole” groups. H&E staining analysis, including score, MLI, MAN, wt% and WA%, showed that “Zisu” and “Luole” significantly alleviated lung injury and the degree of airway remodeling and emphysema compared to “HHY”. In BALF, the number of total leukocyte and the percent neutrophils in “Zisu” and “Luole” groups were evidently lower than “HHY” group. The levels of inflammatory mediators, such as IL-8, MPO, MIP-2, LTB4, TNF-α and neutrophil elastase, in “HHY” group were obviously higher than “Zisu” and “Luole” groups. The ROS-mediated NF-κB p65 and p38MAPK pathways may play an important role. Results indicated that tobacco introduced perilla and basil genes could remarkably attenuate recruitment, infiltration and activation of neutrophils and intervene in airway inflammation, retarding disease progression, especially “Zisu”. Changes in chemical composition via breeding techniques may be a novel way for tobacco harm reduction.

Effect of post COVID-19 on body composition, physical fitness, sleep quality and quality of life among young adults: a cross-sectional study of matched pairs.

Coronavirus 2019 (COVID-19) causes lung tissue inflammation, affects mental health, and disturbs sleep and the musculoskeletal system. This study aimed to investigate the effects of COVID-19 on physical function and quality of life by comparing the body composition, physical fitness, sleep quality and quality of life between Thai young adults with and without post COVID-19 infection. A cross-sectional study was comprised of two matched groups (post COVID-19 group and non COVID-19 group) with 36 participants in each group. Data about body composition, physical fitness, sleep quality and quality of life were collected using the bioelectrical impedance analysis, the 1-min sit-to-stand test, the hand grip strength test, the Pittsburgh sleep quality questionnaire and the EuroQol-5D-5L, respectively. Independent samples T-test, Mann-Whitney U test and Chi-square test were used to compare between the two groups. The changes in oxygen saturation and respiratory rate after the physical fitness test and the sleep quality analysis showed a statistically significant difference between the groups with and without post COVID-19 infection (p = 0.006, p = 0.003 and p = 0.003, respectively). However, quality of life and body composition were not significantly different between groups. COVID-19 influenced the changes in oxygen saturation and respiratory rate after the physical fitness test and the sleep quality analysis in young adults. The results should be utilized to facilitate physical rehabilitation for COVID-19-infected individuals following infection. Those who have not been infected with COVID-19 must be informed of self-protection measures to avoid contracting the virus.

Pokazatelji markera inflamacije, oštećenja organa, oksidativnog oštećenja makromolekula i promena na CT toraksa pacijenata sa COVID-19 pneumonijom

Coronavirus disease 2019 (COVID-19) is a multi-systemic disease caused by Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2. Since the onset of the pandemic, understanding the pathophysiological mechanisms of this disease has posed a significant challenge, with the intent to determine its progression and implement appropriate treatment strategies. The heightened severity and mortality associated with SARS-CoV-2 infection can be attributed, in part, to a phenomenon known as cytokine storm. This refers to an uncontrolled systemic inflammatory response characterized by elevated proinflammatory cytokines and chemokines, leading to an overproduction of free radicals. The aforementioned cytokine storm is accompanied by the excessive generation of reactive oxygen species and affects the virus and directly damages the host's cells. Given that the SARS-CoV-2 virus primarily targets respiratory cells, pneumonia is a common manifestation of the disease. Consequently, chest multidetector computed tomography (MDCT) plays a crucial role in evaluating lung tissue inflammation, determining disease severity, making decisions regarding hospitalization, and assessing the necessity of intensive care unit treatment. Assessing the level of oxidative stress can be accomplished by measuring the products resulting from damage to lipids, proteins, and DNA - whereas the inflammatory and multiorgan impairment biomarkers can be procured from routine laboratory practice. Due to the established association of a cytokine storm with a free radical storm, it might be postulated that during the acute phase of COVID-19 pneumonia the redox biomarkers might correlate with inflammatory and multiorgan impairment biomarkers, as well as chest MDCT findings.

Bio-Responsive Sliver Peroxide-Nanocarrier Serves as Broad-Spectrum Metallo-β-lactamase Inhibitor for Combating Severe Pneumonia.

Metallo-β-lactamases (MBLs) represent a prevalent resistance mechanism in Gram-negative bacteria, rendering last-line carbapenem-related antibiotics ineffective. Here, a bioresponsive sliver peroxide (Ag2 O2 )-based nanovesicle, named Ag2 O2 @BP-MT@MM, is developed as a broad-spectrum MBL inhibitor for combating MBL-producing bacterial pneumonia. Ag2 O2 nanoparticle is first orderly modified with bovine serum albumin and polydopamine to co-load meropenem (MER) and [5-(p-fluorophenyl)-2-ureido]-thiophene-3-carboxamide (TPCA-1) and then encapsulated with macrophage membrane (MM) aimed to target inflammatory lung tissue specifically. The resultant Ag2 O2 @BP-MT@MM effectively abrogates MBL activity by displacing the Zn2+ cofactor in MBLs with Ag+ and displays potent bactericidal and anti-inflammatory properties, specific targeting abilities, and great bioresponsive characteristics. After intravenous injection, the nanoparticles accumulate prominently at infection sites through MM-mediated targeting . Ag+ released from Ag2 O2 decomposition at the infection sites effectively inhibits MBL activity and overcomes the resistance of MBL-producing bacteria to MER, resulting in synergistic elimination of bacteria in conjunction with MER. In two murine infection models of NDM-1+ Klebsiella pneumoniae-induced severe pneumonia and NDM-1+ Escherichia coli-induced sepsis-related bacterial pneumonia, the nanoparticles significantly reduce bacterial loading, pro-inflammatory cytokine levels locally and systemically, and the recruitment and activation of neutrophils and macrophages. This innovative approach presents a promising new strategy for combating infections caused by MBL-producing carbapenem-resistant bacteria.