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Journal of Ethnopharmacology Jan 2024According to the theory of traditional Chinese medicine, the pathogenesis of idiopathic pulmonary fibrosis (IPF) can be attributed to qi deficiency and blood stasis....
Buyang Huanwu decoction ameliorates bleomycin-induced pulmonary fibrosis in rats by attenuating the apoptosis of alveolar type II epithelial cells mediated by endoplasmic reticulum stress.
ETHNOPHARMACOLOGICAL RELEVANCE
According to the theory of traditional Chinese medicine, the pathogenesis of idiopathic pulmonary fibrosis (IPF) can be attributed to qi deficiency and blood stasis. Buyang Huanwu decoction (BHD), a representative Chinese herbal prescription for qi deficiency and blood stasis syndrome, is widely used to treat IPF in clinical practice. However, its potential mechanisms against IPF remain unclear.
AIMS OF THE STUDY
This study was carried out to explore the therapeutic effects and underlying mechanisms of BHD on bleomycin (BLM)-induced pulmonary fibrosis in rats.
MATERIALS AND METHODS
UPLC-MS/MS method was performed to identify the quality of BHD used in this study. Concurrently, a IPF rat model was established by single intratracheal injection of BLM. Pulmonary function test, H&E staining, Masson staining, hydroxyproline assay were conducted to evaluate the therapeutic effects of BHD on BLM-induced pulmonary fibrosis in rats, and the regulatory effect of BHD on endoplasmic reticulum stress (ERS)-mediated alveolar type II epithelial cells (AEC2s) apoptosis in rats was further investigated by TUNEL staining, Western blot, real-time fluorescence quantitative PCR and immunofluorescence co-staining to reveal the potential mechanisms of BHD against IPF.
RESULTS
The UPLC-MS/MS analysis showed that the BHD we used complied with the relevant quality control standards. The data from animal experiments confirmed that BHD administration ameliorated BLM-induced pulmonary function decline, lung fibrotic pathological changes and collagen deposition in rats. Further mechanism study revealed that BHD increased the Bcl-2 protein expression, decreased the Bax protein expression and inhibited the cleavage of CASP3 via suppressing the activation of PERK-ATF4-CHOP pathway under continuous ERS, thereby alleviating BLM-induced AEC2s apoptosis of rats.
CONCLUSION
This study demonstrated that BHD ameliorated BLM-induced pulmonary fibrosis in rats by suppressing ERS-mediated AEC2s apoptosis. Our findings can provide some fundamental research basis for the clinical application of BHD in the treatment of IPF.
Topics: Rats; Animals; Bleomycin; Chromatography, Liquid; Tandem Mass Spectrometry; Idiopathic Pulmonary Fibrosis; Alveolar Epithelial Cells; Apoptosis; Endoplasmic Reticulum Stress
PubMed: 37813290
DOI: 10.1016/j.jep.2023.117300 -
International Journal of Chronic... 2024To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD).
PATIENTS AND METHODS
Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured.
RESULTS
VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively).
CONCLUSION
Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.
Topics: Humans; Sarcopenia; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Treatment Outcome; Drugs, Chinese Herbal; Middle Aged; Muscle Strength; Lung; Time Factors; Exercise Tolerance; Frailty; Comorbidity; Fatigue; Recovery of Function; Functional Status; Frail Elderly; Walking Speed
PubMed: 38737191
DOI: 10.2147/COPD.S441767 -
Journal of Applied Physiology... Nov 2023Increased intrapulmonary shunt (Q/Q) and alveolar dead space (V/V) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients...
Increased intrapulmonary shunt (Q/Q) and alveolar dead space (V/V) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients recovering from severe critical acute illness (NIH category 3-5) would have greater and longer lasting increased Q/Q and V/V than patients with mild-moderate acute illness (NIH 1-2). Fifty-nine unvaccinated patients (33 males, aged 52 [38-61] yr, body mass index [BMI] 28.8 [25.3-33.6] kg/m; median [IQR], 44 previous mild-moderate COVID-19, and 15 severe-critical disease) were studied 15-403 days postacute severe acute respiratory syndrome coronavirus infection. Breathing ambient air, steady-state mean alveolar Pco, and Po were recorded simultaneously with arterial Po/Pco yielding aAPco, AaPo, and from these, Q/Q%, V/V%, and relative alveolar ventilation (40 mmHg/[Formula: see text], VArel) were calculated. Median [Formula: see text] was 39.4 [35.6-41.1] mmHg, [Formula: see text] 92.3 [87.1-98.2] mmHg; [Formula: see text] 32.8 [28.6-35.3] mmHg, [Formula: see text] 112.9 [109.4-117.0] mmHg, AaPo 18.8 [12.6-26.8] mmHg, aAPco 5.9 [4.3-8.0] mmHg, Q/Q 4.3 [2.1-5.9] %, and V/V16.6 [12.6-24.4]%. Only 14% of patients had normal Q/Q and V/V; 1% increased Q/Q but normal V/V; 49% normal Q/Q and elevated V/V; 36% both abnormal Q/Q and V/V. Previous severe critical COVID-19 predicted increased Q/Q (2.69 [0.82-4.57]% per category severity [95% CI], < 0.01), but not V/V. Increasing age weakly predicted increased V/V (1.6 [0.1-3.2]% per decade, < 0.04). Time since infection, BMI, and comorbidities were not predictors (all > 0.11). VArel was increased in most patients. In our population, recovery from COVID-19 was associated with increased Q/Q in 37% of patients, increased V/V in 86%, and increased alveolar ventilation up to ∼13 mo postinfection. NIH severity predicted Q/Q but not elevated V/V. Increased V/V suggests pulmonary microvascular pathology persists post-COVID-19 in most patients. Using novel methodology quantifying intrapulmonary shunt and alveolar dead space in COVID-19 patients up to 403 days after acute illness, 37% had increased intrapulmonary shunt and 86% had elevated alveolar dead space likely due to independent pathology. Elevated shunt was partially related to severe acute illness, and increased alveolar dead space was weakly related to increasing age. Ventilation was increased in the majority of patients regardless of previous disease severity. These results demonstrate persisting gas exchange abnormalities after recovery.
Topics: Male; Humans; Respiratory Dead Space; Acute Disease; COVID-19; Lung; Respiration
PubMed: 37767555
DOI: 10.1152/japplphysiol.00267.2023 -
Respirology (Carlton, Vic.) Sep 2023Weight and muscle loss are predictors of poor outcomes in chronic obstructive pulmonary disease. However, to our knowledge, no study has investigated the predictors of... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVE
Weight and muscle loss are predictors of poor outcomes in chronic obstructive pulmonary disease. However, to our knowledge, no study has investigated the predictors of longitudinal weight loss or its composition from functional and morphological perspectives.
METHODS
This longitudinal observational study with a median follow-up period of 5 years (range: 3.0-5.8 years) included patients with COPD and ever-smokers at risk of COPD. Using chest computed tomography (CT) images, airway and emphysematous lesions were assessed as the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the percentage of low attenuation volume (LAV%). Muscle mass was estimated using cross-sectional areas (CSAs) of the pectoralis and erector spinae muscles, and fat mass was estimated using the subcutaneous fat thickness at the level of the 8th rib measured using chest CT images. Statistical analyses were performed using the linear mixed-effects models.
RESULTS
In total, 114 patients were enrolled. Their body mass index remained stable during the study period while body weight and muscle CSA decreased over time and the subcutaneous fat thickness increased. Reduced forced expiratory volume in 1 s and peak expiratory flow (PEF) at baseline predicted the future decline in muscle CSA.
CONCLUSION
Severe airflow limitation predicted future muscle wasting in patients with COPD and ever-smokers at risk of COPD. Airflow limitation with a PEF slightly below 90% of the predicted value may require intervention to prevent future muscle loss.
Topics: Humans; Smokers; Smoking; Pulmonary Disease, Chronic Obstructive; Lung; Forced Expiratory Volume; Muscles; Body Weight
PubMed: 37364930
DOI: 10.1111/resp.14537 -
Journal of Medical Primatology Apr 2024Animal models of respiratory viral infections are essential for investigating disease pathogenesis and the efficacy of antivirals and vaccine candidates. A major...
BACKGROUND
Animal models of respiratory viral infections are essential for investigating disease pathogenesis and the efficacy of antivirals and vaccine candidates. A major limitation in the research of respiratory diseases in animal models is correlating clinically relevant changes in pulmonary physiology with cellular and molecular mechanistic studies. Few animal models have captured and correlated physiologic changes in lung function and immune response within same experiment, which is critical given the heterogeneous nature of lung disease due to viral infections. In ventilated human patients, pulmonary physiology testing can be used to not only capture oxygenation, ventilation, but also pulmonary mechanics to yield quantitative measures of lung function and scalar tracings of flow-volume and pressure-volume loops. Application of this protocol during mechanical ventilation in non-human (NHP) models would represent a major advance in respiratory viral disease research.
METHODS
We have applied and optimized a human pulmonary physiology testing protocol to ventilated pigtail macaques (Macaca nemestrina) at baseline and 5 days after influenza A (IAV) viral inoculation.
RESULTS
The NHPs manifested clinical disease with hypothermia and loss of body weight. Declines in lung function were striking with a 66%-81% decline in P/F ratio, a measure of oxygenation reflecting the ratio of partial pressure of oxygen in arterial blood (PaO ) to the fraction of inspiratory oxygen concentration (FiO ). There was also a 16%-45% decline in lung compliance.
CONCLUSION
We describe a new approach to performing pulmonary physiology testing protocol in non-human primates to better capture quantitative correlates of respiratory disease and demonstrate protection by therapeutics and vaccines.
Topics: Humans; Animals; Lung; Respiration, Artificial; Oxygen; Primates; Virus Diseases
PubMed: 38454198
DOI: 10.1111/jmp.12694 -
Predicting Radiation-Induced Lung Injury in Patients With Lung Cancer: Challenges and Opportunities.International Journal of Radiation... Mar 2024Radiation-induced lung injury (RILI) is one of the main dose-limiting toxicities in radiation therapy (RT) for lung cancer. Approximately 10% to 20% of patients show... (Review)
Review
Radiation-induced lung injury (RILI) is one of the main dose-limiting toxicities in radiation therapy (RT) for lung cancer. Approximately 10% to 20% of patients show signs of RILI of variable severity. The reason for the wide range of RILI severity and the mechanisms underlying its development are only partially understood. A number of clinical risk factors have been identified that can aid in clinical decision making. Technological advancements in RT and the use of strict organ-at-risk dose constraints have helped to reduce RILI. Predicting patients at risk for RILI may be further improved with a combination of cytokine assessments, γH2AX-assays in leukocytes, or epigenetic markers. A complicating factor is the lack of an objective definition of RILI. Tools such as computed tomography densitometry, fluorodeoxyglucose-positron emission tomography uptake, changes in lung function measurements, and exhaled breath analysis can be implemented to better define and quantify RILI. This can aid in the search for new biomarkers, which can be accelerated by omics techniques, single-cell RNA sequencing, mass cytometry, and advances in patient-specific in vitro cell culture models. An objective quantification of RILI combined with these novel techniques can aid in the development of biomarkers to better predict patients at risk and allow personalized treatment decisions.
Topics: Humans; Lung Neoplasms; Lung Injury; Lung; Radiation Injuries; Biomarkers
PubMed: 37924986
DOI: 10.1016/j.ijrobp.2023.10.044 -
Journal of Nanobiotechnology Sep 2023III-V semiconductor nanowires are envisioned as being integrated in optoelectronic devices in the near future. However, the perspective of mass production of these...
BACKGROUND
III-V semiconductor nanowires are envisioned as being integrated in optoelectronic devices in the near future. However, the perspective of mass production of these nanowires raises concern for human safety due to their asbestos- and carbon nanotube-like properties, including their high aspect ratio shape. Indeed, III-V nanowires have similar dimensions as Mitsui-7 multi-walled carbon nanotubes, which induce lung cancer by inhalation in rats. It is therefore urgent to investigate the toxicological effects following lung exposure to III-V nanowires prior to their use in industrial production, which entails risk of human exposure. Here, female C57BL/6J mice were exposed to 2, 6, and 18 µg (0.12, 0.35 and 1.1 mg/kg bw) of gallium phosphide (III-V) nanowires (99 nm diameter, 3.7 μm length) by intratracheal instillation and the toxicity was investigated 1, 3, 28 days and 3 months after exposure. Mitsui-7 multi-walled carbon nanotubes and carbon black Printex 90 nanoparticles were used as benchmark nanomaterials.
RESULTS
Gallium phosphide nanowires induced genotoxicity in bronchoalveolar lavage cells and acute inflammation with eosinophilia observable both in bronchoalveolar lavage and lung tissue (1 and 3 days post-exposure). The inflammatory response was comparable to the response following exposure to Mitsui-7 multi-walled carbon nanotubes at similar dose levels. The nanowires underwent partial dissolution in the lung resulting in thinner nanowires, with an estimated in vivo half-life of 3 months. Despite the partial dissolution, nanowires were detected in lung, liver, spleen, kidney, uterus and brain 3 months after exposure.
CONCLUSION
Pulmonary exposure to gallium phosphide nanowires caused similar toxicological effects as the multi-walled carbon nanotube Mitsui-7.
Topics: Humans; Mice; Female; Rats; Animals; Mice, Inbred C57BL; Nanotubes, Carbon; Nanowires; Lung
PubMed: 37679803
DOI: 10.1186/s12951-023-02049-0 -
Computed Tomography-Guıded Tru-Cut Bıopsy in the Dıagnosıs of Lung Lesıons; Our Clınıcal Experience.Asian Pacific Journal of Cancer... Sep 2023CT-guided tru-cut biopsy, which is less invasive and cost-effective, is an important diagnostic tool with high accuracy in lesions located peripherally in the lung. In...
INTRODUCTION
CT-guided tru-cut biopsy, which is less invasive and cost-effective, is an important diagnostic tool with high accuracy in lesions located peripherally in the lung. In this article, CT-guided tru-cut biopsy experiences of thoracic surgeons are shared.
MATERIALS AND METHODS
CT-guided tru-cut biopsy was performed on 200 patients with suspected lung lesions in the thoracic surgery clinic. Diagnostic rates of biopsies, complications, factors affecting the development of complications, and complication management were examined.
RESULTS
The diagnostic rate of the biopsies was 88%. Pneumothorax developed in 19.5% and hemothorax in 1% after the procedure. There was a significant relationship between mass dimensions and total complication rates (p=0.017). The relationship between the distance among the pleura and the mass and the development of complications was significant (p<0.001). The relationship between the number of biopsies and the development of pneumothorax was significant (p=0.011). The relationship between the size of the mass and the development of pneumothorax was significant (p=0.011). In univariate binary logistic regression analysis, a significant correlation was found between the size of the mass and the development of total complications (odds ratio (OR)=0.356 (95% CI: (0.146-0.868), (p=0.023)).
DISCUSSION
In the diagnosis of lung lesions, CT-guided tru-cut biopsy is an effective diagnostic tool with high diagnostic power, with its less invasiveness, and lower cost. The increase in the lung parenchyma distance passed with the biopsy needle increased the likelihood of complications most significantly. The size of the mass and the number of biopsies also had significant effects on the development of complications.
Topics: Humans; Pneumothorax; Image-Guided Biopsy; Lung; Biopsy, Needle; Lung Neoplasms; Tomography, X-Ray Computed; Retrospective Studies
PubMed: 37774057
DOI: 10.31557/APJCP.2023.24.9.3059 -
Neurosurgical Focus Oct 2023Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and...
Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study.
OBJECTIVE
Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database.
METHODS
The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality.
RESULTS
The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery-related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non-spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery.
CONCLUSIONS
Initiation of LMWH within 24 hours was associated with a low rate of spine surgery-related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.
Topics: Humans; Heparin, Low-Molecular-Weight; Venous Thromboembolism; Prospective Studies; Anticoagulants; Spinal Cord Injuries; Pulmonary Embolism; Postoperative Hemorrhage; Spinal Injuries; Registries; Heparin
PubMed: 37778033
DOI: 10.3171/2023.7.FOCUS23362 -
Nutrition (Burbank, Los Angeles County,... Aug 2023The energy demands of individuals with cystic fibrosis (CF) vary depending on pancreatic function, body composition, lung function, and clinical status. In clinical...
OBJECTIVE
The energy demands of individuals with cystic fibrosis (CF) vary depending on pancreatic function, body composition, lung function, and clinical status. In clinical practice, predictive equations are used to determine energy requirements yet do not reliably account for these factors. Research regarding energy requirements during CF pulmonary exacerbation (CFPEx) and clinical stability is conflicting. The aim of this study was to investigate potential within-individual changes in measured resting energy expenditure (mREE) using indirect calorimetry (IC) at the commencement and completion of intravenous antibiotic treatment (IVABx) for CFPEx and during clinical stability. Secondary aims were to investigate potential differences between predicted resting energy expenditure (pREE) using Schofield equation and correlations between clinical factors with mREE.
METHODS
Body composition using bioimpedance analysis and mREE were conducted at three time points: commencement of IVABx; completion of IVABx; and clinically stable period thereafter.
RESULTS
Twenty-eight adults with CF completed at least one valid IC measurement. No significant within-person changes in mREE and body composition parameters were observed across time points. The mREE was positively correlated with fat-free mass (kg; r = 0.6; P = 0.008). The mREE was significantly higher than pREE at all time points with the mREE/pREE ratio elevated at time point 1:118% ± 19.5%; time point 2: 112% ± 13.2%; and time point 3: 122 ± 14.3%.
CONCLUSION
The mREE remained stable during CFPEx and clinical stability. The pREE underestimated mREE and application of injury factor adjustment of 110% to 130% could potentially account for this discrepancy. The potential role of IC and body composition in individualizing CF nutritional assessment and prescription requires further exploration.
Topics: Adult; Humans; Basal Metabolism; Cystic Fibrosis; Calorimetry, Indirect; Energy Metabolism; Lung
PubMed: 37263161
DOI: 10.1016/j.nut.2023.112073