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Journal of Ethnopharmacology Jul 2024Exocarpium Citri Grandis (ECG), the epicarp of C. grandis 'Tomentosa' which is also known as Hua-Ju-Hong in China, has been widely used for thousands of years to treat...
ETHNOPHARMACOLOGICAL RELEVANCE
Exocarpium Citri Grandis (ECG), the epicarp of C. grandis 'Tomentosa' which is also known as Hua-Ju-Hong in China, has been widely used for thousands of years to treat inflammatory lung disorders such as asthma, and cough as well as dispelling phlegm. However, its underlying pharmacological mechanisms in acute lung injury (ALI) remain unclear.
AIM OF THE STUDY
To explore the therapeutic effect of ECG on ALI and reveal the potential mechanisms based on experimental techniques in vivo and in vitro.
MATERIALS AND METHODS
Lipopolysaccharides (LPS) induced ALI in mice and induced RAW 264.7 cell inflammatory model were established to investigate the pharmacodynamics of ECG. ELISA kits, commercial kits, Western Blot, qPCR, Hematoxylin and Eosin (H&E) staining, immunohistochemistry, and immunofluorescence technologies were used to evaluate the pharmacological mechanisms of ECG in ameliorating ALI.
RESULTS
ECG significantly attenuated pulmonary edema in LPS-stimulated mice and decreased the levels of IL1β, IL6, and TNF-α in serum and BALF, reduced MDA and iron concentration as well as increased SOD and GSH levels in lung tissues, and also decreased the ROS level in BALF and Lung tissue. Further pharmacological mechanism studies showed that ECG significantly inhibited mRNA expression of inflammatory signaling factors and chemokines, and down-regulated the expression of TLR4, MyD88, NF-κB p65, NF-κB p-p65 (S536), COX2, iNOS, Txnip, NLRP3, ASC, Caspase-1, JAK1, p-JAK1 (Y1022), JAK2, STAT1, p-STAT1 (S727), STAT3, p-STAT3 (Y705), STAT4, p-STAT4 (Y693), and Keap1, and also up-regulated the expression of Trx-1, Nrf2, HO-1, NQO1, GPX4, PCBP1, and SLC40A1. In the LPS-induced RAW264.7 cell inflammatory model, ECG showed similar results to animal experiments.
CONCLUSIONS
Our results showed that ECG alleviated ALI by inhibiting TLR4/MyD88/NF-κB p65 and JAK/STAT signaling pathway-mediated inflammatory response, Txnip/NLRP3 signaling pathway-mediated inflammasome activation, and regulating Nrf2/GPX4 axis-mediated ferroptosis. Our findings provide an experimental basis for the application of ECG.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Acute Lung Injury; Mice; Lipopolysaccharides; RAW 264.7 Cells; Ferroptosis; Male; Inflammasomes; Inflammation; Anti-Inflammatory Agents; Mice, Inbred C57BL; Citrus; Signal Transduction; Plant Extracts; Lung
PubMed: 38588989
DOI: 10.1016/j.jep.2024.118162 -
Frontiers in Pharmacology 2024Patients with sepsis are at an incremental risk of acute lung injury (ALI). Baiqian, also known as rhizoma et radix (Csrer), has anti-inflammatory properties and is...
Integrating UPLC-Q-Orbitrap MS with serum pharmacochemistry network and experimental verification to explore the pharmacological mechanisms of rhizoma et radix against sepsis-induced acute lung injury.
Patients with sepsis are at an incremental risk of acute lung injury (ALI). Baiqian, also known as rhizoma et radix (Csrer), has anti-inflammatory properties and is traditionally used to treat cough and phlegm. This study aimed to demonstrate the multicomponent, multitarget, and multi-pathway regulatory molecular mechanisms of Csrer in treating lipopolysaccharide (LPS)-induced ALI. The bioactive components of Csrer were identified by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). Active targets predicted from PharmMapper. DrugBank, OMIM, TTD, and GeneCards were used to identify potential targets related to ALI. Intersection genes were identified for Csrer against ALI. The PPI network was analysed to identify prime targets. GO and KEGG analyses were performed. A drug-compound-target-pathway-disease network was constructed. Molecular docking and simulations evaluated the binding free energy between key proteins and active compounds. The protective effect and mechanism of Csrer in ALI were verified using an ALI model in mice. Western blot, Immunohistochemistry and TUNEL staining evaluated the mechanisms of the pulmonary protective effects of Csrer. Forty-six bioactive components, one hundred and ninety-two potential cross-targets against ALI and ten core genes were identified. According to GO and KEGG analyses, the PI3K-Akt, apoptosis and p53 pathways are predominantly involved in the "Csrer-ALI" network. According to molecular docking and dynamics simulations, ten key genes were firmly bound by the principal active components of Csrer. The "Csrer-ALI" network was revealed to be mediated by the p53-mediated apoptosis and inflammatory pathways in animal experiments. Csrer is a reliable source for ALI treatment based on its practical components, potential targets and pathways.
PubMed: 38584603
DOI: 10.3389/fphar.2024.1261772 -
Respiratory Investigation May 2024Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the...
BACKGROUND
Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the national administrative database to estimate the incidence and prevalence of lymphangioleiomyomatosis over six years (2014-2019) and describe changes in clinical practice and mortality.
METHODS
We extracted data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between January 2013 and December 2020. This database covers ≥99% of the population. We used the diagnostic code for lymphangioleiomyomatosis to estimate the incidence and prevalence from 2014 to 2019. Additionally, we examined the demographic characteristics, treatments, comorbidities, and mortality of the patients.
RESULTS
In women, the incidence and prevalence of lymphangioleiomyomatosis in 2019 were approximately 3 per 1,000,000 person-years and 28.7 per 1,000,000 persons, respectively. While, in men, the incidence and prevalence of lymphangioleiomyomatosis were <0.2 per 1,000,000 person-years and 0.8 per 1,000,000 persons, respectively. From 2014 to 2019, the proportion of prescriptions of sirolimus and everolimus increased, while the use of home oxygen therapy, chest drainage, comorbid pneumothorax, and bloody phlegm decreased. The mortality rate remained stable at approximately 1%.
CONCLUSIONS
The incidence and prevalence of lymphangioleiomyomatosis were higher in women than those reported previously. Although the incidence did not change during the 6-year period, the prevalence gradually increased. Moreover, lymphangioleiomyomatosis was observed to be rare in men. The practice of treating patients with lymphangioleiomyomatosis changed across the six years while mortality remained low, at approximately 1%.
Topics: Male; Humans; Female; Lymphangioleiomyomatosis; Japan; Sirolimus; Insurance, Health; Everolimus; Incidence; Prevalence
PubMed: 38583226
DOI: 10.1016/j.resinv.2024.03.010 -
Alcohol and Alcoholism (Oxford,... Mar 2024This matched case-control study aimed to provide epidemiologic evidence of increased burden of respiratory symptoms and pulmonary function decline among people living...
AIM
This matched case-control study aimed to provide epidemiologic evidence of increased burden of respiratory symptoms and pulmonary function decline among people living with human immunodeficiency virus (HIV) and a history of heavy alcohol consumption.
METHODS
Cases were participants with HIV (PWH; n = 75, 33%), and controls were participants without HIV (PWoH; n = 150, 67%). PWH were matched to PWoH by age and sex in the ratio of 1:2. Eligible participants responded to the respiratory health National Health and Nutrition Examination Survey questionnaire [prolonged coughs (≥3 months), bringing up of phlegm (≥3 months), and a history of wheezing or whistling in the chest (past year)]. The effects of both alcohol and HIV on participants' pulmonary function were determined using linear regression analysis.
RESULTS
History of heavy alcohol consumption was more prevalent among PWH (40%) compared to PWoH (27%). PWH who had a history of heavy alcohol consumption had a higher prevalence of coughing most days (45% vs. 4%, P = .0010), bringing up phlegm most days (31% vs. 0%, P = .0012), and wheezing or whistling in the chest (40% vs. 20%, P = .058) compared to participants who did not heavily consume alcohol. Furthermore, a history of heavy alcohol consumption was associated with decreased forced expiratory volume (ml) in 1 s/forced vital capacity among PWH (β = - 0.098 95% C.I. -0.16, -0.04, P = .03) after adjusting for having smoked at least 100 cigarettes in life.
CONCLUSION
A history of heavy alcohol use increased respiratory symptoms and suppressed pulmonary function among people living with HIV. This study provides epidemiological evidence of the respiratory symptom burden of people living with HIV who have a history of heavy alcohol consumption.
Topics: Humans; Nutrition Surveys; HIV; HIV Infections; Respiratory Sounds; Case-Control Studies; Alcohol Drinking
PubMed: 38581190
DOI: 10.1093/alcalc/agae021 -
The Medical Journal of Malaysia Mar 2024Cleaners perform a vital role in environmental health by keeping the place clean, but they are also exposed to various hazards. Yet, there is a lack of effective and...
INTRODUCTION
Cleaners perform a vital role in environmental health by keeping the place clean, but they are also exposed to various hazards. Yet, there is a lack of effective and accessible occupational safety standard measures, thus making this to be difficult to monitor the long-term health effects of cleaners. This study aims to determine the respirable dust exposure on respiratory symptoms among cleaners in a public university in Selangor.
MATERIALS AND METHODS
A cross-sectional study was carried out among 51 cleaners. The respondents' background information and respiratory symptoms were gathered using a series of standardised questionnaires validated by the American Thoracic Society (ATS-DLD-78-A). The 8- hour respirable dust exposure to cleaners was measured using an air sampling pump (Gillian & Sensodyne Gil Air 3).
RESULTS
The mean of respirable dust was lower than permissible exposure limit with 0.63±0.57mg/m3. The respiratory symptoms among the cleaners showed no significant association between cough, phlegm, and breathing difficulties with working tenure. Meanwhile, wheezing and coughing with phlegm have an almost significant association with working tenure among cleaners with (Χ=1.00, p=0.08) and (Χ=1.00, p=0.07) respectively. Exposure to respirable dust has exhibited 6 times the prevalence of coughing with phlegm among cleaners (PR=6.28, 95% CI: 0.44, 89.38).
CONCLUSION
The findings of this study demonstrated that the cleaners were significantly affected by the respirable dust. The cleaners' working environment has caused them to be exposed to respirable dust.
Topics: Humans; Occupational Exposure; Air Pollutants, Occupational; Cross-Sectional Studies; Malaysia; Universities; Lung Diseases; Cough; Dust
PubMed: 38555894
DOI: No ID Found -
Frontiers in Cardiovascular Medicine 2024The concepts of "individualization" and "preventive treatment" should be incorporated into the precise diagnosis and treatment of coronary heart disease (CHD). Both...
BACKGROUND
The concepts of "individualization" and "preventive treatment" should be incorporated into the precise diagnosis and treatment of coronary heart disease (CHD). Both hemodynamics and Chinese medicine constitution studies align with these two concepts.
METHODS
This study utilized data from 81 patients with CHD, including 12 patients with balanced constitution (BC), 20 patients with blood stasis constitution (BSC), 17 patients with phlegm-dampness constitution (PDC), 15 patients with qi-deficiency constitution (QDC), and 17 patients with other constitutions. Clinical data provided information on the patients' blood property, heart function, degree of coronary stenosis, coronary hemodynamics, and so on. These parameters were compared between patients with balanced constitution vs. biased constitutions as well as between those with blood stasis constitution, phlegm-dampness constitution, and qi-deficiency constitution.
RESULTS
Compared to biased constitution (BC), patients with balanced constitution exhibited lower total cholesterol (TC) levels and low-density lipoprotein (LDL) levels. Additionally, they had lighter stenosis degrees in the Left anterior descending branch (LAD) and Left circumflex branch (LCX) branches. The hemodynamic condition of the LAD and LCX was better for those with balanced constitution; however there was no difference in heart function. Among the groups categorized by blood stasis, phlegm dampness or qi deficiency constituions, patients classified under phlegm dampness had higher levels of LDL compared to those classified under blood stasis or qi deficiency, while patients classified under qi deficiency had higher levels of blood glucose compared to those classified under blood stasis or phlegm dampness. Hemodynamic environments also differed among the LAD and LCX for each group but there were no significant differences observed in heart function or degree of coronary stenosis among these three groups.
CONCLUSION
The balanced constitution demonstrates superior blood property, degree of coronary artery stenosis, and coronary hemodynamics compared to the biased constitution. Furthermore, among the three constitutions with CHD, variations in blood property and certain hemodynamic parameters are observed. These findings emphasize the significant clinical value of incorporating physical factors into the diagnosis and treatment of patients with CHD.
PubMed: 38529331
DOI: 10.3389/fcvm.2024.1383082 -
Medicine Mar 2024Cryptococcosis presenting as endobronchial obstruction and lung collapse is an extremely rare occurrence. While these patients were treated with antifungal agents,... (Review)
Review
RATIONALE
Cryptococcosis presenting as endobronchial obstruction and lung collapse is an extremely rare occurrence. While these patients were treated with antifungal agents, unfortunately, half of them showed a suboptimal response.
PATIENT CONCERNS
A 45-year-old immunocompetent male was admitted to the hospital due to a cough, yellow phlegm, and dyspnea persisting for 5 months. Chest computer tomography revealed a mass in the right main bronchus accompanied by right lower lobe atelectasis.
DIAGNOSES
Endobronchial cryptococcosis presenting as endobronchial obstruction and lung collapse.
INTERVENTIONS
Early rigid bronchoscopic therapy was performed to resect endobronchial obstruction, which combined with antifungal agent.
OUTCOMES
The patient recovered well with completely clinical and radiologic resolution at 1 year follow-up.
LESSONS
This case provides a good example of successful utilization of the early respiratory interventional therapy combined with antifungal agent in obstructive endobronchial cryptococcosis.
Topics: Humans; Male; Middle Aged; Antifungal Agents; Cryptococcosis; Bronchi; Lung; Bronchial Diseases; Pulmonary Atelectasis; Airway Obstruction
PubMed: 38518007
DOI: 10.1097/MD.0000000000037455 -
Medical Mycology Case Reports Jun 2024Mucormycosis, a rare but life-threatening fungal infection, poses significant challenges in clinical management, particularly in patients with uncontrolled diabetes...
Mucormycosis, a rare but life-threatening fungal infection, poses significant challenges in clinical management, particularly in patients with uncontrolled diabetes mellitus. This case report presents the clinical journey of a 44-year-old woman who developed a rapidly progressing Mucorales infection following a domestic knife injury. Her condition, complicated by diabetic ketoacidosis and co-infection with , led to severe hand phlegm and sepsis. Despite aggressive intervention, the infection continued to advance, ultimately resulting in the patient's demise.
PubMed: 38516607
DOI: 10.1016/j.mmcr.2024.100643 -
Journal of Thoracic Disease Feb 2024Owing to the extremely short supply of donor lungs in Japan, a unique medical consultant (MC) system was initiated in 2002 to increase the organ availability through... (Review)
Review
Owing to the extremely short supply of donor lungs in Japan, a unique medical consultant (MC) system was initiated in 2002 to increase the organ availability through intensive management of donors. First, heart transplant surgeons were sent to procurement hospitals as MCs to assess donor organ function and provide intensive care to donors. MCs requested that donor attending doctors perform frequent phlegm aspiration with a bronchoscope, leading to a higher lung availability and better outcomes after lung transplantation. Since 2011, 25 lung transplant surgeons have been registered as lung MCs to assess and manage donor lungs and communicate donor lung conditions to the lung transplantation teams. In 2014, the efficacy of this MC system on lung transplantation opportunities and outcomes was retrospectively reviewed. One hundred and eighty-seven brain-dead lung donor candidates were chronologically divided into three phases: I (May 1998 to November 2006, n=44) and II (December 2006 to January 2011, n=64), before and after MCs requested that local attending doctors perform aggressive bronchial suctioning using a bronchoscope, respectively; and III (February 2011 to January 2013, n=79), after the emergence of lung MCs. The lung utilization rates in phases I, II, and III were 61.4%, 71.9%, and 74.7% (per donor); 51.1%, 64.8%, and 67.7% (per lung, P=0.03). Graft death rates due to primary graft dysfunction in phases I, II, and III were 13.3%, 3.6%, and 3.7%, respectively (per lung, P=0.04). Recently, we analyzed the utilization rate of 63 brain-dead lung donor candidates for a period of one year, from June 2020 to May 2021, which was 83% (per donor). The lung MC system is effective in maintaining an extremely high lung utilization rate and favorable outcomes after lung transplantation in Japan.
PubMed: 38505018
DOI: 10.21037/jtd-23-290 -
Journal of Traditional Chinese Medicine... Apr 2024To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.
OBJECTIVE
To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.
METHODS
Sprague-Dawley rats with normal glucose levels were randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose [PBG; using the oral glucose tolerance test (OGTT)], hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting.
RESULTS
DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies.
CONCLUSION
DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.
Topics: Rats; Animals; Rats, Sprague-Dawley; Blood Glucose; Glycated Hemoglobin; Chromatography, Liquid; Tandem Mass Spectrometry; Liver; Lipid Metabolism; Glycolipids; Triglycerides; Peptides; Diet, High-Fat
PubMed: 38504539
DOI: 10.19852/j.cnki.jtcm.20230908.001