Copper oxide nanoparticles (CuONPs), widely used across various industries, pose inhalation risks to industrial workers and consumers through respiratory exposure. Although exposure to CuONPs has been implicated in the initiation and progression of respiratory disorders, the molecular mechanisms underlying these effects remain poorly defined. In this study, we investigated the role of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in CuONP-induced respiratory toxicity and asthma exacerbation. Exposure to CuONPs resulted in pronounced inflammatory cell infiltration, elevated cytokine production, and excessive mucus secretion, accompanied by disrupted redox balance, as evidenced by increased malondialdehyde (MDA) levels and decreased glutathione (GSH) concentrations. These changes were associated with upregulation of Nrf2 and its downstream antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutamate-cysteine ligase modifier subunit (GCLM). Although this antioxidant response is consistent with an expected oxidative stress-adaptive pathway, it was not sufficient to prevent CuONP-associated inflammatory and redox disturbances. Consistently, in NCI-H292 cells, CuONP treatment increased the expression of Nrf2, HO-1, and GCLM, whereas siRNA-mediated Nrf2 knockdown abrogated these inductions. In an ovalbumin (OVA)-induced asthma model, CuONP exposure further intensified airway inflammation and oxidative stress, despite elevated Nrf2 expression. However, adeno-associated virus (AAV)-mediated Nrf2 overexpression significantly attenuated CuONP-induced airway inflammatory responses and redox imbalance in asthmatic mice. Taken together, our results indicate that endogenous Nrf2 response is insufficient to counteract CuONP-driven asthma exacerbation, whereas pharmacological or genetic augmentation of Nrf2 signaling may constitute a viable strategy to alleviate nanoparticle-induced respiratory injury.

IntroductionBoehmeria nivea (L.) Gaud. has traditionally been regarded as a medicinal food with applications in various inflammatory disorders. However, its role in chronic obstructive pulmonary disease (COPD) has not yet been clarified.MethodsIn this study, the preventive efficacy of the ethyl acetate fraction of B. nivea (L.) Gaud. leaves (EA-BN) was evaluated in a COPD model established by intratracheal instillation of lipopolysaccharide (LPS; 0.5 mg/kg body weight) and cigarette smoke condensate (CSC; 12.5 mg/kg body weight) in male C57BL/6N mice. The experimental groups received dexamethasone (3 mg/kg) as a positive control or EA-BN at doses of 100 and 200 mg/kg.ResultsEA-BN administration significantly reduced T helper 1 cytokine levels and decreased macrophage and neutrophil counts in bronchoalveolar lavage fluid. Histological analyses revealed that EA-BN mitigated alveolar destruction and inflammatory infiltration, whereas pulmonary function tests demonstrated improvements in the FEV0.1/FVC ratio and lung elastance in the LPS/CSC-induced COPD. Additionally, EA-BN alleviated oxidative stress by promoting the nuclear translocation of Nrf2 and enhancing the expression of its downstream targets, HO-1 and NQO1, leading to a reduction in reactive oxygen species and nitric oxide production. EA-BN downregulated thioredoxin-interacting protein and NLRP3 inflammasome activation, thereby suppressing caspase-1 and IL-1β expression, whereas also attenuating apoptosis by modulating the Bax/Bcl-2/caspase-3 pathway.DiscussionCollectively, these findings suggest that EA-BN possesses antioxidant, anti-inflammatory, and anti-apoptotic properties, supporting its potential as a preventive agent against COPD.

Copper oxide nanoparticles (CuONPs) are used in various industrial and commercial applications and are considered a potential hazard to humans and the environment. In particular, inhalation exposure to CuONPs causes severe damage to the respiratory tissue. Camellia sinensis L. is traditionally used to treat various inflammatory disorders and has been experimentally shown to exhibit anti-inflammatory and antioxidant properties due to its bioactive compounds. This study aimed to investigate the therapeutic effects of Camellia sinensis L. ethanolic extract (CSE) on pulmonary inflammation caused by CuONPs exposure, with an emphasis on the mitogen-activated protein kinase (MAPK) signaling pathway. The administration of CSE reduced the inflammatory cell counts including neutrophils and macrophages in mice exposed to CuONPs, as well as the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. These events were accompanied by decreases in inflammatory cell infiltration into pulmonary tissue and mucus production from goblet cells. In addition, the administration of CSE reduced the activation of proteins involved in the MAPK pathway, including p-p38, p-JNK, p-ERK, and MUC5AC induced by CuONPs exposure. CSE effectively decreased the pulmonary inflammation caused by CuONPs exposure, which is associated with the suppression of the MAPK signaling pathway. Therefore, this evidence suggests that CSE has potential as a herbal remedy for controlling pulmonary inflammation caused by CuONPs exposure.

IMPORTANCE:The 5×FAD transgenic mouse model is widely used in Alzheimer's disease (AD) research, yet its non-cognitive phenotypes -- particularly motor coordination, olfactory sensitivity, and auditory reactivity -- remain poorly characterized across the full disease trajectory. Defining these sensory and sensorimotor deficits may enhance the translational relevance of this model and provide insight into non-cognitive features in preclinical AD studies. OBJECTIVE:To characterize age-related motor, olfactory, and auditory changes in 5×FAD mice and assess associated AD pathologies and neuroinflammation in relevant brain regions. METHODS:5×FAD and control mice were tested at 3, 6, and 12 months. Locomotor activity and motor coordination were assessed using the open field and rotarod tests, respectively. Olfactory and auditory performance were evaluated using the buried food test and the acoustic startle response test, respectively. Amyloid-β pathology and glial activation were examined in relevant nervous system components using western blot and immunohistochemistry analyses. RESULTS:5×FAD mice showed no differences in open-field locomotion at any age, but exhibited a significantly greater passive clinging duration at 12 months compared to wild-type controls (p < 0.001). In the buried food test, olfactory latency was significantly prolonged in 5×FAD mice at 6 months (p = 0.035) and 12 months (p < 0.001). Acoustic startle amplitude was significantly reduced at 6 months (p = 0.030) and 12 months (p = 0.007). Amyloid-β and p-Tau accumulation and glial activation were elevated in the olfactory bulb and auditory cortex in an age-dependent manner. CONCLUSIONS AND RELEVANCE:This study provides an age-related behavioral and pathological characterization of olfactory and auditory impairments in the 5×FAD mouse model, with motor measures included as complementary assessments. Our findings broaden the spectrum of functional deficits associated with the AD pathology in this model.

Mycoleptodonoides aitchisonii, an edible mushroom, has health benefits; however, its long-term safety remains unclear. In this study, acute (single-dose) and 13-week repeated oral toxicity studies were performed in Sprague–Dawley rats. For the acute study, animals received single oral doses of 500, 1000, and 2000 mg/kg. In the 13-week repeated-dose study, animals were administered 0, 500, 1000, and 2000 mg/kg/day. No mortality or treatment-related adverse effects were detected. Minor alterations in hematology, serum chemistry, organ weights, and histopathology were occasionally observed and were considered toxicologically irrelevant. In conclusion, repeated oral administration of M. aitchisonii for 13 weeks at doses up to 2000 mg/kg/day did not adversely affect rats. Under these conditions, the no-observed-adverse-effect level of M. aitchisonii was established as ≥ 2000 mg/kg/day in both sexes.

Allergic asthma is a widespread disease with elevated eosinophil levels. Although corticosteroids are widely prescribed for allergic asthma, numerous patients experience limited sensitivity and side effects. Loranthus tanakae Franch. & Sav., a traditional herbal plant, has anti-inflammatory and antioxidant properties in pulmonary inflammation caused by Asian sand dust and cigarette smoke condensate. To assess the protective effects of L. tanakae, we examined the influence of an L. tanakae ethanol extract (LTE) in ovalbumin (OVA)-induced asthma. Mice received intraperitoneal sensitisation with OVA, and challenged using OVA inhalation. LTE was consecutively orally gavaged for 6 days. Following sacrifice, the bronchoalveolar lavage fluid (BALF) and lung tissue was analysed. The LTE treatment considerably reduced inflammatory cell counts, proinflammatory cytokine levels in the BALF, and immunoglobulin E, compared with the OVA group, along with a reduction in airway hyperresponsiveness. The LTE also improved airway inflammation and suppressed mucus hypersecretion in the lung tissues. Additionally, the expression of MMP-9 and activation of ERK, JNK, and p38 were notably diminished in the LTE groups. This study revealed reduced airway inflammation in OVA-induced asthma via suppressing the MMP-9 and mitogen-activated protein kinase-associated factors. Consequently, our findings demonstrated that LTE is suggested as a potential remedy for allergic asthma.

Silibinin, a major compound of silymarin, has been reported to alleviate respiratory diseases including acute lung injury, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis through its antifibrotic, anti-inflammatory, and antioxidant properties. However, the specific mechanisms underlying its therapeutic effects, particularly in allergic asthma, are not fully understood. With the increasing prevalence and impact of allergic asthma, there is a need to elucidate the exact underlying mechanisms of its potential treatment effects. Herein, we investigated the therapeutic effects of silibinin on allergic asthma using house dust mite (HDM)-exposed mice and an HDM-stimulated human bronchial epithelium cell line, focusing on the roles of the NLR family CARD domain containing 4 (NLRC4) inflammasome and matrix metalloproteinase-9 (MMP-9). To induce airway inflammation, HDM extracts were instilled intranasally on days 0, 4, 8, and 12 to mice. Silibinin (20 and 40 mg/kg) was orally administered daily from days 0-12. The results showed that silibinin treatment attenuated allergic immune responses induced by HDM exposure, as evidenced by decreased airway hyperresponsiveness, reduced inflammatory cells and cytokines, lower immunoglobulin E levls, and decreased mucus production. Furthermore, silibinin treatment suppressed NLRC4 inflammasome activation and downregulated MMP-9 expression in the lungs. In HDM-stimulated cells, silibinin treatment decreased inflammatory cytokine levels and the expression of NLRC4 and interleukin-1β, indicating inhibition of NLRC4 inflammasome activation. Overall, our data demonstrated that silibinin alleviated allergic responses in HDM-induced asthmatic mice by inhibiting NLRC4 inflammasome activation and MMP-9 expression, underscoring its therapeutic potential in the treatment of asthma.

Copper oxide nanoparticles (CuONPs) are increasingly used across various industrial applications, raising concerns about their potential toxicity and necessitating comprehensive safety evaluations. In this study, we first evaluated the respiratory toxicity of CuONP exposure in a mouse model of asthma. CuONP exposure alone exacerbated asthma symptoms, as evidenced by increased airway hyperresponsiveness, inflammatory cell infiltration, and elevated cytokine production with increasing thioredoxin-interacting protein (TXNIP) expression. We then investigated whether TXNIP functions as a critical regulator of asthma exacerbation by examining the effects of TXNIP on the same experimental models using induced TXNIP-overexpressed mice induced by intratracheal injection of adeno-associated virus (AAV)2/8 and TXNIP knock-out (KO) mice. In CuONP-exposed asthmatic animals, TXNIP overexpressed animals significantly increased airway hyperresponsiveness, inflammatory cell counts and the production of helper type 2 cytokines, including interleukin (IL)-5 and IL-13, as well as the IL-1β, IL-6, tumor necrosis factor (TNF)-α, interferon gamma (IFN-γ) and IL-10 compared with the green fluorescent protein (GFP)-expressing controls. These responses were accompanied by the elevation of inflammatory infiltration, mucus production and the expression of apoptotic markers in lung tissues. By contrast, TXNIP KO animals markedly reduced the pathophysiological factors, inflammatory responses, mucus production and the expression of apoptotic markers in lung tissue compared with the wild-type (WT) animals. Collectively, these findings demonstrate that TXNIP plays a crucial role in regulating inflammatory responses and cell death in CuONP-exposed asthmatic mice, suggesting its potential as a therapeutic target for CuONP-induced asthma exacerbation.

Ethnopharmacological relevance Boehmeria nivea (L.) Gaud. (BN) is a well-known traditional herbal medicine used to treat a wide range of conditions, including bleeding, fever, diarrhea, and wounds, as well as respiratory disorders such as cough and wheezing. However, its potential efficacy against allergic airway inflammation has yet to be systematically evaluated. Aim of the study This study aimed to investigate the therapeutic potential of BN, particularly the ethyl acetate fraction (EA-BN), in modulating immune responses in allergic asthma. Material and methods BALB/c mice were sensitized with ovalbumin (OVA) to induce allergic asthma and treated orally with BN fractions (100 mg/kg; EA-BN-L; 100 mg/kg and EA-BN-H; 200 mg/kg). Th2 cytokines (IL-4, IL-5, and IL-13) and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were measured. Bone marrow-derived dendritic cells (BMDCs) stimulated with lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α-stimulated NCI-H292 epithelial cells were used to assess in vitro potential effects. Flow cytometry and qPCR were used to evaluate cytokine levels and transcription factor expression. Results This study demonstrated the significant efficacy of EA-BN in an OVA-induced allergic asthma model. EA-BN treatment markedly suppressed the expression of extracellular cytokines (IL-10, IL-12, and TNF-α), co-stimulatory molecules (CD80 and CD86), and MHC class I/II in both LPS-stimulated BMDCs and splenic DCs in OVA-induced asthmatic mice. In addition, EA-BN reduced GATA-3 expression in CD3+CD4+ T cells, suggesting inhibition of Th2 cell differentiation in splenic T cells from asthmatic mice. Histological analysis revealed that EA-BN attenuated mucus overproduction, and inflammatory cell infiltration in lung tissues, along with a concurrent decrease in Th2 cytokine levels and MUC5AC expression. Furthermore, EA-BN also inhibited Th2 cytokine expression in TNF-α-stimulated NCI-H292 cells. Conclusion EA-BN mediates its immunoregulatory effects by simultaneously suppressing dendritic cell activation and blocking Th2 cell differentiation, ultimately leading to the downregulation of Th2-driven inflammatory responses. These findings support EA-BN as a potential herbal therapeutic candidate for allergic asthma.

Loranthus tanakae Franch. and Sav. is a traditional herbal remedy with anti-inflammatory and antioxidative properties, used to treat joint and respiratory inflammation. In this study, we investigated the therapeutic effects of L. tanakae ethanol extract (LTE) on atopic dermatitis (AD). An ovalbumin (OVA)-induced AD animal model and a human keratinocyte cell line, HaCaT, were used to assess LTE treatment effects on AD. An in vitro experiment showed that LTE treatment significantly decreased the production of regulated upon activation, normal T cell expressed and secreted (RANTES) cytokines and macrophage-derived chemokines (MDC) in tumor necrosis factor-alpha (TNF-α)/interferon-gamma (IFN-γ) (TNF-α/IFN-γ)-stimulated HaCaT cells in a concentration-dependent manner. In addition, treatment with LTE markedly reduced the translocation of signal transducer and activator transcription 1 (STAT1) protein to the nucleus and the phosphorylation of Janus kinase 2 (JAK2) in TNF-α/IFN-γ-stimulated HaCaT cells. In the in vivo experiment, administration of LTE significantly decreased the levels of immunoglobulin E (IgE) and interleukin-13 (IL-13) of OVA-induced AD mice, which was supported by histological evidence. Moreover, LTE treatment markedly reduced inflammatory cell infiltration and edema in the OVA-induced AD mice’s damaged lesions. In addition, applying LTE notably inhibited the phosphorylation of JAK2 and STAT1 in the OVA-induced AD mice, supported by in vitro results. In conclusion, LTE effectively alleviated the AD-induced skin inflammation in the OVA-induced AD animal model and TNF-α/IFN-γ-stimulated HaCaT cells; this was related to the suppression of JAK2 and STAT1 phosphorylation. These findings suggest that LTE has potential as a therapeutic agent for AD management.

Humanized virus suppressing factor-variant 13 (hzVSF-v13), a monoclonal IgG4 antibody, is a potential therapeutic candidate for COVID-19. Although fertility and embryonic developmental toxicity studies are crucial for the safety evaluation of new drugs, the toxicological profile of hzVSF-v13 remains unexplored. This study was performed to assess its effects on general toxicity, fertility, and early embryonic development in Sprague-Dawley rats administered intravenously once weekly at doses of 0, 25, 50, and 100 mg/kg. Males received the test article starting 4 weeks before mating and continuing until the day prior to sacrifice, while females were treated beginning 2 weeks prior to mating and continuing through the implantation. No treatment-related effects were observed on general toxicological parameters, including body weight, food consumption, macroscopic findings, or organ weights in both sexes. Additionally, hzVSF-v13 did not affect the mating performance, fertility, sperm analysis, or litter parameters in cesarean section at doses up to 100 mg/kg. Under the experimental conditions, the no-observed-adverse-effect level (NOAEL) of hzVSF-v13 for general toxicity, fertility, and early embryonic development was considered to be 100 mg/kg.

Asian sand dust (ASD), generated from the deserts of China and Mongolia, mainly affects the human health of several countries in Northeast Asia including China, Korea, and Japan. In this study, we investigated the toxic effects of ASD on respiratory tract and explored the effects of ASD exposure on allergic asthma using ovalbumin-induced asthma model. C57BL/6 male mice were used for both the toxicity and allergic asthma studies. ASD (10, 20, and 40 mg/kg) was administered intranasally on days 1, 3, and 5. For allergic asthma, mice were sensitized with OVA (20 µg/mouse) and aluminum hydroxide (2 mg) on days 1 and 15, followed by OVA inhalation (1

Self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) is a novel RNA interference-based nanoparticle for treating fibrotic diseases. The present non-clinical study investigated the potential 4-week repeated intravenous dose toxicity and toxicokinetics of SAMiRNA-AREG at dose levels of 0, 25, 50, and 100 mg/kg/day in cynomolgus monkeys. During the test period, mortality, clinical observation, body and organ weights, food consumption, ophthalmology, electrocardiography, hematology, serum chemistry, urinalysis, and gross and microscopic pathology were examined. Serum samples were collected at various time points (0, 0.1, 0.5, 1, 3, 6, 10, 24, and 48 h) after dosing on days 1 and 29 for toxicokinetic analysis. The repeated intravenous dose toxicity study revealed no treatment-related significant changes or serious toxicity compared to the vehicle control group. SAMiRNA-AREG exhibited a non-linear toxicokinetic profile, with the t1/2 value ranging from 2.97 to 5.88 h in single dosing and from 2.44 to 4.01 h in repeated dosing. In conclusion, the no-observed-adverse-effect level for SAMiRNA-AREG was considered to be ≥ 100 mg/kg/day with Cmax and AUClast values of 650,181.0–764,279.7 μg/mL and 539,728.0–606,033.5 h ng/mL, respectively, on day 29, and no target organs were identified.

Background and objectivesThe outbreak of the COVID-19 pandemic has made the development of effective treatments a critical global issue. This study investigated whether Korean perilla (Perilla frutescens var. frutescens) leaf ethanol extract (P108) showed therapeutic potential against COVID-19 using the SH101 Roborovski hamster model.Materials and methodsThe COVID-19 infection model was established by intranasal administration of SARS-CoV-2 suspension into SH101 Roborovski hamsters. Experimental groups received P108 at dosages of 1,000 and 3,000 mg/kg/day, with additional groups for normal control (no treatment), vehicle control (0 mg/kg/day with vehicle only), and positive control (Paxlovid at 20 mg/kg/day). All substances were administered orally via gavage using a sonde. Treatment effects were assessed by monitoring changes in body temperature, clinical signs, body weight, levels of D-dimer and fibrin degradation products, interleukin concentrations, viral titers, immune cell counts, and lung pathology. Statistical significance was determined for differences with a p-value ≤ 0.05.ResultsHamsters infected with SARS-CoV-2 exhibited typical COVID-19 disease progression, including marked hypoactivity by 4 days post-inoculation (dpi). Both P108- and Paxlovid-treated groups initially developed fever but subsequently recovered, with body weight restoration comparable to the normal control group. At 5 dpi, high-dose P108 and Paxlovid treatment resulted in reduced viral loads in lung tissues. Notably, high-dose P108 demonstrated cytokine modulation and viral load reduction trends similar to those observed with Paxlovid, as detailed in the Results and Figure Legends. P108 treatment significantly lowered fibrin degradation product levels, IL-6, and TNF-α while increasing IL-10. Histological analysis showed reduced pulmonary inflammation in the P108-treated groups.ConclusionThe results of this study suggest that P108 may inhibit SARS-CoV-2 replication and reduce systemic inflammatory responses. These findings support the continued development of P108 as a candidate for preventive or early-intervention strategies against COVID-19. However, its efficacy following delayed treatment initiation (e.g., after symptom onset) has not yet been demonstrated and warrants further investigation.

IntroductionHumanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice. In this study, we created a novel mouse strain, NOD-CD47nullRag2nullIL-2rγnull (RTKO) mice, and applied it to generate humanized mice.MethodsFour-week-old female NOD-Rag2nullIL-2rγnull (RID) and RTKO mice pre-conditioned with TBI or busulfan (BSF) injection were used for generating human CD34+ hematopoietic stem cell (HSC) engrafted humanized mice. Clinical signs were observed twice a week, and body weight was measured once a week. Flow cytometry for human leukocyte antigens was performed at intervals of four weeks or two weeks, and mice were sacrificed at 48 weeks after HSC injection.ResultsFor a long period from 16 to 40 weeks post transplantation, the percentage of hCD45 was mostly maintained above 25% in all groups, and it was sustained the longest and highest in the RTKO BSF group. Reconstruction of human leukocytes, including hCD3, was also most prominent in the RTKO BSF group. Only two mice died before 40 weeks post transplantation in all groups, and there were no life-threatening GvHD lesions except in the dead mice. The occurrence of GvHD has been identified as mainly due to human T cells infiltrating tissues and their related cytokines.DiscussionHumanized mouse models under all conditions applied in this study are considered suitable models for long-term experiments based on the improvement of human leukocytes reconstruction and the stable animal health. Especially, RTKO mice pretreated with BSF are expected to be a valuable platform not only for generating humanized mice but also for various immune research fields.

Background The medicinal properties and benefits of collagen peptides (CPs) are widely recognized and utilized. However, the potential genotoxicity of CPs remains elusive. Objective The objective of this study was to assess the potential genotoxicity of CP derived from skate ( Raja kenojei ) skin (CPSS). To achieve this, we conducted a comprehensive study using three standard battery systems in accordance with the test guidelines provided by the Organisation for Economic Cooperation and Development and the Korean Ministry of Food and Drug Safety, as well as the principles of Good Laboratory Practice. Results We performed a bacterial reverse mutation (Ames) test using the pre-incubation method, with or without a metabolic activation system (S9 mixture). The Ames test, conducted on Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, as well as Escherichia coli strain WP2 uvr A, demonstrated that CPSS did not cause gene mutations in any of the tested strains, regardless of the dose level. In addition, we performed an in vitro chromosome aberration test using cultured Chinese hamster lung fibroblast cells, with and without the S9 mixture, and an in vivo mouse bone marrow micronucleus test on specific pathogen-free male ICR mice. Both the in vitro chromosomal aberration test and the in vivo micronucleus test revealed no chromosomal aberrations resulting from CPSS treatment. Conclusion Our findings demonstrate that CPSS does not exhibit mutagenic or clastogenic activity in either in vitro or in vivo test systems, supporting its potential as a safe material for medical use.

Asian sand dust (ASD), also called China dust or yellow dust, mainly occurs in East Asia during spring and autumn. Because ASD enters the body mainly through the respiratory system, it can cause respiratory disorders or worsen underlying diseases. Because of this, it has become an important health concern that threatens the well-being of humans and animals. In this study, we investigated the effects of 15 and 30 mg/kg of Pycnogenol (PYC15 and 30 groups), a pine bark extract, on ASD-induced pulmonary inflammation in mice. We evaluated the inflammatory cell counts, inflammatory cytokines, and matrix-metalloproteinase (MMP)-9 expression in animal models. PYC administration significantly decreased inflammatory cell infiltration into lung tissue; this was accompanied by a reduction in the levels of proinflammatory mediators including interleukin (IL)-1β (P < 0.01), IL-6 (P < 0.01) and tumour necrosis factor-α (P < 0.01) in bronchoalveolar lavage fluids of ASD-exposed mice (ASD group). Histological analysis revealed that PYC suppressed ASD-induced pulmonary inflammation. Moreover, PYC suppressed the levels of matrix-metalloproteinase (MMP)-9 in the lung tissue of ASD-exposed mice, indicating that PYC reduced ASD-induced pulmonary inflammation by suppressing MMP-9. Together, these results indicate that PYC as the potential to treat ASD-driven pulmonary inflammation.

As caffeine consumption continues to increase, both positive and negative effects are becoming evident. Caffeine directly affects the cardiovascular system, including heart function and rate. Thus, understanding the current respiratory safety pharmacological responses is of utmost importance. To elucidate the respiratory safety pharmacological characteristics of caffeine, male Sprague-Dawley rats, aged 6 weeks, were intravenously administered doses of 0, 2, 6, and 20 mg/kg of caffeine. Respiratory rate, tidal volume, and minute volume were subsequently measured. In this study, we observed a significant increase in respiratory rate and minute volume, but a remarkable reduction in tidal volume following the intravenous administration of caffeine at doses exceeding 6 mg/kg. These changes were evident within the timeframe of 0.25 to 1.5 h. The data we have collected can serve as valuable foundational scientific information for future research on caffeine, encompassing absorption, distribution, metabolism, excretion, and pharmacological core-battery experiments.