Search Results (924)

Background: Airborne microplastics (AMPs) are an emerging air pollutant and there are growing concerns about their potential effects on respiratory health due to their persistence, inhalability and ability to carry other toxic pollutants. Methods: Relevant peer-reviewed studies released from 2015 to 2025 were located by searches on PubMed, Scopus, and Web of Science. Data from experimental, epidemiological, and review research were amalgamated to investigate sources of airborne microplastics, routes of exposure, analytical methodologies, respiratory toxicological processes, and regulatory viewpoints. Results: Modern studies suggest inhaled antimicrobic peptides can reach the lower respiratory tract and cause chronic pulmonary inflammation via induction of oxidative stress, mitochondrial dysfunction, epithelial barrier damage, inflammasome activation, immune system imbalance and extracellular matrix remodeling. These pathways have been associated with chronic respiratory diseases, such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, and lung carcinoma. Toxicity can be increased by the accumulation of heavy metals, persistent organic pollutants and microbiological impurities. However, the lack of standardised protocols for exposure assessment, inconsistency of sampling and analytical methods and limited human epidemiological data hamper health risk assessment. Conclusions: Airborne microplastics are an emerging environmental health concern with potentially significant effects on respiratory health. Harmonised surveillance strategies, standardised analytical methods, improved inhalation exposure models and prolonged epidemiological studies are urgently needed to improve risk assessment and enable evidence-based air quality policy for the protection of respiratory health. Full article

Urban particulate matter (UPM) is a major environmental pollutant known to induce systemic inflammation. While its respiratory toxicity is well-documented, the potential vulnerability of the female reproductive system to inhaled UPM remains a critical concern. In this study, we evaluated female reproductive outcomes in a murine model following repeated short-term intratracheal instillation of UPM (40–200 mg/kg) for a month. Our results demonstrate that while UPM exposure induced robust, dose-dependent pulmonary inflammation, characterized by immune cell infiltration (CD45+, F4/80+, and Ly6G+) and upregulation of pro-inflammatory (Il-6, Il-1β, and Tnfα) and fibrotic (Col1a1 and Tgfβ1) markers, no apparent adverse effects were observed in the reproductive endpoints examined. No significant alterations were observed in maternal pregnancy outcomes, including oocyte recovery rates, fertilization competence, gestation duration, litter size, and postnatal development of pups. Furthermore, the mRNA expression of inflammatory markers in the ovaries and uteri was not detectable. Direct in vitro exposure of two-cell embryos to UPM did not interfere with preimplantation embryo development. Although benzanthracene slightly reduced the blastocyst formation rate, UPM and polycyclic aromatic hydrocarbons, major toxic components of UPM, did not severely compromise preimplantation embryo development in vitro. In conclusion, these findings suggest that marked UPM-induced pulmonary inflammation is not accompanied by substantial alterations in the female reproductive outcomes examined under short-term exposure conditions. Full article

Background/Objectives: Nipah virus (NiV) is a highly pathogenic zoonotic agent that causes fatal respiratory and neurological diseases, for which no approved vaccines are currently available. To address this unmet need, we developed and evaluated novel mRNA-LNP vaccine candidates. These vaccines employ an epitope- and structure–guided “immune-focusing” strategy, aiming to maximize the exposure of critical neutralizing epitopes on the viral attachment (G) and fusion (F) glycoproteins. Methods: Head-to-head dimeric antigens (2Gs and 2Fs) were engineered by removing subdominant stalk regions and tandemly duplicating epitope-rich globular head domains. Three LNP-encapsulated candidates-NV1 (encoding 2Gs), NV2 (encoding 2Fs), and NV3 (a 1:1 mixture of NV1 and NV2)-were evaluated in BALB/c mice and Syrian hamsters to systematically assess humoral responses, cytokine secretion, BCR/TCR repertoires, and systemic safety. Results: NV1 and NV3 induced potent binding antibodies and strong neutralizing activity against NiV pseudoviruses. Meanwhile, although NV2 lacked neutralizing activity, it induced superior Th1-biased cellular immunity, accompanied by extensive T-cell clonal proliferation. BCR/TCR sequencing revealed unique adaptive immune characteristics that perfectly align with the distinct immunogenic properties described above. Preliminary safety assessments found no toxicity to vital organs, while active germinal center formation confirmed the success of immune mobilization. Conclusions: An epitope-centered dimer design effectively shapes the unique defense mechanisms of the adaptive immune system. NV3 offers a balanced and synergistic strategy that combines potent humoral and cellular immune defenses, providing a highly promising platform for the development of a Nipah virus (NiV) vaccine. Full article

Bovine coronavirus (BCoV) is a major cause of respiratory and enteric diseases in cattle, resulting in substantial economic losses to the global cattle industry. Next-generation epitope-focused vaccines require conserved neutralizing determinants to achieve broad protective efficacy across circulating variants. Here, we applied a reverse-vaccinology and immunoinformatics-guided strategy to identify conserved linear B-cell epitope candidates on the BCoV spike protein. Using ABCPred (16 aa; threshold score 0.51), 139 putative linear B-cell epitopes were predicted, and 10 candidates (B1–B10) were selected based on antigenicity, allergenicity/toxicity filters, and Shannon-entropy-based conservation (≥95%). Each candidate was displayed on Helicobacter pylori ferritin and TEM confirmed the formation of self-assembled nanocages. BALB/c mice (n = 6 per group) were subcutaneously immunized with 50 μg of each epitope–ferritin fusion protein emulsified 1:1 with Montanide ISA 201 in a prime–boost regimen (at a 14-day interval), and sera were collected 14 days after the booster immunization. All 10 constructs induced BCoV-specific binding IgG (endpoint titers ranging from 1:2667 to 1:11,733), but only B1, B2, B4, B6, B7, and B8 elicited detectable in vitro neutralizing activity against both representative strains, whereas B3, B5, B9, and B10 remained below the detection limit (<1:8). Neutralizing titers were 1:24–1:99 for the enteric strain XHD4 and 1:27–1:88 for the respiratory strain HXD1, with no significant difference observed between the two strains (p > 0.05). Overall, these findings identify six conserved B-cell epitope candidates capable of eliciting neutralizing antibody responses against both representative enteric and respiratory field strains, providing experimental evidence to support epitope-focused BCoV vaccine design. Full article

Obligate acidophilic bacteria of the genus Acidithiobacillus are widely used and well known in the biomining industry. Over the past decade, it has been shown that bacterial activity can be determined in short-term experiments via amperometric measurements of microbial oxygen consumption, as changes in the Clark electrode current are proportional to changes in the concentration of dissolved oxygen. This article presents a study of Acidithiobacillus sp. strain Thio1, which was isolated from pyrite–chalcopyrite copper ore and is closely related to A. ferrooxidans. Oxygen consumption by strain Thio1 was measured during the bacterial oxidation of substrates as changes in the electrode current. To evaluate the acute respiratory response of the bacteria to Cu, Zn, and As, respiration suppression was measured at increasing concentrations of the toxicants. The proposed amperometric method is not a substitute for the long-term biogeotechnological evaluation of strain activity using specific ore or pulp samples. At the same time, it can be used as a complementary microbiological method. The proposed approach offers distinct advantages: testing takes mere minutes (rapid analysis), and comparisons of substrates or toxicants can be performed using a single biomass sample (standardization). The amperometric method also demonstrated that oxygen was consumed during the corrosion of solid specimens (steel and chalcopyrite) by Acidithiobacillus sp. strain Thio1. However, applying this method to biocorrosion requires further study because the proportion of oxygen consumption directly related to microbial corrosion remains unknown. Full article

Concurrent exposure to analgesic and psychotropic drugs is frequent in patients with pain, psychiatric comorbidity, frailty, or acute-care needs. The clinically important question is whether analgesics and psychotropic drugs act on the same metabolic, transporter, receptor, ion-channel, or cellular stress systems. This narrative mechanistic review discusses those points of contact. CYP-mediated inhibition or induction, phenoconversion, altered parent-to-metabolite ratios, and blood–brain barrier transporter effects can change both systemic and central exposure, particularly through CYP2D6, CYP3A4, CYP2C9, CYP2B6, and P-glycoprotein. Pharmacodynamic toxicity may involve serotonergic excess, opioid and GABAergic effects in respiratory-control networks, hERG/IKr-related loss of repolarization reserve, or dopamine D2 receptor blockade. Non-opioid analgesics and psychotropic background therapy add further pathways involving renal and gastrointestinal vulnerability, hematological toxicity, mitochondrial injury, and altered central nervous system function. At the cellular level, mitochondrial dysfunction, oxidative stress, calcium dysregulation, and endoplasmic reticulum stress are discussed primarily as mechanistic or preclinical contributors unless direct clinical evidence is available. Overall, analgesic–psychotropic co-exposure is presented as a clinically important example of pathway convergence, while pharmacogenomic and computational approaches are interpreted in relation to drug exposure, organ reserve, and patient-specific vulnerability. Full article

Coral snakes of the American continent are classified into two genera, Micruroides and Micrurus, with as many as 91 species recognized in the latter. Although envenomings caused by Micrurus are rare, they can be life-threatening due to neurotoxic effects leading to flaccid paralysis and potential respiratory failure. Micrurus ancoralis is found in the Pacific lowlands and along the western slope of the cordillera occidental Cordillera in Colombia. Although this species is relatively common within its distribution range, its phylogenetic position and the characterization of its venom have not been investigated. The results of phylogenetic analysis placed M. ancoralis within the triadal/bicolor clade of species with the characteristic triad pattern and group bicolor. Proteomic characterization of the venom showed predominance of phospholipase A₂ (PLA₂) enzymes in its composition, with 51.7% of the total protein content, followed by three-finger toxins (3FTxs; 23.2%) and lower proportions of proteins belonging to several other minor families. Out of 28 chromatographic venom fractions obtained, the seven most abundant were evaluated for toxicity, with three of them (F7, identified as a 3FTx, and F18 and F20 (both identified as PLA₂s)) showing lethal activity by the intraperitoneal route in mice. The PLA₂ activity of F20 was confirmed and its edema-inducing, myotoxic, and lethal effects in mice were demonstrated. A therapeutic equine anti-coral antivenom (INS, Colombia) against coral snake envenomings immunorecognized the whole venom and its fractions in ELISA tests and was able to neutralize 2 × LD₅₀ (medial lethal dose) of M. ancoralis venom by preincubation, with an estimated potency of at least 0.2 mg venom/mL antivenom. This result suggests that envenomings by M. ancoralis could be effectively treated by this antivenom. Full article

Antimony micro/nanoparticles (Sb MNPs) are key environmental Sb species that enter the human body via inhalation, ingestion, and dermal contact, posing potential health risks. Their complex transformation across multiple Sb species hinders accurate quantification, leaving their in vivo transformation mechanisms poorly understood. In this study, in vitro respiratory, gastrointestinal, and sweat models were established to investigate Sb MNP biotransformation, and the gastrointestinal model incorporated human fecal suspension to better mimic in vivo conditions. Transformation dynamics showed that simulated gastric fluid dissolved Sb₂O₃, Sb₂S₃ and Sb₂O₅ MNPs into ionic Sb without altering valence states, while Sb ions remained at low levels. Gastric-derived Sb(III) was oxidized to less toxic Sb(V) in the intestinal phase. In simulated sweat, Sb(III) concentrations increased but accounted for only 1.75% of total exposure, indicating low dermal risk. Notably, Sb₂O₃ MNPs exhibited lability in simulated lung fluids, particularly artificial lysosomal fluid (ALF), where dissolved Sb(III) reached 1276.7 μg/L with an ionic release rate of 63.8%. The low pH of ALF and formation of stable soluble complexes with citrate, lactate, and Cl⁻ might drive Sb₂O₃ dissolution, suggesting high inhalation risk. This study advances the quantitative understanding of Sb MNP biotransformation and thus for human health risk assessment. Full article

Rituximab-induced lung disease (R-ILD) is a rare but potentially serious complication most commonly reported in patients receiving rituximab as part of combination chemotherapy for hematologic malignancies. Pulmonary toxicity associated with rituximab monotherapy in autoimmune disease remains underrecognized. We present a case of organizing pneumonia occurring in a patient with stable rheumatoid arthritis treated with rituximab monotherapy. Existing literature suggests that most reported cases occur in the setting of combination therapy, making this presentation uncommon. This case underscores the importance of maintaining a high index of suspicion for drug-induced lung disease in patients receiving rituximab who develop unexplained respiratory symptoms despite stable autoimmune disease. Early recognition and intervention may result in favorable clinical and radiographic outcomes. Full article

Immune checkpoint inhibitor-related pneumonitis (CIP) is an uncommon but clinically relevant toxicity in renal cell carcinoma (RCC), where immune checkpoint inhibitors are frequently used either as dual immunotherapy or in combination with VEGF-targeted tyrosine kinase inhibitors. In RCC, CIP poses specific diagnostic challenges because respiratory symptoms and computed tomography findings may overlap with pulmonary metastases, infections, thromboembolic events, heart failure, and TKI-related lung toxicity. This review summarizes the incidence of CIP across pivotal RCC trials and real-world cohorts, compares its epidemiology with non-small cell lung cancer, and discusses clinical presentation, radiological patterns, differential diagnosis, and current management strategies. Particular attention is given to RCC-specific mechanisms, including immune-mediated alveolar injury, T cell activation, cytokine dysregulation, macrophage activation, GSDME-mediated pyroptosis, and the potential contribution of VEGF pathway inhibition to pulmonary inflammation. We also review risk factors, steroid-refractory disease, second-line immunosuppression, and the unresolved issue of ICI rechallenge after pneumonitis. A better understanding of these mechanisms and clinical features may improve early recognition, guide multidisciplinary management, and support safer use of immunotherapy-based combinations in patients with RCC. Full article

Background and Objectives: Pulmonary fibrosis (PF) is a life-threatening respiratory disorder involving complex pathophysiological mechanisms such as inflammation, collagen deposition, and epithelial cell injury. Methotrexate (MTX), a chemotherapeutic and immunosuppressive agent, is frequently associated with pulmonary toxicity, representing a significant adverse effect with unpredictable outcomes. Thus, the current study investigates the possible protective effect of dulaglutide (DUL) against MTX-induced lung injury. Methods: Sixty male Wistar rats were allocated into six groups: group 1 served as a control group, group 2 received MTX (14 mg/kg/week, p.o) for 2 weeks, group 3 was treated with MTX treatment (14 mg/kg/week, p.o) prior to dexamethasone (DEXA) (0.5 mg/kg/week i.p), Groups 4–5 were treated concurrently with MTX (14 mg/kg/week, p.o) and DUL at doses of 0.05 and 0.1 mg/kg/week, s.c. and Group 6 received DUL (0.1 mg/kg/week, s.c.) only. Animals were sacrificed on day 15 for histopathological and biochemical assessments. Results: Our data demonstrated that MTX markedly increased some oxidative stress markers, inflammatory biomarkers and fibrotic and apoptotic indicators, alongside a significant decrease in Beclin-1 and Adenosine Monophosphate Activated Protein Kinase (AMPK) levels. DUL administration significantly ameliorated these alternations in a dose-dependent manner, with histopathological findings corroborating biochemical data through Hematoxylin & Eosin (H&E) and Mason’s Trichrome (MTC) staining. Conclusions: DUL confers significant protection against MTX-induced pulmonary fibrosis, likely through its antioxidant, anti-inflammatory, and anti-apoptotic properties, which are associated with the restoration of total AMPK and Beclin-1 levels. This highlights its therapeutic potential in preventing drug-induced lung toxicity. Full article

Background/Objectives: Alongside surgery and systemic treatments, radiotherapy plays a crucial role in the treatment of lung cancer but can affect healthy tissue and cause serious side effects. Compared to photon therapy, proton therapy can lower toxicity because protons deposit most of their energy within the tumor (the Bragg peak), sparing healthy tissue. FLASH radiotherapy (FLASH-RT), which is characterized by using ultra-high dose rates (UHDR), may further enhance healthy tissue sparing. Preclinical studies using electrons, protons, or photons have shown that FLASH-RT may reduce toxicity, while tumor response is maintained, known as the FLASH-effect. FLASH-RT with protons (FLASH-PT) is a promising treatment for lung cancer, integrating the biological advantages of FLASH with the physical advantages of proton beams. Methods: A literature search was performed on preclinical evidence of the FLASH-effect on lung-related endpoints, the proposed mechanisms, and treatment planning and delivery strategies for FLASH-PT in lung cancer. Results: Preclinical studies have shown reduced pulmonary fibrosis, inflammation, vascular damage, and oxidative stress with FLASH-RT. Current evidence suggests that the FLASH-effect likely arises from multiple radiochemical and biological processes, can vary between tissues, and depends on dose, beam and/or delivery characteristics. Despite growing evidence, the exact dose delivery conditions and technological factors required to obtain a FLASH-effect remain unclear. Treatment planning studies achieved clinically acceptable thoracic FLASH-PT plans for lung cancer, with similar or improved organ-at-risk sparing compared with conventional radiotherapy, while meeting (fraction) dose and dose rate criteria for the FLASH-effect. However, clinically feasible technologies for conformal dose delivery under UHDR conditions with respiratory motion mitigation are still under development. Conclusions: FLASH-PT holds the potential to reduce radiation-induced pulmonary side effects and expand the therapeutic window of radiotherapy. Still, key (pre)clinical and technological challenges must be addressed before clinical implementation for patients with lung cancer. Full article

Caused by the SARS-CoV-2 virus, the COVID-19 pandemic is still considered a complex challenge, with manifestations not only of respiratory issues, but also conditions related to chronic cerebrovascular damage. Endothelial biomarkers, neuropathological and neuroimaging findings indicate endothelial dysfunction, microthrombosis, and disruption of the blood–brain barrier (BBB) are central mechanisms for acute and chronic ischemic and hemorrhagic cerebral events. Understanding these mechanisms is vital to reducing their impact on population health, whether through treatment or prevention of adverse outcomes. The objective of this study is to perform a review of the scientific literature on the post-infection effects of SARS-CoV-2 affecting the cerebral endothelium and the BBB, correlating them with potential clinical outcomes. Material and Methods: Analysis of studies extracted from the PubMed database using the following terms: Long-COVID “AND” SARS-CoV-2 “AND” blood–brain barrier. Inclusion criteria: keywords, publications related to the topic, and primary studies published after peer review. Exclusion criteria: preprint studies, publication outside of the timeframe 2020–2025, study design not compatible with this research, and full text not available. Results: An initial 121 studies were identified, of which 105 were excluded due to not meeting all inclusion criteria and 6 studies were inaccessible due to not being in the English language and full-text access limitations. Fifteen articles were included in the analysis, for topics as expression of viral receptors in the endothelium, markers of their activation, cerebral microvascular injury and coagulopathies. To clarify the pathogenic cascade, the evidence was stratified by biological model where in vitro evidence demonstrates that the Spike protein induces direct endothelial toxicity and platelet aggregation, establishing the primary molecular insult. Animal models confirm the translation of this insult into structural degradation of the BBB and pericyte loss. Clinically, infection-phase findings, characterized by multifocal microthrombosis and permeability spikes, act as the determining event that predisposes to the persistent neuroinflammatory environment. Biomarkers of BBB disruption and neuronal damage were consistently reported, with persistence of BBB dysfunction modifying risk stratification and rehabilitation efforts. Reported cases of Long-COVID demonstrated normalization of BBB markers without correlation with long-term symptoms, suggesting that other mechanisms are involved in Long-COVID. Conclusion: Cerebral endotheliopathies and BBB dysfunction in patients with COVID-19 continue to impact the health of the population. The scientific literature indicates that SARS-CoV-2 induces cerebral endothelial injury, BBB disruption, and an increased risk of vascular events related to endotheliopathy, inflammation, and hypercoagulability. Understanding the impact of COVID-19 pathology on the population and developing prospective studies is essential to quantify the prevalence and mechanisms of brain injury. The identification of molecular targets and infection pathways are promising toward defining both preventive and therapeutic strategies to improve outcomes in the Long-COVID population. Full article

Background: Respiratory syncytial virus (RSV) RNA-dependent RNA polymerase (RdRp) complex is an essential molecular machine for viral genome replication. The L protein, the catalytic subunit of this complex (L-RdRp), is well-characterized structurally and represents a highly promising target for the development of novel small-molecule drugs against RSV. Methods: To address the limitations of current QSAR-based virtual screening strategies for RSV L-RdRp inhibitor development, we established a multi-dimensional computer-aided drug screening framework integrating activity, toxicity, drug-likeness, and stability. Results: Two OECD-compliant 2D-QSAR models were developed and rigorously validated to predict inhibitory activity and cytotoxicity, respectively. The optimal inhibitory activity model exhibited strong statistical performance, with R² = 0.8281, $Q_{\mathrm{L}\mathrm{O}\mathrm{O}}^2=$ 0.7653, $R_{\mathrm{t}\mathrm{e}\mathrm{s}\mathrm{t}}^2=$ 0.8713, $Q_{\mathrm{F}\mathrm{n}}^2=$ 0.8594 ∼ 0.8837, CCC_test = 0.9301, MAE_test = 0.1966. Similarly, the best cytotoxicity model achieved R²= 0.8263, $Q_{\mathrm{L}\mathrm{O}\mathrm{O}}^2$ = 0.7422, $R_{\mathrm{t}\mathrm{e}\mathrm{s}\mathrm{t}}^2$ = 0.8951, $Q_{\mathrm{F}\mathrm{n}}^2$ = 0.8108~0.8530, CCC_test = 0.9081, MAE_test = 0.1685. Based on these models, a four-step screening workflow—QSAR-based filtering and molecular docking (15,758 → 2446 → 162 → 19 compounds), ADMET evaluation (19 → 5), and molecular dynamics simulations (MDSs)—was implemented to identify promising L-RdRp inhibitors. Conclusions: Ultimately, five candidate compounds were selected, all of which demonstrated predicted higher inhibitory activity, lower predicted cytotoxicity, a stable predicted binding mode, and favorable oral bioavailability compared with the reference drug remdesivir. These findings provide valuable in silico-derived lead candidates and a reliable computational workflow for identifying experimental L-RdRp inhibitors targeting RSV. Full article

Tuberculosis (TB) remains a major global health challenge, compounded by rising drug resistance. Traditional medicinal plants used for TB-related symptoms represent a valuable yet underexplored source of potential antimycobacterial agents. In this study, the phytochemical content and biological activities of Dombeya rotundifolia and Lippia javanica were evaluated, and antimycobacterial compounds were isolated through bioassay-guided fractionation. Plant leaves were collected, extracted with solvents of varying polarity, and screened for phenolics and flavonoids. Antioxidant activity was assessed using DPPH and ferric reducing power assays, antimycobacterial activity was tested against Mycobacterium smegmatis, anti-inflammatory activity was determined by the egg albumin denaturation method, and cytotoxicity was evaluated in THP-1 cells using the MTT assay. Extraction yields varied, with water extracts of L. javanica showing the highest yield and hexane extracts of D. rotundifolia the lowest. Both plants contained bioactive phytochemicals with measurable antioxidant activity, while acetone and dichloromethane extracts of D. rotundifolia displayed the strongest antimycobacterial activity with MIC values of 0.16 mg/mL. Cytotoxicity assays indicated moderate toxicity at higher extract concentrations. Bioassay-guided isolation led to the identification of two fatty acid fractions with tentative characterization, which showed notable antimycobacterial activity (MIC 0.25 mg/mL). These findings provide preliminary support for the ethnomedicinal use of D. rotundifolia in respiratory conditions traditionally associated with tuberculosis and suggest a potential contribution of its fatty acids to its observed antimycobacterial activity. Full article