Pulmonary light chain deposition disease: Case series and review of the literature.

Pulmonary light chain deposition disease is a rare entity characterized by immunoglobulin deposition within the lung parenchyma with pathologic features distinct from pulmonary amyloidosis. Here, the authors present the clinical presentation, associations, and radiologic features of pulmonary light chain deposition disease in a series of 4 patients as well as discuss the distinctions from amyloidosis. The present case series highlights the frequent presence of both cysts and nodules at CT. Clinically, lymphoma and/or autoimmune disease are often associated.

Long-term outcomes of lung transplantation with ex vivo lung perfusion technique.

Ex vivo lung perfusion (EVLP) has demonstrated encouraging short- and medium-term outcomes with limited data available on its long-term outcomes. This study assesses (1) EVLP long-term outcomes and (2) EVLP era-based sub-analysis in addition to secondary outcomes of recipients with EVLP-treated donor lungs compared with recipients of conventionally preserved donor lungs in unmatched and propensity score-matched cohorts. Double lung transplants performed between 1st January 2012 and 31st December 2021 were included. A total of 57 recipients received EVLP-treated lungs compared to 202 unmatched and 57 matched recipients who were subjected to non-EVLP-treated lungs. The EVLP group had a significantly lower mean PaO2/FiO2 ratio and significantly higher mean BMI than the non-EVLP group in the unmatched and matched cohorts. The proportion of smoking history in the unmatched cohort was significantly higher in the EVLP group, while a similar smoking history was demonstrated in the matched cohorts. No difference was demonstrated in overall freedom from death and retransplantation between the groups in the unmatched and matched cohorts (unmatched: hazard ratio (HR) 1.28, 95% confidence interval (CI) 0.79-2.07, P = 0.32; matched: HR 1.06, 95% CI 0.59-1.89). P = 0.89). In the unmatched cohort, overall freedom from chronic allograft dysfunction (CLAD) was significantly different between the groups (HR 1.64, 95% CI 1.07-2.52, P = 0.02); however, the cumulative CLAD incidence was similar (HR 0.72, 95% CI 0.48-1.1, P = 0.13). In the matched cohort, the overall freedom from CLAD (HR 1.69, 95% CI 0.97-2.95, P = 0.06) and cumulative CLAD incidence (HR 0.91, 95% CI 0.37-2.215, P = 0.83) were similar between the groups. The EVLP era sub-analysis of the unmatched cohort in 2012-2014 had a significantly higher cumulative CLAD incidence in the EVLP group; however, this was not demonstrated in the matched cohort. All secondary outcomes were similar between the groups in the unmatched and matched cohorts. In conclusion, transplantation of marginal donor lungs after EVLP evaluation is non-detrimental compared to conventionally preserved donor lungs in terms of mortality, retransplantation, cumulative CLAD incidence, and secondary outcomes. Although the unmatched EVLP era of 2012-2014 had a significantly higher cumulative CLAD incidence, no such finding was demonstrated in the matched cohort of the same era.

The Lungs in Space: A Review of Current Knowledge and Methodologies.

Space travel presents multiple risks to astronauts such as launch, radiation, spacewalks or extravehicular activities, and microgravity. The lungs are composed of a combination of air, blood, and tissue, making it a complex organ system with interactions between the external and internal environment. Gravity strongly influences the structure of the lung which results in heterogeneity of ventilation and perfusion that becomes uniform in microgravity as shown during parabolic flights, Spacelab, and Skylab experiments. While changes in lung volumes occur in microgravity, efficient gas exchange remains and the lungs perform as they would on Earth; however, little is known about the cellular response to microgravity. In addition to spaceflight and real microgravity, devices, such as clinostats and random positioning machines, are used to simulate microgravity to study cellular responses on the ground. Differential expression of cell adhesion and extracellular matrix molecules has been found in real and simulated microgravity. Immune dysregulation is a known consequence of space travel that includes changes in immune cell morphology, function, and number, which increases susceptibility to infections. However, the majority of in vitro studies do not have a specific respiratory focus. These studies are needed to fully understand the impact of microgravity on the function of the respiratory system in different conditions.

Analysis of the Diversity and Functional Potential of Bacterial Communities in Tuberculomas.

The dynamics of lung microbiota in tuberculosis remains poorly understood. Sequencing of variable regions of the 16S rRNA gene from surgically excised tuberculosis foci and biopsy specimens of normal lung tissue allowed characterization of the diversity and predictive potential of bacterial communities. Taxonomic diversity indices attested to differences in the structure of microbial communities between "healthy" lungs and tuberculomas. The microbial composition of "healthy" lungs varied in taxonomic diversity and was presented by both gram-positive and gram-negative bacteria with sufficiently similar metabolic potential. The microbiota of the examined tuberculomas consisted of Mycobacterium tuberculosis in 99.9% of cases. A significant part of the metabolic pathways predicted by PICRUSt2 included cholesterol catabolism, sulfate assimilation, and various pathways for the biosynthesis of cell wall components.

Factors moderating cadmium bioavailability: Key considerations for comparing blood cadmium levels between groups.

Cadmium (Cd) is recognized as a significant hazard to human health, with exposure linked to a variety of adverse outcomes including various cancers, cardiovascular diseases, chronic kidney disease, and osteoporosis. Residing in areas contaminated with Cd is undoubtedly a risk factor for developing the aforementioned conditions. However, the risk of developing Cd-related disorders is not uniform among individuals. Deficiencies in iron, zinc, and calcium, along with iron deficiency anemia, decreased lung function often seen in chronic obstructive pulmonary disease (COPD), and low circulating levels of parathyroid hormone (PTH), may enhance Cd intestinal absorption. Conversely, chronic liver disorders can lead to the progressive loss of hepatocytes and the release of free Cd into the circulation, resulting in elevated Cd blood levels. Moreover, studies comparing Cd blood levels between different regions within a country or between two groups of individuals, for example, those with and without osteoporosis, should consider all variables that may impact Cd levels. These include age, sex, alcohol consumption, blood levels of iron, calcium, and zinc, the presence of anemia, COPD, PTH levels, and the presence of liver or kidney disease. In this review, we delve into all factors that could influence Cd blood levels, providing a comprehensive analysis.

Initial Respiratory System Involvement in Juvenile Idiopathic Arthritis with Systemic Onset Is a Marker of Interstitial Lung Disease: The Results of Retrospective Cohort Study Analysis.

Background: Pulmonary involvement in systemic juvenile idiopathic arthritis (SJIA) is a rare but dangerous complication. The main risk factors are already known, such as macrophage activation syndrome, a refractory course of systemic juvenile arthritis, infusion reaction to interleukin 1 and/or interleukin 6 blockers, trisomy 21, and eosinophilia. However, information about respiratory system involvement (RSI) at the onset of SJIA is scarce. Our study aimed to evaluate the specific features of children with SJIA with RSI and their outcomes. Methods: In a single-center retrospective cohort study, we compared the information from the medical records of 200 children with SJIA according to ILAR criteria or SJIA-like disease (probable/possible SJIA) with and without signs of RSI (dyspnea, shortness of breath, pleurisy, acute respiratory distress syndrome, and interstitial lung disease (ILD)) at the disease onset and evaluated their outcomes (remission, development of chronic ILD, clubbing, and pulmonary arterial hypertension). Results: A quarter (25%) of the SJIA patients had signs of the RSI at onset and they more often had rash; hepato- and splenomegaly; heart (pericarditis, myocarditis), central nervous system, and kidney involvement; hemorrhagic syndrome; macrophage activation syndrome (MAS, 44.4% vs. 9.0%, p = 0.0000001); and, rarely, arthritis with fewer active joints, compared to patients without RSI. Five patients (10% from the group having RSI at the onset of SJIA and 2.5% from the whole SJIA cohort) developed fibrosing ILD. All of them had a severe relapsed/chronic course of MAS; 80% of them had a tocilizumab infusion reaction and further switched to canakinumab. Unfortunately, one patient with Down's syndrome had gone. Conclusion: Patients with any signs of RSI at the onset of the SJIA are required to be closely monitored due to the high risk of the following fibrosing ILD development. They required prompt control of MAS, monitoring eosinophilia, and routine checks of night oxygen saturation for the prevention/early detection of chronic ILD.

The Impact of Pulmonary Disorders on Neurological Health (Lung-Brain Axis).

The brain and lungs, vital organs in the body, play essential roles in maintaining overall well-being and survival. These organs interact through complex and sophisticated bi-directional pathways known as the 'lung-brain axis', facilitated by their close proximity and neural connections. Numerous studies have underscored the mediation of the lung-brain axis by inflammatory responses and hypoxia-induced damage, which are pivotal to the progression of both pulmonary and neurological diseases. This review aims to delve into how pulmonary diseases, including acute/chronic airway diseases and pulmonary conditions, can instigate neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. Additionally, we highlight the emerging research on the lung microbiome which, drawing parallels between the gut and lungs in terms of microbiome contents, may play a significant role in modulating brain health. Ultimately, this review paves the way for exciting avenues of future research and therapeutics in addressing respiratory and neurological diseases.

Mitochondrial function in lungs of rats with different susceptibilities to hyperoxia-induced Acute Lung Injury.

Adult rats exposed to hyperoxia (>95% O2) die from respiratory failure in 60-72 hours. However, rats preconditioned with >95% O2 for 48 hours followed by 24 hours in room air (H-T) acquire tolerance of hyperoxia, while rats preconditioned with 60% O2 for 7 days (H-S) become more susceptible. Our objective was to evaluate lung tissue mitochondrial bioenergetics in H-T and H-S rats. Bioenergetics were assessed in mitochondria isolated from lung tissue of H-T, H-S, and control rats. Expressions of complexes involved in oxidative phosphorylation (OxPhos) were measured in lung tissue homogenate. Pulmonary endothelial filtration coefficient (Kf) and tissue mitochondrial membrane potential (ΔΨm) were evaluated in isolated perfused lungs. Results show that ADP-induced state 3 OxPhos capacity (Vmax) decreased in H-S mitochondria but increased in H-T. ΔΨm repolarization time following ADP-stimulated depolarization increased in H-S mitochondria. Complex I expression decreased in H-T (38%) and H-S (43%) lung homogenate, whereas complex V expression increased (70%) in H-T lung homogenate. ΔΨm is unchanged in H-S and H-T lungs, but complex II has a larger contribution to ΔΨm in H-S than H-T lungs. Kf increased in H-S, but not H-T lungs. For H-T, increased complex V expression and Vmax counter the effect of the decrease in complex I expression on ΔΨm. A larger complex II contribution to ΔΨm along with decreased Vmax and increased Kf could make H-S rats more hyperoxia susceptible. Results are clinically relevant since ventilation with ≥60% O2 is often required for extended periods in Acute Respiratory Distress Syndrome patients.

Sensitivity of Mouse Lung Nuclear Receptors to Electronic Cigarette Aerosols and Influence of Sex Differences: A Pilot Study.

The emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects. Adult male and female C57BL/6J mice were exposed to electronic cigarettes with 0%, 3%, and 6% nicotine daily (70 mL, 3.3 s, 1 puff per min/30 min) for 14 days, using the inExpose full body chamber (SCIREQ). Following exposure, lung tissues were harvested, and RNA extracted. The expression of 84 NRs was determined using the RT2 profiler mRNA array (Qiagen). Results exhibit a high sensitivity to e-liquid exposure irrespective of the presence of nicotine, with differential expression of NRs, including one (females) and twenty-four (males) in 0% nicotine groups compared to non-exposed control mice. However, nicotine-dependent results were also significant with seven NRs (females), fifty-three NRs (males) in 3% and twenty-three NRs (female) twenty-nine NRs (male) in 6% nicotine groups, compared to 0% nicotine mice. Sex-specific changes were significant, but sex-related differences were not observed. The study provides a strong rationale for further investigation.

Pulmonary damage induction upon Acrylic amide exposure via activating miRNA-223-3p and miRNA-325-3p inflammasome/pyroptosis and fibrosis signaling pathway: New mechanistic approaches of A green-synthesized extract.

Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223-3P and miRNA 325-3P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223-3P and miRNA 325-3P, targeting NLRP-3 & GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223-3P and miRNA 325-3P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.

DLco and echocardiographic parameters in identifying mild pulmonary hypertension in the EUSTAR cohort of systemic sclerosis patients.

BACKGROUND: The 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines define pulmonary hypertension (PH) as a resting mean pulmonary artery pressure (mPAP) > 20 mmHg at right heart catheterization (RHC). Previously, patients with a mPAP between 21 and 24 mmHg were classified in a "grey zone" of unclear clinical significance. RESEARCH QUESTION: What is the diagnostic performance of the main parameters used for PH screening in detecting systemic sclerosis (SSc) patients with mPAP 21-24 mmHg at RHC? STUDY DESIGN AND METHODS: SSc patients from the European Scleroderma Trials and Research (EUSTAR) database with available tricuspid annular plane systolic excursion (TAPSE), systolic PAP (sPAP) and mPAP data were included. Patients with mPAP 21-24 mmHg and patients with mPAP ≤ 20 mmHg were considered for the analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated. RESULTS: TAPSE/sPAP was lower in the group of SSc patients with mPAP 21-24 mmHg than in non-PH group [0.58 (0.46-0.72) mm/mmHg vs 0.69 (0.57-0.81) mm/mmHg, p < 0.01]. No difference was found in other parameters between the two groups. Diffusing capacity of the lungs for carbon monoxide (DLCO) < 80% of the predicted value had the highest sensitivity (88.9%) and NPV (80%), but the lowest specificity (18.2%) and PPV (30.8%) in detecting SSc patients with mPAP 21-24 mmHg. TAPSE/sPAP < 0.55 mm/mmHg had the highest specificity (78.9%), PPV (50%) and accuracy (68.1%); its NPV was of 75.4%, while its sensibility 45.1%. INTERPRETATION: DLCO < 80% of the predicted value is the parameter with the highest sensitivity and NPV in detecting SSc patients with mPAP 21-24 mmHg. TAPSE/sPAP < 0.55 mm/mmHg has the highest specificity, PPV and accuracy and, therefore, can be a useful additional parameter to decrease the number of unnecessary RHC.

Effects of Maternal Smoke Exposure on Endoplasmic Reticulum Stress and Autophagy in the Lungs of Offspring Mice.

BACKGROUND: Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to decreased lung function in offspring. However, the effects of maternal CS exposure on lung autophagy and ER stress in offspring during pregnancy remain unclear. METHODS: C57BL/6J female mice were divided into the AA (air treatment during both pre-pregnancy and pregnancy), AS (air treatment during pre-pregnancy and CS treatment during pregnancy), SA (CS treatment during pre-pregnancy and air treatment during pregnancy), and SS (CS treatment during both pre-pregnancy and pregnancy) groups. The male offspring mice were selected to the study and euthanized 49 days after birth for the study. Hematoxylin and eosin (HE) staining was employed to observe pathological alterations, while transmission electron microscopy (TEM) was utilized to examine ultrastructure and autophagic vesicles. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was applied to identify apoptosis in lung tissues. Immunofluorescence, Real-Time PCR, and Western Blot analyses were conducted to assess the expression of ER stress and autophagy-related markers in lung tissues. RESULTS: The findings revealed that exposure to CS heightened the extent of pathological damage and the abundance of autophagosomes in the lungs of offspring mice. TUNEL results indicated an increased fluorescence intensity in the AS, SA and SS groups, with the most significant in AS and SS groups. Furthermore, CS exposure augmented the fluorescence intensity and expression of ER stress and autophagy-related proteins. The expression of C/EBP-homologous protein (CHOP) exhibited no discernible difference between the SA and SS groups but showed a significant increase in the AS group. Conversely, the expression levels of glucose-regulated protein 78 (GRP78), Caspase-12, Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) exhibited no significant difference between the AS and SA groups, whereas they were significantly upregulated in the SS group. CONCLUSIONS: Preconceptional and gestational exposure to CS heightened ER stress and autophagy in the lungs of mouse offspring. However, in mothers who smoked, withdrawal from CS during pregnancy led to a reduction in ER stress and autophagy in the lungs of their offspring.

Effect of Xe/O2 Inhalation on Hemostasis in Experimental Thromboplastin Pneumonitis.

We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.

Single-cell-resolved interspecies comparison shows a shared inflammatory axis and a dominant neutrophil-endothelial program in severe COVID-19.

A key issue for research on COVID-19 pathogenesis is the lack of biopsies from patients and of samples at the onset of infection. To overcome these hurdles, hamsters were shown to be useful models for studying this disease. Here, we further leverage the model to molecularly survey the disease progression from time-resolved single-cell RNA sequencing data collected from healthy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected Syrian and Roborovski hamster lungs. We compare our data to human COVID-19 studies, including bronchoalveolar lavage, nasal swab, and postmortem lung tissue, and identify a shared axis of inflammation dominated by macrophages, neutrophils, and endothelial cells, which we show to be transient in Syrian and terminal in Roborovski hamsters. Our data suggest that, following SARS-CoV-2 infection, commitment to a type 1- or type 3-biased immunity determines moderate versus severe COVID-19 outcomes, respectively.

Scaled-up Microfluidic Lung Assist Device for Artificial Placenta Application with High Gas Exchange Capacity.

Premature neonates with underdeveloped lungs experience respiratory issues and need respiratory support, such as mechanical ventilation or extracorporeal membrane oxygenation (ECMO). The "artificial placenta" (AP) is a noninvasive approach that supports their lungs and reduces respiratory distress, using a pumpless oxygenator connected to the systemic circulation, and can address some of the morbidity issues associated with ECMO. Over the past decade, microfluidic blood oxygenators have garnered significant interest for their ability to mimic physiological conditions and incorporate innovative biomimetic designs. Achieving sufficient gas transfer at a low enough pressure drop for a pumpless operation without requiring a large volume of blood to prime such an oxygenator has been the main challenge with microfluidic lung assist devices (LAD). In this study, we improved the gas exchange capacity of our microfluidic-based artificial placenta-type LAD while reducing its priming volume by using a modified fabrication process that can accommodate large-area thin film microfluidic blood oxygenator (MBO) fabrication with a very high gas exchange surface. Additionally, we demonstrate the effectiveness of a LAD assembled by using these scaled-up MBOs. The LAD based on our artificial placenta concept effectively increases oxygen saturation levels by 30% at a flow rate of 40 mL/min and a pressure drop of 23 mmHg in room air, which is sufficient to support partial oxygenation for 1 kg preterm neonates in respiratory distress. When the gas ambient environment was changed to pure oxygen at atmospheric pressure, the LAD would be able to support premature neonates weighing up to 2 kg. Furthermore, our experiments reveal that the LAD can handle high blood flow rates of up to 150 mL/min and increase oxygen saturation levels by ∼20%, which is equal to an oxygen transfer of 7.48 mL/min in an enriched oxygen environment and among the highest for microfluidic AP type devices. Such performance makes this LAD suitable for providing essential support to 1-2 kg neonates in respiratory distress.

Preferences, Needs, and Values of Patients With Chronic Obstructive Pulmonary Disease Attending a Telehealth Service: Qualitative Interview Study.

BACKGROUND: Digitally assisted health care services and technologies are gaining popularity. They assist patients in managing their conditions, thereby reducing the burden on health care staff. Digital health care enables individuals to receive care that is more tailored to their needs and preferences. When implemented properly, it can promote equity by considering each person's opportunities and limitations in the context of health care needs, preferences, values, and capabilities. OBJECTIVE: This study aims to understand the needs, values, and preferences of individuals with chronic obstructive pulmonary disease (COPD) who are provided with a 24/7 digital health care service. Furthermore, we aim to understand the dynamics of the communities to which they belong and how these communities intersect. This will provide us with the essential knowledge to establish new methods of providing education, including the development of educational activities for health professionals to engage, train, and empower people living with COPD. METHODS: The study included 7 informants diagnosed with COPD who received 24/7 digital health care service support from a regional project in Region Zealand, Denmark. The informants were visited 4 times during 2 months, including a "Hello" visit, a day with a semistructured interview, and 2 days with field observations. The informants participated in a semistructured interview, following participant observation and an ethnographic approach. The interview content was analyzed using an inductive methodology to categorize the empirical data. RESULTS: Using the inductive approach, we identified 3 main categories related to the informants' needs, values, and preferences: (1) Health, (2) Value Creation, and (3) Resources. These 3 main categories were based on 9 subcategories: (1) health and barriers, (2) self-monitoring, (3) medication, (4) behavior, (5) motivation, (6) hobbies, (7) social networks, (8) health professionals, and (9) technology. These findings revealed that the informants placed value on maintaining their daily activities and preserving their sense of identity before the onset of COPD. Furthermore, they expressed a desire not to be defined by their COPD, as conversations about COPD often shifted away from the topic. CONCLUSIONS: Digital health solutions and the health care professionals who offer them should prioritize the individuals they serve, considering their needs, values, and preferences rather than solely focusing on the medical condition. This approach ensures the highest level of daily living and empowerment for those living with long-term health conditions. The communities surrounding individuals must engage in constant interaction and collaboration. They should work together to incorporate people's needs, values, and preferences into future digital health services, thereby promoting empowerment and self-management. New educational programs aimed at developing the digital health service competencies of registered nurses should facilitate collaboration between the 2 communities. This collaboration is essential for supporting patients with long-term health conditions in their daily activities.

microRNA-guided immunity against respiratory virus infection in human and mouse lung cells.

Viral infectivity depends on multiple factors. Recent studies showed that the interaction between viral RNAs and endogenous microRNAs (miRNAs) regulates viral infectivity; viral RNAs function as a sponge of endogenous miRNAs and result in upregulation of its original target genes, while endogenous miRNAs target viral RNAs directly and result in repression of viral gene expression. In this study, we analyzed the possible interaction between parainfluenza virus RNA and endogenous miRNAs in human and mouse lungs. We showed that the parainfluenza virus can form base pairs with human miRNAs abundantly than mouse miRNAs. Furthermore, we analyzed that the sponge effect of endogenous miRNAs on viral RNAs may induce the upregulation of transcription regulatory factors. Then, we performed RNA-sequence analysis and observed the upregulation of transcription regulatory factors in the early stages of parainfluenza virus infection. Our studies showed how the differential expression of endogenous miRNAs in lungs could contribute to respiratory virus infection and species- or tissue-specific mechanisms and common mechanisms could be conserved in humans and mice and regulated by miRNAs during viral infection.

Solid Lipid Nanoparticles for Pulmonary Delivery of Biopharmaceuticals: A Review of Opportunities, Challenges, and Delivery Applications.

Biopharmaceuticals such as nucleic acids, proteins, and peptides constitute a new array of treatment modalities for chronic ailments. Invasive routes remain the mainstay of administering biopharmaceuticals due to their labile nature in the biological environment. However, it is not preferred for long-term therapy due to the lack of patient adherence and clinical suitability. Therefore, alternative routes of administration are sought to utilize novel biopharmaceutical therapies to their utmost potential. Nanoparticle-mediated pulmonary delivery of biologics can facilitate both local and systemic disorders. Solid lipid nanoparticles (SLNs) afford many opportunities as pulmonary carriers due to their physicochemical stability and ability to incorporate both hydrophilic and hydrophobic moieties, thus allowing novel combinatorial drug/gene therapies. These applications include pulmonary infections, lung cancer, and cystic fibrosis, while systemic delivery of biomolecules, like insulin, is also attractive for the treatment of chronic ailments. This Review explores physiological and particle-associated factors affecting pulmonary delivery of biopharmaceuticals. It compares the advantages and limitations of SLNs as pulmonary nanocarriers along with design improvements underway to overcome these limitations. Current research illustrating various SLN designs to deliver proteins, peptides, plasmids, oligonucleotides, siRNA, and mRNA is also summarized.