MicroRNA-26a in respiratory diseases: mechanisms and therapeutic potential.

MicroRNAs (miRNAs) are short, non-coding single-stranded RNA molecules approximately 22 nucleotides in length, intricately involved in post-transcriptional gene expression regulation. Over recent years, researchers have focused keenly on miRNAs, delving into their mechanisms in various diseases such as cancers. Among these, miR-26a emerges as a pivotal player in respiratory ailments such as pneumonia, idiopathic pulmonary fibrosis, lung cancer, asthma, and chronic obstructive pulmonary disease. Studies have underscored the significance of miR-26a in the pathogenesis and progression of respiratory diseases, positioning it as a promising therapeutic target. Nevertheless, several challenges persist in devising medical strategies for clinical trials involving miR-26a. In this review, we summarize the regulatory role and significance of miR-26a in respiratory diseases, and we analyze and elucidate the challenges related to miR-26a druggability, encompassing issues such as the efficiency of miR-26a, delivery, RNA modification, off-target effects, and the envisioned therapeutic potential of miR-26a in clinical settings.

Increased mortality in acromegaly is due to vascular and respiratory disease and is normalised by control of GH levels-A retrospective analysis from the UK Acromegaly Register 1970-2016.

CONTEXT: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess. OBJECTIVE: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients. METHODS: We studied 1845 subjects from the UK Acromegaly Register (1970-2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality-age at diagnosis, duration of disease, post-treatment and mean GH levels. RESULTS: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06-1.33, p < .001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All-cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24-1.46, p < .001), as were those due to vascular and respiratory diseases. All-cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post-treatment and mean treatment GH levels and all-cause mortality (p < .001 and p < .001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L. CONCLUSION: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels.

Retrospective study of 540 cats with respiratory diseases in Japan (2003-2020).

BACKGROUND: Few epidemiological studies on respiratory medicine and the relationship between clinical signs and various respiratory diseases in cats have been reported. OBJECTIVES: This retrospective study aimed to investigate the prevalence and breed predisposition to feline respiratory diseases in Japan and determine the association between clinical signs, duration and type of respiratory diseases. METHODS: The medical records of cats with feline respiratory diseases were examined to obtain information on age, sex, breed, final diagnosis, clinical signs and duration. The odds ratios (ORs) and 95% confidence intervals were calculated to evaluate breed predispositions. Mann-Whitney U, Kruskal-Wallis and Dunn's tests were used to assess the duration of clinical signs. RESULTS: This study included 540 cats with 615 respiratory diagnoses. The American Shorthair breed was predisposed to bronchopneumonia (BP; OR: 5.0) and pulmonary tumour (PT; OR: 3.6), while the Russian Blue breed exhibited a predisposition to inflammatory lower airway diseases (OR: 3.4), BP (OR: 6.1) and interstitial lung diseases (OR: 11.1). Similarly, the Scottish Fold breed displayed predisposition to PTs (OR: 5.8). The duration of clinical signs among nasal diseases, nasopharyngeal diseases and lower tracheal/bronchial and pulmonary diseases differed significantly (p = 0.001, p = 0.012, p < 0.0001, respectively). CONCLUSIONS: The results suggest that some popular breeds in Japan are predisposed to feline respiratory diseases, especially the American Shorthair, Russian Blue and Scottish Fold breeds. The characteristics of occurrence, clinical signs and duration of each disease will aid in diagnosing, treating, preventing and elucidating the pathophysiology of feline respiratory disease.

Trends in work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK: descriptive findings from The Health and Occupation Research (THOR) network 1996-2019.

BACKGROUND: Occupational exposure to metals can be associated with respiratory diseases which can adversely affect the individual's health, finances and employment. Despite this, little is known about the incidence of these respiratory conditions over prolonged periods of time. AIMS: This study aimed to investigate the trends in the incidence of work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK. METHODS: Cases of occupational respiratory diseases caused by nickel, chromium or cobalt reported to Surveillance of Work-related and Occupational Respiratory Disease (SWORD), the UK-based surveillance scheme between 1996 and 2019 (inclusive), were extracted and grouped into six 4-year time periods. Cases were characterised by causative metal exposure, occupational and industrial sector. Incidence rates diseases (adjusted for physician participation and response rate) were calculated using ONS employment data. RESULTS: Of cases reported to SWORD during the study period, 1% (173 actual cases) of respiratory problems were attributed to nickel, chromium or cobalt. Diagnoses of asthma compromised the largest proportion of diagnoses (74.4%), followed by lung cancer (8.9%) and pneumoconiosis (6.7%). Cases had a mean age of 47 years (SD 13); 93% were men. The annual incidence fell from 1.6 per million employed in the first 4-year period, to 0.2 in the most recent period. CONCLUSIONS: Over 24 years, a decline in the incidence of metal-related occupational respiratory diseases was observed in the UK. This could be attributed to improvements in working conditions which resulted in reduced metal exposure but could also be due to closure of industries that might have generated case returns.

Comparative analysis of antibodies to four major periodontal bacteria in respiratory diseases: a cohort study.

OBJECTIVES: To make a descriptive comparison of antibodies to four major periodontal bacteria and their relation to the respiratory diseases asthma and bronchitis/emphysema, and to cancer incidence. METHODS: The serum of a random sample of men with no history of cancer incidence (n=621) was analysed by the ELISA method for antibody levels of four periodontal bacteria; the anaerobes of the so-called red complex Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD), and the facultative anaerobe Aggregatibacter actinomycetemcomitans (AA). The antibody readings were divided into quartiles and the distribution of cases of the relevant diseases as compared with the non-cases. Comparisons of the quartile distributions were by the Pearson χ2 test. Data and serum from the Oslo II study of Norwegian men from 2000 were used. The ELISA analyses were performed on thawed frozen serum. Cancer data from 17.5 years of follow-up were provided by the Norwegian Cancer Registry. RESULTS: In all, 52 men had reported asthma and 23 men had bronchitis/emphysema at the health screening. Results on cancer incidence are given for all respiratory cancers, n=23, and bronchi and lung cancers separately, n=18. Stratified analyses were performed for the four endpoints showing significant association with low levels of TD antibodies for bronchitis; p=0.035. Both TF and TD were significant for low levels of antibodies among daily smokers; p=0.030 for TF and p<0.001 for TD in the analysis of the full study sample. For PG and AA, no such associations were observed. An association with respiratory cancers was not observed. CONCLUSION: A low level of TD was associated with bronchitis/emphysema compared with the rest of the cohort. In the total study sample, low levels of antibodies to both TF and TD were associated with daily smoking.

Exposure to volatile organic compounds and mortality in US adults: A population-based prospective cohort study.

Volatile organic compounds (VOCs) are ubiquitous in both indoor and outdoor environments. Evidence on the associations of individual and joint VOC exposure with all-cause and cause-specific mortality is limited. Measurements of 15 urinary VOC metabolites were available to estimate exposure to 12 VOCs in the National Health and Nutritional Examination Survey (NHANES) 2005-2006 and 2011-2018. The environment risk score (ERS) was calculated using LASSO regression to reflect joint exposure to VOCs. Follow-up data on death were obtained from the NHANES Public-Use Linked Mortality File through December 31, 2019. Cox proportional hazard models and restricted cubic spline models were applied to evaluate the associations of individual and joint VOC exposures with all-cause and cause-specific mortality. Population attributable fractions were calculated to assess the death burden attributable to VOC exposure. During a median follow-up of 6.17 years, 734 (8.34 %) deaths occurred among 8799 adults. Urinary metabolites of acrolein, acrylonitrile, 1,3-butadiene, and ethylbenzene/styrene were significantly associated with all-cause, cardiovascular disease (CVD), respiratory disease (RD), and cancer mortality in a linear dose-response manner. Linear and robust dose-response relationships were also observed between ERS and all-cause and cause-specific mortality. Each 1-unit increase in ERS was associated with a 33.6 %, 39.1 %, 109.8 %, and 67.8 % increase for all-cause, CVD, RD, and cancer mortality risk, respectively. Moreover, joint exposure to VOCs contributed to 17.95 % of all-cause deaths, 13.49 % of CVD deaths, 35.65 % of RD deaths, and 33.85 % of cancer deaths. Individual and joint exposure to VOCs may enhance the risk of all-cause and cause-specific mortality. Reducing exposure to VOCs may alleviate the all-cause and cause-specific death burden.

[Primary antibody deficiencies and respiratory manifestations in adults].

Primary antibody deficiencies (PAD) are a group of congenital disorders caused by genetic defects that affect the development and function of the body's immune defence mechanisms. Patients with PAD may present with recurrent infections, lymphoproliferation, autoimmune diseases, autoinflammation, or malignancies. Respiratory system manifestations may include bronchiectasis, bronchial asthma, and interstitial lung disease, among others. A comprehensive understanding of PADs will help to distinguish these covert cases from more common respiratory diseases.

The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response.

The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases.

Perfil epidemiológico de internações por doenças infecciosas e bacterianas em menores de 5 anos, de 2017 a 2021 / Perfil epidemiológico de las hospitalizaciones por enfermedades infecciosas y bacterianas más prevalentes en niños menores de 5 años, de 2017 a 2021 / Epidemiological profile of hospitalizations for the most prevalent infectious and bacterial diseases in children under 5 years, from2017 to 2021

Introdução:A internação representa um impacto considerável na vida de qualquer pessoa, podendo tomar proporções ainda maiores quando se trata de uma criança. A impossibilidade de realizar sua rotina, como brincar e ir à escola, faz com que a internação infantil assuma um contexto marcante.Dito isso, nota-se que grande parte dessas internações é evitável, sendo denominadasde Internações por Condições Sensíveis à Atenção Primária. Dessa forma, o atendimento ambulatorial de qualidade poderia resolver a maioria das enfermidades infantis, evitando esse desfecho.Objetivo:Elaborar um perfil epidemiológico de internações por doenças infecciosas e bacterianas mais prevalentes em menores de 5 anos, de 2017 a 2021, no Brasil. Metodologia:A pesquisa em questão se trata de um estudo ecológico de série temporal,elaborado através de informações coletadas por vias secundárias.Os dados foram coletados na plataforma DataSUS e no Sistema de Informação Hospitalar. Posteriormente, os dados foram processados e armazenados no aplicativo Microsoft Excel®, onde foram tratados e selecionados de acordo com sua relevância para a pesquisa. Resultados:Constata-se que a faixa etária situadaabaixo do primeiro ano de vidaapresenta um grau de hospitalização superior ao dascrianças que vãodo primeiro ao quarto ano completo.Quanto àfrequência relativa, depreende-se que diarreia e gastroenterite de origem infecciosa presumível apresentaram o maior índice de prevalência em relação às demais patologias, com o maior número chegando a 23,8% no ano de 2017 e o menor situando-se na faixa de 13,22% em 2020. Conclusões: Apesar do avanço na Atenção Primária à Saúde e da cobertura pré-natal, a assistência ainda é deficitária, sendo necessários mais investimentos na área e o fomento de políticas públicas que abranjam essa população (AU).

Introduction: Hospitalization represents a considerable impact on the life of any person, and can even take on even greater proportions when it comes to a child. The impossibility of realizing their routine, such as playing and going to school, means that hospitalization during childhood takes ona remarkable context. That said, it is noted that mostofthese hospitalizations are avoidable,and are called Ambulatory Care Sensitive Conditions. Thus, quality ambulatory care could solve most childhood illnesses, avoiding this outcome.Objective:To elaborate an epidemiological profile of hospitalizations for the most prevalent infectious and bacterial diseases in children under 5 years of age,from 2017 to 2021,in Brazil. Methodology: The research in question is an ecological study of time series, elaborated through information collected through secondary data sources. Data were collected from the DataSUS platform and the Hospital Information System. Subsequently, data were processed and stored in Microsoft Excel® application, where they were managedand selected according to their relevance to the research. Results:It is observed that the age group below the first year of life presents a higher degree of hospitalization thanthat of children ranging from the first to the fourth year. As for the relative frequency, it can be seen that diarrhea and gastroenteritis of presumable infectious origin had the highest prevalence rate compared to other pathologies, with the highest number reaching 23.8% in 2017 and the lowest being in the range of 13.22% in 2020. Conclusions: Despite the advances in Primary Health Care and prenatal coverage, assistance is still deficient, requiring more investments in the area and the promotion of public policies that cover this population (AU).

Introducción: La hospitalización representa un impacto considerable en la vida de cualquier persona, quepuede adquirir proporciones aún mayores cuando se trata de un niño. La imposibilidadde realizar su rutina, como jugar e ir al colegio, hace que la hospitalización infantiltengaun contexto notable. Dicho esto, cabe señalar que una gran parte de estas hospitalizaciones son evitables, denominándose Hospitalizaciones por Condiciones Sensibles a la Atención Ambulatoria. Así pues, una atención ambulatoria de calidad podría resolver la mayoría de las enfermedades infantiles, evitando este desenlace. Objetivo: Elaborar un perfil epidemiológico de las hospitalizaciones por enfermedades infecciosas y bacterianas más prevalentes en niños menores de 5 años, de 2017 a 2021, en Brasil. Metodología: La investigación en cuestión es un estudio ecológico de series temporales, elaborado a partir de información recogida por vías secundarias. Los datos se recogieron de la plataforma DataSUS y del Sistema de Información Hospitalaria. Posteriormente, los datos se procesaron y almacenaron en la aplicación Microsoft Excel®, donde se trataron y seleccionaron en función de su relevancia para la investigación. Resultados: Se observa que el grupo de edad inferior al primer año de vida presenta un mayor grado de hospitalización que los niños del primero al cuarto año completo. En cuanto a la frecuencia relativa, se puede inferirque la diarreay lagastroenteritis presumible origen infeccioso tuvieron la tasa de prevalencia más alta en relación con las demáspatologías, siendola cifra más alto el 23,8% en 2017 y lamás bajael rango del 13,22% en el 2020. Conclusiones: A pesar de los avances en la Atención Primariade Salud y en la cobertura prenatal, la asistencia aún es deficiente, por lo que se requieren mayoresinversiones en el área y la promoción de políticas públicas que cubran a esta población (AU).

Internações na infância por doenças do aparelho respiratório no Brasil de 2013 a 2022 / Hospitalizaciones infantiles por enfermedades del sistema respiratorio en Brasil de 2013 a 2022 / Hospitalizations during childhood due to respiratory system diseases in Brazil from 2013 to 2022

Introdução: As doenças do sistema respiratório se mostram como uma das causas mais preocupantes de internações hospitalares no país. Nessa perspectiva, o perfil das internações por doenças respiratórias em crianças permite observar os parâmetros desta problemática, fornecendo um conhecimento amplo acerca do processo saúde e doença nessa população. Objetivo: Analisar o perfil epidemiológico das internações hospitalares por causas do aparelho respiratório em crianças de 0 a 9 anos no Brasil e regiões, entre os anos de 2013 e 2022. Metodologia: Trata-se de um estudo ecológico, realizado no Brasil, a partir de dados secundários do Sistema de Informações Hospitalares. A população escolhida para este estudo foram crianças de 0 a 9 anos deidade. Os dados foram coletados em 26 de novembro de 2022. As variáveis dependentes do estudo são as internações de crianças de 0 a 9 anos por doenças do aparelho respiratório no Brasil e suas regiões. Já, como variáveis independentes, tem-se o tempo, do período de janeiro de 2013 a setembro de 2022, regiões e faixa etária. Resultados: Há uma tendência de queda das internações por causa respiratória até o ano de 2016, seguido de um crescimento gradativo até 2019. Entretanto, em 2020, a taxa de hospitalização reduziu drasticamente em todas as localidades. As regiões Sul, Norte e Centro-Oeste permaneceram com taxas maiores que o Brasil em todo o período estudado. A internação em menores de 1 ano representa o maior quantitativo de internações sendo a pneumonia a causa mais prevalente. Conclusões: As taxas de internação infantil por doenças respiratórias representam importante preocupação para saúde pública. Assim, destaca-se a relevância da efetividade da Atenção Primária à Saúde, que possui grande impacto no desfecho dos adoecimentos em crianças, especialmente das doenças respiratórias (AU).

Introduction: Respiratory system diseases are one of the most worrying causes of hospital admissions in the country. From this perspective, the profile of hospitalizations for respiratory diseases in children allows us to notice the parameters of this problem, providing a broad understanding of the health and disease process in this population.Objective: To analyze the epidemiological profile of hospital admissions due to respiratory causes in children aged 0 to 9 in Brazil and its regions between 2013 and 2022. Methodology: This is an ecological study held in Brazil using secondary data from the Hospital Information System. The population chosen for this study consisted of children aged 0 to 9. Data were collected on November 26, 2022. The dependent variables of this study are hospitalizations of children aged 0 to 9 due to respiratory diseases in Brazil and its regions. The independent variables are time, from January 2013 to September 2022, regions, and age group.Results: There was a downward trend in hospitalizations due to respiratory causes until 2016, followed by a gradual increase until 2019. Nonetheless, in 2020, the hospitalization rate fell dramatically in all locations. The South, North and Mid-West regions remained with higher rates than Brazil throughout the studied period. Hospitalization of children under 1 year old represents the largest number of admissions, with pneumonia being Revista Ciência Plural. 2024; 10(1): e31414 3the most prevalent cause.Conclusions: Hospitalization rates during childhood due to respiratory diseases represent a major public health concern. Thus, one can highlight the importance of the effectiveness of Primary Health Care, which has a major impact on the outcome of illnesses in children, especially respiratory diseases (AU).

Introducción: Las enfermedades del sistema respiratorio son una de lascausas más preocupantes de hospitalizaciones en el país. Desde esta perspectiva, el perfil de hospitalizaciones por enfermedades respiratorias en niños permite observar los parámetros de este problema, proporcionando una amplia comprensión del proceso de salud y enfermedad en esta población.Objetivo: Analizar el perfil epidemiológico de las internaciones por causas respiratorias en niños de 0 a 9 años en Brasil y sus regiones entre 2013 y 2022. Metodología: Se trata de un estudio ecológico conducido en Brasil a partir de datos secundarios del Sistema de Información Hospitalaria. La población elegida para este estudio fueron los niños de 0 a 9 años. Los datos se recogieron el 26 de noviembre de 2022. Las variables dependientes del estudio son las hospitalizaciones de niños de 0 a 9 años por enfermedades respiratorias en Brasil y sus regiones. Las variables independientes son el tiempo, de enero de 2013 a septiembre de 2022, las regiones y la franja etaria.Resultados: Se nota una tendencia a la baja de las hospitalizaciones por causas respiratorias hasta 2016, seguida de un aumento gradual hasta 2019. Sin embargo, en 2020, la tasa de hospitalización cayó drásticamente en todas las localidades. Las regiones Sur, Norte y Medio Oeste se mantuvieron con tasas másaltas que Brasil durante todo el período estudiado. Las hospitalizaciones en niños menores de 1 año representan el mayor número de internaciones, siendo la neumonía la causa más prevalente.Conclusiones: Las tasas de hospitalización infantil por enfermedades respiratorias representan un importante problema de salud pública. Así, se subraya la importancia de la eficacia de la Atención Primaria de Salud, que tiene un gran impacto en el resultado de las enfermedades en los niños, especialmente las respiratorias (AU).

Occupational status and chronic respiratory diseases: a cross-sectional study based on the data of the Rafsanjan Cohort Study.

BACKGROUND: The aim of the present study was to investigate the possible connection between occupational status and chronic respiratory diseases (CRDs) among the Iranian population. METHODS: The present cross-sectional study was conducted on 9934 individuals aged 35-70 years enrolled in the Rafsanjan Cohort Study (RCS), a component of the Prospective Epidemiological Research Studies in Iran (PERSIAN). Detailed questionnaires were used to collect information on various factors, such as occupation, sociodemographic characteristics, medical history, anthropometric measurements, physical activity, cigarette and hookah smoking, opium use, and alcohol consumption. The association between occupational class and CRD was evaluated using logistic regression models for rare events. RESULTS: In the present study, 4624 (46.55%) participants were male, and 5310 (53.45%) were female. The prevalence of CRD among all participants was 2.61%. Occupational activities were classified into two categories: In class I, the largest group was the homemaker and unemployment category (41.73%), followed by self-employment (34.39%), employment (13.03%), and retired individuals (10.84%). In class II, there were pistachio farmers (12.61%), copper miners (3.62%), and others in various occupations (83.76%). Subjects with CRD were significantly more likely to be homemakers, unemployed, elderly, female, less educated, and obese. There was no significant relationship between CRD and job type/occupational status after adjusting for some potential confounding variables. CONCLUSIONS: There was no significant relationship between CRD and job type/occupational status. However, longitudinal studies are needed to assess the impact of job type/occupational status on the risk of CRD.

Association and mediation between educational attainment and respiratory diseases: a Mendelian randomization study.

BACKGROUND: Respiratory diseases are a major health burden, and educational inequalities may influence disease prevalence. We aim to evaluate the causal link between educational attainment and respiratory disease, and to determine the mediating influence of several known modifiable risk factors. METHODS: We conducted a two-step, two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) and single nucleotide polymorphisms (SNPs) as instrumental variables for educational attainment and respiratory diseases. Additionally, we performed a multivariable MR analysis to estimate the direct causal effect of each exposure variable included in the analysis on the outcome, conditional on the other exposure variables included in the model. The mediating roles of body mass index (BMI), physical activity, and smoking were also assessed. FINDINGS: MR analyses provide evidence of genetically predicted educational attainment on the risk of FEV1 (ß = 0.10, 95% CI 0.06, 0.14), FVC (ß = 0.12, 95% CI 0.07, 0.16), FEV1/FVC (ß = - 0.005, 95% CI - 0.05, 0.04), lung cancer (OR = 0.54, 95% CI 0.45, 0.65) and asthma (OR = 0.86, 95% CI 0.78, 0.94). Multivariable MR dicated the effect of educational attainment on FEV1 (ß = 0.10, 95% CI 0.04, 0.16), FVC (ß = 0.07, 95% CI 0.01, 0.12), FEV1/FVC (ß = 0.07, 95% CI 0.01, 0.01), lung cancer (OR = 0.55, 95% CI 0.42, 0.71) and asthma (OR = 0.88, 95% CI 0.78, 0.99) persisted after adjusting BMI and cigarettes per day. Of the 23 potential risk factors, BMI, smoking may partially mediate the relationship between education and lung disease. CONCLUSION: High levels of educational attainment have a potential causal protective effect on respiratory diseases. Reducing smoking and adiposity may be a target for the prevention of respiratory diseases attributable to low educational attainment.

[Research progress on the role of N6-methyladenosine methylation in the pathogenesis and development of respiratory diseases].

N6-methyladenosine (m6A) is one of the most common post-transcriptional modifications of eukaryotic mRNA. The m6A modification accelerates mRNA metabolism and translation, and plays an important role in cell differentiation, embryonic development and stress response. As a reversible epigenetic modification, m6A modification plays an important role in many physiological and pathological processes. The m6A modification is closely related to the occurrence and progression of respiratory diseases, and the m6A modification regulatory factor may be a potential target for regulating respiratory diseases. This article reviews the role of m6A modification in the development of respiratory diseases such as lung cancer, acute lung injury (ALI), asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). The purpose of m6A modification is to provide a reference for the pathogenesis of respiratory diseases and the study of targets.

Recent advances in the therapeutic potential of nobiletin against respiratory diseases.

BACKGROUND: Nobiletin is a natural polymethoxylated flavonoid widely present in citrus fruit peels. It has been demonstrated to exert the effects of anti-tumor, anti-inflammation, anti-oxidative, anti-apoptotic and improve cardiovascular function. Increasing evidences suggest that nobiletin plays an important role in respiratory diseases (RDs) treatment. OBJECTIVE: This review aimed to investigate the therapeutic potential of nobiletin against RDs, such as lung cancer, COPD, pulmonary fibrosis, asthma, pulmonary infection, acute lung injury, coronavirus disease 2019, and pulmonary arterial hypertension. METHODS: We retrieved extensive literature of relevant literatures in English until June 26, 2023 from the database of PubMed, Web of Science, and Scopus databases. The keywords of "nobiletin and lung", "nobiletin and respiratory disease", "nobiletin and chronic respiratory diseases", "nobiletin and metabolites", "nobiletin and pharmacokinetics", "nobiletin and toxicity" were searched in pairs. A total of 298 literatures were retrieved from the above database. After excluding the duplicates and reviews, 53 were included in the current review. RESULTS: We found that the therapeutic mechanisms are based on different signaling pathways. Firstly, nobiletin inhibited the proliferation and suppressed the invasion and migration of cancer cells by regulating the related pathway or key target, like Bcl-2, PD-L1, PARP, and Akt/GSK3ß/ß-catenin in lung cancer treatment. Secondly, nobiletin treats COPD and ALI by targeting classical signaling pathway mediating inflammation. Besides, the available findings show that nobiletin exerts the effect of PF treatment via regulating mTOR pathway. CONCLUSIONS: With the wide range of pharmacological activities, high efficiency and low toxicity, nobiletin can be used as a potential agent for preventing and treating RDs. These findings will contribute to further research on the molecular mechanisms of nobiletin and facilitate in-depth studies on nobiletin at both preclinical and clinical levels for the treatment of RDs.

A new perspective on gut-lung axis affected through resident microbiome and their implications on immune response in respiratory diseases.

The highly diverse microbial ecosystem of the human body colonizes the gastrointestinal tract has a profound impact on the host's immune, metabolic, endocrine, and other physiological processes, which are all interconnected. Specifically, gut microbiota has been found to play a crucial role in facilitating the adaptation and initiation of immune regulatory response through the gastrointestinal tract affecting the other distal mucosal sites such as lungs. A tightly regulated lung-gut axis during respiratory ailments may influence the various molecular patterns that instructs priming the disease severity to dysregulate the normal function. This review provides a comprehensive summary of current research on gut microbiota dysbiosis in respiratory diseases including asthma, pneumonia, bronchopneumonia, COPD during infections and cancer. A complex-interaction among gut microbiome, associated metabolites, cytokines, and chemokines regulates the protective immune response activating the mucosal humoral and cellular response. This potential mechanism bridges the regulation patterns through the gut-lung axis. This paper aims to advance the understanding of the crosstalk of gut-lung microbiome during infection, could lead to strategize to modulate the gut microbiome as a treatment plan to improve bad prognosis in various respiratory diseases.

Opportunities and Challenges for Inhalable Nanomedicine Formulations in Respiratory Diseases: A Review.

Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system.