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1.
Immunity ; 55(7): 1216-1233.e9, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35768001

RESUMO

Lung-resident memory B cells (MBCs) provide localized protection against reinfection in respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. We found that two main transcriptionally distinct subsets of MBCs colonized the lung peribronchial niche after infection. These subsets arose from different progenitors and were both class switched, somatically mutated, and intrinsically biased in their differentiation fate toward plasma cells. Combined analysis of antigen specificity and B cell receptor repertoire segregated these subsets into "bona fide" virus-specific MBCs and "bystander" MBCs with no apparent specificity for eliciting viruses generated through an alternative permissive process. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from reinfection while diversifying the initial B cell repertoire.


Assuntos
COVID-19 , Memória Imunológica , Animais , Linfócitos B , Pulmão , Células B de Memória , Camundongos , Reinfecção , SARS-CoV-2
2.
Semin Immunol ; 70: 101846, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37801907

RESUMO

Since the 1960 s, our health has been compromised by exposure to over 350,000 newly introduced toxic substances, contributing to the current pandemic in allergic, autoimmune and metabolic diseases. The "Epithelial Barrier Theory" postulates that these diseases are exacerbated by persistent periepithelial inflammation (epithelitis) triggered by exposure to a wide range of epithelial barrier-damaging substances as well as genetic susceptibility. The epithelial barrier serves as the body's primary physical, chemical, and immunological barrier against external stimuli. A leaky epithelial barrier facilitates the translocation of the microbiome from the surface of the afflicted tissues to interepithelial and even deeper subepithelial locations. In turn, opportunistic bacterial colonization, microbiota dysbiosis, local inflammation and impaired tissue regeneration and remodelling follow. Migration of inflammatory cells to susceptible tissues contributes to damage and inflammation, initiating and aggravating many chronic inflammatory diseases. The objective of this review is to highlight and evaluate recent studies on epithelial physiology and its role in the pathogenesis of chronic diseases in light of the epithelial barrier theory.


Assuntos
Hipersensibilidade , Doenças Metabólicas , Microbiota , Humanos , Inflamação , Doença Crônica , Disbiose
3.
Immunol Rev ; 306(1): 244-257, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34816440

RESUMO

Highly dynamic immune responses are generated toward pathogens or injuries, in vivo. Multiple immune cell types participate in various facets of the response which leads to a concerted effort in the removal and clearance of pathogens or injured tissue and a return to homeostasis. Intravital microscopy (IVM) has been extensively utilized to unravel the dynamics of immune responses, visualizing immune cell behavior in intact living tissues, within a living organism. For instance, the phenomenon of leukocyte recruitment cascade. Importantly, IVM has led to a deep appreciation that immune cell behavior and responses in individual organs are distinct, but also can influence one another. In this review, we discuss how IVM as a tool has been used to study the innate immune responses in various tissues during homeostasis, injury, and infection.


Assuntos
Diagnóstico por Imagem , Microscopia Intravital , Humanos , Imunidade Inata , Microscopia Intravital/métodos , Fígado , Pulmão
4.
Eur J Immunol ; 54(1): e2250274, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37822141

RESUMO

Spinal cord injury (SCI) affects hundreds of thousands of people in the United States, and while some effects of the injury are broadly recognized (deficits to locomotion, fine motor control, and quality of life), the systemic consequences of SCI are less well-known. The spinal cord regulates systemic immunological and visceral functions; this control is often disrupted by the injury, resulting in viscera including the gut, spleen, liver, bone marrow, and kidneys experiencing local tissue inflammation and physiological dysfunction. The extent of pathology depends on the injury level, severity, and time post-injury. In this review, we describe immunological and metabolic consequences of SCI across several organs. Since infection and metabolic disorders are primary reasons for reduced lifespan after SCI, it is imperative that research continues to focus on these deleterious aspects of SCI to improve life span and quality of life for individuals with SCI.


Assuntos
Qualidade de Vida , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Inflamação , Medula Espinal/patologia , Fígado/patologia
5.
Immunology ; 172(3): 500-515, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38584001

RESUMO

Lifestyle factors like poor maternal diet or antibiotic exposure disrupt early life microbiome assembly in infants, increasing the risk of severe lower respiratory infections (sLRI). Our prior studies in mice indicated that a maternal low-fibre diet (LFD) exacerbates LRI severity in infants by impairing recruitment of plasmacytoid dendritic cells (pDC) and consequently attenuating expansion of lung regulatory T (Treg) cells during pneumonia virus of mice (PVM) infection. Here, we investigated whether maternal dietary fibre intake influences Treg cell phenotypes in the mediastinal lymph nodes (mLN) and lungs of PVM-infected neonatal mice. Using high dimensional flow cytometry, we identified distinct clusters of regulatory T cells (Treg cells), which differed between lungs and mLN during infection, with notably greater effector Treg cell accumulation in the lungs. Compared to high-fibre diet (HFD)-reared pups, frequencies of various effector Treg cell subsets were decreased in the lungs of LFD-reared pups. Particularly, recruitment of chemokine receptor 3 (CXCR3+) expressing Treg cells was attenuated in LFD-reared pups, correlating with lower lung expression of CXCL9 and CXCL10 chemokines. The recruitment of this subset in response to PVM infection was similarly impaired in pDC depleted mice or following anti-CXCR3 treatment, increasing immunopathology in the lungs. In summary, PVM infection leads to the sequential recruitment and expansion of distinct Treg cell subsets to the lungs and mLN. The attenuated recruitment of the CXCR3+ subset in LFD-reared pups increases LRI severity, suggesting that strategies to enhance pDCs or CXCL9/CXCL10 expression will lower immune-mediated pathogenesis.


Assuntos
Tolerância Imunológica , Pulmão , Receptores CXCR3 , Linfócitos T Reguladores , Animais , Linfócitos T Reguladores/imunologia , Receptores CXCR3/metabolismo , Camundongos , Pulmão/imunologia , Pulmão/virologia , Feminino , Infecções por Pneumovirus/imunologia , Camundongos Endogâmicos C57BL , Linfonodos/imunologia , Quimiocina CXCL10/metabolismo , Modelos Animais de Doenças , Animais Recém-Nascidos
6.
Thorax ; 79(5): 422-429, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38316550

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 202 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.


Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Humanos , Artéria Pulmonar , Estudos Retrospectivos , Resistência Vascular/fisiologia , Doenças Pulmonares Intersticiais/diagnóstico , Pulmão , Hipertensão Pulmonar/diagnóstico
7.
Eur J Immunol ; 53(9): e2250273, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37366319

RESUMO

During infections, the timings of effector differentiation of pulmonary immune responses are of paramount importance, as pathogen persistence and unsuppressed inflammation can rapidly lead to a loss of function, increased frailty, and death. Thus, both an efficient clearance of the danger and a rapid resolution of inflammation are critical to host survival. We now know that tissue-localized FoxP3+ regulatory T cells, a subset of CD4+ T cells, are highly attuned to the type of immune response, acquiring unique phenotypic characteristics that allow them to adapt their suppressive functions with the nature of inflammatory cells. To achieve this, activated effector TREG cells acquire specialized TH 1, TH 2, and TH 17-like characteristics that allow them to migrate, survive, and time their function(s) through refined mechanisms. Herein, we describe how this process requires a unique developmental path that includes the acquisition of master transcription factors and the expression of receptors adapted to sense local danger signals that are found during pulmonary inflammation. In turn, we offer an overview of how these characteristics promote the capacity of local effector TREG cells to proliferate, survive, and display suppressive strategies to resolve lung injury.


Assuntos
Pneumonia , Linfócitos T Reguladores , Humanos , Fatores de Transcrição/metabolismo , Pneumonia/metabolismo , Inflamação , Diferenciação Celular , Fatores de Transcrição Forkhead/metabolismo
8.
Immunol Cell Biol ; 102(6): 422-424, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38695211

RESUMO

In this article for the Highlights of the 2023 Series, we discuss recent discoveries on regulatory T cells in the lungs and their multifaceted roles in various contexts. Key advancements in Treg immunology have broadened our understanding of lung tissue homeostasis and the potential role of Tregs in pathological processes.


Assuntos
Pulmão , Linfócitos T Reguladores , Animais , Humanos , Homeostase , Pulmão/imunologia , Linfócitos T Reguladores/imunologia
9.
J Virol ; 97(10): e0067423, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37830821

RESUMO

IMPORTANCE: Vaccines targeting highly conserved proteins can protect broadly against diverse viral strains. When a vaccine is administered to the respiratory tract, protection against disease is especially powerful. However, it is important to establish that this approach is safe. When vaccinated animals later encounter viruses, does reactivation of powerful local immunity, including T cell responses, damage the lungs? This study investigates the safety of mucosal vaccination of the respiratory tract. Non-replicating adenoviral vaccine vectors expressing conserved influenza virus proteins were given intranasally. This vaccine-induced protection persists for at least 15 months. Vaccination did not exacerbate inflammatory responses or tissue damage upon influenza virus infection. Instead, vaccination with nucleoprotein reduced cytokine responses and histopathology, while neutrophil and T cell responses resolved earlier. The results are promising for safe vaccination at the site of infection and thus have implications for the control of influenza and other respiratory viruses.


Assuntos
Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Camundongos , Anticorpos Antivirais , Vacinas contra Influenza/imunologia , Pulmão , Camundongos Endogâmicos BALB C , Orthomyxoviridae , Infecções por Orthomyxoviridae/prevenção & controle , Vacinação/métodos , Adenoviridae
10.
J Virol ; 97(12): e0109623, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38038432

RESUMO

IMPORTANCE: Although the current rate of SARS-CoV-2 infections has decreased significantly, COVID-19 still ranks very high as a cause of death worldwide. As of October 2023, the weekly mortality rate is still at 600 deaths in the United States alone, which surpasses even the worst mortality rates recorded for influenza. Thus, the long-term outlook of COVID-19 is still a serious concern outlining the need for the next-generation vaccine. This study found that a prime/pull coronavirus vaccine strategy increased the frequency of functional SARS-CoV-2-specific CD4+ and CD8+ memory T cells in the lungs of SARS-CoV-2-infected triple transgenic HLA-DR*0101/HLA-A*0201/hACE2 mouse model, thereby resulting in low viral titer and reduced COVID-19-like symptoms.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Humanos , Camundongos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Quimiocina CXCL11/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Epitopos , Pulmão/imunologia , Pulmão/virologia , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus , Modelos Animais de Doenças
11.
Curr Top Microbiol Immunol ; 441: 139-183, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37695428

RESUMO

Tuberculosis remains a daunting public health concern in many countries of the world. A consistent observation in the global epidemiology of tuberculosis is an excess of cases of active pulmonary tuberculosis among males compared with females. Data from both humans and animals also suggest that males are more susceptible than females to develop active pulmonary disease. Similarly, male sex has been associated with poor treatment outcomes. Despite this growing body of evidence, little is known about the mechanisms driving sex bias in tuberculosis disease. Two dominant hypotheses have been proposed to explain the predominance of active pulmonary tuberculosis among males. The first is based on the contribution of biological factors, such as sex hormones and genetic factors, on host immunity during tuberculosis. The second is focused on non-biological factors such as smoking, professional exposure, and health-seeking behaviors, known to be influenced by gender. In this chapter, we review the literature regarding these two prevailing hypotheses by presenting human but also experimental animal studies. In addition, we presented studies aiming at examining the impact of sex and gender on other clinical forms of tuberculosis such as latent tuberculosis infection and extrapulmonary tuberculosis, which both appear to have their own specificities in relation to sex. We also highlighted potential intersections between sex and gender in the context of tuberculosis and shared future directions that could guide in elucidating mechanisms of sex-based differences in tuberculosis pathogenesis and treatment outcomes.


Assuntos
Tuberculose Extrapulmonar , Tuberculose Pulmonar , Tuberculose , Animais , Feminino , Humanos , Masculino , Fatores Sexuais , Tuberculose/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico
12.
Exp Physiol ; 109(7): 1051-1065, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38502538

RESUMO

Many animal species do not breathe in a continuous, rhythmic fashion, but rather display a variety of breathing patterns characterized by prolonged periods between breaths (inter-breath intervals), during which the heart continues to beat. Examples of intermittent breathing abound across the animal kingdom, from crustaceans to cetaceans. With respect to human physiology, intermittent breathing-also termed 'periodic' or 'episodic' breathing-is associated with a variety of pathologies. Cardiovascular phenomena associated with intermittent breathing in diving species have been termed 'diving bradycardia', 'submersion bradycardia', 'immersion bradycardia', 'ventilation tachycardia', 'respiratory sinus arrhythmia' and so forth. An examination across the literature of terminology applied to these physiological phenomena indicates, unfortunately, no attempt at standardization. This might be viewed as an esoteric semantic problem except for the fact that many of the terms variously used by different authors carry with them implicit or explicit suggestions of underlying physiological mechanisms and even human-associated pathologies. In this article, we review several phenomena associated with diving and intermittent breathing, indicate the semantic issues arising from the use of each term, and make recommendations for best practice when applying specific terms to particular cardiorespiratory patterns. Ultimately, we emphasize that the biology-not the semantics-is what is important, but also stress that confusion surrounding underlying mechanisms can be avoided by more careful attention to terms describing physiological changes during intermittent breathing and diving.


Assuntos
Mergulho , Respiração , Animais , Mergulho/fisiologia , Humanos , Semântica , Bradicardia/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares , Mecânica Respiratória/fisiologia
13.
Mol Pharm ; 21(7): 3084-3102, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38828798

RESUMO

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.


Assuntos
Lipídeos , Nanopartículas , Nanopartículas/química , Humanos , Lipídeos/química , Sistemas de Liberação de Medicamentos/métodos , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Portadores de Fármacos/química , Animais , Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Lipossomos
14.
Arterioscler Thromb Vasc Biol ; 43(11): 2088-2098, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37675634

RESUMO

Megakaryocytes are commonly known as large, polyploid, bone marrow resident cells that contribute to hemostasis through the production of platelets. Soon after their discovery in the 19th century, megakaryocytes were described in tissue locations other than the bone marrow, specifically in the lungs and the blood circulation. However, the localization of megakaryocytes in the lungs and the contribution of lung megakaryocytes to the general platelet pool has only recently been appreciated. Moreover, the conception of megakaryocytes as uniform cells with the sole purpose of platelet production has been challenged. Here, we review the literature on megakaryocyte cell identity and location with a special focus on recent observations of megakaryocyte subpopulations identified by transcriptomic analyses.


Assuntos
Plaquetas , Megacariócitos , Medula Óssea , Células da Medula Óssea , Trombopoese/genética
15.
Biomarkers ; 29(2): 68-77, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38299991

RESUMO

BACKGROUND: Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain in mites. Data concerning mammalian toxicity of this acaricide are limited; thus the aim of this work was to explore FEN toxicity on Wistar rats, particularly on cardiac, pulmonary, and splenic tissues and in bone marrow cells. METHODS: rats were treated orally with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 days. After treatment, we analyzed lipid profile, oxidative stress and DNA damage in rat tissues. RESULTS: FEN exposure increased creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, elevated total cholesterol (T-CHOL), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) concentrations, while decreasing high-density lipoprotein cholesterol (HDL-C). It inhibited acetylcholinesterase (AChE) activity, enhanced lipid peroxidation, protein oxidation, and modulated antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase). Comet assay indicated that FEN induced a dose-dependent DNA damage, contrasting with the micronucleus test showing no micronuclei formation. Nonetheless, FEN exhibited cytotoxicity to bone marrow cells, as evidenced by a reduction in the number of immature erythrocytes among total cells. CONCLUSION: FEN appears to carry out its genotoxic and cytotoxic activities most likely through an indirect pathway that involves oxidative stress.


Assuntos
Acaricidas , Acetilcolinesterase , Benzoatos , Pirazóis , Ratos , Animais , Ratos Wistar , Acetilcolinesterase/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Catalase/metabolismo , Peroxidação de Lipídeos , Dano ao DNA , Superóxido Dismutase/metabolismo , Colesterol , Lipídeos , Glutationa/metabolismo , Mamíferos/metabolismo
16.
Int J Legal Med ; 138(1): 295-299, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36609734

RESUMO

In times of peace and except for terrorist attacks, fatalities by explosions are rare. Fireworks have deadly potential, especially self-made or illegally acquired devices. The use of professional pyrotechnics by untrained persons poses a life-threatening hazard. We present a case of devastating blunt force and blast injuries to the head and chest of a young man. After ignition of a display shell (syn. a real shell or mortar shell) without the use of a launching pipe, the device hit the man's face, nearly simultaneously followed by the explosion of the burst charge. The autopsy revealed injuries to the face and forehead as well as extensive tissue structure damage and a massive contusion with a bloody edema of the lungs. Autopsy results are supplemented with CT imaging and 3D reconstruction of the fractured mid face, as well as histological and toxicological examinations. This case of a misused display shell demonstrates both its devastating destructive potential and the corresponding and rarely observed injury pattern.


Assuntos
Traumatismos por Explosões , Terrorismo , Ferimentos não Penetrantes , Humanos , Traumatismos por Explosões/etiologia , Traumatismos por Explosões/patologia , Diagnóstico por Imagem , Ferimentos não Penetrantes/etiologia , Pulmão/patologia , Explosões
17.
Transpl Int ; 37: 12573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481465

RESUMO

With the ongoing shortage of donor lungs, ex vivo lung perfusion (EVLP) offers the opportunity for objective assessment and potential therapeutic repair of marginal organs. There is a need for robust research on EVLP interventions to increase the number of transplantable organs. The use of human lungs, which have been declined for transplant, for these studies is preferable to animal organs and is indeed essential if clinical translation is to be achieved. However, experimental human EVLP is time-consuming and expensive, limiting the rate at which promising interventions can be assessed. A split-lung EVLP model, which allows stable perfusion and ventilation of two single lungs from the same donor, offers advantages scientifically, financially and in time to yield results. Identical parallel circuits allow one to receive an intervention and the other to act as a control, removing inter-donor variation between study groups. Continuous hemodynamic and airway parameters are recorded and blood gas, perfusate, and tissue sampling are facilitated. Pulmonary edema is assessed directly using ultrasound, and indirectly using the lung tissue wet:dry ratio. Evans blue dye leaks into the tissue and can quantify vascular endothelial permeability. The split-lung ex vivo perfusion model offers a cost-effective, reliable platform for testing therapeutic interventions with relatively small sample sizes.


Assuntos
Transplante de Pulmão , Animais , Humanos , Transplante de Pulmão/métodos , Análise Custo-Benefício , Pulmão , Circulação Extracorpórea/métodos , Perfusão/métodos , Doadores de Tecidos
18.
Lung ; 202(2): 107-118, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38526572

RESUMO

PURPOSE: Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut-lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM). METHODS: 16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances. RESULTS: In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC. CONCLUSION: Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut-lung communication.


Assuntos
Carcinoma de Células Renais , Microbioma Gastrointestinal , Neoplasias Renais , Humanos , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , Tosse Crônica , Pulmão/química
19.
Rheumatol Int ; 44(4): 693-702, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38319374

RESUMO

BACKGROUND: Systemic sclerosis (SSc), a complex autoimmune disorder, manifests as a convergence of rheumatologic, dermatologic, and pulmonary challenges. Among the severe complications contributing to morbidity and mortality are SSc Associated Interstitial Lung Disease (SSc-ILD) and pulmonary hypertension. Over the past decade, research on pulmonary involvement in SSc has intensified, leading to a heightened understanding of its pathogenesis, diagnostic methods, and therapeutic strategies. AIM: This study aims to provide a data-driven overview of the current state of systemic sclerosis research, identifying emerging trends and fostering informed decisions regarding resource allocation and research priorities. METHODS: A literature search was conducted in the Scopus database, using MESH keywords such as "systemic sclerosis" AND "lungs" OR "pulmonary hypertension" OR "interstitial lung disease". After applying exclusion criteria, a thorough analysis was performed, considering factors such as document category, authorship, journal source, citation frequency, country of publication, language, and keywords. The bibliometric analysis utilized Scopus as the preferred database, leveraging its extensive coverage, user-friendly interface, and commitment to data accuracy. Visual networks were constructed using VOSviewer software to map the relationships between keywords, countries, and authors. Altmetric Attention Scores (AAS) were employed to assess the social impact of articles. RESULTS: The analysis revealed a total of 2538 scholarly items, with 55.7% identified as open access. The USA (n = 532), Italy (n = 458), France (n = 304), Japan (n = 271), and the UK (n = 236) emerged as primary contributors, with English being the predominant language. A notable upward tendency in annual publication and citation scores indicated sustained interest and relevance in SSc-ILD research. The top journals, including Rheumatology United Kingdom, Clinical and Experimental Rheumatology, Clinical Rheumatology, Arthritis and Rheumatology, and Journal of Rheumatology, played a pivotal role in scholarly output. Original Articles (n = 1795; 70.7%) constituted the majority of publications, followed by Reviews, Letters, Notes, and Editorials. The analysis of publication impact within different scholarly formats revealed varying citation patterns, with Original Articles and Reviews leading in influence. The identification of influential research hubs and key contributors provided insights into collaborative efforts and geographic distribution. A strong correlation (rho = 0.612, p < 0.001) was observed between the quantity of Mendeley readers and the citations received by scholarly articles. CONCLUSION: This bibliometric analysis offers a comprehensive overview of SSc-ILD research, highlighting its dynamic and interdisciplinary nature. The surge in publications, citation scores, and the identification of key contributors underscore the continued relevance and impact of this field. The nuanced relationships between social attention and scientific recognition, as revealed by Mendeley readership and AAS, contribute to a deeper understanding of the multifaceted nature of scholarly impact.


Assuntos
Artrite , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Fator de Impacto de Revistas , Bibliometria , Escleroderma Sistêmico/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia
20.
BMC Pulm Med ; 24(1): 163, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570751

RESUMO

BACKGROUND: Observational studies have shown that smoking is related to the diffusing capacity of the lungs for carbon monoxide (DLCO) in individuals with idiopathic pulmonary fibrosis (IPF). Nevertheless, further investigation is needed to determine the causal effect between these two variables. Therefore, we conducted a study to investigate the causal relationship between smoking and DLCO in IPF patients using two-sample Mendelian randomization (MR) analysis. METHODS: Large-scale genome-wide association study (GWAS) datasets from individuals of European descent were analysed. These datasets included published lifetime smoking index (LSI) data for 462,690 participants and DLCO data for 975 IPF patients. The inverse-variance weighting (IVW) method was the main method used in our analysis. Sensitivity analyses were performed by MR‒Egger regression, Cochran's Q test, the leave-one-out test and the MR-PRESSO global test. RESULTS: A genetically predicted increase in LSI was associated with a decrease in DLCO in IPF patients [ORIVW = 0.54; 95% CI 0.32-0.93; P = 0.02]. CONCLUSIONS: Our study suggested that smoking is associated with a decrease in DLCO. Patients diagnosed with IPF should adopt an active and healthy lifestyle, especially by quitting smoking, which may be effective at slowing the progression of IPF.


Assuntos
Estudo de Associação Genômica Ampla , Fibrose Pulmonar Idiopática , Humanos , Fumar/efeitos adversos , Fumar/genética , Fumar Tabaco , Fibrose Pulmonar Idiopática/genética , Monóxido de Carbono
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