| 1. |
- Allam, Venkata Sita Rama Raju, et al.
(författare)
-
Nutraceuticals and mitochondrial oxidative stress : bridging the gap in the management of bronchial asthma
- 2022
-
Ingår i: Environmental Science and Pollution Research. - : Springer Nature. - 0944-1344 .- 1614-7499. ; 29:42, s. 62733-62754
-
Forskningsöversikt (refereegranskat)abstract
- Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.
|
|
| 2. |
- Griekspoor, Petra, et al.
(författare)
-
Marked host specificity and lack of phylogeographic population structure of Campylobacter jejuni in wild birds
- 2013
-
Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 22:5, s. 1463-1472
-
Tidskriftsartikel (refereegranskat)abstract
- Zoonotic pathogens often infect several animal species, and gene flow among populations infecting different host species may affect the biological traits of the pathogen including host specificity, transmissibility and virulence. The bacterium Campylobacter jejuni is a widespread zoonotic multihost pathogen, which frequently causes gastroenteritis in humans. Poultry products are important transmission vehicles to humans, but the bacterium is common in other domestic and wild animals, particularly birds, which are a potential infection source. Population genetic studies of C. jejuni have mainly investigated isolates from humans and domestic animals, so to assess C. jejuni population structure more broadly and investigate host adaptation, 928 wild bird isolates from Europe and Australia were genotyped by multilocus sequencing and compared to the genotypes recovered from 1366 domestic animal and human isolates. Campylobacter jejuni populations from different wild bird species were distinct from each other and from those from domestic animals and humans, and the host species of wild bird was the major determinant of C. jejuni genotype, while geographic origin was of little importance. By comparison, C. jejuni differentiation was restricted between more phylogenetically diverse farm animals, indicating that domesticated animals may represent a novel niche for C. jejuni and thereby driving the evolution of those bacteria as they exploit this niche. Human disease is dominated by isolates from this novel domesticated animal niche.
|
|
| 3. |
- Shastri, Madhur D., et al.
(författare)
-
Interleukin-13 : A pivotal target against influenza-induced exacerbation of chronic lung diseases
- 2021
-
Ingår i: Life Sciences. - : Elsevier. - 0024-3205 .- 1879-0631. ; 283
-
Tidskriftsartikel (refereegranskat)abstract
- Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13based therapeutic entities.
|
|
| 4. |
- Allam, Venkata, et al.
(författare)
-
Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma
- 2023
-
Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 78:7, s. 661-673
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Severe neutrophilic asthma is resistant to treatment with glucocorticoids. The immunomodulatory protein macrophage migration inhibitory factor (MIF) promotes neutrophil recruitment to the lung and antagonises responses to glucocorticoids. We hypothesised that MIF promotes glucocorticoid resistance of neutrophilic inflammation in severe asthma.Methods: We examined whether sputum MIF protein correlated with clinical and molecular characteristics of severe neutrophilic asthma in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. We also investigated whether MIF regulates neutrophilic inflammation and glucocorticoid responsiveness in a murine model of severe asthma in vivo.Results: MIF protein levels positively correlated with the number of exacerbations in the previous year, sputum neutrophils and oral corticosteroid use across all U-BIOPRED subjects. Further analysis of MIF protein expression according to U-BIOPRED-defined transcriptomic-associated clusters (TACs) revealed increased MIF protein and a corresponding decrease in annexin-A1 protein in TAC2, which is most closely associated with airway neutrophilia and NLRP3 inflammasome activation. In a murine model of severe asthma, treatment with the MIF antagonist ISO-1 significantly inhibited neutrophilic inflammation and increased glucocorticoid responsiveness. Coimmunoprecipitation studies using lung tissue lysates demonstrated that MIF directly interacts with and cleaves annexin-A1, potentially reducing its biological activity.Conclusion: Our data suggest that MIF promotes glucocorticoid-resistance of neutrophilic inflammation by reducing the biological activity of annexin-A1, a potent glucocorticoid-regulated protein that inhibits neutrophil accumulation at sites of inflammation. This represents a previously unrecognised role for MIF in the regulation of inflammation and points to MIF as a potential therapeutic target for the management of severe neutrophilic asthma.
|
|
| 5. |
- Chan, Yinghan, et al.
(författare)
-
Nutraceuticals : unlocking newer paradigms in the mitigation of inflammatory lung diseases
- 2023
-
Ingår i: Critical reviews in food science and nutrition. - : Taylor & Francis. - 1040-8398 .- 1549-7852. ; 63:19, s. 3302-3332
-
Forskningsöversikt (refereegranskat)abstract
- Persistent respiratory tract inflammation contributes to the pathogenesis of various chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. These inflammatory respiratory diseases have been a major public health concern as they are the leading causes of worldwide mortality and morbidity, resulting in heavy burden on socioeconomic growth throughout these years. Although various therapeutic agents are currently available, the clinical applications of these agents are found to be futile due to their adverse effects, and most patients remained poorly controlled with a low quality of life. These drawbacks have necessitated the development of novel, alternative therapeutic agents that can effectively improve therapeutic outcomes. Recently, nutraceuticals such as probiotics, vitamins, and phytochemicals have gained increasing attention due to their nutritional properties and therapeutic potential in modulating the pathological mechanisms underlying inflammatory respiratory diseases, which could ultimately result in improved disease control and overall health outcomes. As such, nutraceuticals have been held in high regard as the possible alternatives to address the limitations of conventional therapeutics, where intensive research are being performed to identify novel nutraceuticals that can positively impact various inflammatory respiratory diseases. This review provides an insight into the utilization of nutraceuticals with respect to their molecular mechanisms targeting multiple signaling pathways involved in the pathogenesis of inflammatory respiratory diseases.
|
|
| 6. |
- Eapen, Mathew Suji, et al.
(författare)
-
Chronic Obstructive Pulmonary Disease and Lung Cancer : Underlying Pathophysiology and New Therapeutic Modalities
- 2018
-
Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 78:16, s. 1717-1740
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.
|
|
| 7. |
- Griekspoor, Petra, et al.
(författare)
-
Campylobacter jejuni sequence types show remarkable spatial and temporal stability in Blackbirds
- 2015
-
Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The zoonotic bacterium Campylobacter jejuni has a broad host range but is especially associated with birds, both domestic and wild. Earlier studies have indicated thrushes of the genus Turdus in Europe to be frequently colonized with C. jejuni, and predominately with host-associated specific genotypes. The European Blackbird Turdus merula has a large distribution in Europe, including some oceanic islands, and was also introduced to Australia by European immigrants in the 1850s.METHODS: The host specificity and temporal stability of European Blackbird C. jejuni was investigated with multilocus sequence typing in a set of isolates collected from Sweden, Australia, and The Azores.RESULTS: Remarkably, we found that the Swedish, Australian, and Azorean isolates were genetically highly similar, despite extensive spatial and temporal isolation. This indicates adaptation, exquisite specificity, and stability in time for European Blackbirds, which is in sharp contrast with the high levels of recombination and mutation found in poultry-related C. jejuni genotypes.CONCLUSION: The maintenance of host-specific signals in spatially and temporally separated C. jejuni populations suggests the existence of strong purifying selection for this bacterium in European Blackbirds.
|
|
| 8. |
- Hansbro, Philip M., et al.
(författare)
-
Surveillance and analysis of avian influenza viruses, Australia
- 2010
-
Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 16:12, s. 1896-1904
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated carriage of avian influenza viruses by wild birds in Australia, 2005-2008, to assess the risks to poultry industries and human health. We collected 21,858 (7,357 cloacal, 14,501 fecal) samples and detected 300 viruses, representing a detection rate of ≈1.4%. Rates were highest in autumn (March-May) and differed substantially between bird types, areas, and years. We typed 107 avian influenza viruses and identified 19 H5, 8 H7, and 16 H9 (40% of typed viruses). All were of low pathogenicity. These viruses formed clearly different phylogenetic clades to lineages from Eurasia or North America, suggesting the potential existence of Australian lineages. H7 viruses were similar to highly pathogenic H7 strains that caused outbreaks in poultry in Australia. Several periods of increased detection rates (numbers or subtypes of viruses) were identified. This study demonstrates the need for ongoing surveillance to detect emerging pathogenic strains and facilitate prevention of outbreaks.
|
|
| 9. |
- Kar, Rohan, et al.
(författare)
-
The FBXW7-NOTCH interactome : A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues
- 2021
-
Ingår i: Cancer Reports. - : John Wiley & Sons. - 2573-8348. ; 4:4
-
Forskningsöversikt (refereegranskat)abstract
- Background Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. Recent findings Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like beta TrcP1 and beta TrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. Conclusion The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.
|
|
| 10. |
- Patel, Vyoma K., et al.
(författare)
-
Tackling the cytokine storm using advanced drug delivery in allergic airway disease
- 2023
-
Ingår i: Journal of Drug Delivery Science and Technology. - : Elsevier. - 1773-2247. ; 82
-
Forskningsöversikt (refereegranskat)abstract
- Asthma is one of the leading causes of mortality worldwide presenting a huge socio-economic burden with rising morbidity and mortality rates. It is a chronic inflammatory airway disease that is eminent with multiple epidemiological and pathophysiological features such as over production of pro-inflammatory cytokines that triggers an uncontrolled aberrant inflammatory response known as 'cytokine storm'. This phenomenon interferes with the signalling and production of cytokines over time leading to the progression of disease and the development of complications that lead to fatal consequences in many individuals. Targeting this overproduction and signalling of cytokines may prove a promising approach to develop novel cytokine specific therapies in the treatment of asthma. This review discusses on the various pharmacological strategies, recent advancements in drug delivery systems and significant findings from clinical trials that may have a potential to outweigh the limitations of the current therapies in the treatment of asthma.
|
|
| 11. |
- Paudel, Keshav Raj, et al.
(författare)
-
Recent Advances in Chronotherapy Targeting Respiratory Diseases
- 2021
-
Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 13:12
-
Forskningsöversikt (refereegranskat)abstract
- Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h oscillation (sleep-wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an individual's circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.
|
|
