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Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea. 61Qdns8RY7g31YGFsWcfG1 Video Abstract [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in the pathogenesis of AD, but their crosstalk in AD has not been studied. In this study, the independent role and interaction of mitochondria-related genes and immune cell infiltration in AD were investigated using bioinformatics methods. Methods: The datasets of AD were obtained from NCBI Gene Expression Omnibus (GEO), and the data of mitochondrial genes was from MitoCarta3.0 database. Subsequently, differential expression genes (DEGs) screening and GSEA functional enrichment analysis were performed. The intersection of DEGs and mitochondrial related genes was used to obtain MitoDEGs. The MitoDEGs most relevant to AD were determined by Least absolute shrinkage and selection operator and multiple support vector machine recursive feature elimination, as well as protein–protein interactions (PPI) network and random forest. The infiltration of 28 kinds of immune cells in AD was analyzed by ssGSEA, and the relationship between hub MitoDEGs and the proportion of immune infiltration was studied. The expression levels of hub MitoDEGs were verified in cell models and AD mice, and the role of OPA1 in mitochondrial damage and neuronal apoptosis was investigated. Results: The functions and pathways of DEGs were significantly enriched in AD, including immune response activation, IL1R pathway, mitochondrial metabolism, oxidative damage response and electron transport chain-oxphos system in mitochondria. Hub MitoDEGs closely related to AD were obtained based on PPI network, random forest and two machine learning algorithms. Five hub MitoDEGs associated with neurological disorders were identified by biological function examination. The hub MitoDEGs were found to be correlated with memory B cell, effector memory CD8 T cell, activated dendritic cell, natural killer T cell, type 17 T helper cell, Neutrophil, MDSC, plasmacytoid dendritic cell. These genes can also be used to predict the risk of AD and have good diagnostic efficacy. In addition, the mRNA expression levels of BDH1, TRAP1, OPA1, DLD in cell models and AD mice were consistent with the results of bioinformatics analysis, and expression levels of SPG7 showed a downward trend. Meanwhile, OPA1 overexpression alleviated mitochondrial damage and neuronal apoptosis induced by Aβ1-42. Conclusions: Five potential hub MitoDEGs most associated with AD were identified. Their interaction with immune microenvironment may play a crucial role in the occurrence and prognosis of AD, which provides a new insight for studying the potential pathogenesis of AD and exploring new targets. [ABSTRACT FROM AUTHOR]

Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer's disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: Otitis externa is a commonly diagnosed dermatological disorder in canines. The pathogens primarily involved in canine otitis externa (COE) include Staphylococcus pseudintermedius, Pseudomonas aeruginosa, Proteus mirabilis, and Malassezia pachydermatis. As COE tends to be superficial, medications delivered topically are often effective and practical in managing the condition. As such, there is a wide variety of approved topical products currently available in the market. The efficacy of topical dosage forms can be dependent on various factors such as the pharmacology of active constituents and the physicochemical properties of the formulation, including pH, viscosity, spreadability, and bio-adhesion. Currently, there is a lack of published literature available on the optimal properties of topical COE products. In this study, we compared the physicochemical properties of nine commercially available otic veterinarian products in Australia used clinically to manage COE. Results: Based on our comparative analysis, the pH (6.26 ± 0.04) of an aqueous-based product was similar to a healthy dog's external auditory canal. Products containing polymers exhibited higher viscosity and bio-adhesion. Spreadability was inversely related to viscosity and Osurnia ® a product with high viscosity demonstrated the lowest spreadability. Aqueous-based otic products showed better syringebility whereas oil-based systems required higher force to expel the products. Variability in droplet size was noted. Derm Otic, Baytril Otic, and Aurizon Ear Drops had the lower standard deviation which indicates they would give a more consistent dose. Conclusions: Findings from this work provide considerations for industry researchers or formulation scientists working in the area of otic dosage formulations. [ABSTRACT FROM AUTHOR]

Background: Thalassaemia is a common public health problem in Malaysia and about 4.5 to 6% of the Malays and Chinese are carriers of this genetic disorder. The major forms of thalassaemia result in death in utero of affected foetuses (a-thalassaemia) or life-long blood transfusions for survival in β-thalassaemia. This study, the first nationwide population based survey of thalassaemia in Malaysia, aimed to determine differences in public awareness, perceptions and attitudes toward thalassaemia in the multi-racial population in Malaysia. Methods: A cross-sectional computer-assisted telephone interview survey of a representative sample of multi-racial Malaysians aged 18 years and above was conducted between July and December 2009. Results: Of a total of 3723 responding households, 2846 (76.4%) have heard of thalassaemia. Mean knowledge score was 11.85 (SD ± 4.03), out of a maximum of 21, with higher scores indicating better knowledge. Statistically significant differences (P < 0.05) in total knowledge score by age groups, education attainment, employment status, and average household income were observed. Although the majority expressed very positive attitudes toward screening for thalassaemia, only 13.6% of married participants interviewed have been screened for thalassaemia. The majority (63.4%) were unsupportive of selective termination of foetuses diagnosed with thalassaemia major. Conclusion: Study shows that carrier and premarital screening programs for thalassaemia may be more effective and culturally acceptable in the reduction of pregnancies with thalassaemia major. The findings provide insights into culturally congruent educational interventions to reach out diverse socio-demographic and ethnic communities to increase knowledge and cultivate positive attitudes toward prevention of thalassaemia. [ABSTRACT FROM AUTHOR]

Background: Otitis externa is a commonly diagnosed dermatological disorder in canines. The pathogens primarily involved in canine otitis externa (COE) include Staphylococcus pseudintermedius, Pseudomonas aeruginosa, Proteus mirabilis, and Malassezia pachydermatis. As COE tends to be superficial, medications delivered topically are often effective and practical in managing the condition. As such, there is a wide variety of approved topical products currently available in the market. The efficacy of topical dosage forms can be dependent on various factors such as the pharmacology of active constituents and the physicochemical properties of the formulation, including pH, viscosity, spreadability, and bio-adhesion. Currently, there is a lack of published literature available on the optimal properties of topical COE products. In this study, we compared the physicochemical properties of nine commercially available otic veterinarian products in Australia used clinically to manage COE. Results: Based on our comparative analysis, the pH (6.26 ± 0.04) of an aqueous-based product was similar to a healthy dog's external auditory canal. Products containing polymers exhibited higher viscosity and bio-adhesion. Spreadability was inversely related to viscosity and Osurnia ® a product with high viscosity demonstrated the lowest spreadability. Aqueous-based otic products showed better syringebility whereas oil-based systems required higher force to expel the products. Variability in droplet size was noted. Derm Otic, Baytril Otic, and Aurizon Ear Drops had the lower standard deviation which indicates they would give a more consistent dose. Conclusions: Findings from this work provide considerations for industry researchers or formulation scientists working in the area of otic dosage formulations. [ABSTRACT FROM AUTHOR]