Cystatin SN in type 2 inflammatory airway diseases.

Cystatin SN, encoded by CST1, belongs to the type 2 (T2) cystatin protein superfamily. In the past decade, several publications have highlighted the association between cystatin SN and inflammatory airway diseases including chronic rhinosinusitis, rhinitis, asthma, chronic obstructive pulmonary disease, and chronic hypersensitivity pneumonitis. It is, therefore, crucial to understand the role of cystatin SN in the wider context of T2 inflammatory diseases. Here, we review the expression of cystatin SN in airway-related diseases with different endotypes. We also emphasize the physiological and pathological roles of cystatin SN. Physiologically, cystatin SN protects host tissues from destructive proteolysis by cysteine proteases present in the external environment or produced via internal dysregulated expression. Pathologically, the secretion of cystatin SN from airway epithelial cells initiates and amplifies T2 immunity and subsequently leads to disease. We further discuss the development of cystatin SN as a T2 immunity marker that can be monitored noninvasively and assist in airway disease management. The discovery, biology, and inhibition capability are also introduced to better understand the role of cystatin SN in airway diseases.

Extraction optimization, physicochemical property, antioxidant activity, and α-glucosidase inhibitory effect of polysaccharides from lotus seedpods.

BACKGROUND: Lotus seedpods are an agricultural by-product of lotus (Nelumbo nucifera Gaertn.), which is widely cultivated in Southeast Asia and Australia. Most lotus seedpods are considered waste and are abandoned or incinerated, resulting in significant waste of resources and heavy environmental pollution. For recycling lotus seedpods, the extraction optimization, physicochemical properties, antioxidant activity, and α-glucosidase inhibitory effect of the polysaccharides contained therein were investigated in this study. RESULTS: Hot water extraction of lotus seedpod polysaccharides was optimized by using a response surface methodology combined with a Box-Behnken design, with the optimum conditions being as follows: a liquid/solid ratio of 25.0 mL g-1 , an extraction temperature of 98.0 °C, and an extraction time of 138.0 min. Under these conditions, an experimental yield of 5.88 ± 0.06% was obtained. Physicochemical analyses suggested that lotus seedpod polysaccharides belong to acidic heteropolysaccharides and are principally composed of rhamnose, arabinose, galactose, glucose, mannose, and galacturonic acid. The polysaccharides content has a broad molecular weight distribution (2.15 × 105 to 1.77 × 107 Da), an α-configuration, and mainly possesses smooth and sheet-like structures. Biological evaluations showed that the polysaccharides possessed good scavenging activity on 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, 1,1-diphenyl-2-picryl-hydrozyl, and hydroxyl radicals, and exerted an obvious inhibitory effect on α-glucosidase activity. Moreover, the polysaccharides content was determined to be a mixed-type noncompetitive inhibitor of α-glucosidase. CONCLUSION: The results indicate that lotus seedpod polysaccharides have potential as natural antioxidants and hypoglycaemic substitutes. This study provides the theoretical bases for the exploitation and application of polysaccharides from lotus seedpod by-product resources. © 2022 Society of Chemical Industry.

Non-linear association between diabetes mellitus and pulmonary function: a population-based study.

BACKGROUND: There is increasing evidence that the lung is a target organ of diabetes. This study aimed to examine in detail the association between diabetes mellitus and pulmonary function using a national cohort. We also aimed to explore the non-linear association between pulmonary function and blood glucose, insulin resistance, and C-reactive protein (CRP). METHODS: A total of 30,442 participants from the National Health and Nutrition Examination Survey from the period between 2007 and 2012 were included. The cross-sectional association between diabetes mellitus and pulmonary function was assessed using multiple linear regression. Where there was evidence of non-linearity, we applied a restricted cubic spline with three knots to explore the non-linear association. Partial mediation analysis was performed to evaluate the underlying mechanism. All analyses were weighted to represent the US population and to account for the intricate survey design. RESULTS: A total of 8584 people were included in the final study population. We found that diabetes was significantly associated with reduced forced expiratory volume in one second (FEV1) and forced vital capacity. We further found L-shaped associations between hemoglobin A1c (HbA1c) and pulmonary function. There was a negative association between HbA1c and FEV1 in diabetes participants with good glucose control (HbA1c < 7.0%), but not in patients with poor glucose control. A non-linear association was also found with fasting plasma glucose, 2 h-plasma glucose after oral glucose tolerance test, insulin resistance, and CRP. Finally, we found that diabetes duration did not affect pulmonary function, and the deleterious effect of diabetes on pulmonary function was mediated by hyperglycemia, insulin resistance, low-grade chronic inflammation (CRP), and obesity. CONCLUSIONS: Diabetes mellitus is non-linearly associated with pulmonary function. Our finding of a negative association between HbA1c and FEV1 in diabetes patients with good glucose control but not in patients with poor glucose control indicates that a stricter glycemic target should be applied to diabetic patients to improve pulmonary function. Given, the cross-sectional nature of this research, a longitudinal study is still needed to validate our findings.

Obstructive sleep apnea is associated with coronary microvascular dysfunction: A systematic review from a clinical perspective.

There is now increasing evidence demonstrating that obstructive sleep apnea (OSA) contributes to microvascular disorder. However, whether OSA is associated with impaired coronary flow reserve is still unclear. Therefore, we conducted this systematic review and meta-analysis to summarize current evidence. In a systematic review, PubMed, Embase, the Cochrane Library and Web of Science were searched; five observational studies fulfilled the selection criteria and were included in this study. Data were extracted from selected studies and meta-analysis was performed using random-effects modelling. In all, 829 OSA patients and 507 non-OSA subjects were included and assessed for coronary flow reserve (CFR), the clinical indicator of coronary microvascular dysfunction (CMD). For all studies, OSA was significantly associated with reduced CFR. The pooled weighted mean difference (WMD) of CFR was -0.78 (95% confidence interval [CI] -1.25 to -0.32, p ï¼œ 0.001, I2  = 84.4%). The difference in the apnea-hypopnea index (AHI) between studies can explain 89% of heterogeneity (coef = -0.05, 95% CI -0.12 to 0.02, p = .078) in a meta-regression, indicating the CFR tended to negatively correlate with severity of OSA. The Egger regression test did not show statistical significance (p = .49). In conclusion, there are plausible biological mechanisms linking OSA and CMD, and the preponderance of evidence from this systematic review suggests that OSA, especially severe OSA, is associated with reduced CFR. Future studies are warranted to further delineate the exact role of OSA in CMD occurrence and development in a prospective setting.

Could Vitamin D be Associated with Proliferative Diabetic Retinopathy? Evidence from Pooling Studies.

Contrasting data about the association between proliferative diabetic retinopathy (PDR) and vitamin D status remain unknown. First, a hospital-based cross-sectional study consisting of 889 diabetic retinopathy (DR) and non-DR (NDR) patients was admitted. Further the accumulated evidence was performed to explore the association and dose-response relationship. Our study indicated that the odd ratio for PDR in vitamin D deficiency (VDD) individuals was significantly increased (1.60, 95% CI 1.06-2.42), compared with NDR in vitamin D sufficiency individuals, adjusted by age, sex, diabetic duration, and HbA1c. Four studies plus our study with data on vitamin D levels in 4970 patients with PDR and NDR subjects are compared. Association between vitamin D deficiency and risk of PDR exists (OR=1.69, 95% CI 1.40-2.05; I2=0%, p=0.61). Association between a nonlinear trend for vitamin D decrease with risk of DR was significant (chi2=16.53, p=0.0003). No significant heterogeneity in identified studies was found (goodness of fit chi2=2.98, p=0.225). It is concluded that vitamin D deficiency is significantly associated with risk of proliferative diabetic retinopathy.

Non-linear association of anthropometric measurements and pulmonary function.

This study examined the association of anthropometric measurements [body mass index (BMI), waist circumference (WC), percentage body fat (PBF), body roundness index (BRI) and A Body Shape Index (ABSI)] with pulmonary function using a United States national cohort. This cross-sectional study included 7346 participants. The association between anthropometric measurements and pulmonary function was assessed by multivariable linear regression. Where there was evidence of non-linearity, we applied a restricted cubic spline to explore the non-linear association. All analyses were weighted to represent the U.S. population and to account for the intricate survey design. After adjusting for age, race, education, smoking, and physical activity, both underweight and obesity were associated with reduced forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Furthermore, the associations between BMI and FEV1, as well as FVC, were reversed U-shape in both males and females. Similar non-linear association shape occurred in WC, PBF, BRI and ABSI. Conclusion: BMI, WC, PBF, BRI, ABSI are non-linearly associated with pulmonary function. Reduced pulmonary function is a risk factor for future all-cause mortality and cardiovascular events; thus, this nonlinearity may explain the U-shape or J-shape association of BMI with overall mortality and cardiovascular events.

Bidirectional relationship between diabetes and pulmonary function: a systematic review and meta-analysis.

AIM: Evidence of the lungs being a target organ of diabetes-related pathophysiology is increasing, and decreased pulmonary function increases the risk of diabetes after adjusting for demographic and metabolic factors. This systematic review and meta-analysis evaluates the bidirectional relationship between diabetes and pulmonary function. METHODS: MEDLINE, Embase, The Cochrane Library and Web of Science databases were searched, and all studies describing this bidirectional relationship were identified. Two reviewers independently extracted study characteristics and assessed the risk of bias. RESULTS: A total of 93 studies were included in the meta-analysis. The pooled weighted mean difference (WMD) between diabetes patients and non-diabetic participants for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were -5.65% and -5.91%, respectively, of predicted values. Diabetes-related microvascular complications and poor glycaemic control were associated with poorer pulmonary function in those with diabetes. In addition, diabetes was associated with a restrictive spirometry pattern (RSP) in both cross-sectional studies [odds ratio (OR): 2.88, 95% confidence interval (CI): 2.18-3.81, I2 = 0.0%] and prospective cohort studies [hazard ratio (HR): 1.57, 95% CI: 1.04-2.36]. In five longitudinal studies, the conclusions were inconsistent as to whether or not diabetes accelerates pulmonary function decline. However, every 10% decrease in baseline predicted FVC value was associated with a 13% higher risk of incident diabetes (HR: 1.13, 95% CI: 1.09-1.17, I2 = 0.0%). CONCLUSION: There is a bidirectional relationship between diabetes and pulmonary function. However, further investigations into whether dynamic changes in glycaemic levels before and shortly after diabetes onset mediate the deleterious effects on pulmonary function, or vice versa, are now required.

Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies.

OBJECTIVES: Maternal diabetes mellitus (including pre-existing and gestational diabetes mellitus) is linked with adverse infant outcomes. However, the question of whether maternal diabetes increases the risk of persistent pulmonary hypertension of the newborn (PPHN) is unclear. Herein, we conducted a systematic review and meta-analysis to summarize clinical evidence to determine the association between maternal diabetes mellitus and PPHN. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, Cochrane Library, Web of Science and Google Scholar to identify relevant studies according to predefined criteria. Data from selected studies were extracted, and meta-analysis was performed using fixed effects modelling. RESULTS: In all, we included 7 unique studies with aggregated data on 2 million individuals and >5,000 cases of PPHN. Maternal diabetes was significantly associated with a higher risk of PPHN (risk ratio [RR], 1.37; 95% confidence interval [CI], 1.23 to 1.51). Both case-control and cohort studies exhibited that the presence of maternal diabetes increased the risk of PPHN (case-control: RR, 1.91; 95% CI, 1.02 to 2.79; cohort: RR, 1.36; 95% CI, 1.22 to 1.50). By omitting 1 study at a time, sensitivity analysis made sure that no individual study was entirely responsible for the combined results. CONCLUSIONS: Maternal diabetes was associated with increased risk of PPHN. For babies with refractory hypoxemia, with mothers with diabetes, PPHN should be taken into consideration in clinical practice.