Background: Local renin-angiotensin system (RAS) activation has been shown to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). It has been reported that ...angiotensin-converting enzyme 2 (ACE2) could inhibit RAS-mediated epithelial injury and fibrogenesis and that ACE2 deficiency could aggravate acute and chronic lung injury. Through research, it could be deduced that ACE2 could protect against pulmonary fibrosis as a therapeutic target. Methods: Time-course analysis of the pathological characteristics of bleomycin-induced lung fibrosis was undertaken in a mouse model, and the effect of exogenous ACE2 on lung fibrosis was studied. Immunohistchemistry (IHC) staining and western blot (WB) testing for AGT and ACE2 were performed to evaluate the regulation of local RAS. TUNEL staining was used to observe epithelial apoptosis. Leukocyte common antigen (LCA) and pulmonary surfactant-associated protein A (SP-A) IHC staining and WB testing were performed to assess the inflammatory response and epithelial regeneration. Masson's staining and a hydroxyproline assay were performed to examine collagen deposition. IHC staining and WB testing for TGF-β1 and α-SMA were performed to investigate the regulation of pro-fibrotic cytokines and the activation of fibroblasts. Results: Exogenous ACE2 attenuated bleomycin-induced lung fibrosis by reversing the reduction of local ACE2 and by suppressing the elevation of AGT. ACE2 decreased the apoptosis index and LCA levels and ameliorated the dynamic change in SP-A level, thus protecting against epithelial injury. Reductions of TGF-β1 and α-SMA were also found in ACE2-treated mice, indicating the inhibition of fibrogenesis. Conclusion: ACE2 attenuated bleomycin-induced lung fibrosis as an anti-inflammatory anti-apoptotic and anti-fibrotic agent, and it might be a promising therapeutic target for IPF.
Purpose To compare autograft with allograft in anterior cruciate ligament reconstruction by conducting a meta-analysis of randomized controlled trials (RCTs) and a systematic review of overlapping ...systematic reviews. Methods PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 28, 2014, to identify Level I and II evidence RCTs with a minimum follow-up of 2 years and systematic reviews that compared autograft with allograft in anterior cruciate ligament reconstruction. Both objective and subjective outcomes with respect to knee stability and function were meta-analyzed and summarized. The overall risk ratio (RR) or the weighted mean difference (WMD) was calculated using either a fixed- or random-effects model. The quality of evidence of the systematic review of overlapping systematic reviews was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Results Nine RCTs and 10 systematic reviews were included. In general, statistically significant differences in favor of autograft were observed for clinical failure (RR, 0.47; P = .0007), the Lachman test (RR, 1.18; P = .03), the instrumented laxity test (WMD, −0.88; P = .004), and the Tegner score (WMD, 0.36; P = .004). When subgroup analyses were conducted based on whether irradiation was used, autograft achieved better clinical outcomes than irradiated allograft in terms of the Lysholm score, clinical failure, the pivot-shift test, the Lachman test, the instrumented laxity test, and the Tegner score. In addition, there were no significant differences between the autograft and nonirradiated allograft groups for all 8 indices. The final results of this systematic review of overlapping systematic reviews were in accordance with our meta-analysis. Conclusions Autograft had greater advantages than irradiated allograft with respect to function and stability, whereas there were no significant differences between autograft and nonirradiated allograft. Level of Evidence Level IV, meta-analysis of Level II, III, and IV studies.
The MIKC
C
-type gene family plays important roles in plant growth, development, and tolerance of biotic and abiotic stress, especially during floral organ differentiation. However, there have been ...no studies of MIKC
C
-type genes in rose, and functional differentiation of family members has not been explored. In this study, we identified 42 MIKC
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-type genes in rose, classified the genes into 12 subfamilies, and constructed a phylogenetic tree. We performed expression analysis of these genes, and found that expression patterns correlated with the predicted subfamily, indicating that the features of MIKC
C
-type genes were broadly conserved during evolution. Collinear analysis of MIKC
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genes among Rosaceae species confirmed the occurrence of whole genome duplications (WGD) and revealed some species-specific MIKC
C
genes. Transcriptome analysis showed that the expression of some MIKC
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-type genes responded to low temperatures (4°C, 24 h) during flower organ differentiation. These conserved, duplicated, and novel expression patterns of MIKC
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-type genes may have facilitated the adaptation of rose to various internal and external environmental changes. The results of this study provide a theoretical basis for future functional analysis of the MIKC
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genes in rose and investigation of the evolutionary pattern of the MIKC
C
gene family in the Rosaceae genome.
Background
Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered specific species and ...functional capacities of the microbes. We performed shotgun metagenomic sequencing to compare the gut microbiome composition and function between individuals with and without sarcopenia.
Methods
Participants were from a community‐based observational study conducted among the residents of rural areas in China. Appendicular skeletal muscle mass was assessed using direct segmental multi‐frequency bioelectrical impedance and grip strength using a Jamar Hydraulic Hand dynamometer. Physical performance was evaluated using the Short Physical Performance Battery, 5‐time chair stand test and gait speed with the 6 m walk test. Sarcopenia and its severity were diagnosed according to the Asian Working Group for Sarcopenia 2019 algorithm. The gut microbiome was profiled by shotgun metagenomic sequencing to determine the microbial composition and function. A gut microbiota‐based model for classification of sarcopenia was constructed using the random forest model, and its performance was assessed using the area under receiver‐operating characteristic curve (AUC).
Results
The study sample included 1417 participants (women: 58.9%; mean age: 63.3 years; sarcopenia prevalence: 10.0%). β‐diversity indicated by Bray–Curtis distance (genetic level: P = 0.004; taxonomic level of species: P = 0.020), but not α‐diversity indicated by Shannon index (genetic level: P = 0.962; taxonomic level of species: P = 0.922), was significantly associated with prevalent sarcopenia. After adjusting for potential confounders, participants with sarcopenia had higher relative abundance of Desulfovibrio piger (P = 0.003, Q = 0.090), Clostridium symbiosum (P < 0.001, Q = 0.035), Hungatella effluvii (P = 0.003, Q = 0.090), Bacteroides fluxus (P = 0.002, Q = 0.089), Absiella innocuum (P = 0.002, Q = 0.072), Coprobacter secundus (P = 0.002, Q = 0.085) and Clostridium citroniae (P = 0.001, Q = 0.060) than those without sarcopenia. The relative abundance of six species (Desulfovibrio piger, Clostridium symbiosum, Hungatella effluvii, Bacteroides fluxus, Absiella innocuum, and Clostridium citroniae) was also positively associated with sarcopenia severity. A differential species‐based model was constructed to separate participants with sarcopenia from controls. The value of the AUC was 0.852, suggesting that model has a decent discriminative performance. Desulfovibrio piger ranked the highest in this model. Functional annotation analysis revealed that the phenylalanine, tyrosine, and tryptophan biosynthesis were depleted (P = 0.006, Q = 0.071), while alpha‐Linolenic acid metabolism (P = 0.008, Q = 0.094), furfural degradation (P = 0.001, Q = 0.029) and staurosporine biosynthesis (P = 0.006, Q = 0.072) were enriched in participants with sarcopenia. Desulfovibrio piger was significantly associated with staurosporine biosynthesis (P < 0.001).
Conclusions
This large population‐based observational study provided empirical evidence that alterations in the gut microbiome composition and function were observed among individuals with sarcopenia.
To examine the cross-sectional associations between dietary magnesium (Mg) intake and radiographic knee osteoarthritis (OA), joint space narrowing (JSN), and osteophytes (OST) respectively.
A total ...of 1626 subjects were included in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade 2 in at least one leg. JSN and OST were assessed individually according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the various associations after adjusting for potentially confounding factors.
The relative odds of radiographic knee OA were decreased by 0.53 times in the third quintile of Mg intake odds ratio (OR) 0.53, 95% confidence interval (CI) 0.28-1.01, 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.17-0.94) and 0.34 times in the fifth quintile (OR 0.34, 95% CI 0.11-1.00) compared with those in the lowest quintile, while P for trend was 0.111. The relative odds of JSN were decreased by 0.49 times in the third quintile of Mg intake (OR 0.49, 95% CI 0.28-0.88) and 0.37 times in the fifth quintile (OR 0.37, 95% CI 0.14-0.98) compared with those in the lowest quintile, while P for trend was 0.088. There was no significant relationship between dietary Mg intake and the presence of OST.
The findings of this cross-sectional study indicate that Mg intake is inversely associated with radiographic knee OA and JSN. It supports potential role of Mg in the prevention of knee OA.
LevelIII, cross-sectional study.
Abstract
Background
There is paucity of data on the prevalence of ultrasound-detected synovial abnormalities in the general population, and the relationship between synovial changes and knee pain ...remains unclear. We examined the prevalence of synovial abnormalities on ultrasound and the relationship of these features with knee pain and radiographic osteoarthritis (ROA) in a community sample.
Methods
Participants aged 50 years or over were from the Xiangya Osteoarthritis Study, a community-based cohort study. Participants were questioned about chronic knee pain and underwent (1) ultrasonography of both knees to determine presence of synovial hypertrophy (≥ 4 mm), effusion (≥ 4 mm), and Power Doppler signal PDS; yes/no; and (2) standard radiographs of both knees (tibiofemoral and patellofemoral views) to determine ROA.
Results
There were 3755 participants (mean age 64.4 years; women 57.4%). The prevalence of synovial hypertrophy, effusion, and PDS were 18.1% (men 20.2%; women 16.5%), 46.6% (men 49.9%; women 44.2%), and 4.9% (men 4.9%; women 5.0%), respectively, and increased with age (P for trend < 0.05). Synovial abnormalities were associated with knee pain, with adjusted odds ratios (aORs) of 2.39 (95% confidence interval CI 2.00–2.86) for synovial hypertrophy, 1.58 (95%CI 1.39–1.80) for effusion, and 4.36 (95%CI 3.09–6.17) for PDS. Similar associations with ROA were observed, the corresponding aORs being 4.03 (95%CI 3.38–4.82), 2.01 (95%CI 1.76–2.29), and 6.49 (95%CI 4.51–9.35), respectively. The associations between synovial hypertrophy and effusion with knee pain were more pronounced among knees with ROA than those without ROA, and the corresponding
P
for interaction were 0.004 and 0.067, respectively.
Conclusions
Knee synovial hypertrophy and effusion are more common and increase with age, affecting men more than women. All three ultrasound-detected synovial abnormalities associate both with knee pain and ROA, and knee synovial hypertrophy or effusion and ROA may interact to increase the risk of knee pain.
Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. ...Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199). Nrf2 then induces expression of its target genes, including a new target, cadherin 5, a key component of adherens junctions of the BBB. These effects culminate in mitigation of BBB leakage and of neurological deficits after stroke. Collectively, these studies are the first to demonstrate that IPC protects the BBB against ischemic injury by generation of endogenous electrophiles and activation of the Nrf2 pathway through inhibition of Keap1- and GSK3β-dependent Nrf2 degradation.
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Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting ...Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined.
We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1
. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3-5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry.
STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice.
Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.
Acute invasive fungal rhinosinusitis (AIFR) is a rare disease, but the prognosis is by no means ideal. Pathologically, fungal infection is not only located in the sinus cavity, but also invades the ...sinus mucosa and bone wall, the surrounding structures and tissues such as the orbit and anterior skull base are often compromised and are accompanied with intracranial and extracranial complications. Despite decades of efforts, acute invasive fungal rhinosinusitis remains a devastating disease, the mortality of the disease continues to hover around 50%. The main impediments to improving the prognosis of acute invasive fungal rhinosinusitis are the difficulties of early diagnosis and the rapid reversal of immune insufficiency. Moreover, aggressive surgery combined with systemic antifungal therapy are significant positive prognostic factors as well. Progress and standardization of AIFR treatment protocols have been limited by the scarcity of the disease and the absence of published randomized studies. Therewith, how to improve the therapeutic outcome and reduce the mortality rate has always been a challenging clinical discussion. We have summarized the relevant case series and literature from the recent years, management with optimal diagnostic and curative strategies are reviewed.