Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken ...down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-Formula: see text and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-Formula: see text, IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-Formula: see text and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.
The optimal follow-up protocol after treatment of oral cavity cancer patients is still debatable. We aimed to investigate the impact of frequency of different imaging studies and follow-up visits on ...the survival of oral cavity cancer patients. The current study retrospectively reviewed oral cavity cancer patients who underwent surgical intervention in our hospital. Basic demographic data, tumor-related features, treatment modalities, imaging studies, and clinic visits were recorded. Cox proportional hazard model was used to examine the influence of variables on the survival of oral cavity cancer patients. In total, 741 patients with newly diagnosed oral cavity cancer were included in the final analysis. Overall, the frequency of imaging studies was not associated with survival in the multivariate analysis, except PET scan (hazard ratio HR: 5.30, 95% confidence interval CI: 3.57-7.86). However, in late-stage and elder patients, frequent head and neck CT/MRI scan was associated with a better prognosis (HR: 0.55, 95% CI: 0.36-0.84; HR: 0.52, 95% CI: 0.30-0.91, respectively). In conclusion, precision medicine is a global trend nowadays. Different subgroups may need different follow-up protocols. Further prospective study is warranted to clarify the relationship between frequency of image studies and survival of oral cavity cancer patients.
The four and a half LIM domain protein 2 (FHL2) is a member of the four and a half LIM domain (FHL) gene family, and it is associated with cholesterol‐enriched diet‐promoted atherosclerosis. However, ...the effect of FHL2 protein on vascular remodelling in response to hemodynamic alterations remains unclear. Here, we investigated the role of FHL2 in a model of restricted blood flow‐induced atherosclerosis. To promote neointimal hyperplasia in vivo, we subjected FHL2+/+ and FHL2−/− mice to partial ligation of the left carotid artery (LCA). The expression of p‐ERK and p‐AKT was decreased in FHL2−/− mice. FHL2 bound to AKT regulated AKT phosphorylation and led to Rac1‐GTP inactivation. FHL2 silencing in human aortic smooth muscle cells down‐regulated the PDGF‐induced phosphorylation of ERK and AKT. Furthermore, FHL2 silencing reduced cytoskeleton conformational changes and caused cell cycle arrest. We concluded that FHL2 is essential for the regulation of arterial smooth muscle cell function. FHL2 modulates proliferation and migration via mitogen‐activated protein kinase (MAPK) and PI3K‐AKT signalling, leading to arterial wall thickening and thus neointimal hyperplasia.
Fabry disease is a treatable lysosomal storage disorder, which is often misdiagnosed or belatedly diagnosed.
To determine the disease incidence in the Taiwan Chinese population, a Fabry disease ...newborn screening study was initiated. A total of 110 027 newborns were screened by assaying the alpha-galactosidase A (alpha-Gal A) activity using dry blood spots. Low plasma alpha-Gal A activity and presence of a Fabry mutation was demonstrated in 45 neonates (3 females). Eight different mutations were identified, including 3 known missense mutations (R112H, A143T, and R356W), 4 novel missense mutations (G104V, M296L, G360C, and K391T), and one known intronic mutation (IVS4+919G-->A). The IVS4+919G-->A mutation was most common (82% of patients). A total of 20 maternal grandparents of infants harboring this intronic mutation were evaluated by echocardiography, mutation analysis and alpha-Gal A activity assay. The intronic mutation was found in 9 grandfathers and 11 grandmothers. Of these grandparents, 3 grandfathers (33%) but none of the grandmothers had hypertrophic cardiomyopathy. Additionally, 16 males who had been diagnosed with idiopathic hypertrophic cardiomyopathy were screened by mutation analysis and alpha-Gal A activity; 4 (25%) showed deficient plasma alpha-Gal A activity in combination with the intronic mutation.
We found an unexpected high prevalence of the cardiac variant Fabry mutation IVS4+919G-->A among both newborns (approximately 1 in 1600 males) and patients with idiopathic hypertrophic cardiomyopathy in the Taiwan Chinese population. The early identification of undiagnosed patients allows timely therapeutic intervention providing a better clinical outcome.
Background
Few large‐scale cohort studies have investigated the association between community‐acquired pneumonia and the use of angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin II ...receptor blockers (ARBs). We aimed to study whether using ACEIs or ARBs had protective effects for community‐acquired pneumonia.
Methods
This database cohort study was conducted retrospectively in Taiwan. The hypertensive patients were the target population of this study. Patients with ARB use were defined as our first study cohort. The second study cohort comprised patients who used ACEI. Propensity‐score matching at 1:1 was used between ARB users and non‐ARB users. We recruited 67 944 participants for the ARB study and 58 062 participants for the ACEI study. The same matching was also performed between ACEI users and non‐ACEI users. Cox proportional hazard regression was used to analyse the risk of the outcome of viral pneumonia.
Results
The hazard ratio of community‐acquired pneumonia for ARB users relative to non‐ARB users was 0.33. The hazard ratio of community‐acquired pneumonia was 0.71 times in ACEI users compared with ACEI nonusers. In stratification analysis, both ARB and ACEI both exhibited a protective effect for community‐acquired pneumonia in each age and sex group. In the analysis of the effects of therapy duration, patients using ARB for fewer than 100 days exhibited a greater reduction in the risk of community‐acquired pneumonia (adjusted HR = 0.58) compared with the non‐ARB cohort. For the ACEI study, patients who used ACEI for 121‐450 days were more likely to exhibit reduced risks of community‐acquired pneumonia (adjusted HR = 0.5).
Conclusion
Both ACEI and ARB uses were associated with decreased risk of community‐acquired pneumonia infection.
This study examines diatom assemblages in the Matsu Archipelago, an area influenced by Minjiang River runoff. It focuses on harmful algal blooms (HABs) that occurred between August 2021 and July ...2022. Utilizing 18S rRNA metabarcoding and microscopic analysis, we observed a significant diatom bloom during early summer runoff, peaking at 5 × 105 cells L−1. The research reveals dynamic community changes during the runoff season, with dominant genera including Pseudo-nitzschia, Chaetoceros, and Skeletonema. Skeletonema cell density correlated with NO3 levels, Chaetoceros had a slight PO4 affinity, and Pseudo-nitzschia showed a negative correlation with Skeletonema. Pseudo-nitzschia, which prefers high light and pH conditions, had notably high concentrations in the flood season and in the autumn. In both, it was dominated by potential toxin-producing species - P. multistriata and P. pungens during the flooding, and P. cuspidate in the autumn. These findings highlight the intricate relationship between diatom dynamics and environmental factors, providing essential insights for managing HABs, especially Pseudo-nitzschia species, amidst environmental changes.
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•During the flood period, a diatom bloom was observed, with Pseudo-nitzschia, Chaetoceros, and Skeletonema as the dominant genera.•In studying diatom community composition, we suggest that while microscopy provides the total count, sequencing offers a more detailed composition at the species level.
Intercellular cross-talking was suggested in matrix metalloproteinase (MMP)-9 expression with unknown mechanisms. Studies showed cyclophilin A (CypA) playing an important role in regulating MMP-9 ...expression in varied diseases. The aim of the study was to examine the CyPA on the MMP-9 augmentation in monocytic U937 cells after Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) treatment and human gingival fibroblast (hGF) co-culture.
In independent culture or co-culture of hGF and U937 cell, quantitative real-time polymerase chain reaction (qPCR) and zymography were selected to examine the mRNA and protein activity of MMP-9, respectively. The CyPA expression was determined by qPCR.
LPS could enhance MMP-9 mRNA expression and enzyme activity in U937 cell. However, the enhancements were not observed in hGF. Similarly, LPS enhanced CyPA mRNA in U937, but not in hGF. After co-cultured with hGF, however, MMP-9 and CyPA in U937 increased regardless of the presence/absence of LPS. In U937 cells, the extra-supplied CyPA increased MMP-9 mRNA and enzyme activity, whereas the CyPA inhibitor, cyclosporine A, suppressed the LPS- and co-culture-enhanced MMP-9. Moreover, the inhibitors for MAP kinase, including PD98059 (ERK) and SP600125 (JNK), suppressed the CyPA-enhanced MMP-9 in U937.
Through the CyPA pathway, the LPS and the hGF could augment the MMP-9 expression in the U937 cells.
Background and Aims
Colonoscopic polypectomy in end‐stage renal disease (ESRD) patients are at risks of post‐polypectomy bleeding and perforation, but evidences are limited. This study aimed to ...determine the incident polypectomy complications among ESRD patients.
Methods
In the nationwide ESRD cohort, a propensity score matched case–control study design was conducted to assess risk associated with post‐polypectomy bleeding and perforation using the Taiwanese National Health Insurance Research Database from 1997 to 2013 for adults aged 40 years and older; 7011 ESRD and 19 118 non‐ESRD patients met the study criteria. A total of 5302 patients in each group were matched for further analyses. The primary endpoint was post‐polypectomy bleeding or bowel perforation in 30 days. The secondary endpoint was mortality and length of hospital stay for the bleeding complications requiring hospitalization.
Results
Overall incidences of post‐polypectomy bleeding or perforation in patients with ESRD was higher than the non‐ESRD group (5.83% vs 1.78%, P < 0.0001) in the matched cohort. High risk of adverse outcomes was associated with ESRD (adjusted odds ratio aOR, 2.38, 95% confidence interval CI, 1.85–3.05), female patient (aOR, 1.7, 95% CI, 1.37–2.11), history of acute myocardial infarction (aOR, 1.91, 95% CI, 1.1–3.32), liver disease (aOR, 1.79, 95% CI, 1.37–2.34), diabetes (aOR, 1.45, 95% CI, 1.16–1.82), cancer (aOR, 1.4, 95% CI, 1.09–1.81), inpatient setting (aOR, 13.19, 95% CI, 9.73–17.88), and prior use of clopidogrel (aOR, 1.61, 95% CI, 1.03–2.52) and warfarin (aOR, 2.03, 95% CI, 1.21–3.41).
Conclusions
End‐stage renal disease was associated with approximately twofold higher risk of colonoscopic post‐polypectomy bleeding or perforation and should be cautiously performed in this special population cohort.
Thymosin beta-4 (TMSB4X) was recently identified as a differentially expressed gene between malignant and non-malignant thyroid cells via single-cell RNA sequencing. In the present study, we aimed to ...study the immunostaining pattern of TMSB4X in benign and malignant thyroid neoplasms. Immunohistochemical analysis revealed that normal thyroid tissue or benign thyroid disorders exhibited undetectable immunoreactivity against TMSB4X except for positive staining of inflammatory infiltrates and stromal cells associated with autoimmune thyroid disease. By contrast, overexpression of TMSB4X was observed in a variety of thyroid malignancies, including papillary, follicular, poorly differentiated, and undifferentiated thyroid cancer. Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was associated with papillary tumor type, extrathyroidal extension, lymph node metastasis, and BRAF V600E mutation. The results were consistent with those from the public transcriptomic datasets. In summary, TMSB4X expression was aberrantly increased in various types of thyroid cancer, and higher TMSB4X expression was correlated with advanced disease characteristics. Thymosin beta-4 may be a novel downstream effector of the BRAF V600E mutation.
This paper presents a low-power, programmable acoustic signal processor for hearing assistive devices with speech intelligibility enhancement. The reprogrammable design provides considerable ...flexibility for the devices to deal with personal conditions of hearing loss. A spectral-change enhancement (SCE) algorithm is implemented to improve speech intelligibility. The power consumption is minimized by adding dedicated hardware accelerators. The short-time objective intelligibility (STOI) measure is utilized for optimizing the datapath architecture. Optimization on the critical MAC operations results in 34% power and area reductions when compared to the direct-mapped design. A 50% reduction in SRAM storage is also achieved owing to the reduced memory storage for the associated MAC operations. With the aid of the optimized MAC unit and data buffer, the overall execution time is reduced by 99.2%. Designed in a 40-nm CMOS technology, the processor integrates 431k gates in area of 0.3 mm 2 . The design dissipates 1.5 mW at a clock frequency of 10.5 MHz from a 0.7V supply, with a processing latency of 1.05 ms.
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