The allogeneic umbilical cord mesenchymal stem cells regulate the function of T helper 17 cells from patients with rheumatoid arthritis in an in vitro co-culture system

BACKGROUND: Previous in vivo studies have shown that mesenchymal stem cell (MSC) transplantation significantly improves the condition of a number of autoimmune diseases including autoimmune cerebrospinal meningitis, multiple sclerosis, glomerulonephritis and systemic lupus erythematosus. METHODS: To investigate the immunoregulatory effect of stem cell transplantation, human umbilical cord MSCs were co-cultured with peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA). Orphan nuclear receptor gamma (ROR-γ) mRNA and protein expression was detected with real-time PCR and Western blotting. Interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF-α) in the cell culture supernatant were measured using a flow cytometric bead capture method. RESULTS: After 72 hours of co-culture, the mRNA and protein expression levels of ROR-γ in co-cultured PBMCs were decreased compared with that in PBMC of RA patients cultured alone (p < 0.05). Moreover, the decrement was positively related to the disease activity of RA (p < 0.05). Decreased secretion of IL-17, TNF-α and IL-6 were also found in co-culture supernatants of PBMCs from patients with severe and moderate disease activity, but not in supernatant from PBMCs cultured alone. The decreased cytokine expression levels were positively correlated to the concentrations of MSCs. In contrast, PBMCs from healthy controls or patients with mild RA did not show significant differences in ROR-γ expression or cytokine secretion following co-culture with MSCs as compared with those cultured alone. CONCLUSIONS: In vitro co-culture with MSCs down-regulated the inflammatory response of PBMCs from RA patients with severe disease activity, but had no significant effect on PBMCs from healthy controls or patients with mild disease activity, suggesting that the immunoregulatory role of MSCs may associate with the occurrence of inflammatory mediators

Effect of Extraction Temperature on the Functional and Structural Properties of Mullet Scale Gelatin

The functional property is an important factor to measure the quality of fish gelatin, which directly relates to the practical application range and value of fish gelatin. In order to explore the effect of extraction temperature on the functional properties of mullet scale gelatin, this study used a hot water extraction method. Different temperatures (60, 70, 80, 90, 100 ℃) were examined to assess their impact on the surface morphology of fish scales, fish scale gelatin yield, and functional properties (foaming capacity, emulsifying activity, gel strength, gel temperature, and melting temperature). Furthermore, the structural characteristics of fish scale gelatin were investigated using SDS-PAGE, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that as the extraction temperature increased from 60 ℃ to 100 ℃, the damage to the surface of mullet scales became increasingly severe. The fish scale gelatin yield increased from 31.72% to 50.97%, foaming capacity improved from 23.33% to 73.33%, and emulsifying activity increased from 15.13 m2/g to 17.27 m2/g. However, gel strength, gel temperature, and melting temperature decreased from 677.82 g, 20.80 ℃, and 28.70 ℃ to 372.91 g, 15.80 ℃, and 23.90 ℃, respectively. Additionally, with the increase in extraction temperature, the characteristic bands of mullet scale gelatin α1, α2, and β chains on the electrophoresis pattern became increasingly blurred. The infrared spectroscopy results showed that the fish scale gelatin had characteristic absorption peaks (amide A, amide Ⅰ, amide Ⅱ, and amide Ⅲ), with the wavenumber of amide A first increasing and then decreasing. The scanning electron microscopy results showed that the tightness of the porous grid structure of the fish scale gelatin decreased. These findings provide a theoretical basis for the industrialization of mullet scale gelatin

Genome-wide identification of the AcMADS-box family and functional validation of AcMADS32 involved in carotenoid biosynthesis in Actinidia

MADS-box is a large transcription factor family in plants and plays a crucial role in various plant developmental processes; however, it has not been systematically analyzed in kiwifruit. In the present study, 74 AcMADS genes were identified in the Red5 kiwifruit genome, including 17 type-I and 57 type-II members according to the conserved domains. The AcMADS genes were randomly distributed across 25 chromosomes and were predicted to be mostly located in the nucleus. A total of 33 fragmental duplications were detected in the AcMADS genes, which might be the main force driving the family expansion. Many hormone-associated cis-acting elements were detected in the promoter region. Expression profile analysis showed that AcMADS members had tissue specificity and different responses to dark, low temperature, drought, and salt stress. Two genes in the AG group, AcMADS32 and AcMADS48, had high expression levels during fruit development, and the role of AcMADS32 was further verified by stable overexpression in kiwifruit seedlings. The content of α-carotene and the ratio of zeaxanthin/β-carotene was increased in transgenic kiwifruit seedlings, and the expression level of AcBCH1/2 was significantly increased, suggesting that AcMADS32 plays an important role in regulating carotenoid accumulation. These results have enriched our understanding of the MADS-box gene family and laid a foundation for further research of the functions of its members during kiwifruit development

A simple method for deriving functional MSCs and applied for osteogenesis in 3D scaffolds

We describe a simple method for bone engineering using biodegradable scaffolds with mesenchymal stem cells derived from human induced-pluripotent stem cells (hiPS-MSCs). The hiPS-MSCs expressed mesenchymal markers (CD90, CD73, and CD105), possessed multipotency characterized by tri-lineages differentiation: osteogenic, adipogenic, and chondrogenic, and lost pluripotency – as seen with the loss of markers OCT3/4 and TRA-1-81 – and tumorigenicity. However, these iPS-MSCs are still positive for marker NANOG. We further explored the osteogenic potential of the hiPS-MSCs in synthetic polymer polycaprolactone (PCL) scaffolds or PCL scaffolds functionalized with natural polymer hyaluronan and ceramic TCP (PHT) both in vitro and in vivo. Our results showed that these iPS-MSCs are functionally compatible with the two 3D scaffolds tested and formed typically calcified structure in the scaffolds. Overall, our results suggest the iPS-MSCs derived by this simple method retain fully osteogenic function and provide a new solution towards personalized orthopedic therapy in the future

Comparative analysis of the phenolic contents and antioxidant activities of different parts of two pomegranate (Punica granatum L.) Cultivars: ‘Tunisia’ and ‘Qingpi’

Pomegranate (Punica granatum L.), with its abundant phenolic substances and strong antioxidant activity, holds significant research and utilization potential across various organs. However, there have been few studies on the phenolic content and antioxidant activity of different parts of pomegranate, especially the placenta. This study investigated the phenolic content and antioxidant activity of fruits, flowers, and leaves of two pomegranate varieties, ‘Tunisia’ and ‘Qingpi’, throughout their growth and development. Results indicated significant variations in phenolic content among different organs, with petals exhibiting the highest total polyphenol content (TPC, 49.40 mg GAE/g FW) and total anthocyanin content (TMAC, 1938.54 nmol/g FW). Placenta contained the highest levels of total flavonoids (TFC, 173.58 mg RE/g FW) and punicalagin (109.30 mg/g FW). The peel had the highest content of total flavanols (TFAC, 19.42 mg CE/g FW). Over the course of pomegranate development, total polyphenols, total flavonoids, total flavanols, punicalagin, and antioxidant activity declined in different organs. Antioxidant activity followed the order: fruit &gt; flower &gt; leaf, with the placenta exhibiting the highest antioxidant activity among fruits. Antioxidant activity showed a significant positive correlation with total polyphenols (R2 = 0.77-1.00), total flavonoids (R2 = 0.71-0.99, except tegmens), and punicalagin (R2 = 0.71-1.00). This study provides a comparative analysis of the phenolic content and antioxidant activity in different organs of pomegranate, highlighting the placenta as the primary source of punicalagin. This study provides a theoretical basis for the development and utilization of pomegranate phenolic compounds

Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19

Rationale: Use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [IQR 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [IQR 57-69]; 53.5% men), who were admitted to nine hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03). Further subgroup propensity score-matched analysis indicated that, compared to use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01) in COVID-19 patients with hypertension. Conclusions: Among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk

Redefining cardiac biomarkers in predicting mortality and adverse outcomes of inpatients with COVID-19

The prognostic power of circulating cardiac biomarkers, their utility and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multi-centered retrospective study, we enrolled 3,219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effect Cox model, after adjusting for age, gender and comorbidities, the adjusted hazard ratios of 28-day mortality for high-sensitivity cardiac troponin I (hs-cTnI) was 7.12 (95%CI, 4.60-11.03; P&lt;0.001), NT-proB-type natriuretic peptide (NT-proBNP) was 5.11 (95%CI, 3.50-7.47; P&lt;0.001), CK-MB was 4.86 (95%CI, 3.33-7.09; P&lt;0.001), myoglobin was 4.50 (95%CI, 3.18-6.36; P &lt; 0.001), and CK was 3.56 (95%CI, 2.53-5.02; P &lt; 0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 49% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoffs for of these values might be much lower than the current reference standards. These findings can assist better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19 associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials

Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P\u3c0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P\u3c0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P\u3c0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P\u3c0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P\u3c0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project

Star Shaped Long Chain Branched Poly (lactic acid) Prepared by Melt Transesterification with Trimethylolpropane Triacrylate and Nano-ZnO

Long chain branched poly (lactic acid) (LCBPLA) was prepared via transesterification between high molecular weight poly (lactic acid) (PLA) and low molar mass monomer trimethylolpropane triacrylate (TMPTA) during melt blending in the presence of zinc oxide nanoparticles (nano-ZnO) as a transesterification accelerant in a torque rheometer. Compared with the traditional processing methods, this novel way is high-efficiency, environmentally friendly, and gel-free. The results revealed that chain restructuring reactions occurred and TMPTA was grafted onto the PLA backbone. The topological structures of LCBPLA were verified and investigated in detail. It was found that the concentration of the accelerants and the sampling occasion had very important roles in the occurrence of branching structures. When the nano-ZnO dosage was 0.4 phr and PLA was sampled at the time corresponding to the reaction peak in the torque curve, PLA exhibited a star-shaped topological structure with a high branching degree which could obviously affect the melt strength, extrusion foaming performances, and crystallization behaviors. Compared with pristine PLA, LCBPLA showed a higher melt strength, smaller cell diameter, and slower crystallization speed owing to the synergistic effects of nano-ZnO and the long chain branches introduced by the transesterification reaction in the system. However, severe degradation of the LCBPLAs would take place under a mixing time that was too long and lots of short linear chains generated due to the excessive transesterification reaction, with a sharp decline in melt strength