Accumulating evidence suggested that resveratrol (RES) could protect against adverse cardiac remodeling induced by several cardiovascular diseases. However, the role of RES in the setting of heart ...failure with preserved ejection fraction (HFpEF) and the underlying mechanisms of its action remain understood. This study was to determine whether RES could ameliorate HFpEF-induced cardiac remodeling and its mechanisms.
, C57BL/6 mice served as either the sham or the HFpEF model. The HFpEF mice model was induced by uninephrectomy surgery and d-aldosterone infusion. RES (10 mg/kg/day, ig) or saline was administered to the mice for four weeks.
, transforming growth factor β1 (TGF-β1) was used to stimulate neonatal rat cardiac fibroblasts (CFs) and Ex-527 was used to inhibit sirtuin 1 (Sirt1) in CFs. Echocardiography, hemodynamics, western blotting, quantitative real-time PCR, histological analysis, immunofluorescence, and ELISA kits were used to evaluate cardiac remodeling induced by HFpEF. Sirt1 and Smad3 expressions were measured to explore the underlying mechanisms of RES.
HFpEF mice developed left ventricular hypertrophy, preserved ejection fraction, diastolic dysfunction, and pulmonary congestion. Moreover, HFpEF mice showed increased infiltration of neutrophils and macrophages into the heart, including increased interleukin (IL)-1β, IL-6, and TNF-α. We also observed elevated M1 macrophages and decreased M2 macrophages, which were exhibited by increased mRNA expression of M1 markers (iNOS, CD86, and CD80) and decreased mRNA expression of M2 markers (Arg1, CD163, and CD206) in HFpEF hearts. Moreover, HFpEF hearts showed increased levels of intracellular reactive oxygen species (ROS). Importantly, HFpEF mice depicted increased
and
and TGF-β mRNA expressions and decreased protein expression of phosphorylated endothelial nitric-oxide synthase (p-eNOS). Results of western blot revealed that the activated TGF-β/Smad3 signaling pathway mediated HFpEF-induced cardiac remodeling. As expected, this HFpEF-induced cardiac remodeling was reversed when treated with RES. RES significantly decreased Smad3 acetylation and inhibited Smad3 transcriptional activity induced by HFpEF
activating Sirt1. Inhibited Sirt1 with Ex-527 increased Smad3 acetylation, enhanced Smad3 transcriptional activity, and offset the protective effect of RES on TGF-β-induced cardiac fibroblast-myofibroblast transformation in CFs.
Our results suggested that RES exerts a protective action against HFpEF-induced adverse cardiac remodeling by decreasing Smad3 acetylation and transcriptional activity
activating Sirt1. RES is expected to be a novel therapy option for HFpEF patients.
Systemic sclerosis (SSc) is a connective tissue disease with an unknown etiology. Clinically, it is characterized by localized or diffuse skin thickening and fibrosis. The pathogenesis of SSc ...includes microvascular injury, autoimmune-mediated inflammation, and fibroblast activation. These processes interact and contribute to the diverse clinicopathology and presentation of SSc. Given the limited effectiveness and substantial side effects of traditional treatments, the treatment strategy for SSc has several disadvantages. Mesenchymal stem cells (MSCs) are expected to serve as effective treatment options owing to their significant immunomodulatory, antifibrotic, and pro-angiogenic effects. Exosomes, secreted by MSCs via paracrine signaling, mirror the effect of MSCs as well as offer the benefit of targeted delivery, minimal immunogenicity, robust reparability, good safety and stability, and easy storage and transport. This enables them to circumvent the limitations of the MSCs. When using exosomes, it is crucial to consider preparation methods, quality standards, and suitable drug delivery systems, among other technical issues. Therefore, this review aims to summarize the latest research progress on MSCs and exosomes in SSc, offering novel ideas for treating SSc.
Objective
This study aimed to determine the frequency of Epstein–Barr virus (EBV), cytomegalovirus (CMV) in mucosa and blood of inflammatory bowel disease (IBD) patients in China and evaluate their ...correlation with the clinical disease activities.
Methods
Peripheral blood and endoscopic fresh colonic mucosal samples were collected from a cohort of 287 IBD patients and 50 controls. Viral DNA load was analyzed through quantitative real-time PCR. The clinical disease activity of ulcerative colitis (UC) and Crohn’s disease (CD) was assessed by the Mayo Clinic Score and Crohn’s disease activity index, respectively.
Results
Among 287 IBD patients, 228 (79.4%) were positive for EBV and 99 (34.5%) were positive for CMV. EBV and CMV infection rates are significantly higher than those in the control group (28.0%,
p
< 0.05; 4.0%,
p
< 0.05). In addition, EBV/CMV prevalence increases as clinical activities progress For EBV infection, the prevalence was 53.93% (48/89) in the mild group, 87.00% (87/100) in the moderate group, and 94.90% (93/98) in the severe group; and for CMV infection, the prevalence was 3.37% (3/89) in the mild group, 27.00% (27/100) in the moderate group, and 70.41% (69/98) in the severe group. EBV and CMV loads are related to clinical disease activities (
p
< 0.05). In addition, viral load in the intestinal mucosa of patients with acute exacerbation of IBD is higher than that of patients in remission.
Conclusion
High prevalence of EBV and CMV is found in patients with IBD, and their prevalence is related to clinical disease activities. In addition, the viral load in the intestinal mucosa is associated with the status of mucosa in the same patients (active phase versus remission phase). Detection of viral load on mucosal specimens with quantitative real-time PCR is a feasible method to monitor EBV and CMV infection in IBD patients.
Hedgehog (Hh) signaling pathway is an evolutionarily conserved signal transduction pathway that plays an important regulatory role during embryonic development, cell proliferation, and ...differentiation of vertebrates, and it is often inhibited in adult tissues. Recent evidence has shown that Hh signaling also plays a key role in rheumatic diseases, as alterations in their number or function have been identified in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic sclerosis, and Sjogren’s Syndrome. As a result, emerging studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of Hh signaling in rheumatic diseases.
Importing, outsourcing and pollution offshoring Cole, Matthew A.; Elliott, Robert J.R.; Okubo, Toshihiro ...
Energy economics,
November 2021, 2021-11-00, 20211101, Letnik:
103
Journal Article
Recenzirano
Odprti dostop
Focusing on Japan over the period 1988–2013, this paper provides the first test of the extent to which pollution offshoring has occurred for this major industrial economy. In so doing, we identify ...whether the composition of domestic production, imports, overall trade patterns and overseas outsourcing has become more or less pollution intensive. We then focus on the role played by overseas outsourcing in pollution offshoring. Utilising a unique dataset of approximately 4000 Japanese firms for the period 2009–13, we use propensity score matching and difference-in-differences to examine how a firm's CO2 emissions intensity is affected by its decision to outsource some of its production overseas. Our results indicate that the composition of Japanese imports appear to have become dirtier and the carbon embodied within Japanese imports is larger and has grown more rapidly than the carbon embodied within exports. We also find that relative to a control group, the growth rate of pollution intensity of firms that begin overseas outsourcing is 7.3 percentage points lower in the year that they start overseas outsourcing and 7.7 percentage points lower in the following year, suggesting that outsourcing is one route through which pollution offshoring is occurring. New importers also experience slower emissions growth but the reduction is less than for new outsourcers.
•We find evidence to suggest that Japan did offshore pollution over the period 1988–2013.•The carbon content of Japanese imports increased, particularly since 2005.•Overseas outsourcing appears to be playing a role.•Firms that began to outsource experienced reduced CO2 intensity in the following 2 years.•This may have been due to rising Japanese energy costs.
Abstract
Using data from Gaia Data Release 3 and Kepler/K2, we present a catalog of 16 open clusters with ages ranging from 4–4000 Myr that provides detailed information on membership, binary ...systems, and rotation. We assess the memberships in 5D phase space, and estimate the basic parameters of each cluster. Among the 20,160 members, there are 4381 stars identified as binary candidates and 49 stars identified as blue straggler stars. The fraction of binaries varies in each cluster, and the range is between 9% and 44%. We obtain the rotation periods of 5467 members, of which 4304 are determined in this work. To establish a benchmark for the rotation–age–color relation, we construct color–period diagrams. We find that the rotational features of binaries are similar to that of single stars, while the features for binaries are more scattered in the rotation period. Moreover, the morphology of the color–period relationship is already established for Upper Scorpius at the age of 19 Myr, and some stars of varying spectral types (i.e., FG, K, and M type) show different spin-down rates after the age of ∼110 Myr. By incorporating the effects of stalled spin-down into our analysis, we develop an empirical rotation–age–color relation, which is valid with ages between 700–4000 Myr and colors corresponding to a range of 0.5 <
(
G
BP
−
G
RP
)
0
< 2.5 mag.
Copper-catalyzed tandem coupling of 1,4-dihalo-1,3-dienes with azoles via an N−H bond and its adjacent C−H bond activation has been described. The reaction exhibits good regioselectivity when ...unsymmetrical 1,4-dihalo-1,3-diene is employed. This method provided a novel route to the synthesis of nitrogen-bridgehead azolopyridine derivatives.
The bank slope of the Three Gorges Reservoir is affected by seasonal water level fluctuations, which leads to deterioration of the rock mass, resulting in a series of geological disasters such as ...landslides and mudslides. Therefore, to thoroughly understand the degradation mechanism of mechanical characteristics under wetting–drying cycles, uniaxial compression tests and triaxial compression tests were used to reveal the relationship between mechanical characteristics and wetting–drying cycles. The results of the uniaxial compression tests show that with the increase in the number of wetting–drying cycles, the mechanical characteristics show a declining trend, and the compaction stage of the sample increases considerably. It was found that the first ten wetting–drying cycles have a greater impact on the mechanical characteristics of red sandstone under the triaxial compression condition, the mechanical parameters such as deviatoric stress, elasticity modulus dropped rapidly under the first 10 cycles and then tend to be stable. Based on the testing data under wetting–drying cycle condition, the mechanical parameters of the statistics damage constitutive model were modified and the results show that the modified damage constitutive model has a high degree of fit with the test data, indicating that the modified mechanical parameters can better reflect the degradation of red sandstone after the wetting–drying cycles. This understanding of the degradation process of the mechanical characteristics under wetting–drying cycles can provide theoretical guidance for the protection of dangerous slopes in the drawdown zone of the Three Gorges Reservoir.
In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, ...despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein–protein interaction networks, mRNA–lncRNA co-expression networks, and circRNA–microRNA–mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.
The configuration and timing of the Arabia‐Eurasia continental collision, part of the broader Alpine‐Himalayan collisional system, remains controversial. We conducted sandstone petrology, detrital ...zircon U‐Pb‐Hf isotopic and trace element analysis, and Cr‐spinel electron microprobe geochemical analysis of samples from Paleocene to Miocene peripheral foreland strata in interior Fars, southern Iran. These data were used to test competing models for ophiolite obduction and Arabia‐Eurasia collision. In addition, we applied these data to compare the history of outward and upward growth of the Zagros and Himalayan‐Tibetan segments of the Alpine‐Himalayan collisional orogenic belt. The first appearance of radiolarian‐rich chert conglomerate, 100–90 Ma detrital zircons with positive ɛHf(t) values from +1 to +20 and midocean ridge geochemical affinity, and suprasubduction zone (SSZ) affinity Cr‐spinel is in the lower and middle Sachun Formation. These data indicate that obduction occurred before deposition of the upper Maastrichtian‐lower Paleocene Sachun Formation and developed in an intra‐oceanic setting rather than an Arabia‐Eurasia collision setting. Abundant continental‐arc affinity detrital zircon with 180–160 Ma and 50–27 Ma age‐probability peaks and varied ɛHf(t) values are present in the upper Oligocene‐lower Miocene Razak and Agha Jari formations, indicating sedimentary overlap with Eurasia. SSZ‐affinity Cr‐spinel in all samples indicates that ophiolitic rocks were a continual source of detritus in the foreland basin since Paleocene. The depositional age of the basal Razak Formation is between 25.7 and 21.5 Ma. Therefore, we interpret that collision between Arabia and Eurasia must have been initiated before deposition of the Razak Formation.
Key Points
Neyriz ophiolite was obducted onto Arabia during Late Cretaceous‐early Paleocene time
Arabia‐Eurasia intercontinental collision occurred before deposition of 25.7–21.5 Ma Razak formation
Decreases in propagation rate of foreland basin system play an important role in the growth of high elevation orogenic plateau
PDF
