Targeting Reactive Oxygen Species in Atherosclerosis via Chinese Herbal Medicines

Cardio-cerebrovascular disease (CCVD) has become the leading cause of human mortality with the coming acceleration of global population aging. Atherosclerosis is among the most common pathological changes in CCVDs. It is also a multifactorial disorder; oxidative stress caused by excessive production of reactive oxygen species (ROS) has become an important mechanism of atherosclerosis. Chinese herbal medicine (CHM) is a major type of natural medicine that has made great contributions to human health. CHMs are increasingly used in the auxiliary clinical treatment of atherosclerosis. Although their mechanism of action is unclear, CHMs can exert a variety of antiatherosclerosis effects by regulating intracellular ROS. In this review, we discussed the mechanism of ROS regulation in atherosclerosis and analyzed the role of CHMs in the treatment of atherosclerosis via ROS.

Bungowannah Pestivirus Chimeras as Novel Double Marker Vaccine Strategy against Bovine Viral Diarrhea Virus

Marker or DIVA (differentiation of infected from vaccinated animals) vaccines are beneficial tools for the eradication of animal diseases in regions with a high prevalence of the designated disease. Bovine viral diarrhea virus (BVDV)-1 (syn. Pestivirus A) is a flavivirus that infects predominantly cattle resulting in major economic losses. An increasing number of countries have implemented BVDV eradication programs that focus on the detection and removal of persistently infected cattle. No efficient marker or DIVA vaccine is yet commercially available to drive the eradication success, to prevent fetal infection and to allow serological monitoring of the BVDV status in vaccinated farms. Bungowannah virus (BuPV, species Pestivirus F), a related member of the genus Pestivirus with a restricted prevalence to a single pig farm complex in Australia, was chosen as the genetic backbone for a marker vaccine candidate. The glycoproteins E1 and E2 of BuPV were substituted by the heterologous E1 and E2, which are major immunogens, of the BVDV-1 strain CP7. In addition, the candidate vaccine was further attenuated by the introduction of a deletion within the Npro protein coding sequence, a major type I interferon inhibitor. Immunization of cattle with the chimeric vaccine virus BuPV_ΔNpro_E1E2 CP7 (modified live or inactivated) followed by a subsequent experimental challenge infection confirmed the safety of the prototype strain and provided a high level of clinical protection against BVDV-1. The serological discrimination of vaccinated cattle could be enabled by the combined detection of BVDV-1 E2- in the absence of both BVDV NS3- and BVDV Erns-specific antibodies. The study demonstrates for the first time the generation and application of an efficient BVDV-1 modified double marker vaccine candidate that is based on the genetic background of BuPV accompanied by commercially available serological marker ELISA systems.

Circular RNAs in Intervertebral Disc Degeneration: An Updated Review

Low back pain, a common medical condition, could result in severe disability and inflict huge economical and public health burden. Its pathogenesis is attributed to multiple etiological factors, including intervertebral disc degeneration (IDD). Emerging evidence suggests that circular RNAs (circRNAs), a major type of regulatory non-coding RNA, play critical roles in cellular processes that are pertinent to IDD development, including nucleus pulposus cell proliferation and apoptosis as well as extracellular matrix deposition. Increasing number of translational studies also indicated that circRNAs could serve as novel biomarkers for the diagnosis of IDD and/or predicting its clinical outcomes. Our review aims to discuss the recent progress in the functions and mechanisms of newly discovered IDD-related circRNAs.

Systemic deficiency of GM1 ganglioside in Parkinson’s disease tissues and its relation to the disease etiology

Following our initial reports on subnormal levels of GM1 in the substantia nigra and occipital cortex of Parkinson’s disease (PD) patients, we have examined additional tissues from such patients and found these are also deficient in the ganglioside. These include innervated tissues intimately involved in PD pathology such as colon, heart and others, somewhat less intimately involved, such as skin and fibroblasts. Finally, we have analyzed GM1 in peripheral blood mononuclear cells, a type of tissue apparently with no direct innervation, and found those too to be deficient in GM1. Those patients were all afflicted with the sporadic form of PD (sPD), and we therefore conclude that systemic deficiency of GM1 is a characteristic of this major type of PD. Age is one factor in GM1 decline but is not sufficient; additional GM1 suppressive factors are involved in producing sPD. We discuss these and why GM1 replacement offers promise as a disease-altering therapy.

Control of Thousand-Grain Weight by OsMADS56 in Rice

Grain weight and size are important traits determining grain yield and influencing grain quality in rice. In a previous study, a quantitative trait locus controlling thousand-grain weight (TGW) in rice, qTGW10-20.8, was mapped in a 70.7 kb region on chromosome 10. Validation of the candidate gene for qTGW10-20.8, OsMADS56 encoding a MADS-box transcription factor, was performed in this study. In a near-isogenic line (NIL) population segregated only at the OsMADS56 locus, NILs carrying the OsMADS56 allele of IRBB52 were 1.9% and 2.9% lower in TGW than NILs carrying the OsMADS56 allele of Teqing in 2018 and 2020, respectively. Using OsMADS56 knock-out mutants and overexpression transgenic plants, OsMADS56 was validated as the causal gene for qTGW10-20.8. Compared with the recipients, the TGW of the mutants was reduced by 6.0–15.0%. In these populations, decreased grain weight and size were associated with a reduction in the expression of OsMADS56. In transgenic populations of OsMADS56 driven by a strong constitutive promoter, grain weight and size of the positive plants were significantly higher than those of the negative plants. Haplotype analysis showed that the Teqing-type allele of OsMADS56 is the major type presented in cultivated rice and used in variety improvement. Cloning of OsMADS56 provides a new gene resource to improve grain weight and size through molecular design breeding.

Decreased Immune Response in Alexithymic Women: A One-Year Longitudinal Study

Although previous cross-sectional studies suggested significantly dysregulated immune response in alexithymia, there is a lack of longitudinal studies. We sought to determine the reliability of the reported relationship between alexithymia and decreased immune response in a longitudinal study. Thirty-eight healthy women who had participated in a cross-sectional study were recontacted 1-year later. Of this sample, 26 were finally included: 13 females who had been found to be alexithymic, and 13 females who were classified as non-alexithymic under the 20-item Toronto Alexithymia Scale during the first phase of the study. A year later, they were still healthy women without any psychiatric disorders, their ages now ranging from 19 to 28 years old. Lymphocyte subset counts (CD4, CD8), in vitro production of interleukin 1β (IL-1β), IL-2, IL-4, and IL-10 by phytohemagglutinin stimulated peripheral blood lymphocytes, as well as serum cortisol levels, were compared between women with and without alexithymia. One-year later, alexithymic women still had significantly lowered in vitro production of IL-2 and IL-4, with lowered IL-2/IL-10 ratio and a reduced percentage of CD4. This is the first ever published study assessing cytokine production during a follow-up of alexithymics. Although our results should be interpreted with caution due the small sample size, they suggest a sustained reduction in both major type 1 and type 2 cytokines while the former seems to be more affected. The potential long-term health impact, if any, is still to be determined.

Familial Segregation of Venous Thromboembolism in Sweden: A Nationwide Family Study of Heritability and Complex Segregation Analysis

Background This is the first nationwide segregation analysis that aimed to determine whether familial venous thromboembolism (VTE) is attributable to inheritance and/or shared environment, and the possible mode of inheritance. Methods and Results The Swedish Multi‐Generation Register was linked to the Swedish patient register for the period 1964 to 2015. Three generational families of Swedish‐born individuals were identified. Heritability was examined using Falconer regression. Complex segregation analysis was conducted using the Statistical Analysis for Genetic Epidemiology software (version 6.4, 64‐bit Linux). Among the 4 301 174 relatives from 450 558 pedigrees, 177 865 (52% women) individuals were affected with VTE. VTE occurred in 2 or more affected relatives in 61 217 (13.6%) of the pedigrees. Heritability showed age and sex dependence with higher heritability for men and young individuals. In 18 933 pedigrees, VTE occurred only in the first generation and was not inherited. Segregation analysis was performed in the remaining 42 284 pedigrees with inherited VTE and included 939 192 individuals. Prevalence constraints were imposed in the models to allow for the selection of the pedigrees analyzed. The sporadic nongenetic model could be discarded. The major‐type‐only model, with a correlation structure compatible with some polygenic effects, was the preferred model. Among the Mendelian models, the mixed codominant (plus polygenic) model was preferred. Conclusions This nationwide segregation analysis of VTE supports a genetic cause of the familial aggregation of VTE. Heritability was higher for men and younger individuals, suggesting a Carter effect, in agreement with a multifactorial threshold inheritance.

Increasing Rate of Hospitalization For Severe Peptic Ulcer After The Pandemic: Digestive Emergency Data From Two Regional Hospitals.

With the introduction of the coronavirus disease 2019 (COVID-19) vaccine, the pandemic has abated. However, the virus has not been completely contained, and some of the potential effects of the outbreak have not been thoroughly studied. We collected data from two regional emergency centers from May to November 2015-2019, before the outbreak, and from May to November 2020, after the outbreak. We evaluated the incidence of each major type of digestive disease before and after the pandemic in adults at two hospitals, which experienced COVID-19 outbreaks with varying severity. A total of 11,336 patients were enrolled in the study (PUTIAN, n=5503, UNION, n= 5891). From 2015 to 2019, the numbers of patients at the two hospitals increased steadily, but in 2020, the number of patients at UNION declined. The constituent ratios of diseases in each year in the two hospitals differed. The number of patients with peptic ulcer in 2020 was significantly different from that in each year from 2015 to 2019 (PUTIAN 2015-2020, 16.6%, 20.0%, 16.6%, 18.3%, 21.1%, 37.1%; UNION 2015-2020, 31.5%, 34.6%, 31.6%, 31.3%, 31.7%, 43.7%, respectively). The rates of peptic ulcer increased dramatically in both hospitals in 2020. An increase in the incidence of severe peptic ulcer was observed after the pandemic compared to the same period in previous nonpandemic years. Therefore, these factors should be considered in the formulation of public health strategies and the allocation of medical resources in the postepidemic era.

Effective Treatment of Humic Acid Foulants in SAGD Produced Water

Humic acids, one major type of organic foulants in steam assisted gravity drainage (SAGD) produced water, can precipitate on surface and downhole equipment in SAGD facilities, resulting in high cleaning costs, potential equipment damage and decrease of injectivity of disposal wells. In this paper, a cost-effective chemical solution is presented where an alcohol ethoxylate surfactant/chelating agent package can efficiently disperse the organic fouling molecules in SAGD produced water; therefore, the approach is expected to significantly mitigate the humic acid related fouling issues in the SAGD system. In this study, a variety of commercially available surfactant products were evaluated for their aids in well injectivity on humic acid molecules in the freshly obtained SAGD produced water. The lab testing filtration apparatus was specially designed to simulate the sandstone formation geology of SAGD disposal wells. An "efficiency factor" was defined to grade the dispersing performance of the surfactant and/or surfactant/chelating agent package in the lab filtration tests. The efficiency factor provides a reasonable estimation regarding how well the chemical can reduce the plugging risk in a disposal well as compared to the untreated produced water. Among all the surfactant products tested, an alcohol ethoxylate surfactant with the appropriate molecular structure shows distinguished dispersing performance on humic acids in SAGD produced water. However, the surfactant alone was found inconsistent in the dispersing performance when different batches of the produced water were involved. Inclusion of the specific metal chelating agents to the above surfactant formulation improved the dispersing performance consistency. The chelator molecules presumably help destroy the intermolecular bridges among humic acid molecules in the SAGD produced water; thereby, increasing the dispersing effectiveness of the alcohol ethyoxylate surfactants. Tests show that the efficiency factor of the surfactant/chelating agent package is higher than 8, which implies that the formulation could lead to eight times extension of the interval between workovers on SAGD disposal wells, a significant reduction for the operational downtime and costs. This study presented a cost-effective chemical solution to help disperse the humic acid molecules in SAGD produced water, which can help significantly reduce the fouling risk caused by organic foulants, improve injectivity and extend the intervals between workovers of SAGD disposal wells.