Curcumin activates the p38MPAK-HSP25 pathway in vitro but fails to attenuate diabetic nephropathy in DBA2J mice despite urinary clearance documented by HPLC

<p>Abstract</p> <p>Background</p> <p>Curcumin has anti-inflammatory, anti-oxidant, and anti-proliferative properties, and depending upon the experimental circumstances, may be pro- or anti-apoptotic. Many of these biological actions could ameliorate diabetic nephropathy.</p> <p>Methods/Design</p> <p>Mouse podocytes, cultured in basal or high glucose conditions, underwent acute exposure to curcumin. Western blots for p38-MAPK, COX-2 and cleaved caspase-3; isoelectric focusing for HSP25 phosphorylation; and DNase I assays for F- to G- actin cleavage were performed for <it>in vitro </it>analyses. <it>In vivo </it>studies examined the effects of dietary curcumin on the development of diabetic nephropathy in streptozotocin (Stz)-induced diabetes in DBA2J mice. Urinary albumin to creatinine ratios were obtained, high performance liquid chromatography was performed for urinary curcuminoid measurements, and Western blots for p38-MAPK and total HSP25 were performed.</p> <p>Results</p> <p>Curcumin enhanced the phosphorylation of both p38MAPK and downstream HSP25; inhibited COX-2; induced a trend towards attenuation of F- to G-actin cleavage; and dramatically inhibited the activation of caspase-3 in <it>vitro</it>. In curcumin-treated DBA2J mice with Stz-diabetes, HPLC measurements confirmed the presence of urinary curcuminoid. Nevertheless, dietary provision of curcumin either before or after the induction of diabetes failed to attenuate albuminuria.</p> <p>Conclusions</p> <p>Apart from species, strain, early differences in glycemic control, and/or dosing effects, the failure to modulate albuminuria may have been due to a decrement in renal HSP25 or stimulation of the 12/15 lipoxygenase pathway in DBA2J mice fed curcumin. In addition, these studies suggest that timed urine collections may be useful for monitoring curcumin dosing and renal pharmacodynamic effects.</p

Long-term fertilization increases the temperature sensitivity of OC mineralization in soil aggregates of a highland agroecosystem

The mineralization of aggregate-associated organic carbon (OC) and the effect of long-term fertilization on its temperature sensitivity have not been addressed, but are critical for understandingOC sequestration and dynamics in agricultural soil. We measured themineralization of OC in total soils and aggregates after 27 years of application of various fertilizers in a highland agroecosystem in central China and calculated the temperature sensitivity of OC mineralization. Our objectives were to understand the effects of long-term fertilization on OC mineralization in aggregates and its temperature sensitivity, and to determine the contribution of each aggregate size class to OCmineralization in total soils. Long-term fertilization decreased cumulative mineralized OC (Cmin) in b0.053 mm size class but increased Cmin in N2, 0.25&ndash;2, and 0.053&ndash;0.25 mm aggregates. The increases were smaller in treatments with mineral fertilizers than with manure or manure combined with mineral fertilizer. The temperature sensitivity of OCmineralizationwas decreased in N2mmaggregate but increased in b2mmaggregates and total soils by fertilization treatments. The OC mineralization in b0.053 mmsize class accounted for 36% of the OC mineralization in total soils.Manure ormanure combined with mineral fertilizer had a higher potential to change the contribution of aggregates to OC mineralization in total soils. Our results suggest that OC mineralization in total soils was determinedmainly bymineralization in the b0.053mmsize class of these highland agricultural soils, and long-term fertilization increased the temperature sensitivity of OC mineralization in total soils and b2 mm aggregates.</div

Efficacy and safety of mesenchymal stem cells for the treatment of patients infected with COVID-19: a systematic review and meta-analysis protocol

Introduction To date, no specific antivirus drugs or vaccines have been available to prevent or treat the COVID-19 pandemic. Mesenchymal stem cell (MSC) therapy may be a promising therapeutic approach that reduces the high mortality in critical cases. This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy and safety of MSC therapy on patients with COVID-19.Methods and analysis Ten databases including PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, China Biomedical Literature Database (CBM) and Chinese Biomedical Literature Service System (SinoMed) will be searched from inception to 1 December 2020. All published randomised controlled trials, clinical controlled trials and case series that meet the prespecified eligibility criteria will be included. The primary outcomes include mortality, incidence and severity of adverse events, respiratory improvement, days from ventilator, duration of fever, progression rate from mild or moderate to severe, improvement of such serious symptoms as difficulty breathing or shortness of breath, chest pain or pressure, and loss of speech or movement, biomarkers of laboratory examination and changes in CT. The secondary outcomes include dexamethasone doses and quality of life. Two reviewers will independently perform study selection, data extraction and assessment of bias risk. Data synthesis will be conducted using RevMan software (V.5.3.5). If necessary, subgroup and sensitivity analysis will be performed. Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of evidence.Ethics and dissemination Ethical approval is not necessary since no individual patient or privacy data have been collected. The results of this review will be disseminated in a peer-reviewed journal or an academic conference presentation.PROSPERO registration number CRD42020190079

Hemophagocytic Lymphohistiocytosis induced by human granulocytic anaplasmosis: A case report and literature review into the immunopathogenesis

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous collection of immunological disorders characterized by severely disrupted immune homeostasis and dysregulated macrophage overactivation resulting in hyperinflammation, hypercytokinemia, histiocytic phagocytosis in hematolymphoid systems, and life-threatening organ damage. Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum (Ap), one of the most common tick-borne diseases in North America and worldwide. The pathophysiology by which anaplasmosis triggers the development of human HLH remains unclear. Herein, we report a case of severe Anaplasma infection in Central Pennsylvania presenting with classical clinical features and laboratory findings of acquired, secondary HLH. From basic science to clinicopathological studies, we review and summarize the literature emphasizing the unique immunopathogenesis that informs diagnosis and management of Anaplasma-induced HLH

Differential Response of Ileal and Colonic Microbiota in Rats with High-Fat Diet-Induced Atherosclerosis

Growing evidence suggests that gut microbiota are associated with atherosclerosis (AS). However, the functional heterogeneity of each gut segment gives rise to regional differences in gut microbiota. We established a rat model of AS by feeding the rats a high-fat diet for a long period. The pathological and microbiota changes in the ileum and colon of the rats were examined, and correlations between AS and microbiota were analyzed. The aortic mesothelium of the experimental rats was damaged. The intima showed evident calcium salt deposition, indicating that the AS rat model was successfully developed. We noted varying degrees of pathological damage in the ileum and colon of the experimental rats. The 16S rDNA high-throughput sequencing showed significant differences in &alpha;-diversity, &beta;-diversity, and microbiota comparisons in the ileum and colon. Furthermore, the ileum and colon of AS rats showed varying degrees of intestinal microbiota disturbance. This article contributes to the study of the relationship between the microbiota in different regions of the gut and AS, and provides new approaches in gut microbiota intervention for the treatment of AS

Kinesiophobia and self‐management behaviour related to physical activity in Chinese patients with coronary heart disease: The mediating role of self‐efficacy

Abstract Aim The purpose of this study was to explore the relationship among kinesiophobia, self‐efficacy and self‐management behaviour related to physical activity (SMBPA) in Chinese patients with coronary heart disease(CHD) and the mediating role of self‐efficacy between kinesiophobia and SMBPA in Chinese patients with CHD. Design A cross‐sectional study. Methods From March to July 2021, 540 Chinese patients with CHD were investigated with three scales using convenient sampling method. The data were analysed with Pearson correlation, univariate analysis, multivariate linear regression and the PROCESS macro. Results 509 valid questionnaires were collected (effective response rate: 94.2%). Low kinesiophobia and high self‐efficacy were related to high‐levels of SMBPA (all p < .01). Besides, the effect of kinesiophobia on SMBPA was partially mediated by self‐efficacy, and the mediation effect accounted for 35.59% of the total effect

Using Long-Lived Thorium Isotopes to Quantify the Lithogenic Inputs to the Lakes in Qaidam Basin, China

In the last decade, the 232Th&ndash;230Th system has gained popularity as a tracer to quantify lithogenic sources of trace elements to the marine environment. Thorium (Th) isotopes were utilized to quantify the supply of lithogenic inputs to Keluke Lake and Tuosu Lake in Qaidam Basin, China. A total of 33 water samples were collected from Keluke Lake, Tuosu Lake, and Bayin River to measure the concentrations of dissolved 232Th and 230Th. The relationship of 232Th concentration in the water was in the order Bayin River &gt; Keluke Lake &gt; KLK&ndash;TS River &gt; Tuosu Lake, confirming the input of variable lithogenic material sources. Three sources dominate the flux of lithofacies into the lakes: the river input, the deposition of dust and the local input from the sediments surrounding the lakes. On an interannual timescale, the lithogenic flux of Keluke Lake was mainly derived from river input. In summer, the dust flux in the study area could be estimated as 0.133 g/m2/year, while the flux of lithologic material from Bayin River to Keluke Lake was 12.367 g/m2/year. In contrast, the fluvial input to the Tuosu lake was small in comparison to the dust contribution of lithogenic flux. The high Th232-concentration and the vertical sediment flux in this lake may have been caused by resuspension of bottom sediments

Ethanol extract of Schisandrae chinensis fructus ameliorates the extent of experimentally induced atherosclerosis in rats by increasing antioxidant capacity and improving endothelial dysfunction

Context: Schisandrae chinensis fructus, the dried ripe fruit of Schisandra chinensis (Turcz.) Baill. (Magnoliaceae) has been used for thousands of years as a traditional Chinese herb, which can attenuate and prevent the development of cardiovascular events. Objective: To evaluate the effects of the ethanol extracts from Schisandrae chinensis fructus fruit (EESC) on experimental atherosclerosis (AS) in rats. Materials and methods: Treatment with EESC (0.35, 0.7, 1.4 g/kg/d, i.g.) and simvastatin (4 mg/kg/d, i.g.) on AS rats for 3 weeks. Sprague–Dawley rats on normal chow and under water treatment were used as control. The content of schisandrin, schisandrin A and schisandrin B in EESC was detected by HPLC. Aortic pathology changes, serum biochemical indices and nuclear factor E2-related factor 2 (Nrf-2) and heame oxygenase-1 (HO-1) expressions were measured. Results: Schisandrin, schisandrin A and schisandrin B contents were 291.8, 81.46 and 279.1 mg/g of dry weight, respectively. EESC significantly reduced the aortic plaque area (76.5, 90.5 and 73.9% reduction), regulated the levels of serum lipid (p  20 g/kg. Conclusions: EESC positively affects the treatment of AS in vivo and the findings will provide a reliable theoretical basis for developing novel therapeutics

Distribution and mineralization of organic carbon and nitrogen in forest soils of the southern Tibetan Plateau

The forests of the Tibetan Plateau store large amounts of soil organic carbon (OC) but are among the most vulnerable and sensitive ecosystems to environmental change. The lack of knowledge regarding the distribution and turnover of OC and nitrogen (N) in Tibetan Plateau forest soils limits the ability to predict how this ecosystem will respond to climate change. In this study, we collected mineral soils from coniferous and broadleaf forests on the southern Tibetan Plateau and measured' OC and N contents in both bulk soils and water-stable aggregates. We also determined the mineralization of OC and N in bulk soils and examined the effects of N addition on OC mineralization. Our objectives were to investigate the distribution and mineralization of soil OC and N in various forest types and to determine the stability of OC following N addition. Our results showed that OC and N in macroaggregates contributed 76% of the OC and N in bulk soils. Forest type did not affect the OC or N contents of either bulk soils or aggregates. Similarly, OC and N mineralization and their relationships with soil OC or N contents were similar between broadleaf and coniferous forests, indicating that soil OC and N distribution and turnover were insensitive to forest type. Nitrogen mineralization was dominated by ammonification in these forest soils. Nitrogen addition did not affect OC mineralization or its relationship with soil OC or N contents. These results indicate that the OC contents of forest soils of the southern Tibetan Plateau are relatively insensitive to N addition

Study of gene expression profiles and biological mechanism of cerebral palsy using a monozygotic twin pair

10.1375/twin.10.3.496Twin Research and Human Genetics103496-50