Exploration of the protective mechanisms of Icariin against cisplatin-induced renal cell damage in canines

This study delves into the protective mechanisms of Icariin (ICA) against cisplatin-induced damage in Madin-Darby canine kidney (MDCK) cells. Comprising two distinct phases, the investigation initially employed a single-factor randomized design to ascertain the minimal cisplatin concentration eliciting MDCK cell damage, spanning concentrations from 0 to 16 mmol/L. Concurrently, various concentrations of ICA (ranging from 5 to 50 mmol/L) were combined with 1 mmol/L cisplatin to determine the most efficacious treatment concentration. Subsequent investigations utilized four treatment groups: control, 1 mmol/L cisplatin, 1 mmol/L cisplatin + 20 mmol/L ICA, and 1 mmol/L cisplatin + 25 mmol/L ICA, aimed at elucidating ICA's protective mechanisms. Findings from the initial phase underscored a significant reduction in MDCK cell viability with 1 mmol/L cisplatin in comparison to the control (P < 0.01). Notably, the inclusion of 20 and 25 mmol/L ICA substantively ameliorated MDCK cell viability under 1 mmol/L cisplatin (P < 0.01). Moreover, cisplatin administration induced an elevation in inflammatory factors, malondialdehyde (MDA), reactive oxygen species (ROS), and Bax protein levels, while concurrently suppressing superoxide dismutase (SOD), catalase (CAT), and Bcl-2 expression (P < 0.01). Conversely, supplementation of 20 and 25 mmol/L ICA demonstrated a marked increase in mitochondrial membrane potential and levels of SOD, CAT, and Bcl-2 (P < 0.01). These interventions effectively attenuated inflammatory responses and suppressed Bax protein expression (P < 0.05), consequently mitigating cisplatin-induced apoptosis in MDCK cells (P < 0.01). In summary, these findings elucidate the role of ICA in impeding apoptosis in cisplatin-induced MDCK cells by regulating inflammatory responses, oxidative stress, and autophagic protein expression

The Assessment of Global Surface Temperature Change from 1850s: The C-LSAT2.0 Ensemble and the CMST-Interim Datasets

Based on C-LSAT2.0, using high- and low-frequency components reconstruction methods, combined with observation constraint masking, a reconstructed C-LSAT2.0 with 756 ensemble members from the 1850s to 2018 has been developed. These ensemble versions have been merged with the ERSSTv5 ensemble dataset, and an upgraded version of the CMST-Interim dataset with 5° × 5° resolution has been developed. The CMST-Interim dataset has significantly improved the coverage rate of global surface temperature data. After reconstruction, the data coverage before 1950 increased from 78%–81% of the original CMST to 81%–89%. The total coverage after 1955 reached about 93%, including more than 98% in the Northern Hemisphere and 81%–89% in the Southern Hemisphere. Through the reconstruction ensemble experiments with different parameters, a good basis is provided for more systematic uncertainty assessment of C-LSAT2.0 and CMST-Interim. In comparison with the original CMST, the global mean surface temperatures are estimated to be cooler in the second half of 19th century and warmer during the 21st century, which shows that the global warming trend is further amplified. The global warming trends are updated from 0.085 ± 0.004°C (10 yr) −1 and 0.128 ± 0.006°C (10 yr) −1 to 0.089 ± 0.004°C (10 yr) −1 and 0.137 ± 0.007°C (10 yr) −1, respectively, since the start and the second half of 20th century

The neutrophil-to-lymphocyte ratio is associated with mild cognitive impairment in community-dwelling older women aged over 70 years: a population-based cross-sectional study

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation that can be obtained quickly, conveniently, and cheaply from blood samples. However, there is no research to explore the effects of sex and age on the relationship between the NLR and mild cognitive impairment (MCI) in community-dwelling older adults.MethodsA total of 3,169 individuals aged over 60 years in Shanghai were recruited for face-to-face interviews, and blood samples were collected. MCI was assessed by the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale, and neutrophil count and lymphocyte counts were measured in fasting blood samples. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count.ResultsIn females, the NLR in the MCI group was significantly higher than that in the cognitively normal group (2.13 ± 0.94 vs. 1.85 ± 0.83, p < 0.001) but not in men. Logistic regression showed that a higher NLR was an independent risk factor for MCI in women [odds ratio (OR) = 1.28; 95% confidence interval (CI) = 1.09–1.49]. In addition, the elevated NLR quartile was associated with an increased risk of MCI, especially in women older than 70 years (p-value for trend = 0.011).ConclusionCompared with males, female MCI patients had a significantly higher NLR than cognitively normal controls. In addition, elevated NLR was found to be significantly associated with MCI risk in women older than 70 years. Therefore, elderly Chinese women with a higher NLR value may be the target population for effective prevention of MCI

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota

Abstract Mounting evidence has linked changes in human gut microbiota to proton pump inhibitor (PPI) use. Accordingly, multiple studies have analyzed the gut microbiomes of PPI users, but PPI–microbe interactions are still understudied. Here, we performed a meta-analysis of four studies with available 16S rRNA gene amplicon sequencing data to uncover the potential changes in human gut microbes among PPI users. Despite some differences, we found common features of the PPI-specific microbiota, including a decrease in the Shannon diversity index and the depletion of bacteria from the Ruminococcaceae and Lachnospiraceae families, which are crucial short-chain fatty acid-producers. Through training based on multiple studies, using a random forest classification model, we further verified the representativeness of the six screened gut microbial genera and 20 functional genes as PPI-related biomarkers, with AUC values of 0.748 and 0.879, respectively. Functional analysis of the PPI-associated 16S rRNA microbiome revealed enriched carbohydrate- and energy-associated genes, mostly encoding fructose-1,6-bisphosphatase and pyruvate dehydrogenase, among others. In this study, we have demonstrated alterations in bacterial abundance and functional metabolic potential related to PPI use, as a basis for future studies on PPI-induced adverse effects

Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment

Coupling of Defect Modes in Cholesteric Liquid Crystals Separated by Isotropic Polymeric Layers

Cholesteric liquid crystal structures with multiple isotropic defect layers exhibit localized optical modes (defect modes). Coupling effects between these modes were simulated using the finite difference time domain method. Analogous to the well-known result of the tight-binding approximation in solid state physics, splitting of the defect modes takes place, as soon as the structure contains more than one defect layer. The dispersion relation of the mini-bands forming within the photonic band gap of the structure is calculated numerically. The structures might have promising applications for multiwavelength filters and low-threshold lasers

Induction of callus in Cassia mimosoides

In this study, the young leaves of Cassia mimosoides were used as explants. On the basis of 1/2 MS +2.0 mg/L 6-BA +0.5 mg/L NAA medium, we observed the effect of adding different factors on the callus induction of C. mimosoides. The results shown that after 20 days of callus induction, it was found that the addition of 150 mg/L vitamin C (VC) did not affect the induction efficiency, but the growth of callus became slower; and when the concentration was higher than 150 mg/L, the formation of callus would be inhibited. The induction of callus would be restrained while adding different concentrations of Cu2+ into mediums. Moreover, glutamine (Gln) had little effect on the induction of callus. Furthermore, the addition of hydrolyzed casein (CH) would not affect the formation of callus, but the high concentration of CH could affect the growth status of callus. The induction efficiency of callus was severely inhibited by exogenous addition of silver nitrate (AgNO3), and the growth status of callus was poor, and the phenomenons of early rooting had happened at the same time. The results of this study provided a theoretical basis for the subsequent optimization of bud proliferation and rooting in C. mimosoides