Effects of dietary minerals deficiency and supplementation on different parts of muscle minerals content in grazing Mongolian sheep.

Objective: The objective of this study was to investigate the impact of dietary deficiency and supplementation of calcium, zinc, copper, cobalt, manganese or selenium on minerals content in the longissimus dorsi (LD), biceps femoris (BF) and triceps brachii (TB) of grazing Mongolian sheep. Methods: We randomly divided 98 sheep into 7 treatment groups and fed them specific diets for 60 days: a total mineral nutrition diet (LCG), a calcium deficiency diet (LCa), a zinc deficiency diet (LZn), a copper deficiency diet (LCu), a cobalt deficiency diet (LCo), a manganese deficiency diet (LMn) and a selenium deficiency diet (LSe). Then 7 sheep from each group were slaughtered and samples of LD, BF and TB were collected for mineral content analysis. The remaining sheep in each group were subsequently fed specific diets for an additional 41 days: a total mineral nutrition diet (SCG), a calcium supplementation diet (SCa), a zinc supplementation diet (SZn), a copper supplementation diet (SCu), a cobalt supplementation diet (SCo), a manganese supplementation diet (SMn) and a selenium supplementation diet (SSe). Afterward, all sheep were slaughtered, and muscle samples were collected and analyzed. Results: Significant findings emerged that LCa decreased sulfur (S) content in BF and increased Ca content in LD and BF, while SCa increased S and Ca content in BF and TB, respectively (P < 0.05). LZn decreased Zn, S, and potassium (K) content in LD and BF, while SZn increased Zn and S content in LD and BF, respectively (P < 0.05). LCu decreased Cu and iron (Fe) content in LD and TB, while SCu increased Fe content in TB (P < 0.05). LCo decreased phosphorus, S, K, Ca, Mn, Fe, Cu, and Zn content in LD (P < 0.05). LMn decreased Mn content and increased K content in TB, while SMn decreased K content in BF and TB (P < 0.05). LSe and SSe decreased and increased Se content in LD, BF, and TB, respectively (P < 0.05). Conclusion: Dietary mineral levels have varying effects on lamb meat minerals content. It is important to ensure an adequate intake of minerals in the diet to enhance the mineral nutrition of lamb meat.

Transcriptomics and metabolomics analysis reveal the dietary copper deficiency and supplementation effects of liver gene expression and metabolite change in grazing sheep.

BACKGROUND: The appropriate mineral nutrients are essential for sheep growth and reproduction. However, traditional grazing sheep often experience mineral nutrient deficiencies, especially copper (Cu), due to inadequate mineral nutrients from natural pastures. RESULTS: The results indicated that dietary Cu deficiency and supplementation significantly reduced and elevated liver concentration of Cu, respectively (p < 0.05). FOXO3, PLIN1, ACTN2, and GHRHR were identified as critical genes using the weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR), and receiver operating characteristic curve (ROC) validation as potential biomarkers for evaluating Cu status in grazing sheep. Combining these critical genes with gene functional enrichment analysis, it was observed that dietary Cu deficiency may impair liver regeneration and compromise ribosomal function. Conversely, dietary Cu supplementation may enhance ribosomal function, promote lipid accumulation, and stimulate growth and metabolism in grazing sheep. Metabolomics analysis indicated that dietary Cu deficiency significantly decreased the abundance of metabolites such as cholic acid (p < 0.05). On the other hand, dietary Cu supplementation significantly increased the abundance of metabolites such as palmitic acid (p < 0.05). Integrative analysis of the transcriptome and metabolome revealed that dietary Cu deficiency may reduce liver lipid metabolism while Cu supplementation may elevate it in grazing sheep. CONCLUSIONS: The Cu content in diets may have an impact on hepatic lipid metabolism in grazing sheep. These findings provide new insights into the consequences of dietary Cu deficiency and supplementation on sheep liver and can provide valuable guidance for herders to rationalize the use of mineral supplements.

Effects of essential mineral elements deficiency and supplementation on serum mineral elements concentration and biochemical parameters in grazing Mongolian sheep.

Traditional sheep grazing is the pillar industry and the main source of income for local herders in the Inner Mongolia Autonomous Region of China. However, grazing sheep often suffer from mineral deficiency. In the present study, the feeding experiment was performed on 84 grazing Wu Ranke sheep. After being divided into calcium (Ca), zinc (Zn), copper (Cu), cobalt (Co), manganese (Mn), and selenium (Se) treatment groups, they were fed with a mineral deficient diet for 60 days and then a mineral supplement diet for 41 days. Serum samples were collected three times, 10 concentrations of essential mineral elements and 15 concentrations/activity of biochemical parameters were measured to assess the effects of mineral deficiency and supplementation on the physical health of sheep. The results revealed that the sheep showed mineral Ca, Cu, Co, Mn, and Se deficiencies after feeding their respective mineral deficient diet. Deficiency in dietary Ca, Zn, Cu, Co, Mn, and Se may adversely affect the liver, myocardium and pancreas of sheep. The prompt supplementation of dietary Zn, Cu, Co, Mn, and Se may alleviate the damage caused to the liver, myocardium and pancreas, while that of dietary Ca improved energy generation. In conclusion, the adequate supplementation of dietary Ca, Zn, Cu, Co, Mn, and Se is essential for avoiding the impairment caused to the liver, myocardium and pancreas function of sheep by the deficiency in essential dietary minerals.

Isolation of Peptide Inhibiting SGC-7901 Cell Proliferation from Aspongopus chinensis Dallas.

Aspongopus chinensis Dallas is used as a traditional Chinese medicine as well as an edible insect. Although its anti-tumor effects have been observed, the anti-tumor active component(s) in the hemolymph of A. chinensis remains unknown. In this study, a combination usage of ultrafiltration, gel filtration chromatography, FPLC and RP-HPLC to separate and purify active peptides was performed based on the proliferation of the human gastric cancer SGC-7901 cell line treated with candidates. One peptide (MW = 2853.3 Da) was isolated from the hemolymph of A. chinensis. A total of 24 amino acid residues were continuously determined for the active peptide: N'-ECGYCAEKGIRCDDIHCCTGLKKK-C'. In conclusion, a peptide that can inhibit the proliferation of gastric cancer SGC-7901 cells in the hemolymph of A. chinensis was purified in this study, which is homologous to members of the spider toxin protein family. These results should facilitate further works for this peptide, such as the cloning of genes, expression in vitro by prokaryotic or eukaryotic systems, more specific tests of anti-tumor activity, and so on.

A Comparison of Clinical Prognostic Indices in Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with a Pegylated Liposomal Doxorubicin Combination Regimen in China.

Background: There is no consensus regarding the risk stratification scores for elderly patients with diffuse large B-cell lymphoma (DLBCL). We aimed to compare the prognostic predictive ability of the current clinical scoring indices in DLBCL elderly patients treated with the R-CODP regimen (rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone). Methods: We retrospectively collected the data of elderly DLBCL patients who received the R-CODP regimen as the first-line treatment. The efficacy of the regimen was evaluated. The Akaike information criteria (AIC), concordance index (C-index), and integrated discrimination improvement (IDI) were used to assess the fitness and prognostic performance of the current clinical prognostic indices. Results: In the total of 158 patients enrolled, the median follow-up time was 6.7 years (95% CI: 6.3-7.9), and the 5-year OS was 52.8% (95% CI: 45.5%-61.2%). The International Prognostic Index (IPI), National Comprehensive Cancer Network-IPI (NCCN-IPI), and Elderly International Prognostic Index (E-IPI) were all significantly associated with OS (P < 0.001 for all). However, no significance was observed in 5-year OS in the low- vs low-intermediate-risk groups for IPI (P = 0.377), NCCN-IPI (P = 0.238), and E-IPI (P = 0.080). Compared with the IPI and NCCN-IPI, the E-IPI had the lowest AIC value of 747.5 and the highest C-index of 0.692. For predicting 5-year mortality, the E-IPI showed better performance (AUC: 0.715 for E-IPI vs 0.676 for IPI, P = 0.036), with the IDI of 6.29% (95% CI: 3.71%-8.88%, P < 0.001) and 4.80% (95% CI: 1.32%-8.28%, P = 0.007) compared to the IPI and NCCN-IPI, respectively. Conclusion: The E-IPI might be a better prognostic prediction model in Chinese DLBCL generics treated with R-CODP for predicting 5-year mortality. However, the IPI, NCCN-IPI, and E-IPI did not seem to be able to distinguish patients with a favorable prognosis well.

Investigation of Serum and Macular Carotenoids in Central Serous Chorioretinopathy.

Purpose: This study aimed to evaluate serum lutein and zeaxanthin levels and macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC). Methods: Fifty-four patients with acute CSC (28-56 years old; 44 men and 10 women) and 62 matched controls were enrolled. Serum lutein and zeaxanthin were measured using the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. MPOD was measured at 7° of eccentricity and reported in parameters as "max" and "mean" optical density (OD) (Visucam 200; Carl Zeiss Meditec). MPOD was re-measured in 9 patients whose subretinal fluid was absorbed. Results: The average max OD and the mean OD in CSC were 0.275 ± 0.047 d.u. and 0.098 ± 0.018 d.u., respectively, which were significantly lower than the control (p < 0.001). The average MPOD value in the unaffected eyes of patients with CSC was 0.298 ± 0.045 for max OD, 0.106 ± 0.017 for mean OD, and both were significantly lower compared with the affected eyes (p < 0.001 for max OD, p = 0.01 for mean OD). In the 9 follow-up patients, the decrease in MPOD was partially recovered. The mean serum level was 409.80 ± 182.52 ng/ml for lutein and 22.97 ± 12.23 ng/ml for zeaxanthin in patients with CSC. In controls, the mean serum level was 393.38 ± 202.44 ng/ml for lutein and 22.16 ± 10.12 ng/ml for zeaxanthin. The difference was not statistically significant (p = 0.649, p = 0.698, respectively). Conclusion: MPOD decreased within 7° of eccentricity in CSC without serum lutein and zeaxanthin changes. The decrease may be due to the subretinal fluid. Whether local oxidative stress is involved in CSC and the supplementation with lutein and zeaxanthin is helpful for CSC requires further investigation.

Controlled killing of human cervical cancer cells by combined action of blue light and C-doped TiO2 nanoparticles.

In this study, C-doped TiO2 nanoparticles (C-TiO2) were prepared and tested as a photosensitizer for visible-light-driven photodynamic therapy against cervical cancer cells (HeLa). X-ray diffraction and Transmission Electron Microscopy confirmed the anatase form of nanoparticles, spherical shape, and size distribution from 5 to 15 nm. Ultraviolet-visible light spectroscopy showed that C doping of TiO2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO2. In contrast, a combination with blue light significantly reduced the survival of HeLa cells: illumination only decreased cell viability by 30% (15 min of illumination, 120 µW power), and 60% when HeLa cells were preincubated with C-TiO2. We have also confirmed blue light-induced C-TiO2-catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO2/blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO2/blue light treatment. Unlike blue light illumination, which caused the appearance of large necrotic cells with deformed nuclei, cytoplasm swelling, and membrane blebbing, a combination of C-TiO2/blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy.

Gold nanobipyramid-loaded black phosphorus nanosheets for plasmon-enhanced photodynamic and photothermal therapy of deep-seated orthotopic lung tumors.

Various types of photodynamic agents have been explored for photodynamic therapy (PDT) to destroy cancers located in deep tissues. However, these agents are generally limited by low singlet oxygen (1O2) yields owing to weak absorption in the optical transparent window of biological tissues. Accordingly, in this work, we developed a nanocomposite through the assembly of gold nanobipyramids (GNBPs) on black phosphorus nanosheets (BPNSs). This nanocomposite could simultaneously enhance 1O2 generation and hyperthermia by localized surface plasmon resonance in cancer therapy. As two-dimensional inorganic photosensitizers, BPNSs were hybridized with GNBPs to form BPNS-GNBP hybrid nanosheets. The hybridization markedly increased 1O2 production by the BPNSs through plasmon-enhanced light absorption. The nanocomposite exhibited a higher photothermal conversion efficiency than the BPNSs alone. In vitro and in vivo assays indicated that the BPNS-GNBP hybrid nanocomposite exhibited good tumor inhibition efficacy owing to simultaneous dual-modality phototherapy. In vivo, the nanocomposite suppressed deep-seated tumor growth with minimal adverse effects in mice bearing orthotopic A549 human lung tumors. Taken together, these results demonstrated that our BPNS-GNBP nanocomposite could function as a promising dual-modality phototherapeutic agent for enhanced cancer therapy in future cancer treatments. STATEMENT OF SIGNIFICANCE: In this study, we established a new nanocomposite by assembly of gold nanobipyramids (GNBPs) on black phosphorus nanosheets (BPNSs). Characterization of this nanocomposite showed that BPNS-GNBP enhanced 1O2 generation and hyperthermia. BPNS-GNBP exhibited good tumor inhibition efficacy in vivo and in vitro owing to simultaneous dual-modal phototherapy functions. Moreover, BPNS-GNBP suppressed deep-seated tumor growth in vivo and did not show adverse effects in mice bearing orthotopic A549 human lung tumors. Overall, these results showed that BPNS-GNBP may be used as a promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

Effects of a traditional Chinese medicine, Longdanxiegan formula granule, on Toll-like receptor pathway in female guinea pigs with recurrent genital herpes.

OBJECTIVE: The aim of the present study was to investigate the effects of Longdanxiegan formula granule (LDXGFG), a Chinese traditional medicine on Toll-like receptor (TLR) pathway in recurrent genital herpes. MATERIALS AND METHODS: An experimental recurrent genital herpes model was constructed using herpes guinea pig model. The effect of LDXGFG on expression levels of TLR pathway genes were detected using real-time polymerase chain reaction. Furthermore, the dendritic cells and Langerhans cells were isolated and the TLR pathway genes of these cells were assayed after LDXGFG treatment. RESULTS: The result suggested two different expression patterns of TLR pathway genes in genital herpes and recurrent genital herpes, including upregulated genes and downregulated genes. TLR1, TLR4, TLR6, TLR7, TLR8, TLR9, and TLR10 showed a significant decrease while, TLR2, TLR3, and TLR5 increased in genital herpes and recurrent genital herpes guinea pigs. Meanwhile, the downregulated genes in genital herpes and recurrent genital herpes were stimulated by LDXGFG. By contrast, the upregulated genes decreased significantly after LDXGFG treatment. In both dendritic cells and Langerhans cells, the TLR pathway genes exhibited same pattern: the LDXGFG corrected the abnormal expression of TLR pathway genes. CONCLUSION: The present results suggest that LDXGFG is an alternative, inexpensive, and lasting-effect medicine for herpes simplex virus 2 infection.

Reduced cerebral blood flow in genetic prion disease with PRNP D178N-129M mutation: an arterial spin labeling MRI study.

The D178N mutation in the PRNP gene is associated with fatal familial insomnia and Creutzfeldt-Jakob disease (CJD). Typically, the D178N mutation associated with the 129M genotype is related to fatal familial insomnia while the same mutation associated with the 129V genotype is linked to familial CJD. We describe a D178N-129M haplotype in a patient with early, severe dementia and late-onset minor insomnia, mainly presenting as the CJD phenotype. Cerebrospinal fluid 14-3-3 protein was positive. Diffusion weighted imaging demonstrated widespread cortical ribbon-like high signal intensity, which was also seen in the basal ganglia bilaterally. Arterial spin labeling (ASL) MRI showed severe hypoperfusion in the cerebral cortex, basal ganglia and thalami but this was least marked in the thalami. Neuroimaging abnormalities were more prominent in the cerebral cortex than the thalamus, which was in line with the clinical picture of severe dementia rather than insomnia. ASL-MRI seems to be a useful tool for the detection and follow-up of perfusion changes in patients and asymptomatic carriers harboring the PRNP mutation.