Engineered Selenium/Human Serum Albumin Nanoparticles for Efficient Targeted Treatment of Parkinson's Disease via Oral Gavage.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopamine (DA) neurons in the midbrain substantia nigra pars compacta (SNpc). While existing therapeutic strategies can alleviate PD symptoms, they cannot inhibit DA neuron loss. Herein, a tailor-made human serum albumin (HSA)-based selenium nanosystem (HSA/Se nanoparticles, HSA/Se NPs) to treat PD that can overcome the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) is described. HSA, a transporter for drug delivery, has superior biological characteristics that make it an ideal potential drug delivery substance. Findings reveal that HSA/Se NPs have lower toxicity and higher efficacy than other selenium species and the ability to overcome the IEB and BBB to enrich DA neurons, which then protect MN9D cells from MPP+-induced neurotoxicity and ameliorate both behavioral deficits and DA neuronal death in MPTP-model mice. Thus, a therapeutic drug delivery system composed of orally gavaged HSA/Se NPs for the treatment of PD is described.

Efficacy and safety of herbal medicines intervention for cachexia associated with cancer: A systematic review and meta-analysis.

As a worldwide public health issue, cancer-induced cachexia can result in decreasing physical function and survival rate. However, the therapeutic effects of conventional approaches, including pharmacotherapy, exercise and nutritional intervention, are far from satisfactory. Herbal medicines (HMs), especially Traditional Chinese Medicine (TCM), are reported to effectively treat cachexia for centuries. The inclusion criteria of all participants in this study pointed to the diagnosis of cachexia, the trial group used herbal medicine (HM) in complementary and alternative medicine, etc. Twelve databases, including EMbase, PubMed, Web of science, Cochrane CENTRAL, CINAHL, CINAHLPlus, PsycINFO, AMED, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Chongqing VIP (CQVIP) were retrieved from inception to March 28, 2022. We conducted the meta-analysis utilizing RevMan 5.3. A trial sequential analysis (TSA) was conducted to assess the adequacy of the sample size for the outcomes. We have registered the protocol and the registration number was CRD42022336446. A total of 66 studies were included, containing 3654 patients diagnosed with cancer cachexia, of which 1833 patients were assigned to the trial group and 1821 patients were treated in the control group. Outcomes cover the primary indicator KPS (RR = 1.84, 95%CI = [1.61, 2.09], p < 0.00001), and other outcomes including adverse events rate (RR = 0.37, 95%CI = [0.23, 0.58], p < 0.0001), albumin (MD = 2.14, 95%CI = [1.56, 2.71], p < 0.00001), haemoglobin (MD = 4.88, 95%CI = [3.26, 6.50], p < 0.00001), TCM syndrome effect (MD = 1.47, 95%CI = [1.31, 1.65], p < 0.00001), effect of weight (RR = 1.62, 95%CI = [1.34, 1.95], p < 0.00001), effect of appetite (RR = 1.23, 95%CI = [1.13, 1.34], p < 0.00001), FAACT (RR = 7.81, 95%CI = [6.12, 9.50], p < 0.00001), PG-SGA (MD = -2.16, 95%CI = [-2.65, -1.67], p < 0.00001) and QOL (MD = 5.76, 95%CI = [4.04, 7.48], p < 0.00001), suggesting that HMs or HMs combined with conventional treatment have an ameliorating effect on cachexia in each respect. Subgroup analysis showed that the five HMs with the best effect on improving KPS and their optimal doses were Coicis Semen (Yiyiren) in 10 g group, Citri Reticulatae Pericarpium (Chenpi) in 15 g group, Dioscoreae Rhizoma (Shanyao) in 10 g group, Ophiopogonis Radix (Maidong) in 10 g group and Ginseng Radix Et Rhizoma (Renshen) in 20 g group. In addition, there were HM combinations of levels 2-6. Egger's test showed publication bias for five outcomes. HMs have a significant effect on improving cancer cachexia on FAACT, TCM syndrome, KPS, QOL, appetite, nutritional status (evaluated by PG-SGA scale), weight, levels of albumin and haemoglobin. And the Adverse events rate is less than that of Western Medicine. The herbs with the best curative effect and their optimal dose were Dioscoreae R. (10 g), Citri R.P. (15 g), Coicis S. (10 g), Ophiopogonis R. (10 g) and Ginseng R.E.R. (20 g). Due to the quality of included studies is not high, further high-quality studies are needed to firmly establish the clinical efficacy of HM.

The key to improving the beauty of the giant retaining wall in valleys: Increasing visual extension.

The retaining wall is a passive engineering measure to prevent and control unsafe factors caused by rock collapse in the valleys. Existing studies have mainly focused on its functional robustness and safety features, with few exploring its visual quality in the landscape. A multiple regression analysis was applied to evaluate the Scenic Beauty Estimation (SBE) of the giant retaining wall in Jiuzhaigou's (a world natural heritage site) Heye Village, then the factors affecting SBE were analyzed. It is found that enhancing the sense of perspective and spatial hierarchy of retaining-wall murals in narrow roads contributes to the extension of observers' sight, which is the key to improving SBE. Furthermore, the showcase of folk culture in murals can realize the beautification function of the giant retaining walls. In addition, the SBE of giant retaining walls is also linked to coordination, where the walls embellished with the natural landscape and folk culture murals have better SBE performance than those with local stones. This study provides a reference for constructing scenic beauty after fulfilling the safety function of retaining wall engineering.

The gut microbiome stability is altered by probiotic ingestion and improved by the continuous supplementation of galactooligosaccharide.

The stable gut microbiome plays a key role in sustaining host health, while the instability of gut microbiome also has been found to be a risk factor of various metabolic diseases. At the ecological and evolutionary scales, the inevitable competition between the ingested probiotic and indigenous gut microbiome can lead to an increase in the instability. It remains largely unclear if and how exogenous prebiotic can improve the overall gut microbiome stability in probiotic consumption. In this study, we used Lactobacillus plantarum HNU082 (Lp082) as a model probiotic to examine the impact of the continuous or pulsed supplementation of galactooligosaccharide (GOS) on the gut microbiome stability in mice using shotgun metagenomic sequencing. Only continuous GOS supplement promoted the growth of probiotic and decreased its single-nucleotide polymorphisms (SNPs) mutation under competitive conditions. Besides, persistent GOS supplementation increased the overall stability, reshaped the probiotic competitive interactions with Bacteroides species in the indigenous microbiome, which was also evident by over-abundance of carbohydrate-active enzymes (CAZymes) accordingly. Also, we identified a total of 793 SNPs arisen in probiotic administration in the indigenous microbiome. Over 90% of them derived from Bacteroides species, which involved genes encoding transposase, CAZymes, and membrane proteins. However, neither GOS supplementation here de-escalated the overall adaptive mutations within the indigenous microbes during probiotic intake. Collectively, our study demonstrated the beneficial effect of continuous prebiotic supplementation on the ecological and genetic stability of gut microbiomes.

Insights into mechanism on organic acids assisted translocation of uranium in Brassica juncea var. foliosa by EXAFS.

Citric acid (CA) and Lactic acid (LA) were used as additives to study the mechanism of organic acid promoting the root-to-shoot translocation of uranium (U) in Brassica juncea var. foliosa from molecular and tissue levels. Firstly, the distribution of U in plants under the condition of different organic acids concentrations were studied. The accumulation of U in leafs of 1 mM CA group and 5 mM LA group reached 2225 and 1848 mg/kg respectively, which was about 5 times that of the control group. Secondly, the speciation and distribution of U in plant roots after exposure to different culture solutions were studied by EXAFS and SEM. The result of EXAFS found that the complex of U with organic acids resulted in the U accumulated in the roots was the uranyl carboxylate speciation, while the control group only was the uranyl phosphate speciation. SEM results showed that the lactic acids could enhanced the translocation of U from the cortex to the stele. Thirdly, we further studied the apoplastic pathway and the symplastic pathway of U translocation using transpiration inhibitor and metabolism inhibitor. Compared with the control group, it was likely that the complex of U with organic acids were translocated into the shoot of plants through the apoplastic pathway.

Urinary metabolites of cinobufagin in rats and their antiproliferative activities.

Cinobufagin was one of the important cardenolidal steroids and a major component of Chan'Su, a famous traditional Chinese medicine. The urinary metabolites of cinobufagin after single oral doses of 25 mg kg⁻¹ in rats were investigated. Eleven metabolites were isolated and purified by liquid-liquid extraction, open-column chromatography, medium-pressure liquid chromatography, as well as semi-preparative high-performance liquid chromatography. Their structures were elucidated by chemical and various spectroscopic methods, which were identified as desacetylcinobufagin (M-1), 3-oxo-desacetylcinobufagin (M-2), 3-oxo-cinobufagin (M-3), 3-epi-desacetylcinobufagin (M-4), 3-epi-12ß-hydroxyl desacetylcinobufagin (M-5), 5ß-hydroxyl cinobufagin (M-6), 5ß-hydroxyl desacetylcinobufagin (M-7), 12ß-hydroxyl cinobufagin (M-8), 1ß,12ß-dihydroxyl cinobufagin (M-9), 12ß-hydroxyl desacetylcinobufagin (M-10) and 1ß,12ß-dihydroxyl desacetylcinobufagin (M-11), respectively. Among them, M-1 was the main urinary metabolite of cinobufagin with a yield of 17.7%. Most metabolites were hydroxylated products of cinobufagin at C-1ß, 5ß and 12ß positions, as well as deacetylated products at C-16. Except M-1, M-4 and M-7, the other eight metabolites were novel in vivo metabolites of cinobufagin. Some metabolites showed potential cytotoxicity against human hepatoma cells (HepG2) and human leukaemia (K562, HL-60) cells; however, their cytotoxicities generally decreased after metabolic conversion.

Novel indole C-glycosides from Isatis indigotica and their potential cytotoxic activity.

Two novel indole C-glycosides, which were the first reported alkaloids C-glycosides from Isatis indigotica, together with five known alkaloids were isolated. The novel alkaloids were elucidated to be indole-3-acetonitrile-4-methoxy-2-C-ß-D-glucopyranoside (1) and N-methoxy-indole-3-acetonitrile-2-C-ß-D-glucopyranoside (2) on the basis of spectroscopic analysis. 1 exhibited significant cytotoxic activities against human myeloid leukemia HL-60 and human liver cancer HepG2 cells with the IC(50) of 1.3 ± 0.1 and 2.1 ± 0.3 µM, respectively. 2 showed potential cytotoxic activities against HL-60 and human myeloid leukemia Mata cells with the IC(50) of 5.1 ± 0.4 and 12.1 ± 0.8 µM, respectively.