Natural compounds efficacy in complicated diabetes: A new twist impacting ferroptosis.

Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets ß Insulin secretion and programmed cell death of T2DM target organs are involved in the pathogenesis of T2DM and its complications. Targeting suppression of ferroptosis with specific inhibitors may provide new therapeutic opportunities for previously untreated T2DM and its target organs. Current studies suggest that natural bioactive compounds, which are abundantly available in drugs, foods, and medicinal plants for the treatment of T2DM and its target organs, have recently received significant attention for their various biological activities and minimal toxicity, and that many natural compounds appear to have a significant role in the regulation of ferroptosis in T2DM and its target organs. Therefore, this review summarized the potential treatment strategies of natural compounds as ferroptosis inhibitors to treat T2DM and its complications, providing potential lead compounds and natural phytochemical molecular nuclei for future drug research and development to intervene in ferroptosis in T2DM.

Mn Single-Atom Nanozymes with Superior Loading Capability and Superb Superoxide Dismutase-like Activity for Bioassay.

Single-atom nanozymes (SANs) with highly exposed active sites and remarkable catalytic activity have shown noteworthy practicability in heterogeneous catalysis-based bioassay. Nevertheless, most of them were reported with peroxidase-like activity and ordinary loading capability. It is still a challenge to prepare high-loading SANs with desirable superoxide dismutase (SOD)-like activity. In this work, Mn SAN was successfully confined in the frameworks of Prussian blue analogues formed on Ti3C2 MXene sheets with the assistance of massive surfactants, which show a superior loading efficiency of 13.5 wt % (typically <2.0 wt %). The prepared Mn SAN exhibits desirable superoxide radical anion elimination capability because of its SOD-like activity. Moreover, due to the wide-spectrum absorption behavior of the carriers, Mn SAN shows a synergistically quenching efficiency up to 98.89% on the emission of the reactive oxygen species-mediated chemiluminescent (CL) system. Inspired by these features, a CL quenching method was developed on a lateral flow test strip platform by utilizing Mn SAN as a signal quencher and acetamiprid as a model analyte. The method for detecting acetamiprid shows a detection range of 1.0-10,000 pg mL-1 and a limit of detection of 0.3 pg mL-1. Its accuracy has been validated by detecting acetamiprid in medicinal herbs with acceptable recoveries. This work opens an avenue for preparing SANs with a surfactant-assisted protocol and pioneers the study of SANs with SOD-like activity in bioassay.

Evaluation of cerium oxide as a phosphate binder using 5/6 nephrectomy model rat.

BACKGROUND: The number of chronic kidney disease (CKD) patients continues to increase worldwide. CKD patients need to take phosphate binders to manage serum phosphorus concentrations. Currently, several types of phosphate binder, including lanthanum carbonate, are used. However, they each have disadvantages. METHODS: In this study, we evaluated cerium oxide as a new phosphate binder in vitro and in vivo. First, cerium oxide was mixed with phosphoric acid at pH 2.5 or 7.0, and residual phosphoric acid was measured by absorption photometry using colorimetric reagent. Second, cerium oxide was fed to 5/6 nephrectomy model rats (5/6Nx), a well-known renal damage model. All rats were measured food intake, water intake, feces volume, and urine volume, and collected serum and urine were analyzed for biochemical markers. RESULTS: Cerium oxide can adsorb phosphate at acidic and neutral pH, while lanthanum carbonate, which is a one of popular phosphate binder, does not dissolve at neutral pH. Cerium oxide-treatment reduced serum phosphate concentrations of 5/6Nx rats without an increase in serum alanine transaminase levels that would indicate hepatotoxicity, and cerium oxide-treatment maintained serum creatinine and blood urea nitrogen levels, while those of normal 5/6Nx rats increased slightly. CONCLUSIONS: These results suggest that cerium oxide can be a potential phosphate binder. Decreased body weight gain and increased water intake and urine volume in 5/6Nx rats were thought to be an effect of nephrectomy because these changes did not occur in sham operation rats. Additional investigations are needed to evaluate the longer-term safety and possible accumulation of cerium oxide in the body.

Water dispersible cobalt single-atom catalysts with efficient Chemiluminescence enhancement for sensitive bioassay.

Single-atom catalysts (SACs) have been applied in various fields as they display extremely high utilization efficiency of catalytic sites. A majority of SACs prepared by high-temperature calcination suffer from poor water dispersion and lose of labelling groups. Herein cobalt SACs (CSACs) were synthesized with a solvothermal method by adopting hybridized MOFs Fe2O3/MIL-100(Fe) as the carriers to load cobalt atoms. Compared with original MOFs MIL-100(Fe), the carriers possess superior loading capacity, and the loading amount of cobalt element is up to 4.69 wt%. The implantation of cobalt atoms in hybridized MOFs Fe2O3/MIL-100(Fe) vastly improved the specific surface of the carriers for 68 times. CSACs at 1.0 µg mL-1 can catalyze H2O2 to generate numerous reactive oxygen species and enormously boost the chemiluminescent emission of luminol-H2O2 system up to 2297 times. The CSACs also exhibit satisfactory dispersion in aqueous medium. Benefiting from these attracting features, the CSACs were applied as sensitive signal probes for detecting carbendazim in Chinese medicinal herbs with a chemiluminescent immunoassay method. The dynamic range is 10 pg mL-1 - 50 ng mL-1 and the limit of detection is 1.8 pg mL-1. The proof-of-principle work paves a pathway to the exploitation of SACs as sensitive probes for tracing biological recognition events.

Metabolome and transcriptome analyses identify the plant immunity systems that facilitate sesquiterpene and lignan biosynthesis in Syringa pinnatifolia Hemsl.

BACKGROUND: Syringa pinnatifolia Hemsl. is a shrub belonging to the Oleaceae family. The peeled woody stems and roots of S. pinnatifolia are used in Chinese traditional medicine. This plant has been used for centuries, and modern pharmacological research has revealed its medicinal value. However, the wild populations of S. pinnatifolia have been decreasing, and it has been listed as an endangered plant in China. To elucidate the molecular mechanism leading to the synthesis of the major components of S. pinnatifolia for its further development and sustainable use, this study compared peeled stems and twigs at the metabolic and molecular levels. RESULTS: Peeled stems with the purple substance visible (SSP) and peeled twigs without the purple substance (TSP) were compared at different levels. Microscopic observation showed resin-like fillers in SSP and wood fiber cell walls approximately 1.0 µm thicker than those in TSP (wood fiber cell thickness approximately 2.7 µm). In addition, 104 volatile organic compounds and 870 non-volatile metabolites were detected in the non-targeted and widely-targeted metabolome analyses, respectively. Among the 76 differentially accumulated metabolites (DAMs) detected, 62 were up-accumulated in SSP. Most of these DAMs were terpenes, of which 90% were identified as sesquiterpenes in the volatile organic compound analysis. In the analysis of the non-volatile metabolites, 21 differentially accumulated lignans were identified, of which 18, including five subtypes, were accumulated in SSP. RNA sequencing revealed 4,421 upregulated differentially expressed genes (DEGs) and 5,522 downregulated DEGs in SSP compared with TSP, as well as 33,452 genes that were not differentially expressed. Analysis of the DEGs suggested that sesquiterpenes and lignans were mostly biosynthesized via the mevalonate and phenylpropanoid pathways, respectively. Additionally, in SSP, the enriched Gene Ontology terms included response to biotic stimulus and defense response, while the enriched Kyoto Encyclopedia of Genes and Genomes pathways included plant-pathogen interaction and many other pathways related to plant immunity. CONCLUSIONS: This study provides metabolome and transcriptome information for S. pinnatifolia, suggesting that biotic stimuli, including pathogens, are potential and valuable approaches to promoting the biosynthesis of the metabolites linked to the medicinal properties of this plant.

[Differences between male and female leaves of Schisandra sphenanthera: based on RNA-Seq].

Schisandra sphenanthera is dioecious and only the fruits of female plants can be used as medicine and food. It is of great significance for the cultivation and production of S. sphenanthera to explore the differences between male and female plants at the non-flowering stage and develop the identification markers at non-flowering or seedling stage. In this study, the transcriptome of male and female leaves of S. sphenanthera at the non-flowering stage was sequenced by Illumina high-throughput sequencing technology and analyzed based on bioinformatics. A total of 236 682 transcripts were assembled by Trinity software and 171 588 were chosen as unigenes. Finally, 1 525 differentially expressed genes(DEGs) were identified, with 458 up-regulated and 1 067 down-regulated in female lea-ves. The down-regulated genes mainly involve photosynthesis, photosynthesis-antenna protein, carbon fixation in photosynthetic or-ganisms, and other pathways. Real-time quantitative PCR(qPCR) identified two genes between male and female leaves and one of them was a HVA22-like gene related to floral organ development and abscisic acid(ABA). Enzyme linked immunosorbent assay(ELISA) was applied to determine the content of ABA, auxin, gibberellin, and zeatin riboside(ZR) in leaves of S. sphenanthera. The results showed that the content of ABA and ZR in male leaves was significantly higher than that in female leaves. The involvement of down-regulated genes in female leaves in the photosynthesis pathway and the significant differences in the content of endogenous hormones between male and female leaves lay a scientific basis for analyzing the factors affecting sex differentiation of S. sphenanthera.

Schisandra Fruit Vinegar Lowers Lipid Profile in High-Fat Diet Rats.

Hyperlipidemia and its associated obesity, hepatic steatosis, and NAFLD are worldwide problems. However, there is no ideal pharmacological treatment for these. Therefore, the complementary therapies that are both natural and safe have been focused. Healthy foods, such as fruit vinegar, may be one of the best choices. In this study, we made a special medicinal fruit vinegar, Schisandra fruit vinegar (SV), and examined its lipid-lowering effects and the underlying mechanisms in a high-fat diet rat model. The results showed that SV significantly reduced the body weight, liver weight, liver index, the serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA), increased the content of high-density lipoprotein cholesterol (HDL-C) and the activity of superoxide dismutase (SOD), upregulated the expressions of peroxisome proliferative activated receptor (PPAR-α), peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), and carnitine palmitoyltransferase 1 (CPT1) proteins, increased the contents of key component of antioxidant defense NF-E2-related factor 2 (NRF2) and its downstream heme oxygenase-1 (HO-1) protein, and downregulated the expression of Kelch-like ECH-associated protein 1 (KEAP1). These results suggest that SV has weight loss and lipid-lowering effects in HFD rats, which may be related to its upregulation of the expressions of ß-oxidation -elated PPAR-α, CPT1, and ACOX1 and the regulation of the expressions of antioxidant pathway-related KEAP1-NRF2-HO-1. Therefore, all these data provide an experimental basis for the development of SV as a functional beverage which is safe, effective, convenient, and inexpensive.

[Analysis of bacterial community structure and diversity during mountain-agarwood formation].

As an important substitute for agarwood, mountain-agarwood, belonging to the family Oleaceae, comes from the root, stem and thick branch of Syringa pinnatifolia, which has a wide range of application in Inner Mongolia, China. It has good clinical efficacy in the use of cardiovascular diseases. However, the formation speed of mountain-agarwood is extremely slow, and its cultivated seedlings have low resin content. Therefore, how to speed up the formation of mountain-agarwood and increase the resin content is a hot research topic in this field. In this work, 16 S rDNA amplicon sequencing method was used to systematically analyze the bacterial communities of different samples of mountain-agarwood. Our data revealed that the samples of mountain-agarwood had more obvious species diversity than the ones of non-mountain-agarwood, especially the wild mountain-agarwood samples. By analysis of bacterial community composition and species abundance, Sphingomonas, Modestobacter and unidentified Cyanobacteria genus were three dominant bacterial genera in all samples. In addition, there are two identified genera of dominant bacteria, namely Actinoplanes and Microbacterium in both wild and cultivated mountain-agarwood, by bacterial community composition and species richness analysis. Meanwhile, Roseomonas was the dominant bacterial genus in both wild and cultivated non-mountain-agarwood samples. Our work could provides basic data for exploring the mechanism of the mountain-agarwood formation, and help to exploit resource of endophytic bacteria reasonably.

[Microscopic histochemical comparison during mountain-agarwood formation].

Mountain-agarwood plays an important role in ethnic medicine in China for its pharmaceutical value. Modern pharmacological researches demonstrated that mountain-agarwood was effective for its anti-myocardial ischemia, antibacterial, anti-inflammatory, antitumor and analgesic effects. Mountain-agarwood derives from the peeled roots, stems or twigs of Syringa pinnatifolia which belongs to Syringa genus. It often depends on the purple substance and fragrance to estimate the formation of mountain-agarwood. However, the mechanism of mountain-agarwood formation has not been reported. To observe the microcosmic change in the process during the formation of mountain-agarwood, this study described the microscopic and histochemical characteristics of mountain-agarwood formation through histochemical staining. Our results showed that a significant difference of the distribution of tyloses existed during mountain-agarwood formation. It was observed that inchoate mountain-agarwood had more starch granules and viable cells than mountain-agarwood formed with high level or low level. The amount of polysaccharide and degree of lignification were increased during the mountain-agarwood formation. The results indicated that the mountain-agarwood, which meets the quality requirements for pharmaceutical use, contained the following characteristics: a large amount of purple tyloses in heartwood; yellow-brown tyloses distributing in heartwood and sapwood which were less in the latter; lignification with high level; a few viable cells; lots of polysaccharide and few starch granules in xylem rays cell. This study is aimed to reveal the change of histochemical characteristics during mountain-agarwood formation, and lay the foundation for exploring the mechanism of mountain-agarwood formation.

[Advances on terpenoids from genus Syringa].

Syringa plants are of important value in ornamental, economic and medical fields. The terpenoids in Syringa plants mainly include iridoids, sesquiterpenoids, and triterpenoids, most showing activities such as cardioprotective, neuroprotective, hypoglycemic, anti-flu virus, anti-bacterial, anti-inflammatory, and anti-oxidation effects. Among the above active compounds, sesquiterpenoids have attracted increasing attention. In this review, the phytochemical and pharmacological activities of Syringa terpenoids were summarized in order to provide an overview for further research and development of Syringa plants.

[Analysis of bacteria distribution characteristics in different layers of agarwood based on Hiseq sequencing].

To explore the diversity of bacterial community structure between different layers of agarwood, Hiseq(high-throughput sequencing) was used to analyze the bacterial community structure of samples from different layers of agarwood. Our results showed that 1 150 096 optimized sequences and 9 690 OTUs were obtained from 15 samples of 5 layers of agarwood, which belonged to 28 bacterial phyla, 61 classes, 110 orders, 212 families and 384 genera. Further analysis revealed that the normal layer(NL) had the lowest bacterial species richness and the smallest number of OTUs. And the total number of OTUs of the agarwood layer(AL) and NL was zero, which was quite different.At the same time, there were significant differences in bacterial community structure and species diversity between NL and the other four layers. While there were some common dominant bacterial genera in both transition layer(TL) and NL. The similarity of bacterial distribution in 4 non-NL layers was relatively high, which had four common genera, such as Acidibacter, Bradyrhizobium, Acidothemus and Sphingomonas. While Acidibacter, Bradyrhizobium and Acidothemus were the dominant bacterial genus of DA and AL, and all of these layers contained volatile oil. In addition, the Bradyrhizobium was the most abundant in agarwood layer. Our results showed that bacterial community diversity and abundance were decreasing from DL to AL, and different layers showed significant differences in bacterial enrichment. It provided the clues to investigate how bacteria participate in the formation of agarwood.

Regulatory Effect of Anwulignan on the Immune Function Through Its Antioxidation and Anti-Apoptosis in D-Galactose-Induced Aging Mice.

BACKGROUND: Aging is a spontaneous and inevitable phenomenon of biology, which can lead to the gradual deterioration of tissues and organs. One of the age-related deterioration processes is immunosenescence, which leads to changes in the function of immune systems, including immune cells and associated cytokines. A proper modulation of immune responses can improve the age-related immunosenescence process and then reach healthy aging. Schisandra sphenanthera, a traditional Chinese medicine, has been used as both a medicine and a nutritional supplement for thousands of years. Anwulignan, a monomer compound of Schisandra sphenanthera lignans, has been reported to possess an immunomodulatory effect. Therefore, this study was designed to further explore whether Anwulignan could also modulate the immune functions in aging model mice and the underlying mechanism. METHODS: D-galactose (D-gal) is often used as an inducer of immunosenescence in animals. In this study, a mice model was created by subcutaneous D-gal (220 mg kg-1) for successive 42 days. Then, the blood and spleen tissue samples were taken for the analysis and observation of cytokine levels, immunoglobulin levels, leukocyte numbers, and the phagocytic activity of macrophages, as well as the histological changes, the proliferation ability of lymphocytes, and the biochemical parameters in the spleen tissue. RESULTS: Anwulignan significantly increased the serum levels of IL-2, IL-4, IFN-γ, lgG, lgM, and lgA, decreased the content of TNF-α and IL-6 in the aging mice, and increased the blood leukocyte number, the phagocytic activity, the lymphocyte proliferation, and the spleen index in vitro. Anwulignan also significantly increased the activities of SOD and GSH-Px, decreased the contents of MDA and 8-OHdG in the spleen tissue, up-regulated the expressions of Nrf2, HO-1, and Bcl2, down-regulated the expressions of Keap1, Caspase-3, and Bax in the spleen cells, and reduced the apoptosis of spleen lymphocytes. CONCLUSION: Anwulignan can restore the immune function that is declined in D-gal-induced aging mice partly related to its antioxidant capacity by activating the Nrf2/ARE pathway and downstream enzymes, as well as its anti-apoptotic effect by regulating Caspase-3 and the ratio of Bcl2 to Bax in the spleen.

Schisantherin A Improves Learning and Memory of Mice with D-Galactose-Induced Learning and Memory Impairment Through Its Antioxidation and Regulation of p19/p53/p21/Cyclin D1/CDK4/RB Gene Expressions.

Schisantherin A (SCA) was evaluated for possible function in restoring the learning and memory impairment induced by D-galactose in mice. ICR mice were treated with D-galactose subcutaneously (220 mg·kg-1), and followed by SCA in different doses (1.25, 2.50 and 5.00 mg·kg-1, administered orally) for 42 days. Effects of SCA on learning and memory were examined by step-through tests and Morris water maze tests. The activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA) in the peripheral blood and hippocampus of mice were assayed by water-soluble tetrazolium-1 (WST-1) and thiobarbituric acid (TBA) methods. The contents of 8 hydroxy deoxy guanosine (8-OHdG) in the hippocampus of mice were detected by immunosorbent assay methods, respectively. Quantitative real-time PCR and Western Blot were respectively used to detect the expression of p19, p53, p21, cyclin D1, CDK4 and RB genes, and the phosphorylation of RB in the hippocampus of mice. We found that SCA significantly improved the learning and memory impairment induced by D-galactose in mice. After SCA treatment, SOD activity was increased and the content of MDA was decreased in both peripheral blood and hippocampus of mice. 8-OHDG content was also decreased in the hippocampus of mice. Furthermore, the expression of p19, p53 and p21 genes was reduced and the expression of cyclin D1 and CDK4 and the phosphorylation of RB protein were elevated in the hippocampus. SCA may improve the learning and memory impairment induced by D-galactose by enhancing the antioxidant capacity, and regulating the expression of p19/p53/p21/cyclinD1/CDK4 genes, and the phosphorylation of RB protein in the hippocampus of mice.

Tanshinone I alleviates insulin resistance in type 2 diabetes mellitus rats through IRS-1 pathway.

Tanshinone I from tanshen has been used in traditional Chinese medicine for treating cardiovascular diseases and inflammatory diseases. Given the link between inflammation and Type 2 diabetes mellitus (T2DM), we suspect that tanshinone I may have a beneficial effect on T2DM. This study was to investigate the potential effects of tanshinone I on T2DM and its underlying mechanism. T2DM was thus induced in Sprague-Dawley (SD) rats using streptozotocin (STZ) and high-fat diet. It was observed that T2DM rats had higher levels of total cholesterol (TC), nonesterified fatty acids (NEFAs), total triglyceride (TG) and total low density lipoprotein cholesterol (LDL-C) compared with normal, healthy SD rats. Treatment with tanshinone I decreased these levels and lowered blood glucose level in T2DM rats. In addition, enzyme-linked immunosorbent assay (ELISA) analysis showed that T2DM rats had elevated levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, Western blot analysis revealed that T2DM rats had enhanced nuclear translocation of NF-κB as well as elevated phosphorylation of Ser307 in IRS-1(insulin receptor substrate 1). Treatment by tanshinone I lowered the levels of IL-6 and TNF-α, decreased nuclear translocation of NF-κB as well as phosphorylation of Ser307 in IRS-1. These results demonstrated that tanshinone I could alleviate T2DM syndrome in rats.

Study of the Hypoglycemic Activity of Derivatives of Isoflavones from Cicer arietinum L.

The chickpea, a food and medicine used by the people of Xinjiang, has a beneficial hypoglycemic effect. To better utilize this national resource and develop hypoglycemic agents from components of the chickpea, a series of new derivatives of isoflavone compounds from the chickpea were synthesized. An insulin-resistant (IR) HepG2 cell model was used to screen the hypoglycemic activities of these compounds. And the structure-activity relationships of these compounds were explored. Additionally, several combinations of these compound displayed higher hypoglycemic activity than any single compound, and they had similar hypoglycemic activity to that of the positive control group (p > 0.05). In addition, combination 3 and combination 6 exerted different effects on the insulin sensitivity of H4IIE cells stimulated with resistin. And the results indicated that combination 3 would have higher hypoglycemic activity. These findings demonstrate the characteristics of multiple components and targets of Chinese herbal medicine. This evidence may provide new ideas for the development of hypoglycemic drugs.

New species and revisions of Pediciidae (Diptera) from the Middle Jurassic of northeastern China and Russia.

Two new species of Praearchitipula Kalugina, 1985, P. apprima sp. nov. and P. mirabilis sp. nov., are described and illustrated from the late Middle Jurassic Jiulongshan Formation of Daohugou in eastern Inner Mongolia, China. In addition, we propose to transfer Architipula abnormis Hao & Ren, 2009 (which is from the same locality of Daohugou) from Architipula of Limoniidae to Praearchitipula of Pediciidae: Praearchitipula abnormis (Hao & Ren, 2009) comb. nov. In addition, we propose to transfer Praearchitipula spasskia Kalugina, 1985 to the genus Mesotipula (Limoniidae, Architipulinae). We also suggest treating Praearchitipula lata Kalugina, 1985 as a junior synonym of Praearchitipula notabilis Kalugina, 1985. An emended generic diagnosis of Praearchitipula is provided.