Protective effects and mechanism of chemical- and plant-based selenocystine against cadmium-induced liver damage.

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys2) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys2-enriched agricultural products.

Effects of selenium-cadmium co-enriched Cardamine hupingshanensis on bone damage in mice.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.

First Report of Root-knot Nematode, Meloidogyne enterolobii on Passiflora edulis in Yulin, China.

Passion fruit (Passiflora edulis), a medicinal plant, was introduced into China in the early 19th century, is mainly cultivated in southern provinces (Liang et al. 2019). During March 2023, a survey was carried out and 167 samples were taken from passion fruit cultivated area in Yulin (22.6570263°E; 110.1765019°N) apart from the planting base appeared yellow leaves, stunted growth, and distinctive galls on the roots. Within the galls, Meloidogyne sp. females and egg masses were observed. From the rhizosphere soil, second-stage juveniles (J2) were extracted, and population density was 105/500 g soil. The species was determined to be Meloidogyne enterolobii based on morphological characteristics, including female perineal pattern, and genetic analyses. Female (n = 10) perineal patterns showed oval shape, with coarse and smooth striae, dorsal arch rounded to square, and lateral lines not distinct. The male head cap was high and rounded, with the head region only slightly set off from the body, knobs large, ovoid to rounded. The measurements of males (n = 10) included body length, 1,230.7 ± 244.94 (997 to 1,569) µm; a, 38.58 ± 7.8 (33.45 to 47.05) µm; c, 113.03 ± 26.22 (80.82 to 144.23) µm; stylet, 15.68 ± 1.1 (14.5 to 17.4) µm; spicules, 31.83 ± 2.84 (28.69 to 36.1) µm; tail, 11.09 ± 1.72 (8.02 to 13.38) µm; and gubernaculum length, 8.34 ± 0.28 (8.11 to 8.98) µm. Measurements of J2 (n = 20) included body length, 455.75 ± 44.94 (381 to 512) µm; a, 26.32 ± 3.89 (18.18 to 32.70) µm; c, 8.56 ± 1.2 (6.36 to 10.80) µm; stylet, 12.44 ± 0.76 (11.2 to 13.8) µm; DGO, 3.65 ± 0.54 (2.84 to 4.68) µm; tail, 53.89 ± 6.36 (39.8 to 62.2) µm; and hyaline tail terminus, 11.77 ± 2.83 (7.14 to 16.2) µm. These morphological characteristics are similar to those reported in the original description of M. enterolobii (Yang and Eisenback 1983). The sequences of the partial ITS region was amplified with V5367 (5'-TTGATTACGTCCCTGCCCTTT-3') and 26S (5'-TTTCACTCGCCGTTACTAAGG-3') primers (Vrain et al. 1992). The region between cytochrome oxidase subunit II (COII) and the 16S rRNA mitochondrial DNA (mtDNA COII) was also amplified with the primers C2F3 (5'-GGTCAATGTTCAGAAATTTGTGG-3') (Powers and Harris 1993) and MRH106 (5'-AATTTCTAAAGACTTTTCTTAGT-3') (Stanton et al. 1997). The ITS region yielded a fragment of 757 bp (OR072957) and mtDNA COII of 706 bp (OR078415). A BLAST search indicated the sequences were 100% identical to several sequences of M. enterolobii (MT406250, MH756127 and AY831967, MN269940, respectively). To confirm pathogenicity, 20 passion fruit (P. edulis Sim. f. flavicarpa) 30-day-old seedlings were transplanted into pots with an autoclaved mixture of sand and field soil (3:1) and maintained in the glasshouse at 25 ± 2°C with 65 ± 5% relative humidity. After eight weeks, fifteen plants were inoculated with 500 J2/pot (nematode culture collected from the original field), and another five uninoculated plants served as a control. Two months later, aboveground symptoms were similar to those observed in the field. Nematode reproduction occurred and root galls were observed. The reproduction factor (nematode final population density/initial population density) was 4.8. The disease caused by M. enterolobii was severe in Yulin city of Guangxi. Guangxi is an important area for passion fruit culture, with about 2000 ha, which is responsible for two-thirds of China production (Xing et al. 2020). This is the first record of P. edulis natural infection with M. enterolobii in the Yulin City of Guangxi, China.

Fangji Dihuang formulation ameliorated DNCB-induced atopic dermatitis-like skin lesions by IL-17 signaling pathway: integrating network analysis and experimental validation.

Background: The Fangji Dihuang formulation (FJDHF) is a widely recognized Traditional Chinese Medicine (TCM) formula that consists of five plant drugs: Stephaniae Tetrandrae Radix, Cinnamomi Ramulus, Rehmanniae Radix, Saposhnikoviae Radix, and Glycyrrhiza Urensis Fisch. This formulation has been known to exhibit clinical therapeutic effects in the treatment of inflammatory skin diseases. However, there is a lack of pharmacological research on its anti-atopic dermatitis (AD) activity. Methods: To investigate the potential anti-AD activity of FJDHF, DNCB was used to induce AD-like skin inflammation in the back of mice. Following successful modeling, the mice were administered FJDHF orally. The extent of the inflammatory skin lesions was recorded at day 4, 7, 14 and 28. UHPLC-Q-Exactive Orbitrap MS was used to identify and match the compounds present in FJDHF with ITCM, TCMIP and TCMSID. In silico predictions of potential target proteins of the identified compounds were obtained from SwishTargetPrediction, ITCM and TargetNet databases. AD-related genes were identified from GSE32924 data set, and FJDHF anti-AD hub genes were identified by MCODE algorithm. ClueGo enrichment analysis was employed to identify the core pathway of FJDHF's anti-AD effect. To further investigate the anti-AD effect of FJDHF, single-cell RNA sequencing data set (GSE148196) from AD patients was analyzed to determine the target cells and signaling pathways of FJDHF in AD. Finally, rt-PCR, flow cytometry, and mouse back skin RNA sequencing were utilized to validate our findings. Results: FJDHF was found to be effective in improving the degree of the AD-like lesions in the mice. Network pharmacological analysis revealed the core pathway of FJDHF to be the IL-17 signaling pathway, which is interactively associated with cytokines. Single-cell RNA sequencing analysis suggested that FJDHF may play an anti-AD role by influencing dendritic cells. Flow cytometry and rt-PCR results showed that FJDHF can reduce the influence of AD sample of IL-4, IFN-γ and the expression of IL-17. The RNA sequencing of mouse back skin also confirmed our conclusion. Conclusion: FJDHF may inhibit DNCB-induced AD-like skin inflammation in mice by inhibiting the IL-17 signaling pathway. Thus, FJDHF can be considered as a potential therapeutic agent for AD.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

The skeletal safety of milk-derived proteins: A meta-analysis of randomized controlled trials.

PURPOSE: There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. METHODS: The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. RESULTS: Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. CONCLUSION: Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.

The Effects of Dairy Product Supplementation on Bone Health Indices in Children Aged 3 to 18 Years: A Meta-Analysis of Randomized Controlled Trials.

Childhood and adolescence are critical periods for optimizing skeletal growth. Dairy products are valuable sources of bone-beneficial nutrients, particularly calcium and protein. A random-effects meta-analysis of published randomized controlled trials was performed to quantitatively assess the effects of dairy supplementation on bone health indices in children and adolescents. The PubMed and Web of Science databases were searched. Dairy supplementation increased whole-body bone mineral content (BMC) (+25.37 g) and areal bone mineral density (aBMD) (+0.016 g/cm2), total hip BMC (+0.49 g) and aBMD (+0.013 g/cm2), femoral neck BMC (+0.06 g) and aBMD (+0.030 g/cm2), lumbar spine BMC (+0.85 g) and aBMD (+0.019 g/cm2), and height (0.21 cm). When expressed as a percentage difference, whole-body BMC was increased by 3.0%, total hip BMC by 3.3%, femoral neck BMC by 4.0%, lumbar spine BMC by 4.1%, whole-body aBMD by 1.8%, total hip aBMD by 1.2%, femoral neck aBMD by 1.5%, and lumbar spine aBMD by 2.6%. Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. Serum 25-hydroxyvitamin D concentrations (+4.98 ng/mL) increased with vitamin D-fortified dairy supplementation. The positive effects on bone mineral mass parameters and height were generally consistent across subgroups defined by sex, geographical region, baseline calcium intake, calcium from the supplementation, trial duration, and Tanner stages. In summary, dairy supplementation during growth leads to a small but significant increase in bone mineral mass parameters, and these findings are generally supported by the changes in several biochemical parameters related to bone health.

Lycium barbarum glycopetide prolong lifespan and alleviate Parkinson's disease in Caenorhabditis elegans.

Introduction: Lycium barbarum glycopeptide (LbGp) is the main bioactive compound extracted from the traditional Chinese medicine. L. barbarum berries and has been proven to have numerous health benefits, including antioxidative, anti-inflammatory, anticancer, and cytoprotective activities. However, the antiaging effect of LbGp remains unknown. Methods: The lifespan and body movement of C. elegans were used to evaluate the effect of LbGp on lifespan and health span. The thrashing assay was used to determine the role of LbGp in Parkinson's disease. To investigate the mechanisms of LbGp-induced antiaging effects, we analyzed changes in lifespan, movement, and the expression of longevity-related genes in a series of worm mutants after LbGp treatment. Results: We found that LbGp treatment prolonged the lifespan and health span of C. elegans. Mechanistically, we found that LbGp could activate the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, as well as the nuclear receptor DAF-12, thereby upregulating longevity-related genes to achieve lifespan extension. In addition, we found that the lifespan extension induced by LbGp partially depends on mitochondrial function. Intriguingly, LbGp also ameliorated neurodegenerative diseases such as Parkinson's disease in a DAF-16-, SKN-1-, and HSF-1-dependent manner. Conclusion: Our work suggests that LbGp might be a viable candidate for the treatment and prevention of aging and age-related diseases.

Mechanisms of dihydromyricetin against hepatocellular carcinoma elucidated by network pharmacology combined with experimental validation.

CONTEXT: Dihydromyricetin (DMY) is extracted from vine tea, a traditional Chinese herbal medicine with anti-cancer, liver protection, and cholesterol-lowering effects. OBJECTIVE: This study investigated the mechanism of DMY against hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Potential DMY, HCC, and cholesterol targets were collected from relevant databases. PPI networks were created by STRING. Then, the hub genes of co-targets, screened using CytoHubba. GO and KEGG pathway enrichment, were performed by Metascape. Based on the above results, a series of in vitro experiments were conducted by using 40-160 µM DMY for 24 h, including transwell migration/invasion assay, western blotting, and Bodipy stain assay. RESULTS: Network pharmacology identified 98 common targets and 10 hub genes of DMY, HCC, and cholesterol, and revealed that the anti-HCC effect of DMY may be related to the positive regulation of lipid rafts. Further experiments confirmed that DMY inhibits the proliferation, migration, and invasion of HCC cells and reduces their cholesterol levels in vitro. The IC50 is 894.4, 814.4, 467.8, 1,878.8, 151.8, and 156.9 µM for 97H, Hep3B, Sk-Hep1, SMMC-7721, HepG2, and Huh7 cells, respectively. In addition, DMY downregulates the expression of lipid raft markers (CAV1, FLOT1), as well as EGFR, PI3K, Akt, STAT3, and Erk. DISCUSSION AND CONCLUSION: The present study reveals that DMY suppresses EGFR and its downstream pathways by reducing cholesterol to disrupt lipid rafts, thereby inhibiting HCC, which provides a promising candidate drug with low toxicity for the treatment of HCC.

First report of Botryosphaeria dothidea causing brown leaf spot on Daimyo oak, Quercus dentata in China.

Quercus dentata is a deciduous oak species widely distributed in northern China, with short petioles and dense grayish brown stellate tomentose on the abaxial surface (Lyu et al., 2018). Q. dentata is cold-tolerant (Du et al., 2022), and its broad leaves are used for tussah silkworm rearing, traditional Chinese medicine, kashiwa mochi in Japan, and Manchu delicacy in Northeast China (Wang et al., 2023). In June 2020, a single Q. dentata plant with brown leaf spots was observed in the Oak Germplasm Resources Nursery (N41°82', E123°56') in SYAU, Shenyang, China. From 2021 through 2022, other two nearby Q. dentata plants (six trees in all) became diseased with similar brown spots on their leaves. The small brown lesions with subcircular or irregular shape gradually expanded, and then the entire leaf turned brown. Under magnification, the diseased leaves contain many conidia. To identify the pathogen, diseased tissues were surface sterilized in 2% sodium hypochlorite for 1 min, and washed in sterile distilled water. Lesion margins were plated onto potato dextrose agar and incubated at 28°C in darkness. The aerial mycelium changed color, from white to dark gray, and dark olive green pigmentation was observed on the medium reverse side after 5 days of incubation. The emerging fungal isolates were repurified by the single-spore method. The mean length and width of spores were 20.32 ± 1.90 × 5.2 ± 0.52 µm (n=50). These morphological characteristics resembled the description of Botryosphaeria dothidea (Slippers et al., 2014). For molecular identification, internal transcribed spacer (ITS) region, translation elongation factor1 alpha (tef1-α), and beta-tubulin (tub) were amplified. These new sequences GenBank accession nos. are OQ383627.1, OQ387861.1 and OQ387862.1. Blastn searches showed 100% homology with ITS sequence of B. dothidea strain P31B (KF293892.1) and 98 to 99% similarity with tef and tub sequences of B. dothidea isolate ZJXC2 (KP183219.1) and B. dothidea isolate SHSJ2-1 (KP183133.1). The sequences were also concatenated for phylogenetic analysis (maximum likelihood). Result support isolate SY1 in the same clade as B. dothidea. Based on the multi-gene phylogeny and morphology, the isolated fungus associated with brown leaf spot on Q. dentata was identified as B. dothidea. Pathogenicity tests were performed on five-year-old potted plants. Conidial suspensions (106 conidial/mL) were applied on punctured leaves using a sterile needle and non-punctured leaves. Non-inoculated plants spayed with sterile water served as control. Plants were placed in a growth chamber at 25°C on a 12h fluorescent light/dark regime. Symptoms similar to those from natural infections were observed after 7 to 9 days (non-punctured also infected). No symptoms were found on non-inoculated plants. The pathogenicity test was repeated three times. Fungi re-isolated from inoculated leaves were comfirmed as B. dothidea on the basis of morphological and molecular characterization as described above, fulfilling Koch's postulates. B. dothidea was previously reported as a pathogen causing branch diebacks and twig dieback on sycamore, red oak (Quercus rubra), and English oak (Quercus robur) in Italy (Turco et al., 2006). It has also been reported to cause leaf spot on Celtis sinensis, Camellia oleifera and Kadsura coccinea in China (Wang et al., 2021; Hao et al., 2022; Su et al., 2021). To our knowledge, this is the first report of B. dothidea inducing leaf spot on Q. dentata in China.

First Report of Root-Knot Nematode Meloidogyne enterolobii on Antirrhinum majus in China.

Antirrhinum majus L. is a medicinal and ornamental herb commonly grown in China. In October 2022, A. majus plants were observed stunted in growth with yellowish leaves and containing a large number of galls on roots in a field in Nanning, Guangxi, China (N22°47'23.35″, E108°23'4.26). Ten samples were collected randomly from rhizosphere soil and roots of A. majus. Second-stage juveniles (J2) were isolated from fresh soil with a Baermann funnel, and a mean of 36 ± 2.9 per 500 cm3 of soil was recorded. Gall roots were dissected using a microscope, where 2+ 0.42 males per sample were recovered. The species was determined to be Meloidogyne enterolobii based on morphological characteristics, including the female perineal pattern, and DNA studies. Female perineal patterns and morphometric data were similar to the original description of M. enterolobii Yang and Eisenback 1983 from Enterolobium contortisilquum (Vell.) Morong in China (Yang and Eisenback 1983). The measurements of males (n = 10) included body length, 1600.7 ± 55.32 (1421.3 to 1924.3) µm; body diameter = 41.3 ± 0.80 (37.8 to 45.4) µm, stylt length = 20.5 ± 0.40 (19.1 to 22.2) µm, spicules length = 30.0 ± 0.47 (28.2 to 32.0) µm and DGO = 4.5 ± 0.3 (3.8 to 5.2) µm. Measurements of J2 (n = 20) included body length, 441.9 ± 5.42 (403.2 to 493.3) µm; body diameter = 16.6 ± 0.30 (14.4 to 8.7) µm, a = 26.8 ± 0.54 (21.9 to 31.2), c = 8.7 ± 0.27 (6.4 to 10.8), stylet length = 12.6 ± 0.17 (11.2 to 14.3) µm, DGO = 3.8 ± 0.10 (2.9 to 4.8) µm, tail length = 51.6 ± 1.27 (42.3 to 63.1) µm and hyaline tail terminus length = 11.7 ± 0.15 (10.2 to 13.1) µm. These morphological characteristics are similar to the original description of M. enterolobii (Yang and Eisenback 1983). Pathogenicity tests were conducted on A. majus 'Taxiti' plants directly germinated from seeds in a 10.5-cm-diameter pot filled with 600 ml of sterilized peat moss/sand (1:1, v/v) soil in the glasshouse. After 1 week, fifteen plants were inoculated with 500 J2/pot (nematode culture collected from the original field) and five uninoculated plants served as a control. After 45 days, aboveground parts of all inoculated plants showed symptoms similar to those observed in the field. No symptoms were observed on control plants. The RF value of the inoculated plants was determined by the method of Belair and Benoit (1996) 60 days after inoculation, and the average was 14.65. J2 were used in this test and sequenced on 28S rRNA-D2/D3, ITS, COII -16SrRNA 3 region and confirmed to be M. enterolobii. Species identification was confirmed by using polymerase chain reaction primers D2A/D3B (De Ley et al. 1999), F194/5368r (Ferris et al. 1993), C2F3/1108 (Powers and Harris, 1993). The sequences obtained GenBank accession numbers OP897743 (COII), OP876758 (rRNA) and OP876759 (ITS) were 100% similar to other M. enterolobii populations from China (MN269947), (MN648519) and (MT406251). M. enterolobii is a highly pathogenic species and has been reported in vegetables, ornamental plants, guava (Psidium guajava L.), and weeds in China, Africa and America (Brito et al. 2004; Xu et al. 2004; Yang and Eisenback 1983). The medicinal plant Gardenia jasminoides J. Ellis was also infected by M. enterolobii in China (Lu et al. 2019). Of concern is its ability to develop on crop genotypes carrying RKN resistance genes in tobacco (Nicotiana tabacum L.), tomato (Solanum lycopersicum L.), soybean (Glycine max (L.) Merr.), potato (Solanum tuberosum L.), cowpea (Vigna unguiculata (L.) Walp.), sweetpotato (Ipomoea batatas (L.) Lam.), and cotton (Gossypium hirsutum L.). Consequently, this species was added to the European and Mediterranean Plant Protection Organization A2 Alert List in 2010. This is the first natural infection report of M. enterolobii in Guangxi, China on the medicinal and ornamental herb A. majus. Acknowledgments This research was funded by the National Natural Science Foundation of China (31860492), Natural Science Foundation of Guangxi (2020GXNSFAA297076), and Guangxi Academy of Agricultural Sciences Fund, China (2021YT062, 2021JM14, 2021ZX24). References: Azevedo de Oliveira, S., et al. 2018. PLoS One 13:e0192397. Belair, G., and Benoit, D. L. 1996. J. Nematol. 28:643. Brito, J. A., et al. 2004. J. Nematol. 36:324. De Ley, P., et al. 1999. Nematol. 1:591-612. Ferris, V. R., et al. 1993. Fundam. Appl. Nematol. 16:177-184. Lu, X. H., et al. 2019. Plant Dis. 103:1434. Powers, T. O. and Harris, T. S. 1993. J. Nematol. 25:1-6 Vrain, T. C., et al. 1992. Fundam. Appl. Nematol. 15:563. Yang, B. and Eisenback, J. D. 1983. J. Nematol. 15:381.

GSH-specific fluorescent probe for sensing, bioimaging, rapid screening of natural inhibitor Celastrol and ccRCC theranostics.

High level of intracellular glutathione (GSH) has been identified as a major barrier for cancer therapy. Therefore, effective regulation of GSH can be regarded as a novel approach for cancer therapy. In this study, an off-on fluorescent probe (NBD-P) is developed for selective and sensitive sensing GSH. NBD-P has a good cell membrane permeability that can be applied in bioimaging endogenous GSH in living cells. Moreover, the NBD-P probe is used to visualize GSH in animal models. In addition, a rapid drug screening method is successfully established using the fluorescent probe NBD-P. A potent natural inhibitor of GSH is identified as Celastrol from Tripterygium wilfordii Hook F, which effectively triggers mitochondrial apoptosis in clear cell renal cell carcinoma (ccRCC). More importantly, NBD-P can selectively respond to GSH fluctuations to distinguish cancer tissues from normal tissues. Thus, the present study provides insights into fluorescence probes for the screening GSH inhibitors and cancer diagnosis, as well as in-depth exploration of the anti-cancer effects of Traditional Chinese Medicine (TCM).

HS-SPME coupled with GC-MS for elucidating differences between the volatile components in wild and cultivated Atractylodes chinensis.

INTRODUCTION: Atractylodes chinensis is a Chinese herb that is used in traditional medicine; it contains volatile components that have enormous potential for pharmaceutical, food, and cosmetic applications. The destruction of wild resources demands significant improvement in the quality of artificial cultivation of Atractylodes chinensis. However, little is known about the compositional differences in the volatile substances derived from the wild and cultivated varieties of Atractylodes chinensis. OBJECTIVES: We aimed to evaluate the specific components of Atractylodes chinensis and analyse the similarities and differences between the volatile components and metabolic pathways in the wild and cultivated varieties. MATERIAL AND METHODS: Metabolomic analysis using gas chromatography-mass spectrometry (GC-MS) was employed following the extraction of volatile components from Atractylodes chinensis using headspace solid-phase microextraction (HS-SPME). RESULTS: A total of 167 volatile metabolites were extracted, and 137 substances were matched with NIST and Wiley databases. Among them, 76 compounds exhibited significant differences between the two sources; these mainly included terpenes, aromatics, and esters. KEGG enrichment analysis indicated that the differential metabolites were primarily involved in the biosynthesis of secondary metabolites, terpene biosynthesis, and limonene and pinene degradation; all these pathways have geranyl diphosphate (GDP) as the common link. CONCLUSION: The total content of volatile substances extracted from wild Atractylodes chinensis was 2.5 times higher than that from the cultured variety; however, each source had different dominant metabolites. This study underscores the necessity for protecting wild Atractylodes chinensis resources, while enhancing the quality of cultivated Atractylodes chinensis.

Effect of 3,3'-diselenodipropionic Acid on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

3,3'-Diselenodipropionic acid (DSePA), a synthetic organoselenium compound, has received considerable attention because of its antioxidant properties and safety. Its protective effect against dextran sodium sulfate (DSS)-induced mouse ulcerative colitis (UC) and the role of T helper 17 (Th17) cell proliferation were investigated. Fifty C57BL/6 male mice were randomly assigned to one of five groups: control (Con), DSePA, DSS, low-dose DSePA (LSe), and high-dose DSePA (HSe). Mice in the DSS, LSe, and HSe groups drank 2% DSS to induce UC, and received normal saline, 1 and 2 mg/mL DSePA solution by intraperitoneal injection, respectively. The DSePA group only received 2 mg/mL DSePA solution. After 5 weeks, DSS challenge induced UC in the mice, which manifested as decreased body weight, shortened colon length, the loss of goblet cells, activated proliferating cells, and multiple signs of intestinal lesions by histological observation, all of which were reversed to varying degrees by DSePA administration. DSS upregulated the colonic protein expression of the macrophage marker F4/80 and proinflammatory cytokines (IL-1ß, IL-6, and TNFα), whereas DSePA administration downregulated the expression of these factors. DSS upregulated the mRNA expression of retinoic acid receptor-related orphan receptor γt (RORγt, mainly expressed in Th17 cells), IL-17A, and IL-17F and the levels of IL-17A and IL-17F in the colon, whereas DSePA administration decreased them. No difference was observed between the Con group and the DSePA group without DSS induction. Thus, DSePA administration ameliorated DSS-induced UC by regulating Th17-cell proliferation and the secretion of proinflammatory cytokines.

Molecular mechanism of the unusual biphasic effects of the natural compound hinokitiol on iron-induced cellular DNA damage.

Hinokitiol is a natural monoterpene compound found in the heartwood of cupressaceous plants that have anticancer and anti-inflammatory properties. However, few studies have focused on its effect on iron-mediated cellular DNA damage. Here we show that hinokitiol exhibited unusual biphasic effects on iron-induced DNA damage in a molar ratio (hinokitiol/iron) dependent manner in HeLa cells. Under low ratios (<3:1), hinokitiol markedly enhanced DNA damage induced by Fe(II) or Fe(II)-H2O2; However, when the ratios increased over 3:1, the DNA damage was progressively inhibited. We found that the total cytoplasmic and nuclear iron concentration increased as the ratios of hinokitiol/iron increased. However, the cellular level of labile iron pool (LIP) only increased at ratios lower than 3, and the ROS generation is consistent with LIP change. Hinokitiol was found to interact with iron to form lipophilic hinokitiol-iron complexes with different stoichiometry and redox-activity by complementary applications of various analytical methods. Taken together, we propose that the enhancement of iron-induced cellular DNA damage by hinokitiol at low ratios (<3:1) was due to formation of lipophilic and redox-active iron complexes which facilitated cellular iron uptake and •OH production, while the inhibition at ratios higher than 3 was due to formation of redox-inactive iron complexes. These new findings will help us to design more effective drugs for the prevention and treatment of a series of iron-related diseases via regulating the two critical physicochemical factors (lipophilicity and redox activity of iron complexes) by simple natural compounds with iron-chelating properties.

Construction of Literature Knowledge Ontology for Traditional Chinese Medicine Clinical Trials： A Review / 中国实验方剂学杂志

ObjectiveTo effectively organize the interdisciplinary knowledge of traditional Chinese medicine （TCM） and evidence-based medicine contained in the clinical trial literature of TCM and facilitate the processing and mapping of multi-source data， this paper organized the knowledge of clinical trial literature of TCM by ontology modeling. MethodThe seven-step method and skeleton method were used to develop the ontology. After the structure and language characteristics of TCM clinical trial literature were analyzed， the ontological and non-ontological resources such as top-level framework of Scientific Evidence and Provenance Information Ontology （SEPIO） and TCM language system （TCMLS） were reused to determine the domain concepts and attribute relationship. Finally， the core concepts and attribute relationship such as disease， syndrome， symptom， grouping， intervention measures， outcome indicators and literature quality information were determined. ResultThe information contained in the clinical trial literature of TCM was divided into five categories. According to the Cochrane risk of bias assessment tool and CONSORT 2010 statement， the literature quality evaluation information was mapped to the ontology， and a total of 68 categories， 8 object attributes， and 38 data attributes were established， which basically realized the structured expression of clinical trial literature. ConclusionThe ontology of TCM clinical trial literature constructed in this study can well organize， utilize， and present the construction and association of internal knowledge system in TCM clinical trial literature， underpinning the reasoning of strength of evidence and information of diagnosis and treatment in the future.

Separation, characterization and anti-psoriasis effect of self-assembled nanoparticles from Shaoyao Gancao Decoction / 中国中药杂志

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.

Research progress of JAK/STAT signaling pathway in the intervention of diabetic microvascular complications / 中国临床药理学与治疗学

Diabetic microvascular complications are the main reason for the high mortality of diabetic patients. There is still a great shortage of existing therapeutic drugs, so there is an urgent need for more effective new drugs. Janus kinase/signal transducer and activator of transcription (JAK/STAT) is involved in the progression of diabetic microvascular complications, which can be improved by regulating this pathway. Therefore, this article reviews the progress of JAK/STAT in diabetic microvascular complications (diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy), and summarizes the potential drugs that intervene JAK/ stat to improve diabetic microvascular complications in recent years from three aspects of therapeutic drugs, preclinical drugs, and traditional Chinese medicine, in order to provide ideas for drug development and treatment of diabetic microvascular complications.

Effects of lime and oxalic acid on antioxidant enzymes and active components of Panax notoginseng under cadmium stress.

Cadmium (Cd) pollution poses potential safety risks for Panax notoginseng cultivation, a medicinal plant in Yunnan. Under exogenous Cd stress, field experiments were conducted to understand the effects of lime (0, 750, 2250 and 3750 kg hm-2) applied and oxalic acid (0, 0.1 and 0.2 mol L-1) leaves sprayed on Cd accumulation, antioxidant system and medicinal components of P. notoginseng. The results showed that Lime and foliar spray of oxalic acid were able to elevate Ca2+ and alleviate Cd2+ toxicity in P. notoginseng under Cd stress. The addition of lime and oxalic acid increased the activities of antioxidant enzymes and alters osmoregulator metabolism. The most significant increase in CAT activities increased by 2.77 folds. And the highest increase of SOD activities was 1.78 folds under the application of oxalic acid. While MDA content decreased by 58.38%. There were very significant correlation with soluble sugar, free amino acid, proline and soluble protein. Lime and oxalic acid were able to increase calcium ions (Ca2+), decrease Cd content and improve the stress resistance of P. notoginseng, while increasing the production of total saponins and flavonoids. Cd content were the lowest, 68.57% lower than controls, and met the standard value (Cd ≤ 0.5 mg kg-1, GB/T 19086-2008). The proportion of SPN was 7.73%, which reached the highest level of all treatments, the flavonoids content increased significantly by 21.74%, which reached the medicinal standard value and optimal yield.

Present Status, Challenges, and Prospects of Dihydromyricetin in the Battle against Cancer.

Dihydromyricetin (DHM) is a natural flavonoid compound extracted from Ampelopsis grossedentata that has been used for centuries in traditional Chinese medicine. DHM has attracted intensive attention due to its numerous beneficial activities, such as hepatoprotection, cardioprotection, antioxidant, and anti-inflammation. In addition, DHM inhibits the progression of cancers such as lung cancer, hepatocellular cancer, breast cancer, melanoma, and malignant reproductive systems through multiple mechanisms, including antiangiogenesis, antiproliferation, apoptosis, and inhibition of invasion and migration. Notably, DHM also activates autophagy at different levels, exerting a dual-regulatory effect on cancers. Mechanistically, DHM can effectively regulate mammalian target of rapamycin (mTOR), noncoding RNA-mediated signaling, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, nuclear factor-κB (NF-κB), p53, and endoplasmic reticulum stress (ER stress)-driven signaling in different types of cancers. DHM has also been shown to have inhibitory effects on various regulators that trigger epithelial-mesenchymal transition (EMT). Furthermore, DHM exhibits a remarkable anticancer reversal ability when used in combination with drugs such as adriamycin, nedaplatin, and other drugs. However, the low bioavailability of DHM limits its potential applications, which are improved through structural modification and the exploration of novel dosage forms. Therefore, DHM may become a promising candidate for treating malignancies alone or combined with conventional anticancer strategies used in clinical practice.