Current research and evidence gaps on placental development in iron deficiency anemia.

Studying the effects of maternal iron deficiency anemia (IDA) is complex owing to its diverse causes, each independently impacting the placenta and fetus. Simple treatment with iron supplements does not always resolve the anemia. Therefore, delving into how IDA alters placental development at a molecular level is crucial to further optimize treatment. This review addresses the effects of IDA on placental structures and functions, including changes in oxygen levels, blood vessels, and the immune system. Profound understanding of physiological characteristics and regulatory mechanisms of placental development is key to explain the mechanisms of abnormal placental development in pregnancy-associated disorders. In turn, future strategies for the prevention and treatment of pregnancy complications involving the placenta can be devised. These studies are significant for improving human reproductive health, enhancing sociodemographic qualities, and even lifelong wellbeing, a focal point in future placental research.

JinChan YiShen TongLuo Formula ameliorate mitochondrial dysfunction and apoptosis in diabetic nephropathy through the HIF-1α-PINK1-Parkin pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The JinChan YiShen TongLuo (JCYSTL) formula, a traditional Chinese medicine (TCM), has been used clinically for decades to treat diabetic nephropathy (DN). TCM believes that the core pathogenesis of DN is "kidney deficiency and collateral obstruction," and JCYSTL has the effect of "tonifying kidney and clearing collateral," thus alleviating the damage to kidney structure and function caused by diabetes. From the perspective of modern medicine, mitochondrial damage is an important factor in DN pathogenesis. Our study suggests that the regulation of mitophagy and mitochondrial function by JCYSTL may be one of the internal mechanisms underlying its good clinical efficacy. AIM OF THE STUDY: This study aimed to investigate the mechanisms underlying the renoprotective effects of JCYSTL. MATERIALS AND METHODS: Unilateral nephrectomy combined with low-dose streptozotocin intraperitoneally injected in a DN rat model and high glucose (HG) plus hypoxia-induced HK-2 cells were used to explore the effects of JCYSTL on the HIF-1α/mitophagy pathway, mitochondrial function and apoptosis. RESULTS: JCYSTL treatment significantly decreased albuminuria, serum creatinine, blood urea nitrogen, and uric acid levels and increased creatinine clearance levels in DN rats. In vitro, medicated serum containing JCYSTL formula increased mitochondrial membrane potential (MMP); improved activities of mitochondrial respiratory chain complexes I, III, and IV; decreased the apoptotic cell percentage and apoptotic protein Bax expression; and increased anti-apoptotic protein Bcl-2 expression in HG/hypoxia-induced HK-2 cells. The treatment group exhibited increased accumulation of PINK1, Parkin, and LC3-II and reduced P62 levels in HG/hypoxia-induced HK-2 cells, whereas in PINK1 knockdown HK-2 cells, JCYSTL did not improve the HG/hypoxia-induced changes in Parkin, LC3-II, and P62. When mitophagy was impaired by PINK1 knockdown, the inhibitory effect of JCYSTL on Bax and its promoting effect on MMP and Bcl-2 disappeared. The JCYSTL-treated group displayed significantly higher HIF-1α expression than the model group in vivo, which was comparable to the effects of FG-4592 in DN rats. PINK1 knockdown did not affect HIF-1α accumulation in JCYSTL-treated HK-2 cells exposed to HG/hypoxia. Both JCYSTL and FG-4592 ameliorated mitochondrial morphological abnormalities and reduced the mitochondrial respiratory chain complex activity in the renal tubules of DN rats. Mitochondrial apoptosis signals in DN rats, such as increased Bax and Caspase-3 expression and apoptosis ratio, were weakened by JCYSTL or FG-4592 administration. CONCLUSION: This study demonstrates that the JCYSTL formula activates PINK1/Parkin-mediated mitophagy by stabilizing HIF-1α to protect renal tubules from mitochondrial dysfunction and apoptosis in diabetic conditions, presenting a promising therapy for the treatment of DN.

[Evidence mapping analysis of traditional Chinese medicine intervention in pulmonary fibrosis].

This study utilized evidence mapping methodology to systematically identify, describe, and evaluate the evidence from relevant research on traditional Chinese medicine(TCM) interventions in patients with pulmonary fibrosis. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched from database inception to March 2023 for systematic reviews/Meta-analysis/network Meta-analysis on TCM interventions in pulmonary fibrosis. The quality of included studies was assessed using the AMSTAR 2 scale, and the evidence mapping approach was employed to present comprehensive information on populations, intervention methods, the sample size in systematic reviews/Meta-analysis, and conclusion classifications. Ultimately, 44 systematic reviews/Meta-analysis/network Meta-analysis were included. Apart from syndrome differentiation and treatment, TCM injections accounted for a significant proportion of the observed interventions. The treatment methods were mainly focused on nourishing Qi and Yin, promoting blood circulation, resolving stasis, and dredging collaterals. The results from the included studies demonstrated that TCM treatment for pulmonary fibrosis could improve efficacy, increase lung function, improve PaO_(2 )levels, increase the 6-minute walk distance(6MWD), alleviate clinical symptoms, and enhance patients' quality of life. Based on the assessment using the AMSTAR 2 scale, methodological issues were identified, including the lack of protocol registration, failure to provide a list of excluded literature, and incomplete explanations regarding the impact of heterogeneity and bias on the results. The evidence mapping revealed that 42 conclusions were beneficial, while two conclusions were potentially beneficial. Overall, the quality of evidence was relatively low, primarily due to methodological imprecision and publication bias. Although TCM showed certain efficacy in the treatment of pulmonary fibrosis, the quality of reported literature, methodological quality, and overall evidence quality need improvement. It is recommended to conduct high-quality and standardized studies in the future to provide better evidence-based guidance.

Combination of Lactobacillus fermentum NS9 and aronia anthocyanidin extract alleviates sodium iodate-induced retina degeneration.

It is important to explore the effective approaches to prevent dry age-related macular degeneration (AMD). In this study, significantly decreased full-field electroretinograms wave amplitudes and disordered retina structures were detected in rat retinas of sodium iodate induced dry AMD model. Six a- and b-wave amplitudes and the antioxidant activities were significantly increased, and the outer nuclear layer thickness was significantly improved in the rat retinas treated with the combination of Lactobacillus fermentum NS9 (LF) and aronia anthocyanidin extract (AAE) compared with the model. The effects were much better than the treatment with AAE alone. The proteomics analysis showed the expressions of α-, ß- and γ-crystallins were increased by 3-8 folds in AAE treated alone and by 6-11 folds in AAE + LF treatment compared with the model, which was further confirmed by immuno-blotting analysis. Analysis of gut microbial composition indicated that higher abundance of the genus Parasutterella and species P. excrementihominis was found in the AAE + LF treatment compared with the other groups. The results indicated that the combined treatment of AAE + LF is a potential way to prevent the retina degeneration which is significantly better than the AAE treated alone.

As a novel anticancer candidate, ether extract of Dendrobium nobile overstimulates cellular protein biosynthesis to induce cell stress and autophagy.

Increasing data has confirmed the potential anticancer properties of Dendrobium, a traditional Chinese herb. However, most anticancer compositions from the plant of Dendrobium were usually extracted by high polar solvent, while weak polar compositions with excellent anticancer activity remained largely unexplored. In this study, the differences between ether extract and ethanol extract of Dendrobium nobile Lindl. on chemical components and anticancer activities were investigated, as well as the anticancer mechanisms among different extracts. The results demonstrated that the ether extract exhibited a stronger anticancer effect than ethanol extract, and its anticancer effect was mainly due to weak polar compounds rather than polysaccharides and alkaloids. Quantitative proteomics suggested that the ether extract significantly stimulated the over-expression of immature proteins, the endoplasmic reticulum stress and unfolded protein response were subsequently induced, the intracellular reactive oxygen species level was seriously elevated, and oxidative stress occurred in the meanwhile. Eventually, autophagy and apoptosis were activated to cause cell death. Our findings demonstrate that the ether extract of D. nobile is a potential candidate for anticancer drug development, and that future research on anticancer drugs derived from medicinal plants should also concentrate on weak polar compounds.

[Regulatory Effect of Vitamin D on Renin Expression at Maternal-Fetal Interface].

Objective: To investigate the regulatory effect and mechanism of vitamin D on the local renin-angiotensin system at maternal-fetal interface in the pathological process of preeclampsia (PE). Methods: The mRNA and protein expression of renin in decidua of normal pregnancy and PE placentas was determined by RT-PCR and Western blot. Normal decidual tissues were treated with active and inactive vitamin D for 48 h in vitro and the expressions of renin and vitamin D deactivating enzyme CYP24A1 were determined by RT-PCR and Western blot. Normal decidual stromal cells and glandular epithelial cells were isolated and purified, and identified by immunocytochemical staining. RT-PCR was used to examine the mRNA of vdr, cyp27 b1, cyp24 a1, and renin in the two types of cells and in decidual tissue, and the mRNA products were subjected to gel electrophoresis. These two cell types were treated with active and inactive vitamin D in vitro and the expressions of renin and vitamin D deactivating enzyme CYP24A1 were determined by RT-PCR and Western blot. Decidual gland epithelial cells were treated with protein kinase A (PKA) activator forskolin or inhibitor H89 to explore the interaction between PKA pathway and vitamin D in the regulation of renin expression. Results: The expression of renin in PE decidua was significantly higher than that of normal control at transcriptional and translational levels ( P<0.05). Vitamin D treatment could significantly down-regulate the expression of renin in normal decidua tissues ( P<0.05), while it significantly up-regulated CYP24A1 expression ( P<0.001). Decidual stromal cells and gland epithelial cells were successfully isolated from decidual tissue. Compared with that in decidual stromal cells, the mRNA level of vitamin D-related molecules in gland epithelial cells was more similar to that in decidual tissue. Active or inactive vitamin D treatment significantly inhibited the expression of renin in glandular epithelial cells ( P<0.05), but the expression of renin in decidual stromal cells was not affected. However, the treatment of active or inactive vitamin D in these two kinds of cells significantly increased the expression of CYP24A1 ( P<0.001). Active vitamin D could significantly inhibit the upregulation of renin by PKA agonist forskolin, and could inhibit the expression of renin through synergy with PKA inhibitor H89. Conclusion: The expression of renin in placental decidua is up-regulated in patients with PE, and the activation of local renin-angiotensin system at the maternal-fetal interface may be involved in the pathogenesis of PE. Vitamin D can specifically down-regulate renin expression in human decidual gland epithelial cells by competing with the PKA pathway. Vitamin D supplementation may have potential value for clinical intervention of PE.

Construction of a Meta-Evidence Prototype Database of Traditional Chinese Medicine Splenogastric Diseases and Its Application in an Automatic Meta-Analysis System.

Background: Traditional Chinese medicine splenogastric diseases (TCMSDs) are equivalent to digestive system diseases in modern medicine. The forms of clinical evidence of TCMSDs include clinical trials, such as randomized controlled trials (RCTs) and systematic reviews (SRs). SRs mainly rely on manual operations and have the shortcomings of time consumption and low efficiency; therefore, they cannot meet the needs of rapid clinical decision-making. It is urgent to establish a new and smart form of a database to support the progress of SRs. Methods: We searched and screened all TCMSD RCT reports, in both Chinese and English, and extracted them into meta-evidence through predesigned structural Microsoft Excel tables. All meta-evidence was imported into an online clinical meta-evidence collection and management system after data quality checking. The meta-evidence database of traditional Chinese medicine (TCM) splenogastric disease (MED-TCMSD) was then tested as a backend of an automatic meta-analysis system. Results: A total of 405 cases of TCMSD RCTs were processed into meta-evidence. The most common diseases were stomach stuffiness disease, epigastralgia, and chronic atrophic gastritis. Banxiaxiexin decoction and its modifications were the most used interventions. More than half of the cases employed TCM in conjunction with regular therapeutics. The top reported outcomes included clinical effects, adverse events, and TCM syndromes. The MED-TCMSD worked well as a part of the automatic meta-analysis system. Conclusions: We developed and tested a new form of clinical evidence, meta-evidence, for automatic SR and fast evidence-based decision-making. As an example of the MED, the MED-TCMSD can improve the production and updating efficiency of the evidence of TCMSDs. The methods of constructing the MED-TCMSD can be further applied to the development of MEDs of other diseases.

MAP3Kε1/2 Interact with MOB1A/1B and Play Important Roles in Control of Pollen Germination through Crosstalk with JA Signaling in Arabidopsis.

Restriction of pollen germination before the pollen grain is pollinated to stigma is essential for successful fertilization in angiosperms. However, the mechanisms underlying the process remain poorly understood. Here, we report functional characterization of the MAPKKK kinases, MAP3Kε1 and MAP3Kε2, involve in control of pollen germination in Arabidopsis. The two genes were expressed in different tissues with higher expression levels in the tricellular pollen grains. The map3kε1 map3kε2 double mutation caused abnormal callose accumulation, increasing level of JA and precocious pollen germination, resulting in significantly reduced seed set. Furthermore, the map3kε1 map3kε2 double mutations obviously upregulated the expression levels of genes in JA biosynthesis and signaling. The MAP3Kε1/2 interacted with MOB1A/1B which shared homology with the core components of Hippo singling pathway in yeast. The Arabidopsis mob1a mob1b mutant also exhibited a similar phenotype of precocious pollen germination to that in map3kε1 map3kε2 mutants. Taken together, these results suggested that the MAP3Kεs interacted with MOB1s and played important role in restriction of the precocious pollen germination, possibly through crosstalk with JA signaling and influencing callose accumulation in Arabidopsis.

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. METHODS: Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. RESULTS: Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD = -0.73; 95% CI (-0.97, -0.51)), FPG (MD = -0.86, 95% CI (-1.10, -0.62)), and 2hPG (MD = -1.26, 95% CI (-1.64, -0.89)). Improved insulin resistance was assessed by lowering FINS (MD = -2.05, 95% CI (-2.62, -1.48)), HOMA-IR (MD = -0.71, 95% CI (-1.03, -0.39)), and BMI (MD = -1.07, 95% CI (-1.76, -0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD = -0.5, 95% CI (-0.61, -0.39)), TC (MD = 0.64, 95% CI (-0.78, -0.49)), and LDL (MD = 0.86, 95% CI (-1.06, -0.65)) and the upregulation of HDL (MD = 0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. CONCLUSION: There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.

Electromyographic features and efficacy of orofacial myofunctional treatment for skeletal anterior open bite in adolescents: an exploratory study.

BACKGROUND: Due to the multifactorial aetiology and unpredictable long-term stability, skeletal anterior open bite (SAOB) is one of the most intractable conditions for orthodontists. The abnormal orofacial myofunctional status (OMS) may be a major risk factor contributing to the development and relapse of SAOB. This study is aimed at evaluating the OMS and the efficacy of orofacial myofunctional therapy (OMT) alone for SAOB subjects. METHODS: Eighteen adolescents with SAOB (4 males, 14 females; age: 12-18 years) and eighteen adolescents with normal occlusion (2 males, 16 females; age: 12-18 years) were selected. The electromyographic activity (EMGA) associated with mastication and closed mouth state was measured. Lateral cephalography was used to evaluate craniofacial morphology. Wilcoxon signed rank tests and t-tests were performed to evaluate myofunctional and morphological differences. Pearson or Spearman correlation analysis was used to investigate the correlations between EMGA and morphological characteristics. SAOB subjects were given OMT for 3 months, and the EMGA was compared between before and after OMT. RESULTS: During rest, anterior temporalis activity (TAA) and mentalis muscle activity (MEA) increased in SAOB subjects, but TAA and masseter muscle activity (MMA) decreased in the intercuspal position (ICP); and upper orbicularis activity (UOA) and MEA significantly increased during lip sealing and swallowing (P < 0.05). Morphological evaluation revealed increases in the FMA, GoGn-SN, ANS-Me, N-Me, L1-MP, U6-PP, and L6-MP and decreases in the angle of the axis of the upper and lower central incisors and OB in SAOB subjects (P < 0.05). TAA, MMA and anterior digastric activity (DAA) in the ICP were negatively correlated with vertical height and positively correlated to incisor protrusion. MEA was positively correlated with vertical height and negatively correlated with incisor protrusion; and the UOA showed a similar correlation in ICP, during sealing lip and swallowing. After SAOB subjects received OMT, MEA during rest and TAA, MMA and DAA in the ICP increased, while UOA and MEA decreased (P < 0.05). CONCLUSION: SAOB subjects showed abnormal OMS features including aberrant swallowing patterns and weak masticatory muscles, which were interrelated with the craniofacial dysmorphology features including a greater anterior facial height and incisor protrusion. Furthermore, OMT contributes to OMS harmonization, indicating its therapeutic prospect in SAOB.

Pu-erh tea ameliorates obesity and modulates gut microbiota in high fat diet fed mice.

Obesity is regarded to be associated with fat accumulation, chronic inflammation, and gut microbiota dysbiosis. Raw and ripened pu-erh tea extract (PETe) have the effect of reducing body weight gain and fat accumulation, which are associated with gut microbiota. However, little is known about the difference of raw and ripened PETe on the regulation of gut microbiota. Here, our results suggested that supplementation of raw and ripened PETe displayed similar anti-obesogenic effect in high fat diet (HFD)-induced obesity mice, by attenuating the body weight gain, fat accumulation, oxidative injury, and low-grade inflammation, improving the glucose tolerance, alleviating the metabolic endotoxemia, and regulating the mRNA and protein expression levels of the lipid metabolism-related genes. 16S rRNA sequencing of fecal samples indicated that raw and ripened PETe intervention displayed different regulatory effect on the HFD-induced gut microbiota dysbiosis at different taxonomic levels. The microbial diversity, the relative abundance of Firmicutes and Bacteroidetes as well as F/B ratio were reversed more closer to normal by ripened PETe. Phylotypes of Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, Muribaculaceae, and Rikenellaceae which are negatively correlated with obesity were enhanced notably by the intervention of ripened PETe, while Erysipelotrichaceae and Lactobacillaceae which have positive correlation with obesity were decreased dramatically. In addition, the treatment of ripened PETe had better effect on the increase of benefical Bacteroides, Alistipes, and Akkemansia and decrease of obesity associated Faecalibaculum and Erysipelatoclostridium (p < 0.05). These findings suggested that pu-erh tea especially ripened pu-erh tea could serve as a great candidate for alleviation of obesity in association with the modulation of gut microbiota.

Lemon essential oil/vermiculite encapsulated in electrospun konjac glucomannan-grafted-poly (acrylic acid)/polyvinyl alcohol bacteriostatic pad: Sustained control release and its application in food preservation.

Lemon essential oils (LEO), as natural bacteriostatic agents, show significant loss in the preparation processes of food packaging materials, therefore, an effective encapsulation of LEO is urgent for realizing the protection. In this study, LEO was absorbed by thermally stable and porous vermiculite (VML) to form LEO/VML complex, which is further coupled with konjac glucomannan-grafted-poly (acrylic acid)/polyvinyl alcohol (KGM-g-PAA/PVA) composite. KGM-g-PAA/PVA bacteriostatic water-absorbing pad was prepared via electrospinning technique, which can minimize the loss of LEO. The VML (1 g) can significantly reduce LEO loss and achieve sustained control LEO release from the pad, which follows the predominant mechanism of Fick diffusion law. The sustained control LEO release from the pad can effectively inhibit the growth of E. coli during storage, thus prolonging shelf life of chilled pork for 3 day. This study suggests that KGM-g-PAA/PVA pad may have a great potential in the field of intelligent packaging.

The Arabidopsis AGC kinases NDR2/4/5 interact with MOB1A/1B and play important roles in pollen development and germination.

Pollen formation and pollen tube growth are essential for the delivery of male gametes into the female embryo sac for double fertilization. Little is known about the mechanisms that regulate the late developmental process of pollen formation and pollen germination. In this study, we characterized a group of Arabidopsis AGC kinase proteins, NDR2/4/5, involved in pollen development and pollen germination. The NDR2/4/5 genes are mainly expressed in pollen grains at the late developmental stages and in pollen tubes. They function redundantly in pollen formation and pollen germination. At the tricellular stages, the ndr2 ndr4 ndr5 mutant pollen grains exhibit an abnormal accumulation of callose, precocious germination and burst in anthers, leading to a drastic reduction in fertilization and a reduced seed set. NDR2/4/5 proteins can interact with another group of proteins (MOB1A/1B) homologous to the MOB proteins from the Hippo signaling pathway in yeast and animals. The Arabidopsis mob1a mob1b mutant pollen grains also have a phenotype similar to that of ndr2 ndr4 ndr5 pollen grains. These results provide new evidence demonstrating that the Hippo signaling components are conserved in plants and play important roles in sexual plant reproduction.

Dendrobium liquor eliminates free radicals and suppresses cellular proteins expression disorder to protect cells from oxidant damage.

Dendrobium liquor obtained by soaking Dendrobium in Chinese liquor is considered as a health drink in China. Here, we found the pretreatment of extract of Dendrobium nobile Lindl. liquor (DNLE) attenuated the oxidative damage to cells caused by H2 O2 , while the abilities of DNLE of eliminating extracellular free radicals and promoting the activities of intracellular antioxidant enzymes were observed. Quantitative proteomics identified 375 differentially expressed proteins caused by H2 O2 treatment in 293T cells. However, only 12 differentially expressed proteins were found in DNLE-pretreated cells which under the same oxidative damage. This suggested that the pretreatment of DNLE could suppress the disorder of protein expressions caused by oxidative stress which could induce cell death. Besides, DNLE was helpful for avoiding the unfolded protein response (UPR) and cell cycle disorder caused by oxidative stress. Taken together, these results demonstrated that Dendrobium liquor could be a healthy herbal drink with antioxidant function. PRACTICAL APPLICATIONS: Dendrobium is used as an edible herb and a tonic food in traditional Chinese medicine. Dendrobium liquor obtained by soaking Dendrobium with Chinese liquor is also regarded as a nourishing health drink. However, there is rare research data on biological activity of Dendrobium liquor. Our current results demonstrated that the extract of Dendrobium nobile Lindl. liquor (DNLE) possessed the ability of eliminating free radicals in/out the human cells. More importantly, DNLE could help cells to resist the interference on cell life activities caused by oxidative stress. Since many evidences suggested that oxidative stress is linked to human disease and aging, and chemical antioxidant has some side effects on health, Dendrobium liquor can serve as a natural health drink with antioxidant function. Furthermore, the active ingredients in DNLE also possess the potential to be developed as natural antioxidant additive in food and cosmetics.

Screening and identification of potential tyrosinase inhibitors from Semen Oroxyli extract by ultrafiltration LC-MS and in silico molecular docking.

There is an increasing interest in screening and developing natural tyrosinase inhibitors widely applied in medicinal and cosmetic products, as well as in the food industry. In this study, an approach by ultrafiltration LC-MS and molecular docking was used to screen and identify tyrosinase inhibitors from Semen Oroxyli extract. The samples were first incubated with the tyrosinase to select the optimal binding conditions including tyrosinase concentration, incubation time and the molecular weight of ultrafiltration membrane. By comparison of the chromatographic profiles of the extracts after ultrafiltration with activated and inactivated tyrosinase, the potential inhibitors were obtained and then identified by LC-MS. The relative binding affinities of the potential inhibitors were also calculated based on the decrease of peak areas of those. As a result, seven compounds were fished out as tyrosinase inhibitors by this assay. Among them, oroxin A and baicalein showed higher tyrosinase inhibitory than resveratrol as positive drug, and their binding mode with enzyme was further verified via the molecular docking analysis. The test results showed that the proposed method was a simple, rapid, effective, and reliable method for the discovery of natural bioactive compounds, and it can be extended to screen other bioactive compounds from traditional Chinese medicines.

Qingshen Buyang Formula Attenuates Renal Fibrosis in 5/6 Nephrectomized Rats via Inhibiting EMT and Wnt/ß-Catenin Pathway.

As renal fibrosis significantly contributes to various kinds of chronic kidney diseases, this study aimed to investigate the renal protective effects of Qingshen Buyang Formula against renal fibrosis on 5/6 nephrectomized rats, and its underlying mechanisms were explored. A total of 24 male Sprague-Dawley rats were randomly divided into sham operation group (Sham group), 5/6 nephrectomy group (5/6Nx group), and Qingshen Buyang Formula treatment group (QBF group). The intervention was intragastric administration for 12 weeks. In the end, the blood samples were collected to test renal functional parameters, urine proteins were measured, and the left kidneys were removed for histological studies, as well as mRNA and protein expression analysis. The results showed that Qingshen Buyang Formula significantly decreased BUN, Scr, and proteinuria in 5/6Nx rats. Meanwhile, it ameliorated the kidney injury and fibrosis, exemplified by the depressed expression of collagen I and fibronectin (FN), which are the main components of ECM. Furthermore, the process of EMT inhibited the Wnt/ß-catenin signaling pathway related genes, such as Wnt4, TCF4, ß-catenin, and p-GSK3ß. Collectively, the Qingshen Buyang Formula can improve renal function and attenuate renal fibrosis, and its underlying mechanisms may be related with inhibiting EMT and Wnt/ß-catenin signaling pathway.

[Quantitative proteomics of inhibitory mechanism of Dendrobium denneanum ether extract on lung cancer cells].

Dendrobium denneanum have been used for a long time as rare medicinal herbs in traditional Chinese medicine. Our previous works found that ether extract of D. denneanum had higher anticancer activities than alcohol or water extract,thus with better development prospects. Quantitative proteomics based on SILAC technique was used to investigate the anticancer mechanism of D. denneanum on lung tumor cell line A549,and 4 855 proteins were detected in A549 cells. Quantitative proteomics experiments found that 193 proteins of A549 cells were up-regulated,and 44 proteins were down-regulated by ether extract of D. denneanum. Those proteins are associated with synthesis,transport and metabolism of biological macromolecules,chaperone,DNA repair,oxidoreductase,cell adhesion,cell cycle,apoptosis and autophagy. Through the function analysis of differentially expressed proteins,it was inferred that ether extract of D. denneanum caused cell protein metabolism disorder,endoplasmic reticulum stress response,abnormal self-repair mechanism of cells,damage of cell adhesion and proliferation; besides,it caused a dramatic increase in ROS level in A549 cells,and upset the balance of intracellular oxidation reduction system. Affected by the above factors,lung cancer cells initiated apoptosis and autophagy,which accelerated cell death. This research explains the anticancer mechanism of D. denneanum from the perspective of quantitative proteomics,and lays a foundation for future research and development of new anticancer drugs based on ether extract of D. denneanum.

Ginkgo biloba sarcotesta polysaccharide inhibits inflammatory responses through suppressing both NF-κB and MAPK signaling pathway.

BACKGROUND: Polysaccharides, common components of natural products extensively studied as dietary supplements and functional foods, have been found to have various activities. In the present study, a water-soluble polysaccharide, namely GBSP3a, was isolated and purified from G. biloba sarcotesta. The anti-inflammatory activity of GBSP3a in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and the potential underlying molecular mechanisms were then assessed. RESULTS: GBSP3a exerted its anti-inflammatory effect by remarkably inhibiting the secretion of pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin E2 (PGE2 ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in LPS-stimulated RAW264.7 macrophages. Excessive mRNA and protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were dose-dependently inhibited by GBSP3a in LPS-stimulated RAW264.7 cells. Further research suggested that the anti-inflammatory effect of GBSP3a can be attributed to the modulation of the NF-κB and MAPK signaling pathways. CONCLUSION: GBSP3a exhibits anti-inflammatory activity and exerts its anti-inflammatory effect probably through suppressing both NF-κB and MAPK signaling pathway, indicating that GBSP3a could be used for the development of anti-inflammatory agent or nutraceuticals. © 2018 Society of Chemical Industry.

Yiqihuoxue Formula Activates Autophagy and Offers Renoprotection in a Rat Model of Adenine-Induced Kidney Disease.

Chronic kidney disease (CKD) is a worldwide health problem for which effective therapeutic methods are still lacking. Traditional Chinese medicine (TCM) has been indicated as an effective alternative treatment for kidney disease. In this study, a clinically effective therapy, yiqihuoxue (YQHX) formula, was administrated to adenine-induced kidney disease rats for 6 weeks. We found that the adenine rats displayed a significant reduction in renal function as evidenced by the increased levels of serum creatinine (Scr), blood urea nitrogen (BUN), and 24-h urinary albumin level, which were attenuated by the YQHX treatment. The glomerulosclerosis, interstitial fibrosis, arteriolosclerosis, interstitial inflammation, and tubular dilatation were reversed by the YQHX treatment in the adenine rats. Furthermore, the hepatic damage characterized by increased levels of aspartate aminotransferase and alanine aminotransferase and inflammatory cell infiltration was improved by YQHX. In addition, the number of apoptotic cells in the adenine rats was obviously reduced by the YQHX treatment as manifested by the lower expression level of cleaved caspase-3 protein. Moreover, the YQHX treatment downregulated the expression levels of fibronectin, type I collagen, α-smooth muscle actin, and TGF-ß1 in the adenine rats. Furthermore, autophagy was activated by the YQHX treatment, which manifested as an increased LC3-II and Beclin-1 expression levels and a decreased p62 level. In conclusion, the YQHX formula might retard the progression of kidney disease by activating autophagy.

Genome-wide researches and applications on Dendrobium.

MAIN CONCLUSION: This review summarizes current knowledge of chromosome characterization, genetic mapping, genomic sequencing, quality formation, floral transition, propagation, and identification in Dendrobium. The widely distributed Dendrobium has been studied for a long history, due to its important economic values in both medicine and ornamental. In recent years, some species of Dendrobium and other orchids had been reported on genomic sequences, using the next-generation sequencing technology. And the chloroplast genomes of many Dendrobium species were also revealed. The chromosomes of most Dendrobium species belong to mini-chromosomes, and showed 2n = 38. Only a few of genetic studies were reported in Dendrobium. After revealing of genomic sequences, the techniques of transcriptomics, proteomics and metabolomics could be employed on Dendrobium easily. Some other molecular biological techniques, such as gene cloning, gene editing, genetic transformation and molecular marker developing, had also been applied on the basic research of Dendrobium, successively. As medicinal plants, insights into the biosynthesis of some medicinal components were the most important. As ornamental plants, regulation of flower related characteristics was the most important. More, knowledge of growth and development, environmental interaction, evolutionary analysis, breeding of new cultivars, propagation, and identification of species and herbs were also required for commercial usage. All of these studies were improved using genomic sequences and related technologies. To answer some key scientific issues in Dendrobium, quality formation, flowering, self-incompatibility and seed germination would be the focus of future research. And genome related technologies and studies would be helpful.