Transcriptome and metabonomics combined analysis revealed the energy supply mechanism involved in fruiting body initiation in Chinese cordyceps.

Chinese cordyceps was one of most valuable traditional Chinese medicine fungi. To elucidate the molecular mechanisms related to energy supply mechanism involved in the initiation and formation of primordium in Chinese cordyceps, we performed the integrated metabolomic and transcriptomic analyses of it at pre-primordium period, primordium germination period and after-primordium period, respectively. Transcriptome analysis showed that many genes related to 'starch and sucrose metabolism', 'fructose and mannose metabolism', 'linoleic acid metabolism', 'fatty acids degradation' and 'glycerophospholipid metabolism' were highly up-regulated at primordium germination period. Metabolomic analysis showed many metabolites regulated by these genes in these metabolism pathways were also markedly accumulated at this period. Consequently, we inferred that carbohydrate metabolism and ß-oxidation pathway of palmitic acid and linoleic acid worked cooperatively to generate enough acyl-CoA, and then entered TCA cycle to provide energy for fruiting body initiation. Overall, our finding provided important information for further exploring the energy metabolic mechanisms of realizing the industrialization of Chinese cordyceps artificial cultivation.

Research Progress of Ferula ferulaeoides: A Review.

Ferula ferulaeoides (Steud.) Korov is one of the traditional ethnic medicines in Xinjiang Uygur and Kazakh of China, which mainly contains volatile oils, terpenoids, coumarins and other chemical components. Previous work has shown that F. ferulaeoides exhibited insecticide, antibacterial, antitumor properties, and so on. In this paper, the chemical composition, pharmacological activity, and quality control of F. ferulaeoides were reviewed, and the application of F. ferulaeoides in the food industry was explored, so as to provide some reference for the quality evaluation of F. ferulaeoides and its further development and utilization.

Uncovering Gene Expression Profiles of Three Morphologic Mycelium Forms of the Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycota) Using High-Throughput Sequencing.

The asexual form of Ophiocordyceps sinensis has been controversial, but various morphologic mycelium appeared when O. sinensis was cultured under experimental conditions. To explore the generation mechanism of morphologic mycelium, developmental transcriptomes were analyzed from three kinds of mycelium (aerial mycelium, hyphae knot, and substrate mycelium). The results showed that diameter and morphology of these three kinds of mycelium were obviously different. KEGG functional enrichment analysis showed that the differential expressed genes (DEGs) of substrate mycelium were enriched in ribosomes and peroxisomes, indicating that prophase culture was rich in nutrients and the metabolism of substrate mycelium cells was vigorous in the stage of nutrient absorption. The up-DEGs of hyphae knot were mainly enriched in the oxidative phosphorylation pathway, indicating that oxidative phosphorylation was the main energy source for mycelium formation in the stage of nutrient accumulation and reproductive transformation. The up-DEGs of aerial mycelium were mainly enriched in the synthesis and degradation pathways of valine, leucine, and isoleucine, suggesting that the occurrence of aerial mycelium was related to amino acid metabolism at the later stage of culture, and nutritional stress accelerated the reproduction of asexual spores. In addition, the important roles of mycelium formation related genes were verified by combined analysis of qRT-PCR and transcriptome sequencing. Collectively, this study will provide theoretical guidance for inhibiting the occurrence of aerogenous mycelium and promoting the development of mycelium into pinhead primordia in the culture of O. sinensis in the future.

ompX contribute to biofilm formation, osmotic response and swimming motility in Citrobacter werkmanii.

Citrobacter werkmanii, an aerobe and mesophilic Proteobacterium, is universal in industrial putrefaction, coastal water, and human blood. Our previous studies have discovered that outer membrane protein X (OmpX) of C. werkmanii is involved in calcium response, but the underlying mechanisms and its molecular characteristics remain elusive. To that end, the ompX gene was deleted from the genome of C. werkmanii and its phenotypic variations were thoroughly investigated in conjunction with the wild type (WT) and complementary strains using biochemical and molecular techniques such as RNA-Seq, respectively. The results demonstrated that deleting ompX reduces biofilm formation on polystyrene and glass surfaces. Meanwhile, ΔompX's swimming ability but not for its twitching or swarming abilities, was also reduced on semi-solid plates compared with WT, which was caused by inhibition of flagellar assembly genes, such as flgC, flhB, and fliE, etc. Furthermore, ompX inactivation altered susceptibility to various bactericide classes, as well as responses to Ca2+ and Mg2+ stress. In addition, when compared to WT, ΔompX captures a total of 1,357 deferentially expressed genes (DEGs), of which 465 were up-regulated and 892 were down-regulated, which can be enriched into various GO ontology and KEGG pathway terms. Furthermore, ompX, as well as ompD and ompW, can be modulated at the transcriptional levels by rbsR and tdcA. Overall, the ompX gene contributed to a variety of biological functions in C. werkmanii and could be served as a targeted site for controlling biofilm formation and developing new bactericides.

Targeting cancer stem cells and signalling pathways through phytochemicals: A promising approach against colorectal cancer.

BACKGROUND: Cancer stem cells (CSCs) are strongly associated with high tumourigenicity, chemotherapy or radiotherapy resistance, and metastasis and recurrence, particularly in colorectal cancer (CRC). Therefore, targeting CSCs may be a promising approach. Recently, discovery and research on phytochemicals that effectively target colorectal CSCs have been gaining popularity because of their broad safety profile and multi-target and multi-pathway modes of action. PURPOSE: This review aimed to elucidate and summarise the effects and mechanisms of phytochemicals with potential anti-CSC agents that could contribute to the better management of CRC. METHODS: We reviewed PubMed, EMBASE, Web of Science, Ovid, ScienceDirect and China National Knowledge Infrastructure databases from the original publication date to March 2022 to review the mechanisms by which phytochemicals inhibit CRC progression by targeting CSCs and their key signalling pathways. Phytochemicals were classified and summarised based on the mechanisms of action. RESULTS: We observed that phytochemicals could affect the biological properties of colorectal CSCs. Phytochemicals significantly inhibit self-renewal, migration, invasion, colony formation, and chemoresistance and induce apoptosis and differentiation of CSCs by regulating the Wnt/ß-catenin pathway (e.g., diallyl trisulfide and genistein), the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway (e.g., caffeic acid and piperlongumine), the neurogenic locus notch homolog protein pathway (e.g., honokiol, quercetin, and α-mangostin), the Janus kinase-signal transducer and activator of transcription pathway (e.g., curcumin, morin, and ursolic acid), and other key signalling pathways. It is worth noting that several phytochemicals, such as resveratrol, silibinin, evodiamine, and thymoquinone, highlight multi-target and multi-pathway effects in restraining the malignant biological behaviour of CSCs. CONCLUSIONS: This review demonstrates the potential of targeted therapies for colorectal CSCs using phytochemicals. Phytochemicals could serve as novel therapeutic agents for CRC and aid in drug development.

[Reflections on supervision strategies of new Tibetan drug registration].

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.

Xuebijing Administration Alleviates Pulmonary Endothelial Inflammation and Coagulation Dysregulation in the Early Phase of Sepsis in Rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injection is a Chinese herbal-derived drug composed of radix paeoniaerubra, rhizomachuanxiong, Salvia miltiorrhiza, floscarthami, and Angelica sinensis. This study aimed to investigate the effects of Xuebijing administration on pulmonary endothelial injury and coagulation dysfunction in a cecal ligation and puncture (CLP)-induced sepsis rat model. MATERIALS AND METHODS: A CLP-induced sepsis rat model was established. The CLP rats were treated with a vehicle or Xuebijing via intravenous infusion and sacrificed at 2, 4, 6, 8, or 12 h after CLP for lung tissue and blood sample collection. The mean arterial pressure (MAP) was monitored. Transmission microscopy examination and H&E staining were performed to observe pulmonary structural alterations. Enzyme linked immunosorbent assay (ELISA) was performed to measure the plasma levels of epithelial markers, proinflammatory cytokines, and coagulation-related proteins. RESULTS: Compared with vehicle treatment, Xuebijing administration maintained the MAP in the normal range until 11 h after CLP. Transmission microscopy and H&E staining revealed that Xuebijing administration alleviated alveolar-capillary barrier impairments and lung inflammation in CLP rats. ELISA showed that Xuebijing administration effectively reversed CLP-induced elevations in the plasma levels of epithelial markers endothelin-1 and von Willebrand factor, starting 6 and 8 h after CLP, respectively. Xuebijing administration also significantly abolished CLP-induced rises in circulating proinflammatory cytokines interleukin 6 (IL-6) at 6 h after CLP, IL-1ß at 2 and 12 h after CLP, and TNF-α at 2, 4, 6, 8, and 12 h after CLP. In addition, Xuebijing administration strongly reversed CLP-induced alterations in circulating active protein C and tissue-type plasminogen activator, starting 4 h and 2 h after CLP, respectively. CONCLUSIONS: Xuebijing ameliorates pulmonary endothelial injury, systemic inflammation, and coagulation dysfunction in early sepsis.

Genomic insights into the evolutionary history and diversification of bulb traits in garlic.

BACKGROUND: Garlic is an entirely sterile crop with important value as a vegetable, condiment, and medicine. However, the evolutionary history of garlic remains largely unknown. RESULTS: Here we report a comprehensive map of garlic genomic variation, consisting of amazingly 129.4 million variations. Evolutionary analysis indicates that the garlic population diverged at least 100,000 years ago, and the two groups cultivated in China were domesticated from two independent routes. Consequently, 15.0 and 17.5% of genes underwent an expression change in two cultivated groups, causing a reshaping of their transcriptomic architecture. Furthermore, we find independent domestication leads to few overlaps of deleterious substitutions in these two groups due to separate accumulation and selection-based removal. By analysis of selective sweeps, genome-wide trait associations and associated transcriptomic analysis, we uncover differential selections for the bulb traits in these two garlic groups during their domestication. CONCLUSIONS: This study provides valuable resources for garlic genomics-based breeding, and comprehensive insights into the evolutionary history of this clonal-propagated crop.

Transcriptome Sequencing to Identify Candidate Genes for Mycelium Period Metabolism of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes), Exposed to Light Treatment.

The Chinese caterpillar mushroom, Ophiocordyceps sinensis, is rare in traditional Chinese herbal medicine. It was reported that the development of ascospores in sexual stage of Chinese Cordyceps requires certain UV irradiation, but whether light has effect on the asexual stage of O. sinensis is unclear. It is important and necessary to identify the candidate genes involved in asexual stages (mycelium period) metabolism of O. sinensis exposed to light treatment. In this study, the isolated and purified monoascospore strains from O. sinensis were treated with 10 days light (L10) and dark as control. Transcriptome sequencing (RNA-seq) was conducted to investigate the effect of light treatment on O. sinensis at the gene level and the changes in various metabolic pathways. The results showed that the colony surface was covered with villous aerial hyphae with a yellow circular mycelium ribbon in the center of the colony, and the content of polysaccharides, urea, adenosine, and cordycepin were significantly enhanced by L10 treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation analysis showed that cell structure and catalytic metabolism were the significant items classified, and crucial genes affecting the anabolic pathways of polysaccharides, urea, adenosine, and cordycepin were also identified. In addition, the important roles of photoreceptor genes CRYD, WC-1, and FRQ were verified by combined analysis of qRT-PCR and transcriptome sequencing. Collectively, this study would be helpful to better understand the influence of light on the asexual stage of Chinese Cordyceps and provide a preliminary light treatment reference for Cordyceps artificial cultivation.

Isoliquiritigenin mitigates oxidative damage after subarachnoid hemorrhage in vivo and in vitro by regulating Nrf2-dependent Signaling Pathway via Targeting of SIRT1.

BACKGROUND: Oxidative stress is a crucial factor leading to subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). Isoliquiritigenin has been verified as a powerful anti-oxidant in a variety of diseases models and can activate sirtuin 1 and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, the effects of isoliquiritigenin against EBI after SAH and the underlying mechanisms remain elusive. PURPOSE: The primary goal of this study is to verify the therapeutic effects of isoliquiritigenin on EBI after SAH and the possible molecular mechanisms. STUDY DESIGN: A prechiasmatic cistern SAH model in rats and a hemoglobin incubation SAH model in primary neurons were established. Isoliquiritigenin was administered after SAH induction. EX527 was employed to inhibit sirtuin 1 activation and ML385 was used to suppress Nrf2 signaling. METHODS: In our study, neurological scores, brain edema, biochemical estimation, western blotting, and histopathological study were performed to explore the therapeutic action of isoliquiritigenin against SAH. RESULTS: Our data revealed that isoliquiritigenin significantly mitigated oxidative damage after SAH as evidenced by decreased reactive oxygen species overproduction and enhanced intrinsic anti-oxidative system. Concomitant with the reduced oxidative insults, isoliquiritigenin improved neurological function and reduced neuronal death in the early period after SAH. Additionally, isoliquiritigenin administration significantly enhanced Nrf2 and sirtuin 1 expressions. Inhibition of Nrf2 by ML385 reversed the anti-oxidative and neuroprotective effects of isoliquiritigenin against SAH. Moreover, inhibiting sirtuin 1 by EX527 pretreatment suppressed isoliquiritigenin-induced Nrf2-dependent pathway and abated the cerebroprotective effects of isoliquiritigenin. In primary cortical neurons, isoliquiritigenin treatment also ameliorated oxidative insults and repressed neuronal degeneration. The beneficial aspects of isoliquiritigenin were attributed to the promotion of sirtuin 1 and Nrf2 signaling pathways and were counteracted by EX527. CONCLUSION: Our findings suggest that isoliquiritigenin exerts cerebroprotective effects against SAH-induced oxidative insults by modulating the Nrf2-mediated anti-oxidant signaling in part through sirtuin 1 activation. Isoliquiritigenin might be a new potential drug candidate for SAH.

[Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions"].

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Glaucocalyxin A impairs tumor growth via amplification of the ATF4/CHOP/CHAC1 cascade in human oral squamous cell carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The natural extract glaucocalyxin A (GLA), purified from the aboveground sections of the Chinese traditional medicinal herb Rabdosia japonica (Burm. f.) Hara var. glaucocalyx (Maxim.) Hara, has various pharmacological benefits, such as anti-bacterial, anti-coagulative, anti-neoplastic, and anti-inflammatory activities. Although GLA has shown anti-tumor activity against various cancers, the therapeutic potential and biological mechanisms of GLA remain to be further explored in oral squamous cell carcinoma (OSCC). AIM OF THE STUDY: This study aimed to elucidate the therapeutic potential and regulatory mechanisms of GLA in OSCC. MATERIALS AND METHODS: The cell proliferation and apoptosis effects of GLA were analyzed by CCK-8, clone formation, Annexin V/PI staining, and apoptotic protein expression in vitro. An OSCC xenograft model was applied to confirm the anti-neoplastic effect in vivo. Furthermore, the changes of reactive oxygen species (ROS) were determined by DCFH-DA probe and GSH/GSSG assay, and inhibited by the pan-caspase inhibitor Z-VAD(OMe)-FMK and the ROS scavenger N-acetylcysteine (NAC). The modulation of GLA on mitochondria and ER-dependent apoptosis pathways was analyzed by JC-1 probe, quantitative real-time PCR, and Western blot. Finally, public databases, clinical samples, and transfection cells were analyzed to explore the importance of GLA's indirect targeting molecule CHAC1 in OSCC. RESULTS: GLA significantly inhibited cell proliferation and induced apoptosis in vitro and in vivo. GLA perturbed the redox homeostasis, and cell apoptosis was totally rescued by Z-VAD(OMe)-FMK and NAC. Furthermore, GLA activated the mitochondrial apoptosis pathway. Simultaneously, the overexpression and knockdown of CHAC1 dramatically affected GLA-mediated apoptosis. The endoplasmic reticulum stress-associated ATF4/CHOP signal was identified to participate in GLA-upregulated CHAC1 expression. Finally, we found that CHAC1 expression was lower in OSCC compared with normal tissues and positively correlated with 4-Hydroxynonenal (4-HNE) level. High CHAC1 expression also indicated better overall survival. Moreover, CHAC1 selectively regulated the viability of oral cancer cells. CONCLUSION: GLA is a promising therapeutic agent that activates the ROS-mediated ATF4/CHOP/CHAC1 axis in OSCC patients.

Internal phosphorus cycling in macrophyte-dominated eutrophic lakes and its implications.

Macrophyte-dominated eutrophication (MDE) generally exhibits different characteristics from phytoplankton-dominated eutrophication (PDE). However, the significance of P cycling on eco-environmental management of MDE lakes is still not fully recognized. In this study, P-cycling mechanism was studied in a typical MDE lake (Wuliangsu Lake, China) based on a Before-After-Control-Impact design, taking advantage of the contrasting states between its 13 sub-lakes (with/without macrophytes and with/without external water flow). Our study demonstrated that P cycling predominantly occurs through "macrophyte ↔ sediment" in the MDE lakes, rather than "water ↔ sediment" as in PDE lakes; the biodynamics of the macrophytes acts as a primary driving force for this self-enforced P cycling. Our findings challenge the present lake eutrophication management strategies, which primarily limited to the water nutrient content, and demonstrate that successful MDE lake restoration should focus on stressors caused by the sustainable "macrophyte-sediment" P cycling. Macrophyte harvesting immediately before withering is recommended as the most sustainable technique in environment management for periodically frozen shallow MDE lakes. By this technique, sediment P can be gradually pumped up by the overgrown macrophytes each year until the advent of an alternative stable state (low sediment P, small biomass, and higher diversity), thereby forming a positive feedback loop "macrophyte harvesting → less sediment P → less macrophyte → higher diversity." Also, the catastrophic shift from MDE to PDE is no longer a concern. Furthermore, the macrophyte debris will not pose a problem as long as the macrophytes are removed during the harvest.

[Research and development strategies of new Chinese medicines based on new regulations].

In recent years, only a small number of new Chinese medicines have been approved for marketing, which has embodied the bottleneck in the development of the Chinese medicine industry. To tackle this problem, the National Medical Products Administration has issued a series of regulations and technical requirements. In the context of new regulations, this study deeply explored the research and development strategies of new Chinese medicines under the guidance of the new classification of drug registration, and discussed the key technical issues in the research and development.

A systematic review and meta-analysis of effect evaluation of traditional Chinese medicine in treating acute respiratory distress syndrome.

BACKGROUND: It was to systematically evaluate the effects of traditional Chinese medicine (TCM) in the treatment of acute respiratory distress syndrome (ARDS), and provide a theoretical basis for the clinical treatment of ARDS. METHODS: English databases of PubMed, Embase, Medline, Spring, Cochrane Library, and Web of Science were searched, and the randomized controlled trial literatures on the treatment of ARDS patients with TCM published from January 1, 2001 to December 31, 2020 were screened. Then, Cochrane Handbook 5.0.2 was employed to evaluate the risk of bias in the included literatures, and Review Manager 5.3 was utilized for meta-analysis. RESULTS: A total of 16 studies met the requirements and were included, with a total of 1,460 participants. The meta-analysis results showed that the mortality rate of patients in the observation group was remarkably reduced after treatment with TCM [mean deviation (MD) =0.51; 95% confidence interval (CI): 0.32-0.84; Z=2.69; P=0.007]. The effective rate of clinical treatment was improved (MD =2.64; 95% CI: 1.79-3.90; Z=4.90; P<0.00001). Arterial partial pressure of oxygen (PaO2) increased remarkably (MD =12.29; 95% CI: 8.88-15.71; Z=7.05; P<0.00001). The oxygenation index (PaO2/FiO2) increased remarkably (MD =50.70; 95% CI: 32.78-68.63; Z=5.54; P<0.00001). Interleukin-6 (IL-6) levels were remarkably reduced (MD =-8.32; 95% CI: -11.48 to -5.17; Z=5.17; P<0.00001). The level of C-reactive protein (CRP) decreased remarkably (MD =-9.23; 95% CI: -14.23 to -4.24; Z=3.62; P=0.0003). Compared with the control group, the above 8 analysis indicators showed statistically considerable differences. However, difference of partial pressure of carbon dioxide (PaCO2) level (MD =-0.16; 95% CI: -2.97-2.65; Z=0.11; P=0.91) was not obvious between groups. DISCUSSION: The treatment of ARDS with TCM can reduce the mortality rate of patients, improves the effective rate of clinical treatment, reduces the average mechanical ventilation time, increases the levels of PaO2, PaO2/FiO2, and reduces the levels of IL-6, tumor necrosis factor α (TNF-α), and CRP. The use of TCM has a significant treatment effect on ARDS.

Utilizing network pharmacology and molecular docking to explore the underlying mechanism of Guizhi Fuling Wan in treating endometriosis.

BACKGROUND: Guizhi Fuling Wan (GZFLW) is a widely used classical Chinese herbal formulae prescribed for the treatment of endometriosis (EMs). This study aimed to predict the key targets and mechanisms of GZFLW in the treatment of EMs by network pharmacology and molecular docking. METHODS: Firstly, related compounds and targets of GZFLW were identified through the TCMSP, BATMAN-TCM and CASC database. Then, the EMs target database was built by GeneCards. The overlapping targets between GZFLW and EMs were screened out, and then data of the PPI network was obtained by the STRING Database to analyze the interrelationship of these targets. Furthermore, a topological analysis was performed to screen the hub targets. After that, molecular docking technology was used to confirm the binding degree of the main active compounds and hub targets. Finally, the DAVID database and Metascape database were used for GO and KEGG enrichment analysis. RESULTS: A total of 89 GZFLW compounds and 284 targets were collected. One hundred one matching targets were picked out as the correlative targets of GZFLW in treating EMs. Among these, 25 significant hub targets were recognized by the PPI network. Coincidently, molecular docking simulation indicated that the hub targets had a good bonding activity with most active compounds (69.71%). Furthermore, 116 items, including the inflammatory reaction, RNA polymerase, DNA transcription, growth factor activity, and steroid-binding, were selected by GO enrichment analysis. Moreover, the KEGG enrichment analysis results included 100 pathways focused on the AGE-RAGE pathway, HIF pathway, PI3K Akt pathway, MAPK pathway, and TP53 pathway, which exposed the potential mechanisms of GZFLW in treating EMs. Also, the MTT colorimetric assay indicated that the cell proliferation could be inhibited by GZFLW. Compared with the control group, the protein levels of P53, BAX, and caspase3 in the drug groups were all increased in Western blotting results. The results of flow cytometry showed that the percentage of apoptotic cells in the GZFLW group was significantly higher than that in the control group. CONCLUSION: Through the exploration of network pharmacology and molecular docking technology, GZFLW has a therapeutic effect on EMs through multi-target mechanism. This study provided a good foundation for further experimental research.

The effect of traditional Chinese medicine fumigation and washing as a complementary and alternative therapy on the recovery of joint function after development dysplasia of the hip in children: A protocol for systematic review and meta-analysis.

BACKGROUND: Development dysplasia of the hip (DDH) is a common childhood orthopedic disease in clinic. The cause of DDH is not yet clear. If DDH is not treated promptly or correctly, it will seriously affect the life quality of the child. At present, surgery is the main means of treating older DDH, but it is easy to appear development dysplasia of the hip after surgery, and the joint movement is limited after surgery. For modern medicine, it has not many treatments to solve this problem. As one of the commonly used treatment methods, but the effect of routine functional exercise is not ideal. Traditional Chinese medicine fumigation and washing belongs to the category of Chinese medicine external treatment, which can directly act on the focus. It has the functions of relaxing muscles and tendons and removing obstruction from meridians, activating blood to eliminate stagnation. It has achieved good effects in relieving joint disorders, but it is lack of the high-quality evidence support, so there is controversy about the clinical application of traditional Chinese medicine fumigation and washing. This study will conduct a systematic review to compare the application effect and safety of traditional Chinese medicine fumigation and washing as a complementary and alternative therapy and traditional rehabilitation training in the treatment of postoperative joint function recovery after development dysplasia of the hip in children. The research results will provide evidence-based medical evidence to support the choice of treatment for the disease. METHODS: Using computer to retrieve PubMed, ScienceDirect, Web of Science, EMBase, Cochrane Library, WANFANG Database, CNKI, and VIP Database, CBM, and using the method of combining mesh words with item words to retrieve the Chinese and English databases, to retrieve the randomized controlled study on the application of traditional Chinese medicine fumigation and washing on the recovery of joint function after development dysplasia of the hip in children. The retrieval time is from January 1990 to January 2021. Two researchers screen and evaluate the quality of the retrieved literatures according to the inclusion and exclusion criteria. In the event of a disagreement, a third researcher will join the discussion to resolve the disagreement. Using Revman 5.3 software to conduct meta-analysis. RESULTS: This study will compare the application effect and safety of traditional Chinese medicine fumigation and washing as a complementary and alternative therapy and traditional rehabilitation training in the treatment of postoperative joint function recovery after development dysplasia of the hip in children. CONCLUSION: The results of this study will be published in an internationally influential academic journal to provide evidence-based medical evidence for the selection of supplement and alternative therapies on the recovery of joint function after development dysplasia of the hip in children. ETHICS AND DISSEMINATION: This study does not involve specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of this study. OSF REGISTRATION: DOI 10.17605/OSF.IO/RUHK5.

Chemical Components of Aqueous Extracts of Melia azedarach Fruits and Their Effects on The Transcriptome of Staphylococcus aureus.

Staphylococcus aureus is the causative agent of numerous and varied clinical infections. Crude aqueous extracts of Melia azedarach fruits inhibit the planktonic growth and initial biofilm formation of S. aureus in a dose-dependent manner. Moreover, the biofilm topologies became sparse and decreased as the concentration of the aqueous extracts increased. RNA-Seq analyses revealed 532 differentially expressed genes (DEGs) after S. aureus exposure to 0.25 g/ml extracts; 319 of them were upregulated, and 213 were downregulated. The majority of DEGs were categorized into abundant sub-groups in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, untargeted UHPLC-MS/MS analyses of the aqueous extracts of M. azedarach fruits demonstrated a highly complex profile in positive and negative electrospray ionization modes. The extracts primarily consisted of lipids and lipid-like molecules, organic acids and their derivatives, phenylpropanoids, polyketides, organoheterocyclic compounds, and benzenoids annotated by abundant lipid maps and KEGG pathways. Overall, this study provides evidences that the aqueous extracts of M. azedarach fruits can control S. aureus infections and sought to understand the mode of action of these extracts on S. aureus.

New phenylpropanoid-substituted and benzyl-substituted flavonols from Alangium chinense.

Two previously undescribed flavonols with phenylpropanoid or benzyl substitution, named alangsine A (1), and alangsine B (2), together with four known compounds (3-6) were isolated from the leaves of Alangium chinense. Alangsine A was a racemic mixture, which was further separated into two enantiomers via high-performance liquid chromatography on a chiral column. The absolute configurations of the enantiomer pairs were deduced from the circular dichroism (CD) spectra. The activity of the isolated compounds towards neuronal excitability was examined.

Omega-3 polyunsaturated fatty acids: a promising approach for the management of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease with a risk of malignant transformation. Although the etiology of OLP is still uncertain, growing evidence suggests that oral microbiota, antigen-specific, and non-specific mechanisms are involved in the pathogenesis of OLP. Antigen-specific mechanisms include antigen presentation, T-cell activation, nuclear factor-kappa B signaling pathway, and cytokine secretion, while non-specific mechanisms consist of matrix metalloproteinases (MMP)-9 upregulation, psychological pressure, oxidative damage, aberrant expression of microRNAs (miRNAs), and autophagy. Till now, there is no cure for OLP, and the main purpose of OLP therapy is symptomatic control. FINDING: Seafood and its derivative omega-3 polyunsaturated fatty acids (n-3 PUFAs) can suppress antigen presentation, T-cell activation, and nuclear factor-kappa B signaling pathway, modulate the overexpressed inflammatory cytokines, inhibit the expression of MMP-9, as well as regulate the expression of miRNAs and autophagy. And they are possible agents for ameliorating psychological disorder and oxidative damage. Moreover, n-3 PUFAs supplementation has a beneficial effect on preventing tumorigenesis. CONCLUSION: n-3 PUFAs consumption may provide a non-toxic, inexpensive administration for OLP.