Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1.

BACKGROUND: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui. METHODS: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments. RESULTS: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract. CONCLUSIONS: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

A case report of classic galactosemia with a GALT gene variant and a literature review.

BACKGROUND: Galactosemia is an autosomal recessive disorder resulting from an enzyme defect in the galactose metabolic pathway. The most severe manifestation of classic galactosemia is caused by galactose-1-phosphate uridylyltransferase (GALT) deficiency, and this condition can be fatal during infancy if left untreated. It also may result in long-term complications in affected individuals. CASE PRESENTATION: This report describes a patient whose initial clinical symptoms were jaundice and liver dysfunction. The patient's liver and coagulation functions did not improve after multiple admissions and treatment with antibiotics, hepatoprotective and choleretic agents and blood transfusion. Genetic analysis revealed the presence of two variants in the GALT gene in the compound heterozygous state: c.377 + 2dup and c.368G > C (p.Arg123Pro). Currently, the variant locus (c.377 + 2dup) in the GALT gene has not been reported in the Human Gene Mutation Database (HGMD), while c.368G > C (p.Arg123Pro) has not been reported in the Genome Aggregation Database (GnomAD) nor the HGMD in East Asian population. We postulated that the two variants may contribute to the development of classical galactosemia. CONCLUSIONS: Applications of whole-exome sequencing to detect the two variants can improve the detection and early diagnosis of classical galactosemia and, more specifically, may identify individuals who are compound heterozygous with variants in the GALT gene. Variants in the GALT gene have a potential therapeutic significance for classical galactosemia.

Is the suppression of CD36 a promising way for atherosclerosis therapy?

Atherosclerosis is the main underlying pathology of many cardiovascular diseases and is marked by plaque formation in the artery wall. It has posed a serious threat to the health of people all over the world. CD36 acts as a significant regulator of lipid homeostasis, which is closely associated with the onset and progression of atherosclerosis and may be a new therapeutic target. The abnormal overexpression of CD36 facilitates lipid accumulation, foam cell formation, inflammation, endothelial apoptosis, and thrombosis. Numerous natural products and lipid-lowering agents are found to target the suppression of CD36 or inhibit the upregulation of CD36 to prevent and treat atherosclerosis. Here, the structure, expression regulation and function of CD36 in atherosclerosis and its related pharmacological therapies are reviewed. This review highlights the importance of drugs targeting CD36 suppression in the treatment and prevention of atherosclerosis, in order to develop new therapeutic strategies and potential anti-atherosclerotic drugs both preclinically and clinically.

Peony-like 3D-MoS2/graphene nanostructures with enhanced mimic peroxidase performance for colorimetric determination of dopamine.

Fast and quantitative detection of dopamine (DA) is highly desirable but still challenging in the clinical diagnosis due to the complexity of the biological samples. Herein, a novel peony-like 3D-MoS2/Graphene (peony-like 3D-MoS2/GR) nanomaterial is designed and characterized. The nanomaterial exhibits outstanding the peroxidase-like activity, which can be employed as a nanozyme for facile and fast colorimetric determination of dopamine. The peony-like 3D-MoS2/GR-based colorimetric assay presents a wide liner dependence on the DA concentration in the range of 1-400 µM and a low detection limit of 0.21 µM. Such excellent results originate from its unique structure, which offers abundant active sites, high specific surface area, interconnected network and the special microenvironment. Furthermore, this reported colorimetric assay is successfully employed for detection of DA in human serum and urine samples. The recovery percentage ranges from 98 to 105.6%. Hence, the peony-like 3D-MoS2/GR paves a new avenue for detection of DA in real biological systems.

Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection.

Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD. In-depth network analysis results of the top diseases, functions, pathways and upstream regulators implied that a common underlying mechanism linking DHI's role in stroke and CAD treatment was inflammatory response in the process of atherosclerosis. Experimentally, DHI exerted comprehensive anti-inflammatory effects on LPS, ox-LDL or cholesterol crystal-induced NF-κB, c-jun and p38 activation, as well as IL-1ß, TNF-α, and IL-10 secretion in vascular endothelial cells. Ten of 14 predicted ingredients were verified to have significant anti-inflammatory activities on LPS-induced endothelial inflammation. DHI exerts pharmacological efficacies on both stroke and CAD through multi-ingredient, multi-target, multi-function and multi-pathway mode. Anti-endothelial inflammation therapy serves as a common underlying mechanism. This study provides a new understanding of DHI in clinical application on cardiovascular and cerebrovascular diseases.

Bidirectional regulation of angiogenesis by phytoestrogens through estrogen receptor-mediated signaling networks.

Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERα and ERß by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERα and ERß were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERα, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERß, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERα and ERß may be critical in the balance of pro- or anti-angiogenesis process.

Tracing the legacy of the early Hainan Islanders--a perspective from mitochondrial DNA.

BACKGROUND: Hainan Island is located around the conjunction of East Asia and Southeast Asia, and during the Last Glacial Maximum (LGM) was connected with the mainland. This provided an opportunity for the colonization of Hainan Island by modern human in the Upper Pleistocene. Whether the ancient dispersal left any footprints in the contemporary gene pool of Hainan islanders is debatable. RESULTS: We collected samples from 285 Li individuals and analyzed mitochondrial DNA (mtDNA) variations of hypervariable sequence I and II (HVS-I and II), as well as partial coding regions. By incorporating previously reported data, the phylogeny of Hainan islanders was reconstructed. We found that Hainan islanders showed a close relationship with the populations in mainland southern China, especially from Guangxi. Haplotype sharing analyses suggested that the recent gene flow from the mainland might play important roles in shaping the maternal pool of Hainan islanders. More importantly, haplogroups M12, M7e, and M7c1* might represent the genetic relics of the ancient population that populated this region; thus, 14 representative complete mtDNA genomes were further sequenced. CONCLUSIONS: The detailed phylogeographic analyses of haplogroups M12, M7e, and M7c1* indicated that the early peopling of Hainan Island by modern human could be traced back to the early Holocene and/or even the late Upper Pleistocene, around 7-27 kya. These results correspond to both Y-chromosome and archaeological studies.

[GC-MS analysis of essential oils from seeds of Myristica fragrans in Chinese market].

OBJECTIVE: To analyze the constituents of the essential oils extracted from nine samples of commercial seeds of Myristica fragrans Houtt respectively and to provide qualities control foundations. METHOD: Water steam distillation and GC-MS were used. RESULT: 95-118 compounds were separated respectively. 79 Compounds being identified which were 95.18%-98.70% of the total essential oil. CONCLUSION: Myristicin (39.63%) and terpene series were the main compounds.