Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis.

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.

Levistilide A ameliorates neuroinflammation via inhibiting JAK2/STAT3 signaling for neuroprotection and cognitive improvement in scopolamine-induced Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with cognitive impairment and dementia, which has become a major public health problem. There are no effective therapeutic agents used to treat AD in clinic for the extremely complex pathogenesis. Here we identify Levistilide A (LA), one of the major active natural terpene lactone constituents from Chinese herbal medicine Angelicae sinensis and Chuanxiong Rhizoma, as a potent neuroinflammation inhibitor for neuroprotection and cognitive improvement of AD. We show that LA suppresses neuronal apoptosis, restores cholinergic system function, and lowers neuroinflammation in vivo to improve scopolamine (SCOP)-induced learning and memory deficits. In addition, LA inhibits the release of IL-1ß, IL-6 and TNF-α, while increasing the production of IL-4 and IL-10 for anti-inflammatory effects in LPS or Aß-induced BV2 and HMC3 cells. Furthermore, the conditioned medium (CM) from LA-treated BV2 or HMC3 cells enhances the viability of SH-SY5Y and HT-22 cells, and LA reverses M1 to M2 phenotype transformation of BV2 and HMC3 cells accompanied by the inhibited Iba-1 expression and mRNA level of IL-1ß, IL-6, TNF-α and NOS2, and the increased expression of ARG1, CD206 and CD163. Mechanistically, we analyze JAK2/STAT3 signaling as possible targets of LA using network pharmacology approaches, and further experimentally validate that LA inhibits the phosphorylation of JAK2 and STAT3, and STAT3 expression within nucleus both in vitro and in vivo. Collectively, we identify LA as a potential neuroinflammation inhibitor for neuroprotection and cognitive improvement, which is expected to be a candidate for AD therapy.

Lonicera japonica polysaccharides alleviate D-galactose-induced oxidative stress and restore gut microbiota in ICR mice.

Lonicera japonica polysaccharides (LJPs) exhibit anti-aging effect in nematodes. Here, we further studied the function of LJPs on aging-related disorders in D-galactose (D-gal)-induced ICR mice. Four groups of mice including the control group, the D-gal-treated group, the intervening groups with low and high dose of LJPs (50 and 100 mg/kg/day) were raised for 8 weeks. The results showed that intragastric administration with LJPs improved the organ indexes of D-gal-treated mice. Moreover, LJPs improved the activity of superoxide dismutase (SOD), catalase (CAT) as well as glutathione peroxidase (GSH-Px) and decreased the malondialdehyde (MDA) level in serum, liver and brain. Meanwhile, LJPs restored the content of acetylcholinesterase (AChE) in the brain. Further, LJPs reversed the liver tissue damages in aging mice. Mechanistically, LJPs alleviate oxidative stress at least partially through regulating Nrf2 signaling. Additionally, LJPs restored the gut microbiota composition of D-gal-treated mice by adjusting the Firmicutes/Bacteroidetes ratio at the phylum level and upregulating the relative abundances of Lactobacillaceae and Bifidobacteriacesa. Notably, the KEGG pathways involved in hazardous substances degradation and flavone and flavonol biosynthesis were significantly enhanced by LJPs treatment. Overall, our study uncovers the role of LJPs in modulating oxidative stress and gut microbiota in the D-gal-induced aging mice.

Khellin as a selective monoamine oxidase B inhibitor ameliorated paclitaxel-induced peripheral neuropathy in mice.

BACKGROUND: Treatment of paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is full of challenges because of the unclear pathogenesis of PIPN. Herbal folk medicine Khellin (Khe) is a natural compound extracted from Ammi visnaga for treatment of renal colics and muscle spasms. PURPOSE: Here, we aimed to assess the potential of Khe in ameliorating PIPN-like pathology in mice and investigate the underlying mechanisms. METHODS: PIPN model mice were conducted by injection of PTX based on the published approach. The capability of Khe in ameliorating the PTX-induced neurological dysfunctions was assayed by detection of nociceptive hypersensitivities including mechanical hyperalgesia, thermal hypersensitivity, and cold allodynia in mice. The underlying mechanisms were investigated by assays against the PIPN mice with MAOB-specific knockdown in spinal cord and dorsal root ganglion (DRG) tissues by injection of adeno-associated virus (AAV)-MAOB-shRNA. RESULTS: We determined that MAOB not MAOA is highly overexpressed in the spinal cord and DRG tissues of PIPN mice and Khe as a selective MAOB inhibitor improved PIPN-like pathology in mice. Khe promoted neurite outgrowth, alleviated apoptosis, and improved mitochondrial dysfunction of DRG neurons by targeting MAOB. Moreover, Khe inhibited spinal astrocytes activation and suppressed neuroinflammation of spinal astrocytes via MAOB/NF-κB/NLRP3/ASC/Caspase1/IL-1ß pathway. CONCLUSION: Our work might be the first to report that MAOB not MAOA is selectively overexpressed in the spinal cord and DRG tissues of PIPN mice, and all findings have highly addressed the potency of selective MAOB inhibitor in the amelioration of PIPN-like pathology and highlighted the potential of Khe in treating PTX-induced side effects.

Baicalin protects against insulin resistance and metabolic dysfunction through activation of GALR2/GLUT4 signaling.

BACKGROUND: Type 2 diabetes mellitus is a complex metabolic disorder associated with obesity, glucose intolerance and insulin resistance. Activation of GALR2 has been proposed as a therapeutic target for the treatment of insulin resistance. The previous studies showed that baicalin could mitigate insulin resistance, but the detailed mechanism of baicalin on insulin resistance has not been fully explored yet. PURPOSE: In the present study, we evaluated whether baicalin mitigated insulin resistance via activation of GALR2 signaling pathway. STUDY DESIGN/METHODS: Baicalin (25 mg/kg/d and 50 mg/kg/d) and/or GALR2 antagonist M871 (10 mg/kg/d) were injected individually or in combinations into obese mice once a day for three weeks, and normal and GALR2 knockdown myotubes were treated with baicalin (100 µM and 400 µM) or metformin (4 mM) in the absence or presence of M871 (800 nM) for 12 h, respectively. The molecular mechanism was explored in skeletal muscle and L6 myotubes. RESULTS: The present findings showed that baicalin mitigated hyperglycemia and insulin resistance and elevated the levels of PGC-1α, GLUT4, p-p38MAPK, p-AKT and p-AS160 in skeletal muscle of obese mice. Strikingly, the baicalin-induced beneficial effects were abolished by GALR2 antagonist M871 in obese mice. In vitro, baicalin dramatically augmented glucose consumption and the activity of PGC1α-GLUT4 axis in myotubes through activation of p38MAPK and AKT pathways. Moreover, baicalin-induced elevations in glucose consumption related genes were abolished by GALR2 antagonist M871 or silencing of GALR2 in myotubes. CONCLUSIONS: The present study for the first time demonstrated that baicalin protected against insulin resistance and metabolic dysfunction mainly through activation of GALR2-GLUT4 signal pathway. Our findings identified that activation of GALR2-GLUT4 signal pathway by baicalin could be a new therapeutic approach to treat insulin resistance and T2DM in clinic.

AHR/ROS-mediated mitochondria apoptosis contributes to benzo[a]pyrene-induced heart defects and the protective effects of resveratrol.

Benzo[a]pyrene (BaP), a prototypical polycyclic aromatic hydrocarbon, is widely present in the environment. BaP-induced heart defects have been frequently reported, but the underlying molecular mechanisms remain elusive. Here, we found that BaP increased heart malformations in zebrafish embryos in a concentration-dependent manner, which were attenuated by supplementation with either CH223191 (CH), an aryl hydrocarbon receptor (AHR) inhibitor, or N-acetyl-l-cysteine (NAC), a reactive oxygen species (ROS) scavenger. While CH and NAC both inhibited BaP-induced ROS generation, NAC had no effect on BaP-induced AHR activation. We further demonstrated that BaP increased mitochondrial ROS, decreased mitochondrial membrane potential, and caused endogenous apoptosis, with all these effects being counteracted by supplementation with either CH or NAC. Resveratrol (RSV), a natural AHR antagonist and ROS scavenger, also counteracted the heart malformations caused by BaP. Further experiments showed that RSV attenuated BaP-induced oxidative stress, mitochondrial damage and apoptosis, but had no significant effect on AHR activation. In conclusion, our findings show that BaP induces oxidative stress via AHR activation, which causes mitochondria-mediated intrinsic apoptosis, resulting in heart malformations in zebrafish embryos, and that RSV had a protective effect against BaP-induced heart defects mainly by inhibiting oxidative stress rather than through antagonism of AHR activity.

Integrative analysis of TNFRSF6B as a potential therapeutic target for pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most lethal malignant tumors worldwide with poor outcomes. Previous studies have shown that tumor necrosis factor receptor superfamily member 6b (TNFRSF6B) plays an important role in cancer progression and immunosuppression. However, the mechanisms by which TNFRSF6B influence pancreatic cancer, and the regulatory networks involved remain to be further studied. METHODS: This study analyzed the mRNA information and clinical data of patients from The Cancer Genome Atlas (TCGA) and the ONCOMINE databases. The gene co-expression data regarding TNFRSF6B was obtained from the c-BioPortal and used to explore the functional network of TNFRSF6B in pancreatic cancer, as well as its function in tumor immunity. Short hairpin (sh) RNA knock-down experiments were performed to examine the functional roles of TNFRSF6B in pancreatic cancer cell lines. RESULTS: The expression of TNFRSF6B was elevated in pancreatic cancer tissues compared to normal pancreatic tissues, and its high expression was associated with poor prognosis of patients with pancreatic cancer. TNFRSF6B was found to be widely involved in cell cycle processes, apoptosis, apoptosis signaling pathways, immune responses, and responses to interferon. Knock-down of TNFRSF6B expression inhibited pancreatic cancer cell proliferation and invasion in vitro. Moreover, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was found to be co-expressed with TNFRSF6B, and there was a positive correlation between these molecules in pancreatic cancer cells. CONCLUSIONS: This report suggested that TNFRSF6B has a critical role in the progression and metastasis of pancreatic cancer. These findings provide novel insights into the role of TNFRSF6B in the functional network of pancreatic cancer, and suggest that TNFRSF6B may be a potential therapeutic target.

Effect of catechin and commercial preparation of green tea essence on the pharmacokinetics of l-dopa in rabbits.

The aim of this study was to investigate drug interactions of L-dopa/carbidopa with catechin and green tea essence in rabbits following the simultaneous administration via an intramuscular injection of catechin or via an intragastric route for green tea essence with L-dopa/carbidopa. The results indicated that catechin at doses of 10, 20 and 50 mg/kg increased the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t ) of L-dopa by about 69, 78 and 42%, respectively. The metabolic ratios of the AUC0-t for 3-O-methyldopa (3-OMD)/L-dopa significantly decreased by about 56, 68 and 76% (P < 0.05), respectively. In addition, a single dose of 5/1.25 mg/kg L-dopa/carbidopa was co-administrated with 150 mg/kg green tea essence via an intragastric route with an oral-gastric tube. Comparing the related pharmacokinetic parameters of L-dopa, the clearance and metabolic ratio of L-dopa decreased by 20 and 19% (P < 0.05), respectively. In conclusion, catechin and green tea essence can significantly affect the metabolism of L-dopa by the catechol-O-methyltransferase (COMT) metabolic pathway. Catechin can enhance L-dopa bioavailability, and both catechin and green tea essence decreased 3-OMD formation. Therefore, catechin and green tea essence may increase L-dopa efficacy for Parkinson's disease treatment.

High-Dose Vitamin C Tends to Kill Colorectal Cancer with High MALAT1 Expression.

BACKGROUND: Vitamin C (Vc) deficiency is frequently observed in cancer sites and has been proposed to have an antitumor effect. However, the mechanism of Vc's killing effect is not clear. Besides, epigenetic alterations exhibit significant effects on colorectal cancer (CRC). This study aimed to explore the mechanism of Vc's killing effect and its association to epigenetic alterations in CRC. METHODS: Cell morphology, apoptosis, proliferation, and cycle were assayed to test Vc's suppressive function in CRC cell lines. Xenograft and peritoneal implantation metastasis models were performed to evaluate the high-dose Vc's inhibitory effect on tumor growth and metastasis. Immunohistochemistry was used to measure CD31 expression in solid tumors. A literature summary was applied for screening differently expressed long noncoding RNAs (lncRNAs) in CRC tissues and was closely associated with CRC progression. The qPCR was used to detect the expression of these lncRNAs. The association between Vc and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was evaluated in MALAT1-transfected CRC cells and a xenograft model. RESULTS: Vc was confirmed to function in proliferation suppression, apoptosis induction, and S phase arresting in CRC cell lines. High-dose Vc, but not physiologically low-dose Vc, was identified as a suppressive function on tumor growth in xenograft models and an inhibitory effect on implantation metastasis in peritoneal implantation metastasis mice. Furthermore, a consistent downregulation of MALAT1 induced by Vc was verified among CRC cell lines and tumor tissues from both mouse models. Finally, experiments on MALAT1-knockdown CRC cells and its xenograft model suggested that Vc had a tendency in killing CRC with high MALAT1 expression. CONCLUSIONS: Our findings demonstrate that high-dose Vc has more efficiency in suppressing CRC with higher MALAT1 expression. It gives high-dose Vc the possibility of a better curative effect on CRC with overexpressed MALAT1. Further clinical studies are still needed.

Monochromatic Blue Light Activates Suprachiasmatic Nucleus Neuronal Activity and Promotes Arousal in Mice Under Sevoflurane Anesthesia.

Background: Monochromatic blue light (MBL), with a wavelength between 400-490 nm, can regulate non-image-forming (NIF) functions of light in the central nervous system. The suprachiasmatic nucleus (SCN) in the brain is involved in the arousal-promoting response to blue light in mice. Animal and human studies showed that the responsiveness of the brain to visual stimuli is partly preserved under general anesthesia. Therefore, this study aimed to investigate whether MBL promotes arousal from sevoflurane anesthesia via activation of the SCN in mice. Methods: The induction and emergence time of sevoflurane anesthesia under MBL (460 nm and 800 lux) exposure was measured. Cortical electroencephalograms (EEGs) were recorded and the burst-suppression ratio (BSR) was calculated under MBL during sevoflurane anesthesia. The EEGs and local field potential (LFP) recordings with or without locally electrolytic ablated bilateral SCN were used to further explore the role of SCN in the arousal-promoting effect of MBL under sevoflurane anesthesia. Immunofluorescent staining of c-Fos was conducted to reveal the possible downstream mechanism of SCN activation. Results: Unlike the lack of effect on the induction time, MBL shortened the emergence time and the EEG recordings showed cortical arousal during the recovery period. MBL resulted in a significant decrease in BSR and a marked increase in EEG power at all frequency bands except for the spindle band during 2.5% sevoflurane anesthesia. MBL exposure under sevoflurane anesthesia enhances the neuronal activity of the SCN. These responses to MBL were abolished in SCN lesioned (SCNx) mice. MBL evoked a high level of c-Fos expression in the prefrontal cortex (PFC) and lateral hypothalamus (LH) compared to polychromatic white light (PWL) under sevoflurane anesthesia, while it exerted no effect on c-Fos expression in the ventrolateral preoptic area (VLPO) and locus coeruleus (LC) c-Fos expression. Conclusions: MBL promotes behavioral and electroencephalographic arousal from sevoflurane anesthesia via the activation of the SCN and its associated downstream wake-related nuclei. The clinical implications of this study warrant further study.

Hyperelodiones A-C, monoterpenoid polyprenylated acylphoroglucinols from Hypericum elodeoides, induce cancer cells apoptosis by targeting RXRα.

Hyperelodiones A-C, three undescribed monoterpenoid polyprenylated acylphloroglucinols possessing 6/6/6 fused tricyclic core, were isolated from Hypericum elodeoides Choisy. Their gross structures were elucidated by HRESIMS and NMR data. The absolute configurations of hyperelodiones A-C were assigned by their calculated and compared electronic circular dichroism (ECD) spectra combined with their common biosynthetic origin. A fluorescence quenching assay suggested that hyperelodiones A-C could bind to RXRα-LBD, whereas hyperelodione C showed the strongest interaction with a KD of 12.81 µΜ. In addition, hyperelodiones A-C dose-dependently inhibited RXRα transactivation and the growth of HeLa and MCF-7 cells. Among them, hyperelodione C showed the most potent inhibitory activities and dose-dependent PARP cleavage. Molecular docking results suggested that hyperelodione C showed a different interaction mode compared with hyperelodione A and hyperelodione B. Thus, hyperelodione C can be considered as a promising lead compound for cancer therapy, which can bind to RXRα-LBD and induce HeLa and MCF-7 cell apoptosis.

A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae.

BACKGROUND: Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. METHODS: In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC. RESULTS: In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice. CONCLUSIONS: We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC.

Cytotoxic Components from Hypericum elodeoides Targeting RXRα and Inducing HeLa Cell Apoptosis through Caspase-8 Activation and PARP Cleavage.

To find small-molecule regulators of RXRα, a phytochemical study of Hypericum elodeoides was conducted. Fifteen compounds, including the new 1 and 6, were isolated from the whole plant of H. elodeoides. The absolute configuration of 1 was assigned by comparison of experimental and calculated ECD data. Compounds 1 and 6 exhibited concentration-dependent inhibitory effects on RXRα transcription and selectively inhibited the proliferation of HeLa cells. Western blot analysis suggested that 1 and 6 induced apoptosis of HeLa cells with time- and dose-dependent PARP cleavage. A caspase activation assay indicated that these two compounds triggered caspase-8 activation to induce apoptosis by the extrinsic pathway. Molecular docking results suggested that 1 and 6 interacted with the Arg319 moiety of RXRα-LBD. Ligands binding to RXRα have shown promise in the discovery of anticancer drugs. A fluorescence quenching assay indicated the binding of 1 and 6 to the RXRα with the binding constant ( KD) fitted as 68.3 and 14.0 µM, respectively. A preliminary SAR study of the isolates was conducted to enhance the knowledge of the RXRα ligands. Thus, 1 and 6 might act as the small-molecule regulators of RXRα, which target RXRα and mediate HeLa cell apoptosis through the extrinsic pathways.

Systems pharmacology-based investigation of Sanwei Ganjiang Prescription: related mechanisms in liver injury.

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.

The Mechanisms of Bushen-Yizhi Formula as a Therapeutic Agent against Alzheimer's Disease.

Bushen-Yizhi prescription (BSYZ) has been an effective traditional Chinese medicine (TCM) prescription in treating Alzheimer's disease (AD) for hundreds of years. However, the underlying mechanisms have not been fully elucidated yet. In this work, a systems pharmacology approach was developed to reveal the underlying molecular mechanisms of BSYZ in treating AD. First, we obtained 329 candidate compounds of BSYZ by in silico ADME/T filter analysis and 138 AD-related targets were predicted by our in-house WEGA algorithm via mapping predicted targets into AD-related proteins. In addition, we elucidated the mechanisms of BSYZ action on AD through multiple network analysis, including compound-target network analysis and target-function network analysis. Furthermore, several modules regulated by BSYZ were incorporated into AD-related pathways to uncover the therapeutic mechanisms of this prescription in AD treatment. Finally, further verification experiments also demonstrated the therapeutic effects of BSYZ on cognitive dysfunction in APP/PS1 mice, which was possibly via regulating amyloid-ß metabolism and suppressing neuronal apoptosis. In conclusion, we provide an integrative systems pharmacology approach to illustrate the underlying therapeutic mechanisms of BSYZ formula action on AD.

Effectiveness of acupuncture for breast cancer related lymphedema: protocol for a single-blind, sham-controlled, randomized, multicenter trial.

BACKGROUND: Although various treatments for breast cancer related lymphedema exist, there is still a need for a more effective and convenient approach. Pilot studies and our clinical observations suggested that acupuncture may be a potential option. This study aims to verify the effectiveness of acupuncture on BCRL and evaluate its safety using a rigorously designed trial. METHODS/DESIGN: Women who are clinically diagnosed as unilateral BCRL, with a 10% to 40% increase in volume compared to the unaffected arm, will be recruited. Following baseline assessment, participants will be randomized to either the real acupuncture group or sham-acupuncture group at a ratio of 1:1, and given a standard real acupuncture or sham-acupuncture treatment accordingly on both arms followed by the same usual care of decongestive therapy. Volume measurements of both arms will be performed for every participant after each treatment. Data collected at baseline and the last session will be used to calculate the primary outcome and secondary outcomes. Other data will be exploited for interim analyses and trial monitoring. The primary outcome is the absolute reduced limb volume ratio. Secondary outcomes are incidence of adverse events and change in quality of life. A t test or non-parameter test will be used to compare the difference between two groups, and assess the overall effectiveness of acupuncture using the SPSS software (version 12). DISCUSSION: This study will help expand our knowledge about the effectiveness of acupuncture on BCRL, and how acupuncture might be used in the management of this condition. Acupuncture may be a promising complement or alternative to conventional lymphedema treatment methods, if its effectiveness is confirmed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803736 (Registered on October 31, 2016).

Wogonin inhibits multiple myeloma-stimulated angiogenesis via c-Myc/VHL/HIF-1α signaling axis.

Angiogenesis is associated with the progression of multiple myeloma (MM). Wogonin is an active mono-flavonoid with remarkable antitumor activity. However, its impact on MM-stimulated angiogenesis remains largely unknown. Here, we demonstrated that wogonin decreased expression and secretion of pro-angiogenic factors in MM cells via c-Myc/HIF-1α signaling axis, reducing MM-stimulated angiogenesis and MM cell proliferation in vivo. Overexpression of c-Myc in MM cells disrupted the balance between VHL SUMOylation and ubiquitination, and thus inhibited proteasome-mediated HIF-1α degradation. Impaired function of VHL ubiquitination complex in c-Myc-overexpressing cells was fully reversed by wogonin treatment via increasing HIF-1α-VHL interaction and promoting HIF-1α degradation. Collectively, our in vitro and in vivo studies reveal for the first time that wogonin represses MM-stimulated angiogenesis and tumor progression via c-Myc/VHL/HIF-1α signaling axis.

Dammarane-type triterpenoids from Gentianella azurea.

Thirteen new dammarane-type triterpenoids (1-13) and four known analogues, gentirigenic acid (14) and the gentirigeosides A, B, and E (15-17), were isolated from Gentianella azurea. Their structures were elucidated by detailed analysis of the NMR, MS, and X-ray crystallographic data. This is the first report of dammarane-type triterpenoids in the Gentianella genus. In addition, the known structures of gentirigenic acid (14) and the gentirigeosides A, B, and E (15-17) were revised based on the X-ray diffraction analysis. Gentirigeoside A (15) was found to inhibit nitric oxide production in RAW 264.7 macrophages with an IC50 value of 6.6 ± 2.1 µM.

Caesalminaxins A-L, cassane diterpenoids from the seeds of Caesalpinia minax.

Fourteen new cassane diterpenoids, caesalminaxins A-L (1-14), and three known compounds were isolated from the seeds of Caesalpinia minax. Among the new diterpenoids, compounds 3 and 4 possess a rare spiro C/D ring system. The C-16 epimeric mixture 1/2 has an unprecedented carbon skeleton, presumably derived from 3 by cleavage of the C-13-C-14 bond. Compound 5 is the first example of a cassane diterpenoid with a spiro A/B ring system. The structures of the compounds were elucidated on the basis of 1D and 2D NMR analysis, and the absolute configurations of 3, 4, 9, and 11 were determined by single-crystal X-ray crystallography. Biosynthesis pathways for 1/2, 3, and 5 are postulated. Compounds 4, 8, and the known bonducellpin D exhibited moderate activity against four tested human cancer cell lines, HepG-2, K562, HeLa, and Du145.

Guanidine alkaloids from Plumbago zeylanica.

Eleven new guanidine alkaloids, plumbagines A-G (2-8) and plumbagosides A-D (9-12), as well as two known analogues (1, 13), were isolated from the aerial parts of Plumbago zeylanica. Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR, MS, IR, and CD methods. The absolute configuration of 1 was determined by single-crystal X-ray diffraction of its derivative (1a).