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.

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.

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.

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.

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).

[Effects of puerarin on the vascular active factor related to cerebral vasospasm after aneurysm subarachnoid hemorrhage].

OBJECTIVE: To investigate the effects and possible mechanisms of puerarin on the vascular active factors correlated to cerebral vasospasm (CVS) after aneurysm subarachnoid hemorrhage (aSAH). METHODS: Fifty-four patients with aSAH were randomly assigned to the puerarin group (30 cases) and the control group (24 cases) by lot. On the basis of routine treatment, the patients in the puerarin group were intravenously dripped with 0.5 g puerarin by adding in 250 mL glucose injection once daily. The injection was given starting from the 3rd day of the disease course, for 14 successive days. The plasma levels of nitric oxide (NO), endothelin-1 (ET-1), thromboxane B, (TXB2), 6-Keto-prostaglandin F1alpha (6-K-PGF1alpha) were compared between the two groups pre- and post-therapy. The incidence of cerebral vasospasm (CVS) was observed using transcranial Doppler (TCD). The Glasgow outcome scale (GOS) were compared at discharge between the two groups. RESULTS: Compared with the control group, the plasma levels of NO, ET-1, and 6-K-PGF1alpha increased in the puerarin group (P < 0. 05), the TXB2 level decreased (P < 0.05), the incidence of CVS decreased (P < 0.05), the mean MCA velocity increased (P < 0.05), and the GOS at discharge increased (P < 0.05). CONCLUSIONS: Puerarin is an effective agent for the prophylaxis and treatment of the CVS in patients after aSAH. Moreover, it can improve the prognosis. The mechanism might be correlated with improving the levels of the vascular active factors, i.e., increasing the plasma levels of NO and PGl2, decreasing TXA, in plasma, increasing the cerebral blood flow, and improving cerebral perfusion.

Ghrelin suppression and fat loss after left gastric artery embolization in canine model.

PURPOSE: To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. METHODS: The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A(5) hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8 weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at week 8 for evaluation of abdominal fat. RESULTS: In LGAE-treated animals, plasma ghrelin and body weight significantly decreased compared to control animals (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000, respectively). Subcutaneous fat size was also significantly reduced (P = 0.011 and P = 0.027 for groups A and B, respectively). The decreasing percentage in ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were negatively correlated with the size of area supplied by left gastric artery (r = -0.693, P = 0.026). CONCLUSION: LGAE could suppress the plasma concentration of ghrelin, which results in subcutaneous fat size reduction and weight loss. Compensatory ghrelin production might occur in the remnant gastric fundus after LGAE.

Postoperative low pelvic radiotherapy and chemotherapy for stage II and III rectal cancer.

OBJECTIVES: To evaluate whether postoperative low pelvic radiotherapy (RT) combined with chemotherapy is an appropriate treatment for stage II and III rectal cancer. METHODS: Between November 1997 and May 2006, 104 patients with stage II and III rectal cancer underwent surgery as the primary treatment followed by postoperative RT combined with chemotherapy in our institute and were reviewed retrospectively. Sixty-nine patients received low pelvic RT only (upper margin at 1 cm above the low end of the sacroiliac joint; median dose 54 Gy) (low pelvic RT group) and the other 35 patients received whole pelvic RT (upper margin at the mid L5; median dose 43.2 Gy) and subsequently received a boost to the low pelvis (total median dose 54 Gy) (whole pelvic RT group). RESULTS: The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 72% versus 63%, 86% versus 84%, and 66% versus 62% for low pelvic versus whole pelvic RT group. There were no statistical differences in these 2 groups. Two patients (2.9%) of the low pelvic RT group and 2 patients (5.7%) of the whole pelvic RT group developed upper pelvis relapse, which was out of the low pelvic field. The incidence of Grade 3 to 5 small bowel late complications of the low pelvic RT group was significantly less than that of the whole pelvic RT group (4.3% vs. 20%) (P=0.029). CONCLUSIONS: Low pelvic RT significantly reduces small bowel late complications and does not compromise the overall survival rate, local control rate, and distant metastasis-free rate.