Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

Comparison between tension band and cerclage with X-Plate and lag screws in treatment of comminuted patellar fractures

BackgroundComminuted patellar fractures are not rare, and the ideal treatment method remains controversial. The present study was conducted to evaluate effects and compare complications of two different methods used to treat comminuted patellar fractures.MethodsFrom March 2010 to August 2016, 102 cases of 34-C2 or 34-C3 comminuted patellar fractures were treated at our hospital, wherein patients received two different treatments: titanium cable tension band with cerclage method (group A) and intrafragmentary screws with X-shaped plating technique (group B). At follow-ups, articular step-off, range of motion (ROM), Lysholm scores, time of union, and complications were recorded and analyzed. Radiographic and clinical data as well as rate of complications were statistically analyzed.ResultsIn total, 87 patients were included in the final analysis (n = 47 in group A and n = 40 in group B). No significant differences were noted in terms of cost of implant, age, gender, rate of 34-C3 fractures, rate of layered inferior pole fractures, postoperative articular step-off and union time. At 2-year follow-up, average Lysholm scores, ROM and rate of complications were (89.0 ± 4.5), (122°±12°) and (27.7%) in group A and (90.2 ± 3.9), (124°±11°) and (17.5%) in group B, respectively, with no significant differences (p > 0.05). The mean time of surgery in group B was shorter than that in group A with significant difference (p < 0.05).ConclusionsTreatment using the intrafragmentary screws and plate method for amenable comminuted patellar fractures achieved similar complication rate and favorable functional outcomes at the 2-year follow-up, which was comparable to the titanium cable tension band with cerclage method. Thus, the intrafragmentary screws and plate method is effective, safe and convenient for 34-C2/C3 comminuted patellar fractures, especially appropriate for patients with layered fragments.     

Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

The Transmission of Trauma from Mother to Infant: Radioactive Residues and Counter-Transference in the Case of a Haitian Mother and Her Two-Year-Old Son*

ABSTRACT

Close observation of the interactions between a traumatised mother and her infant son provides information on the modes of transmission of psychic trauma in the mother–infant dyad. Following the presentation of a current literature review on the theme, the subject of “radioactive residue” and counter-transference in the transmission of psychic trauma from mother to infant will be illustrated through a clinical case study that focuses on a Haitian mother and her two-year-old infant son who has been referred to a “transitional care nursery” in urban Paris. The encounter with this mother–infant dyad is analysed through observing the quality of the interactions that take place between the mother and infant in order to determine how a particularly traumatic narrative impacts the mother–infant relationship, in addition to relations with the clinician. Mother and infant respond to one another through the emission and reception of “radioactive residues” as hypothesized by Gampel. This clinical case study shows that there is a need to consider transcultural factors and collective experience and history when analysing traumatic events. Additionally, the case study shows that counter-transference can be an effective clinical tool for gaining access to an infant's experience as the recipient of a traumatic narrative.