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".     

The effect of drugs on implant osseointegration- A narrative review

ObjectiveThis narrative review aims to investigate the effects of drugs on implant osseointegration, analyzing their potential positive or negative impact on the direct structural and functional connection between bone and load-carrying implants.BackgroundThe review seeks to provide a comprehensive understanding of osseointegration, which refers to the successful integration of an implant with living bone, resulting in no progressive relative movement between them. Exploring the effects of drugs on implant osseointegration is crucial for optimizing outcomes and enhancing patient care in orthopedic implant procedures.MethodsRelevant studies on the effects of drugs on implant osseointegration were identified through a literature search. Electronic databases, including PubMed, Embase, and Google Scholar, were utilized, employing appropriate keywords and MeSH terms related to osseointegration, implants, and drug interventions. The search was limited to English studies.DiscussionThis overview presents a detailed analysis of the effects of drugs on implant osseointegration. It explores drugs such as bisphosphonates, teriparatide, statins, angiotensin-converting enzyme inhibitors, beta-blockers, nitrites, and thiazide diuretics as promoters of osseointegration. Conversely, loop diuretics, non-steroidal anti-inflammatory drugs, corticosteroids, cyclosporine A, cisplatin, methotrexate, antibiotics, proton pump inhibitors (PPIs), antiepileptics, selective serotonin reuptake inhibitors (SSRIs), and anticoagulants are discussed as inhibitors of the process. The role of vitamin D3 remains uncertain. The complex relationship between drugs and the biology of implant osseointegration is emphasized, underscoring the need for further in vitro and in vivo studies to validate their effectsConclusionThis narrative review contributes to the literature by providing an overview of the effects of drugs on implant osseointegration. It highlights the complexity of the subject and emphasizes the necessity for more extensive and sophisticated studies in the future. Based on the synthesis of the reviewed literature, certain drugs, such as bisphosphonates and teriparatide, show potential for promoting implant osseointegration, while others, including loop diuretics and certain antibiotics, may impede the process. However, additional research is required to solidify these conclusions and effectively inform clinical practice.     

Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Computer-aided diagnosis tool for cervical cancer screening with weakly supervised localization and detection of abnormalities using adaptable and explainable classifier

While pap test is the most common diagnosis methods for cervical cancer, their results are highly dependent on the ability of the cytotechnicians to detect abnormal cells on the smears using brightfield microscopy. In this paper, we propose an explainable region classifier in whole slide images that could be used by cyto-pathologists to handle efficiently these big images (100,000x100,000 pixels). We create a dataset that simulates pap smears regions and uses a loss, we call classification under regression constraint, to train an efficient region classifier (about 66.8% accuracy on severity classification, 95.2% accuracy on normal/abnormal classification and 0.870 KAPPA score). We explain how we benefit from this loss to obtain a model focused on sensitivity and, then, we show that it can be used to perform weakly supervised localization (accuracy of 80.4%) of the cell that is mostly responsible for the malignancy of regions of whole slide images. We extend our method to perform a more general detection of abnormal cells (66.1% accuracy) and ensure that at least one abnormal cell will be detected if malignancy is present. Finally, we experiment our solution on a small real clinical slide dataset, highlighting the relevance of our proposed solution, adapting it to be as easily integrated in a pathology laboratory workflow as possible, and extending it to make a slide-level prediction.     

A comparison of mobilization and mobilization with movement on pain and range of motion in people with lateral ankle sprain: A randomized clinical trial

BackgroundMaitland and Mulligan mobilization techniques are two manual therapy methods to increase the range of motion following immobility treatment. The present study was conducted to compare two therapeutic methods, namely mobilization and mobilization with movement (MWM), on the pain and range of motion in people with lateral ankle sprain.MethodsA total of 40 individuals with grade two lateral ankle sprain were randomly divided into two groups, including the Maitland's mobilization intervention group, and the Mulligan's mobilization intervention group. Both groups underwent treatment every other day for two consecutive weeks. The pain intensity was measured using the Visual Analogue Scale (VAS), and the ankle dorsiflexion movement range using the Weight Bearing Lunge Test (WBLT) before and one day after the intervention.ResultsThere were no significant differences between the two groups in terms of pain (P = 0.297) and range of motion (P = 0.294) before the intervention. Meanwhile, after the intervention, a significant change was observed in both groups in terms of these variables, which indicates the effectiveness of both interventions (P < 0.001) and the greater effect of the mobilization with movement in reducing pain (P = 0.037) and increasing the range of motion (P = 0.021).ConclusionsBoth techniques significantly improved the range of motion and reduced pain in people with lateral ankle sprain, but Mulligan's technique was significantly more effective among the two, perhaps due to joining active and passive mobilizing tensile forces as well as interaction of afferents and efferents in the reflex arc.