ABSTRACT
Malignant tumors， with the increasing crude morbidity and mortality year by year， have become the major diseases threatening human health. The conventional therapeutic drugs against tumors have serious adverse reactions， which can cause a heavy burden on patients. The active components of Chinese medicine can effectively inhibit tumor growth， improve the quality of life of patients， and have few toxic and side effects. Alkaloids of Chinese medicine are natural organic compounds widely existing in a variety of Chinese herbal medicines. In recent years， they have attracted more and more attention because of their anti-tumor effect. The anti-tumor mechanisms of alkaloids of Chinese medicine mainly include the induction of apoptosis， inhibition of tumor cell migration and invasion， suppression of proliferation， induction of autophagy of tumor cells， cell cycle arrest， inhibition of tumor angiogenesis， regulation of microRNA， and modulation of immunity. In addition， Chinese medicine alkaloids can also reverse tumor drug resistance and reduce the stemness of tumor stem cells. Alkaloids of Chinese medicine can regulate the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， c-Jun N-terminal kinase （JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， mammalian target of rapamycin （mTOR）， Notch， Hedgehog， Wnt/β-catenin， and other signaling pathways to participate in the processes of tumor proliferation， invasion and metastasis， autophagy and apoptosis， and affect the occurrence and development of tumors in multiple links and ways. The derivatives and nano-preparations of alkaloids can improve the solubility， utilization， and anti-tumor activity of alkaloids， bringing a broader prospect for the clinical application of alkaloids. This review summarized the recent anti-tumor research on alkaloids， their representative derivatives， and nano-preparations to provide references for the in-depth research on the anti-tumor effect of alkaloids.
ABSTRACT
Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
Subject(s)
Animals , Rats , Aconitine/pharmacology , Analgesics/pharmacology , Pharmaceutical Preparations , Rats, Sprague-DawleyABSTRACT
Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
ABSTRACT
Purpose@#Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role of LETM1 in GC. This study aims to investigate the effects of LETM1 on proliferation, migration, and invasion of GC cells. @*Materials and Methods@#The expression levels of LETM1 in the normal gastric mucosal epithelial cells (GES-1) and GC cells were analyzed by quantitative real-time polymerase chain reaction and western blotting. CCK-8, wound healing, and Transwell invasion assays were performed to evaluate the effect of LETM1 knockdown or overexpression on the proliferation, migration, and invasion of the GC cells, respectively. Additionally, the effect of LETM1 knockdown or overexpression on GC cell apoptosis was determined by flow cytometry. Furthermore, the effect of LETM1 knockdown or overexpression on the expression levels of PI3K/Akt signaling pathway-related proteins was evaluated by western blotting. @*Results@#The GC cells exhibited markedly higher mRNA and protein expression levels of LETM1 than the GES-1 cells. Additionally, the knockdown of LETM1 remarkably suppressed the GC cell proliferation, migration, and invasion, and promoted the apoptosis of GC cells, which were reversed upon LETM1 overexpression. Furthermore, the western blotting analysis indicated that LETM1 facilitates GC progression via the PI3K/Akt signaling pathway. @*Conclusions@#LETM1 acts as an oncogenic gene to promote GC cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. Therefore, LETM1 may be a potential target for GC diagnosis and treatment.
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Objective To estimate the status of understanding hierarchical medical mode in chronic disease management among medical staff and residents in Xiamen .Methods The multi-stage sampling was used in the study to select 49 physicians from the tertiary hospitals , 58 general practitioners ( GPs ) and health managers from 5 community health services centers , and 499 residents from 5 communities in Xiamen.We conducted a face-to-face survey to estimate their basic information , recognition for hierarchical medical mode , and patients'willingness for community first contact care .The data was described by mean value of frequency and constituent ratio , the chi-square test or Fisher's exact test was used for comparison among groups .Logistic regression was performed to analyze the factors influencing the residents 'preference for treatment in community medical institutions . Results The physicians from tertiary hospitals or community health service centers were almost all familiar with Xiamen mode (91/107, 85%), and more than half of them knew about the hierarchical medical system (67/107, 62.6%), 86.9% (93/107) of them knew about the guide of hierarchical medical system , 58.9%(63/107) of them received the relative training before .The physicians from community had higher knowledge , more frequency training , more referral experiences and more effective evaluation than the physicians from hospitals (all P<0.05).In our study, 86.2%(344/399) of residents were willing to see doctors in community health centers and 77.9%(311/399) of them were willing to return to community health service centers from tertiary hospitals for disease convalescence or chronic disease management;53.6% (214/399) of residents preferred to utilize community first contact care when they got chronic diseases , and they were more satisfied with the consultation and diagnosis process in community .The residents who knew about the hierarchical medical system were more likely to utilize community first contact care and return to community for medical care . However, the female or the higher-income residents were less likely to see doctors in community .Patients who had experienced transfer to community or had higher satisfaction to community care were more willing to return from hospitals to community for disease convalescence .The mode showed that the system was more effective in measuring and controlling blood pressure or blood glucose for patients who joined the patients 'network than for those did not join.(P<0.05).Conclusion Medical staff are familiar with hierarchical medical system , and the residents are likely to use community health service as their first contact care in Xiamen.The utilization of community first contact care is influenced by sex , family income, previous experience, knowledge of the system , and satisfaction to the system of patients .
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Objective To investigate the influencing factors for knowledge,attitude and practice(KAP)of the Three-manager mode about hierarchical medical system of Chronic diseases of the community residents in Xiamen,and provide references for the implementation of hierarchical medical system.Methods Multi-stage random sampling method was adopted,and 400 residents were randomly sampled from 5 communities of Xiamen for questionnaire survey.The survey features the dependent variable of the community residents′ knowing and joining-in the Three-manager mode,the internal factors(social demographic characteristics),and the external factors(medical expenditure and healthcare insurance).On such basis,four logistic regression models were built for analysis of such influencing factors.Results 41.10% of the surveyed were aware of the Three-manager mode,and 39.71% of the hypertension/diabetes patients among them joined in the hypertension network or diabetes network.Age,education,medical expenditure and referral experiences were significant influencing factors for KAP level of the Three-manager mode,while the residents of older age,higher education and referral experiences were high in their KAP;those of lower per capita monthly income,hypertension or diabetes,with coverage of medical insurance and satisfied with medical consultation in community were high in their awareness of Three-manager mode.Conclusions The KAP level of Three-manager mode of the community residents in Xiamen is acceptable,yet expected of further improvement.Room of further improvement includes enhancement of synergy of the Three-manager mode,enhanced motivation of government financial support and medical insurance,better service functions of community institutions,and especially the construction of hierarchical medical system.
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Objective To examine the utilization and cost of inpatient care and their influencing factors among the eld-erly in China from the view of social-ecology and to estimate the conditional and the unconditional cost,so as to provide refer-ence for allocating health resource efficiently among the elderly. Methods We build a social-ecological model( SEM) of the in-patient services utilization to estimate personal,familial and community circumstance factors of inpatient service utilizing a two-part model. Using joint modeling of likelihood and cost of inpatient care to estimate the parameter and predict the conditional and unconditional cost of inpatient. Data were extracted from Chinese longitudinal healthy longevity survey ( CLHLS) in 2011 on 8483 men more than 60 years old. Results The average cost of the elderly,24. 6% of whom actually utilize the services,is￥8082. 8. There are many reasons account for the utilization of inpatient care. In micro system,it was found that the elderly with chronic condition,having bad self-reported health and worse sleep quality have higher proportion of utilization and more cost of inpatient services. In mezzo system,the married men are more likely use inpatient services and spend more money curing disease than other groups. In macro system,the man who reside in the city or own more than one kind of social security have higher pro-portion and cost of inpatient care utilization. The predicted conditional and unconditional cost of inpatient service is ￥8397. 32,￥2478. 92,respectively. The male are higher than the female,theurban are higher than others. The elderly from 80 to 89 years old have the most expense in conditional predicted cost and 70~79 years old have most expense in unconditional predicted cost. Conclusion Social-ecological factors influence the behaviors of inpatient care utilization. Having chronic disease,self-reported health,sleep quality,marital status,residence and social security levels from different aspects are the primary factors which influ-ence proportion and expenditure of inpatient service utilization. The elderly with different characteristics have different conditional costs and unconditional costs,we should allocate health resources efficiently to promote the equity in health care utilization.
ABSTRACT
Objective To examine the utilization and cost of inpatient care and their influencing factors among the eld-erly in China from the view of social-ecology and to estimate the conditional and the unconditional cost,so as to provide refer-ence for allocating health resource efficiently among the elderly. Methods We build a social-ecological model( SEM) of the in-patient services utilization to estimate personal,familial and community circumstance factors of inpatient service utilizing a two-part model. Using joint modeling of likelihood and cost of inpatient care to estimate the parameter and predict the conditional and unconditional cost of inpatient. Data were extracted from Chinese longitudinal healthy longevity survey ( CLHLS) in 2011 on 8483 men more than 60 years old. Results The average cost of the elderly,24. 6% of whom actually utilize the services,is￥8082. 8. There are many reasons account for the utilization of inpatient care. In micro system,it was found that the elderly with chronic condition,having bad self-reported health and worse sleep quality have higher proportion of utilization and more cost of inpatient services. In mezzo system,the married men are more likely use inpatient services and spend more money curing disease than other groups. In macro system,the man who reside in the city or own more than one kind of social security have higher pro-portion and cost of inpatient care utilization. The predicted conditional and unconditional cost of inpatient service is ￥8397. 32,￥2478. 92,respectively. The male are higher than the female,theurban are higher than others. The elderly from 80 to 89 years old have the most expense in conditional predicted cost and 70~79 years old have most expense in unconditional predicted cost. Conclusion Social-ecological factors influence the behaviors of inpatient care utilization. Having chronic disease,self-reported health,sleep quality,marital status,residence and social security levels from different aspects are the primary factors which influ-ence proportion and expenditure of inpatient service utilization. The elderly with different characteristics have different conditional costs and unconditional costs,we should allocate health resources efficiently to promote the equity in health care utilization.