Strategy and challenge of innovative drug research and development from clinically effective ingredients of traditional Chinese medicine / 中国中药杂志

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.

A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models / 国际口腔科学杂志·英文版

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.

Stapled anoplin peptide combined with photothermal therapy enhances oncolytic immunotherapy of triple-negative breast cancer / 中国中药杂志

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.

Prevalence of diabetes mellitus among Uygur children in Hotan Prefecture of Xinjiang, China / 中国当代儿科杂志

OBJECTIVES@#To investigate the prevalence of diabetes mellitus (DM) among Uygur children in Hotan Prefecture of Xinjiang, China, as well as the factors influencing the development of DM.@*METHODS@#The cluster random sampling method was used to select 5 308 children, aged 4-18 years, from the middle and primary schools and kindergartens in Hotan Prefecture of Xinjiang. The survey methods included questionnaire survey and the measurement of height and weight. All subjects were tested for fasting fingertip blood glucose to investigate the prevalence of DM and impaired fasting glucose (IFG).@*RESULTS@#A total of 5 184 valid questionnaires were collected. Fourteen children (0.27%) were found to have DM, among whom 8 had type 1 DM, 2 had type 2 DM, and 4 had unclassified DM. Twenty-nine children (0.56%) were found to have IFG. There was no significant difference in the prevalence rate of DM and IFG between boys and girls (P>0.05). The prevalence rate of DM was 0.18% in the 4-<10 years group, 0.47% in the 10-<15 years group, and 0.07% in the 15-18 years group (P=0.072).The prevalence rate of IFG in the above three age groups was 0.18%, 0.94%, and 0.42%, respectively, with a significant difference among groups (P=0.007). The proportion of family history of DM and the proportion of overweight/obesity in children with DM were significantly higher than those in children without DM (P<0.05), while the proportion of children with DM who preferred coarse grains was significantly lower than that in children without DM (P<0.05).@*CONCLUSIONS@#The prevalence of DM and IFG in Uyghur children in Hotan Prefecture of Xinjiang is relatively low. There is no significant difference in the prevalence of DM among children of different genders or age groups, but the prevalence of IFG in children of different age groups is different. A family history of DM, overweight or obesity, and low intake of coarse grains might be associated with the development of DM.

Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction

@#Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.

Combating COVID-19 with integrated traditional Chinese and Western medicine in China

COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved rapid containment of this highly infectious disease following the principles of early detection, early quarantine and early treatment with integrated traditional Chinese and Western medicine. The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence. Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The three Chinese patent medicines (/ (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), (Honeysuckle Flower Cold-Relieving Granules) and (Stasis-Resolving & Toxin-Removing) were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication. The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.

Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians / 中华医学杂志(英文版)

BACKGROUND@#Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy.@*METHODS@#A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis.@*RESULTS@#The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001).@*CONCLUSIONS@#The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.

Influence of two different crosslinkers on physiochemical properties and bioactivity of a composite bone scaffold composed of beta-tricalcium phosphate and gelatin / 中国组织工程研究

BACKGROUND:The physiochemical properties and bioactivity of composite scaffolds can be altered by different crosslinkers.OBJECTIVE:To compare the physiochemical properties and bioactivity of composite scaffolds composed of β-tricalcium phosphate and gelatin,which are crosslinked by 1％ genipin or gluteraldehyde,respectively.METHODS:Porous scaffolds composed of β-tricalcium phosphate and gelatin were made by phase separation/freeze-drying technique.Crosslinking time was 72 hours when genipin acted as a crosslinker and 24 hours when glutaraldehyde as a crosslinker.Physiochemical properties including porosity,degree of cross-linking,in vitro swelling ratio,degradation rate and compressive strength were detected.Bioactivities analyses were performed through co-culturing rabbit periosteal osteoblasts with 25％,50％ and 100％ scaffold extracts for 24,48,72 hours.The proliferation rate and cytotoxicity gradation were evaluated.In addition,bilateral 8-mm skull defects were made in 18 rabbits and repaired with scaffolds crosslinked by genipin or gluteraldehyde,respectively.Gross observation,X-ray analysis and histological observation were performed at 4,8 and 12 postoperative weeks.RESULTS AND CONCLUSION:(1) The porosity,compressive strength and maximum compressive force showed no statistical difference between the two crosslinker groups.Compared with the gluteraldehyde group,higher degree of crosslinking and lower swelling ratio and degradation rate were observed in the genipin group (P ＜ 0.05).(2) In the genipin group,less than 50％ growth inhibition was observed when co-cultured with 100％ scaffold extract for 24 hours.Thus,the cytotoxicity was graded as 2,and the remains were graded as 1 or 0.In the gluteraldehyde group,excessive 50％ growth inhibition was observed when co-cultured with 100％ scaffold extract for 24 hours,and the cytotoxicity was graded as 3.For 25％ and 50％ subgroups (culture for 24 hours) and 100％ subgroup (culture for 48 hours),the cytotoxicity was graded as 2,and the remains were graded as 1.(3) X-ray and histological observation showed the in-growth of new bone tissues from the periphery of the defect and the scaffold degraded centripetally.New bone formation was better in the genipin group than the gluteraldehyde group at 8 and 12 postoperative weeks (P ＜ 0.05).To conclude,both genipin and gluteraldehyde can be used as crosslinkers to prepare the composite bone scaffold composed of β-tricalcium phosphate and gelatin.Two scaffolds have similar physicochemical properties;however,the former has a superior bioactivity except for a longer time for crosslinking with genipin.

Ischemic preconditioning induces chaperone hsp70 expression and inhibits protein aggregation in the CA1 neurons of rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism.</p><p><b>METHODS</b>Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10-min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions.</p><p><b>RESULTS</b>Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region (P < 0.01 vs 10-min ischemia group). Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates (P < 0.01 vs 10-min ischemia group).</p><p><b>CONCLUSION</b>Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.</p>

Phenethyl alcohol glycosides in Epimeredi indica / 中草药

Object To study the chemical constituents from Epimeredi indica and search for the natu-ral compounds with bioactivities. Methods Three compounds were isolated by a combination of RP-18and silica gel column chromatographies, and their structures were identified by spectral methods. ResultsA novel 2- (3-methoxy-4-hydroxy) phenyl-ethanol 1-O-a-L- [(1→3 )-rhamnopyranosyl- 6-feruloyl] gluco-side ( I ) along with known 2-(3, 4-dihydroxy) phenyl ethanol 1-O-?-L-[(1→3)-rhamnopyranoside-4-O-caffeoyl-] glucoside (verbascoside) ( Ⅱ ), and 2-(3, 4-dihydroxy) phenyl ethanol (1→1) (2→2)-[(1→3)-rhamnopyranoside-4-O-caffeoyl glucoside (oraposide) (Ⅲ) were isolated from E. indica. ConclusionCompound I is a new compound named as epimeredinoside A and compounds Ⅱ and Ⅲ are isolated fromthis plant for the first time.

Correlation between release rate in vitro and adsorption in vivo of Shenshen sustained-release Capsule / 中成药

AIM: To study the correlation between the release rate in vitro and the absorption in vivo of Shenshen sustained-release Capsule(SSRC phenylethanoid glycosides). METHODS: Release rate of SSRC in vitro was tested with D-800LS dissolution tester. 8 rats were randomly divided into two groups. One group was orally fed on SSRC. Plasma levels were determined by UV and the absorption fraction was calculated according to Wagner-Nelson's formula. RESULTS: The correlation coefficient between the release rate in vitro and the absorption fraction in vivo was 0.9654 . CONCLUSION: There is a significant correlation between release rate in vitro and absorption in vivo to SSRC.