1.Research progress on carrier-free and carrier-supported supramolecular nanosystems of traditional Chinese medicine anti-tumor star molecules
Zi-ye ZANG ; Yao-zhi ZHANG ; Yi-hang ZHAO ; Xin-ru TAN ; Ji-chang WEI ; An-qi XU ; Hong-fei DUAN ; Hong-yan ZHANG ; Peng-long WANG ; Xue-mei HUANG ; Hai-min LEI
Acta Pharmaceutica Sinica 2024;59(4):908-917
Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.
3.Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury
Peng QI ; Meng-Jie HUANG ; Wei WU ; Xue-Wen REN ; Yong-Zhi ZHAI ; Chen QIU ; Hai-Yan ZHU
Chinese Journal of Traumatology 2024;27(2):97-106
Purpose::Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis.Methods::Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization.Results::Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. Conclusion::This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.
4.Research status of Wnt5a-Frizzled-2 pathway and ischemia-reperfusion injury
Zhi-Peng SUN ; Shu-Su DONG ; Chuan-Cheng MA ; Chen-Ying WANG ; Fei CHEN ; Hai-Ying WANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1972-1976
The Wnt signaling pathway includes both classical and non classical pathways,Wnt5a-Frizzled-2 pathway participates in the Wnt/Ca2+signaling pathway in the non-classical pathway,which is activated by the Wnt-related protein Wnt5a and its ligand Frizzled-2.It can regulate some key sites in cells to affect cell signal transduction,and is closely related to cell growth process.Activation of Wnt5a-Fizzled-2 pathway occurs in some tissues with abundant blood supply,such as heart and brain tissues,during ischemia-reperfusion.Activation of the Wnt5a-Frizzled-2 pathway causes these intracellular calcium overload,ultimately promoting apoptosis.This article reviews the abnormal activation of Wnt5a-Frizzled-2 signaling pathway in ischemia-reperfusion injury diseases and the induced calcium overload leading to apoptosis,in order to provide reference for the study of physiological mechanisms of ischemia-reperfusion injury.
5.Clinical trial of bevacizumab combined with TOMIRI chemotherapy in the treatment of patients with advanced colorectal cancer
Ye FENG ; Hai GUO ; Jun-Bin ZHAO ; Zhi-Xue LI ; Hai-Peng LIU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2170-2173
Objective To observe the clinical efficacy and safety of bevacizumab injection combined with raltitrexed injection and irinotecan injection(TOMIRI)in the treatment of patients with advanced colorectal cancer.Methods Patients with advanced colorectal cancer were divided into control group and treatment group according to the cohort method.The control group received 180 mg·m-2 irinotecan with intravenous infusion for 30 to 90 min on the first day+3 mg·m-2 raltitrexed with intravenous infusion for 15 min,once every three weeks.On the basis of control group,the treatment group was given 5 mg·kg-1 bevacizumab with intravenous infusion,once every three weeks.Two groups were treated for 4 cycles with 3 weeks per cycle.The clinical efficacy,lesion diameter,Karnofsky performance status(KPS),and adverse drug reactions were compared between two groups.Additionally,based on follow-up results,the progression-free survival(PFS)within 12 months was compared between the two groups.Results The treatment and control groups enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 83.02%(44 cases/53 cases)and 54.72%(29 cases/53 cases)with statistically significant difference(P<0.05).After treatment,the tumor diameters of treatment and control groups were(2.44±0.30)and(3.35±0.38)cm;the KPS scores were(78.01±0.79)and(70.69±0.72)points;the PFS was(11.26±1.43)and(8.01±0.97)months,there were statistically significant differences of above indexes between two groups(all P<0.05).The adverse drug reactions in the treatment group were anemia,abnormal liver and renal function,nausea and vomiting,and leukopenia,which in the control group were gastrointestinal reaction,nausea and vomiting,abnormal liver and kidney function,blood toxicity,anemia and skin rash.The total incidence of adverse drug reactions in treatment and control groups were 11.32%and 28.30%(P>0.05).Conclusion Bevacizumab injection combined with TOMIRI can helps to enhance the clinical efficacy of advanced colorectal cancer and improve patients'quality of life,improve patient quality of life,prolong PFS,and without increasing the incidence of adverse drug reactions.
6.Molecular epidemiological analysis of plague at the border area of Yunnan Province
Feng-Yi YANG ; Rong YANG ; Si-Ru LI ; Jin-Jiao KONG ; Hong-Li TAN ; Hai-Peng ZHANG ; Peng WANG ; You-Hong ZHONG ; Li-Yuan SHI ; Zhi-Zhong SONG
Chinese Journal of Zoonoses 2024;40(5):401-407
This study was aimed at exploring the epidemiological characteristics of plague,and the evolutionary relation-ships among the isolated plague strains in the Yunnan border area,to provide clues for further studying epidemic causes and ep-idemiological patterns.Plague epidemic data in the border area during the second epidemic period(1982-2007)were collected and analyzed with descriptive epidemiological methods.Whole genome sequences of 262 strains of Yersinia pestis in the border area were obtained for phylogenetic analysis.Plague outbreaks occurred in 17 counties(cities)among 25 border counties(cit-ies);a total of 552 epidemic foci and 123 human cases were identified.The 1.ORI2,1.ORI3,1.IN3,2.ANT and 2.MED geno-types were identified among Yersinia pestis isolated from the Yunnan border area,among which the 1.ORI2 population was dominant.A total of 258 strains of Yersinia pestis from the 1.OR12 population belonged to four subclusters.The Myanmar and Vietnam clade was embedded within the Yunnan clade in the overall phylogeny.The above results indicated that during the sec-ond period of the epidemic,the intensity of plague epidemics in Yunnan's border areas was high,showing a trend of devel-opment from west to south and east.Our findings indicated a risk of cross-border transmission of plague between Yunnan and neighboring countries;therefore,the surveillance,pre-vention,and control of plague in border areas should be strengthened.
7.The first female case of human monkeypox in Yunnan Province
Yang ZHOU ; De-Li QI ; Zheng-Ji CHEN ; Zhi-Peng MAO ; Min DAI ; Yu-Dong GAO ; Si-Yi LUO ; Shao-Hua PAN ; Hong-Hai SU
Chinese Journal of Zoonoses 2024;40(6):599-603
This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.
8.Analysis of influencing factors of multi-site musculoskeletal disorders among workers in the chemical pharmaceutical industry
Zhiheng PENG ; Hai ZHANG ; Yinan HE ; Yuchao FENG ; Bo LUO ; Jinlan HUANG ; Yimin LIU ; Zhongxu WANG ; Ning JIA ; Zhi WANG
China Occupational Medicine 2023;50(6):601-606
{L-End}Objective To analyze the prevalence of multi-site work-related musculoskeletal disorders (WMSDs) and their influencing factors among workers in the chemical pharmaceutical industry. {L-End}Methods A total of 563 workers from three chemical pharmaceutical factories in Guangzhou City were selected as the research subjects using the judgment sampling method. The prevalence of multi-site WMSDs in the past 12 months was investigated using the electronic questionnaire of Chinese Version of Musculoskeletal Disorders Questionnaire. {L-End}Results The prevalence of multi-site WMSDs in the research subjects was 30.0% (169/563). The results of multivariable logistic regression analysis showed that workers who smoked regularly/frequently and those who had their hands above shoulder level for long periods of time had a lower risk of multi-site WMSDs than those who never/occasionally smoked (all P≤0.05). Workers with a high school, secondary specialty, college degree, or above had a lower risk of multi-site WMSDs than those with a middle school education or below (all P<0.05). The longer the daily working hours, the higher the risk of multiple WMSDs (all P<0.05). Workers with regular/frequently work shifts had a lower risk of multi-site WMSDs than those with none/occasional work shifts (P<0.05). {L-End}Conclusion The prevalence of multi-site WMSDs among workers in the chemical pharmaceutical industry is relatively high. The influencing factors are individual factors, unreasonable work organization and poor ergonomics factors.
9. Mechanism of ophiopogonin D in treatment of pulmonary fibrosis based on network pharmacology and experimental verification
Wen-Pan PENG ; Yun-Hai ZHOU ; Juan -Man WU ; Gui-Qing PENG ; Yan-Lan GU ; Song YU ; Ming-Zhi PU ; Yong XU
Chinese Pharmacological Bulletin 2023;39(8):1557-1565
Aim To predict the potential mechanism of ophiopogonin D (OPD) against pulmonary fibrosis by network pharmacology, and further verify it by experiment in vivo. Methods This study found that ophiopogon was the most frequently used drug in the treatment of pulmonary fibrosis with deficiency of Qi and Yin through data mining. In order to explore its material basis, network pharmacology analysis was carried out. A model of pulmonary fibrosis was established by bleomycin, and different concentrations of ophiopogonin D were administered to verify the results of the pharmacological network. Results Firstly, through network pharmacology analysis, it was found that mitophagy might be the potential target for ophiopogon to exert anti-pulmonary fibrosis effect. Meanwhile, network topology analysis showed that OPD had the greatest relationship with mitophagy. Animal experiments showed that OPD could relieve pulmonary fibrosis and reduce collagen deposition in mice. At the same time, the detection of mitophagy related proteins showed that the compound could increase the expression of PINK1 and Parkin proteins, reduce the content of P62 protein in lung tissue, and reduce the intracellular ROS level. Conclusions OPD can improve mitochondrial function and play an anti-pulmonary fibrosis role by promoting PINKl/Parkin dependent mitophagy in lung tissue.
10.Construction of iPSC-derived Inhibitory Neural Network Tissue with Synaptic Transmission Potentials
Li-zhi PENG ; Qing-shuai WEI ; Yuan-huan MA ; Jin-hai XU ; Bin JIANG ; Yuan-shan ZENG ; Xiang ZENG ; Ying DING
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):18-25
ObjectiveDirected differentiation of human induced pluripotent stem cells (hiPSCs) into spinal cord γ-aminobutyric acid (GABA)-ergic progenitor cells were implanted into an decellularized optical nerve (DON) bioscaffold to construct a hiPSC-derived inhibitory neural network tissue with synaptic activities. This study aimed to provide a novel stem cell-based tissue engineering product for the study and the repair of central nervous system injury. MethodsThe combination of stepwise directional induction and tissue engineering technology was applied in this study. After hiPSCs were directionally induced into human neural progenitor cells (hNPCs) in vitro, they were seeded into a DON for three-dimensional culture, allowing further differentiation into inhibitory GABAergic neurons under the specific neuronal induction environment. Transmission electron microscopy and whole cell patch clamp technique were used to detect whether the hiPSCs differentiated neurons could form synapse-like structures and whether these neurons had spontaneous inhibitory postsynaptic currents, respectively, in order to validate that the hiPSC-derived neurons would form neural networks with synaptic transmission potentials from a structural and functional perspective. ResultsThe inhibitory neurons of GABAergic phenotype were successfully induced from hiPSCs in vitro, and maintained good viability after 28 days of culture. With the transmission electron microscopy, it was observed that many cell junctions were formed between hiPSC-derived neural cells in the three-dimensional materials, some of which presented a synapse- like structure, manifested as the slight thickness of cell membrane and a small number of vesicles within one side of the cell junctions, the typical structure of a presynatic component, and focal thickness of the membrane of the other side of the cell junctions, a typical structure of a postsynaptic component. According to whole-cell patch-clamp recording, the hiPSC-derived neurons had the capability to generate action potentials and spontaneous inhibitory postsynaptic currents were recorded in this biotissue. ConclusionsThe results of this study indicated that hiPSCs can be induced to differentiate into GABAergic progenitor cells in vitro and can successfully construct iPSC-derived inhibitory neural network tissue with synaptic transmission after implanted into a DON for three-dimensional culture. This study would provide a novel neural network tissue for future research and treatment of central nervous system injury by stem cell tissue engineering technology.

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