Value of cytotoxic T lymphocyte and natural killer cell levels in prognosis evaluation of patients with ST-elevation myocardial infarction / 中国基层医药

Objective:To analyze the value of cytotoxic T lymphocyte and natural killer cell levels in prognosis evaluation of patients with ST-elevation myocardial infarction (STEMI).Methods:A total of 158 patients with STEMI who underwent percutaneous coronary intervention in The Second People's Hospital of Liaocheng from September 2020 to August 2021 were included in this study. The ratio of cytotoxic T lymphocytes to natural killer cells was measured immediately after admission and 48 hours after surgery. These patients were followed up for 1 month after treatment. They were divided into the adverse cardiovascular event group (occurrence group) and no adverse cardiovascular event group (non-occurrence group) according to the occurrence of cardiovascular adverse events. The influential factors of the prognosis of STEMI and the correlation between the influential factors and STEMI were analyzed.Results:Among 158 patients with STEMI, 27 patients had adverse cardiovascular events, accounting for 17.09%. There were significant differences in systolic blood pressure, left ventricular ejection fraction, and low-density lipoprotein levels between the occurrence and non-occurrence groups ( t = 2.82, 4.27, 2.32, all P < 0.05). At 48 hours after surgery, the levels of cytotoxic T lymphocytes [(22.75 ± 8.39)%, (29.23 ± 4.61)%] and natural killer cells [(13.73 ± 4.64)%, (20.64 ± 4.52)%] in the peripheral blood in the occurrence and non-occurrence groups were significantly decreased compared with before surgery [ t = -5.05, -83.68, -142.71, -7 084.80, all P < 0.001]. Before and 48 hours after surgery, the levels of cytotoxic T lymphocytes [(27.47 ± 3.35)%, (22.75 ± 8.39)%] and natural killer cells [(21.42 ± 4.36)%, (13.73 ± 4.64)%] in the peripheral blood in the occurrence group were significantly lower than those in the non-occurrence group ( t = 7.68, 13.10, 4.16, 5.76, all P < 0.001). Univariate analysis showed that preoperative cytotoxic T lymphocytes < 27.47%, preoperative natural killer cells < 21.42%, left ventricular ejection fraction, and low-density lipoprotein may be the risk factors that affect the prognosis of patients with STEMI ( P < 0.000, 0.012, 0.019, 0.033). Cox regression analysis showed that preoperative cytotoxic T lymphocytes < 27.47% and preoperative natural killer cells < 21.42% were independent risk factors affecting the prognosis of patients with STEMI (both P < 0.001). Conclusion:Reduced levels of baseline cytotoxic T lymphocytes and natural killer cells in patients with STEMI suggest an increased risk of poor prognosis.

Guideline for the prevention and control of occupational exposure risks to cytotoxic drugs in medical institutions / 中国药房

To provide prevention and control strategies of occupational exposure risks to cytotoxic drug in medical institutions， improve the awareness of protection among medical staff，and reduce potential occupational exposure risks，the Guidelines for the Prevention and Control of Occupational Exposure Risk to Cytotoxic Drugs in Medical Institutions is developed. Based on the World Health Organization Guidelines Development Manual，the exposure risk issues of the cytotoxic drug collected from the time that it entered the hospital to the several stages after delivery to hospital，such as transportation，receipt，storage，unpacking，dispensing，use of finished products，and waste disposal. Delphi method is used to construct identification of clinical issues，and evidence-based research method is used to develop relevant evidence. Quality evaluation is conducted by using the recommended GRADE method. The consensus is reached on the recommendation opinions and evidence levels through expert consensus method. By combining engineering controls，administrative controls and personal protective equipment at different levels，a graded control approach is established. A total of 37 clinical issues are identified，resulting in 36 recommendations. This guideline provides reference and supplementation for the formulation of cytotoxic drug prevention and control measures in medical institutions.

Seven drimane-type sesquiterpenoids from an earwig-associated Aspergillus sp / 中国天然药物

Drimane-type sesquiterpenoids are widely distributed in fungi. From the ethyl acetate extract of the earwig-derived Aspergillus sp. NF2396, seven new drimane-type sesquiterpenoids, named drimanenoids A-G (1-7), were isolated. Their structures were elucidated by diverse spectroscopic analysis including high-resolution ESI-MS, one- and two-dimensional NMR spectroscopy. Drimanenoids A-F (1-6) are new members of drimane-type sesquiterpenoid esterified with unsaturated fatty acid side chain at C-6. Drimanenoids C (3), D (4) and F (6) showed antibacterial activity against five types of bacteria with different inhibition diameters. Drimanenoid D (4) exhibited moderate cytotoxicity against human myelogenous leukemia cell line K562 with an IC50 value of 12.88 ± 0.11 μmol·L-1.

Predictive value of sCTLA-4 and RAD51C proteins for recurrence after interventional therapy for cervical cancer patients / 中华内分泌外科杂志

Objective:To analyze the predictive value of soluble cytotoxic T lymphocyte-associated antigen 4 (sCTLA-4) and RAD51 paralogous gene C (RAD51C) protein in the recurrence of cervical cancer patients after interventional therapy.Methods:A total of 107 patients with cervical cancer who underwent interventional surgery in our hospital from May. 2015 to Apr. 2019 were selected as the research group. postoperative recurrence were recorded. Another 107 patients with benign cervical disease during the same period were selected as the control group. The protein expressions of sCTLA-4 and RAD51C were compared between the two groups and patients with or without recurrence. Logistic regression was used to analyze the influencing factors of postoperative recurrence of cervical cancer patients, and a nomogram model of postoperative recurrence of cervical cancer patients was constructed and verified by calibration curve. The postoperative recurrence rate of cervical cancer patients with different sCTLA-4 and RAD51C protein expressions was compared.Results:The level of sCTLA-4 and the high expression rate of RAD51C protein in the study group were higher than those in the control group ( P<0.05). High-risk human papillomavirus positive, vascular infiltration, interstitial infiltration ≥1/2, paracterine infiltration, high expression of RAD51C protein and high SCTLA-4 level were independent risk factors for postoperative recurrence of cervical cancer ( P<0.05). High-risk human papillomavirus, vascular invasion, interstitial invasion, parametrial invasion, RAD51C protein and sCTLA-4 levels were used to construct a nomogram prediction model for postoperative recurrence of cervical cancer patients. The consistency indices were 0.610 (95% CI: 0.511-0.702), 0.616 (95% CI: 0.517-0.708), 0.640 (95% CI: 0.541-0.730), 0.609 (95% CI: 0.510-0.702), 0.728 (95% CI ranged from 0.633 to 0.809), 0.817 (95% CI ranged from 0.731 to 0.885), and the calibration curve validation showed high consistency. The net benefit rate of combined detection of sCTLA-4 and RAD51C proteins was greater than that of single detection. Conclusions:sCTLA-4 and RAD51C proteins are highly expressed in cervical cancer patients, and the high expression of both indicates that cervical cancer patients have a higher risk of recurrence after surgery. Clinically, the detection of sCTLA-4 and RAD51C protein expression can be used to screen patients with high recurrence risk.

Review of advances in chemotherapy for thyroid cancer / 中华内分泌外科杂志

The incidence of thyroid cancer has continued to increase. Most thyroid cancer patients have good prognosis, but there are still some patients who will develop into the middle or late stage. The status of cytotoxic treatment in thyroid cancer treatment is controversial. Chemotherapy, as a classical malignant tumor treatment, has its unique significance for the special type and the special period of thyroid cancer. Chemotherapy can be an option for systemic treatment if no other treatment is available for patients of differentiated thyroid carcinoma refractory to radiodine in rapid progression and life-threatening period. For patients of anaplastic thyroid cancer in progression period, chemotherapy can be selected if there are no other treatments in clinical trials. And "Chemical therapy plus" treatment model might play an important role in thyroid treatment, because with the development of targeted drugs and immunotherapy, chemotherapy combined with other treatments can reduce the dosage of chemotherapy drugs to reduce the toxic side effect, and can improve other therapeutic effects.

Advances in application of regulatory T cells in transplant immune tolerance: from basic to clinical research / 器官移植

Regulatory T cells (Treg) are important inhibitory immune cells to establish immune tolerance, which play a pivotal role in regulating excessive immune response and autoimmune diseases of the host. Previous studies related to transplant immune tolerance have confirmed that increasing the number of Treg in vivo or enhancing the function of Treg serve as a therapeutic strategy to induce transplant immune tolerance. At present, Treg-based induction methods for transplant immune tolerance include adoptive infusion of Treg, in vivo amplification of Treg and utilization of antigen-specific Treg. In this article, the characteristics and mechanism of Treg, the latest research progress on basic experiments and clinical practice of Treg related to transplant immune tolerance at home and abroad were reviewed, and future challenges and development of Treg therapy were prospected, aiming to unravel the significance and application prospect of Treg in transplant immune tolerance, explore the advantages and limitations of Treg therapeutic strategies, and provide reference and evidence for subsequent research in this field.

Chemical constituents from leaves of Craibiodendron yunnanense / 中国中药杂志

The present study investigated the chemical constituents from the leaves of Craibiodendron yunnanense. The compounds were isolated and purified from the leaves of C. yunnanense by a combination of various chromatographic techniques including column chromatography over polyamide, silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified by extensive spectroscopic analyses including MS and NMR data. As a result, 10 compounds, including melionoside F(1), meliosmaionol D(2), naringenin(3), quercetin-3-O-α-L-arabinopyranoside(4), epicatechin(5), quercetin-3'-glucoside(6), corbulain Ib(7), loliolide(8), asiatic acid(9), and ursolic acid(10), were isolated. Compounds 1 and 2 were two new compounds, and compound 7 was isolated from this genus for the first time. All compounds showed no significant cytotoxic activity by MTT assay.

Cembranoids and their bioactivities in soft coral Sarcophyton glaucum / 中国中药杂志

Chemical constituents in soft coral Sarcophyton glaucum were separated and purified by various chromatographic methods. Based on the spectral data, physicochemical properties, and comparison with the data reported in the literature, nine cembranoids, including a new cembranoid named sefsarcophinolide(1) together with eight known cembranoids, namely(+)-isosarcophine(2), sarcomilitatin D(3), sarcophytonolide J(4),(1S,3E,7E,13S)-11,12-epoxycembra-3,7,15-triene-13-ol(5), sarcophytonin B(6),(-)-eunicenone(7), lobophytin B(8), and arbolide C(9), were identified. As revealed by biological activity experiment results, compounds 2-6 had weak acetylcholinesterase inhibitory activity, and compound 5 displayed weak cytotoxicity against K562 tumor cell line.

A new macrocyclic flavonoid from Onychium japonicum / 药学学报

Seven compounds were isolated from Onychium japonicum by macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were identified by NMR, MS and other spectroscopic methods as onychone A (1), quercetin (2), quercetin-3-O-α-L-rhamnoside (3), kaempferol-7-O-β-D-glucopyranoside (4), kaempferol-3-O-α-L-rhamnopyranoside (5), (-)-prunin (6), and norathyriol (7). Compound 1 is a novel macrocyclic flavonoid, and all the others are reported from this plant for the first time. In vitro cytotoxic activities of compounds 1-7 were evaluated by MTS testing with five cancer cell lines. Compound 7 exhibited weak cytotoxicity against tumor cell lines A549, SMMC-7721, and SW480.

Cytotoxic sesquiterpene aryl esters from Armillaria gallica 012m / 中草药·英文版

OBJECTIVE@#To study the chemical constituents of the EtOAc extract of Armillaria gallica 012m.@*METHODS@#The chemical constituents of the EtOAc extract of A. gallica 012m were isolated and purified by various column chromatography and their structures were elucidated on the basis of the 1D and 2D NMR spectroscopic and HRESIMS data. Cytotoxicity of all isolates against A549, HCT-116, M231 and W256 human tumor cells was determined by the MTT method.@*RESULTS@#A new sesquiterpene aryl ester, armimelleolide C ( 1), and eight known ones including armillarivin ( 2), melleolide F ( 3), 6'-chloromelleolide F ( 4), melleolide ( 5), melleolide K ( 6), melledonol ( 7), 13-hydroxydihydromelleolide ( 8), and armillane ( 9), were isolated from the EtOAc extract of A. gallica 012m. All isolates showed potential cytotoxic activities against at least one of the human cancer cell lines with IC50 values ranging from (3.17 ± 0.54) to (17.57 ± 0.47) μmol/L. Compound 1 showed significant inhibitory activity against M231 with an IC50 value of (7.54 ± 0.24) μmol/L compared with paclitaxel as the positive control. Compounds 2, 3, and 7, 9 showed obvious inhibitory activity against HCT-116 and were better than that of the positive control.@*CONCLUSION@#The chemical constituents including a new sesquiterpene aryl ester armimelleolide C ( 1) from the EtOAc extract of A. gallica 012m have a variety of structures and potential antitumor activities.

Directional screening and identification of potential cytotoxic components from Achnatherum inebrians by a combination of surface palsmon resonance and chromatography / 中草药·英文版

OBJECTIVE@#To establish a method for directional screening of the cytotoxic components from the medicinal herb of Achnatherum inebrians by a combination of surface plasmon resonance (SPR) biosensor and chromatographic isolation technology.@*METHODS@#Under the guidance of bioactive assessment based on binding abilities between objects and the α-Mannosidase (α-Man) target, the active components from different solvents extracts, different polar extraction parts and fractions were screened orderly and directionally using SPR. Components with a high binding ability to α-Man can be precisely oriented in a narrower fractions range and are easy to isolate. Three human cancer cells were used to evaluate the cytotoxic activity of component with the highest affinity to α-Man.@*RESULTS@#Eight compounds were isolated and identificated from A. inebrians for the first time. Deoxyvasicinone possessed the highest affinity to α-Man among them. Moreover, deoxyvasicinone showed good effects on inhibited proliferation of human hepatoma cells HepG2 (IC50 = 5.7 μmol/L), human breast cancer cells MCF7 (IC50 = 7.21 μmol/L) and human lung cancer cells HCC827 (IC50 = 0.75 μmol/L), respectively. In particular, its inhibitory effect on HCC827 was stronger than the positive drug gefitinib (IC50 = 1.65 μmol/L).@*CONCLUSION@#A comprehensive strategy of directional screening potential cytotoxic components from herb based on biomolecular interaction and chromatography was established. Deoxyvasicinone as an effective anti-cancer component was initially isolated from A. inebrians. It is expected that this screening strategy could provide new perspectives for rapid screening and identification of active components from natural plants with the complex matrix.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts

Abstract Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Resumo Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Abstract Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Resumo Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

A pair of new isoflavonoid enantiomers from Dalbergia benthamii Prain / 药学学报

Thirteen isoflavones were separated and purified from an ethanol extract of the rhizome of Dalbergia benthamii Prain by using silica gel, Sephadex LH-20, recrystallization et al. Their structures were identified by physicochemical properties and spectral analysis such as MS, 1D/2D-NMR as dalbergibenthamin (1), butesuperin A (2), xanthocercin A (3), butesuperin B (4), di-O-methylalpinum isoflavone (5), 2′-deoxgisoaunculutin (6), robustone (7), 4′-hydroxy-5,7-dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (8), formononetin (9), 6″-O-rhamnosyldaidzin (10), 3′,4′-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (11), derrubone dimethyl enter (12), and derrubone (13). Compound 1 is a pair of new isoflavonoid enantiomers, compound 12 is a new natural product and compounds 1-7 and 10-13 were obtained from D. benthamii Prain for the first time. In vitro cytotoxic activities of the compounds were explored by MTS testing with HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines. Results show that compound 8 significantly inhibited cellular proliferation. The IC50 of compound 8 in A-549 and SW480 cells was 16.68 ± 0.19 and 15.21 ± 0.60 μmol·L-1.

Expert consensus on the clinical application of antibody drug conjugates in the treatment of malignant tumors (2023 edition) / 中华肿瘤杂志

Antibody-drug conjugates (ADCs) are a class of targeted biological agents that link cytotoxic drugs to monoclonal antibodies through linkers. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. September 30, 2022, 14 anti-tumor ADC drugs have been approved for marketing in the world, and four ADCs have been approved in China. With the improvement of the clinical accessibility of ADC drugs, clinicians urgently need to understand the molecular characteristics and mechanisms of ADCs, and clarify the indications for rational use of drugs. Patients' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. In view of this, on the basis of the "Expert Consensus on the Clinical Application of Antibody-drug Conjugates for the Treatment of Malignant Tumors (2020 edition)", Professional Committee on Clinical Research of Oncology Drugs, Chinese Anti-Cancer Association fully combines the existing clinical research evidence and the feasibility of current ADC drugs in China to update the consensus content. This consensus aims to provide a systematic overview of ADC drugs, so as to provide practical and effective suggestions and references for clinicians to apply and manage ADC drugs more accurately.

Research on anti-tumor mechanism of attenuated Salmonella typhimurium VNP20009 / 药学学报

Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4+ T cells and CD8+ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.

Cytotoxic and Apoptotic Properties of the Flavonoid-rich Ethyl Acetate Fraction of the Crude Methanol Leaf Extract of Syzygium samarangense (Blume) Merr. (Myrtaceae) against MCF-7 Breast Cancer Cells

Introduction@#Breast cancer is the most common cancer among women in the Philippines and about 3 in every 100 Filipina will be diagnosed with breast cancer in their lifetime. There is a need to discover safe, yet inexpensive herbal extracts with potential cytotoxic properties as potential treatment modalities to treat breast cancer. @*Objectives@#This study seeks to explore the cytotoxic and apoptotic properties of the ethyl acetate fraction of the defatted crude methanol leaf extract of Syzygium samarangense in MCF-7 breast cancer cell lines. @*Methods@#Screening for flavonoids of the extracts was performed using TLC, total flavonoids, total phenols, FTIR and LC-MS spectroscopy. The hydrogen peroxide and ferric reducing anti-oxidant power were used as substrates to assess in vitro anti-oxidative properties of the extracts. The MTT dye viability assay was used to assess the cytotoxic properties of the extracts against MCF-7 cells. Apoptotic properties of the extracts in MCF-7 cells were determined by caspase-3 activation assay, DNA fragmentation patterns and fluorescence microscopy after annexin-V and propidium iodide staining. @*Results@#The abundance of flavonoids in the ethyl acetate fraction of the crude methanol leaf extract was established by TLC, FTIR, LC-MS/MS, total flavonoid and total phenol analyses. The in vitro anti-oxidative properties of this extract was comparable to ascorbic acid. The median inhibitory concentration (IC50) of this extract in MCF-7 breast cancer cell lines was 7.2 mcg/mL while doxorubicin registered an IC50 of 1.2 mcg/mL. At this concentration, the extract was not cytotoxic to normally-dividing breast epithelial cells. Cytotoxicity of the extract was mediated via apoptosis as demonstrated by DNA fragmentation, caspase-3 activation and fluorescence microscopic analyses. @*Conclusion@#The study shows that the flavonoid-rich ethyl acetate fraction of the crude methanol leaf extract of S. samarangense possesses potent apoptotic and cytotoxic properties against MCF-7 breast cancer cell lines at low concentrations.

Mechanism of cytotoxic T lymphocyte－derived exosomes inhibiting hepatic stellate cell activation / 临床肝胆病杂志

ObjectiveTo investigate whether cytotoxic T lymphocyte （CTL）－derived exosomes can downregulate HBx expression and inhibit hepatic stellate cell （HSC） activation. MethodsThe supernatants of HepG2， HepGA14， and CTL cells were collected to extract exosomes， which were referred to as NC－exo， HBV－exo， and CTL－exo， respectively）. Transmission electron microscopy was used to observe their morphology， and Western Blot was used to measure the expression of the markers of exosomes CD63 and TSG101. NC－exo， HBV－exo， and CTL－exo labeled by BODIPY dye were mixed with HBV－exo at different ratios and were then co－cultured with HSC LX－2 （HSC－LX2）. A fluorescence microscope was used to observe whether exosomes could enter LX－2 cells， and an fluorescence microscope was used to observe cell morphological changes； quantitative real－time PCR （qPCR） was used to measure the expression of the activated biomarkers such as transforming growth factor－β1 （TGF－β1）， ɑ－smooth muscle actin （ɑ－SMA）， and collagen type I （Collagen I） in LX－2 cells. CTL－exo was added to the HepGA14 culture system； then qPCR was used to measure the mRNA expression level of HBV DNA， cccDNA， and HBx in exosomes in HepGA14 cells， and Western Blot was used to measure the protein expression level of HBx in exosomes. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe exosomes were all microcysts with a double－layer membrane structure and were circular or elliptical in shape， with the expression of the signature proteins CD63 and TSG101， and the vesicles had a diameter of 50－100 nm. The fluorescence microscope showed that exosomes could enter LX－2 cells， and HSC were enlarged with extended cell processes. The results of qPCR showed that there were significant differences in the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes between the NC－exo， HBV－exo， NC－exo+HBV－exo， and Con groups （F=444.678， 417.144， and 571.508， all P<0.05）. After the intervention of HepGA14 cells with CTL－exo， qPCR results showed that compared with the control group， there were significant reductions in the expression levels of HBV DNA and cccDNA in HepGA14 cells （all P<0.05）， the relative mRNA expression level of HBx in exosomes （P<0.05）， and the protein expression level of HBx （P<0.05）. CTL－exo and HBV－exo were mixed at different ratios （2∶1， 5∶1， 10∶1） and were then used for the intervention of LX－2 cells， and qPCR results showed that the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes in LX－2 cells gradually decreased with the increase in the ratio of CTL－exo between groups （P<0.05）. ConclusionCTL－exo can downregulate the protein expression of HBx in HBV－exo to inhibit HSC activation， suggesting that CTL－exo has an anti－hepatitis B liver fibrosis effect.

Research progress on the role of costimulatory signaling pathway in xenotransplantation / 器官移植

Organ shortage is a critical factor limiting the development of organ transplantation. Xenotransplantation is expected to resolve the problem of organ shortage, which has become a new research hotspot. Study of costimulatory signaling pathway related to T cell regulation is a hot topic in terms of immunity of xenotransplantation. Since the discovery of costimulatory molecule CD28, multiple costimulatory molecules have been identified, including costimulatory and coinhibitory receptors and their related ligands. Specific T cell activation of donors is the key factor leading to acute immune rejection. The expression and induction of costimulatory molecules on T cells differ during different immune stages, and these costimulatory molecules play a key role in maintaining T cell tolerance and the balance of T cell immune response. At present, increasing attention has been diverted to the role of costimulatory signaling pathway in organ transplantation. In this article, the latest research progress in costimulatory signaling pathway related to xenotransplantation immunity was reviewed, aiming to provide reference for the optimization of xenotransplantation immunosuppression regimen.