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Drug-induced mucosal alterations observed during esophagogastroduodenoscopy

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World Journal of Gastroenterology 2024年第16期30卷 2220-2232页

作者： Masaya Iwamuro Seiji Kawano Motoyuki Otsuka Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract,i.e.,the esophagus,stomach,and duodenum.These include pill-induced esophagitis,desquamative esophagitis,worsening of gastroesophageal reflux,chemotherapy-induced esophagitis,proton pump inhibitor-induced gastric mucosal changes,medication-induced gastric erosions and ulcers,pseudomelanosis of the stomach,olmesartan-related gastric mucosal inflammation,lanthanum deposition in the stomach,zinc acetate hydrate tabletinduced gastric ulcer,immune-related adverse event gastritis,olmesartan-associated sprue-like enteropathy,pseudomelanosis of the duodenum,and lanthanum deposition in the duodenum.For endoscopists,acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions.This minireview aims to provide essential information on druginduced mucosal alterations observed on esophagogastroduodenoscopy,along with representative endoscopic images.

关键词： Diagnosis Esophagogastroduodenoscopy Non-neoplastic lesions Esophageal lesions Gastric lesions Duodenal lesions

A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT

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Chinese Journal of Natural Medicines 2024年第2期22卷 112-126页

作者： REN Boxue LI Yang DI Lei CHENG Ranran LIU Lijuan LI Hongmei LI Yi TANG Zhangrui YAN Yongming LU Tao FU Rong CHENG Yongxian WU Zhaoqiu State Key Laboratory of Natural Medicines Department of PharmacologySchool of PharmacyChina Pharmaceutical UniversityNanjing 211198China Institute for Inheritance-Based Innovation of Chinese Medicine School of Pharmaceutical SciencesShenzhen University Health Science CenterShenzhen 518060China

The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53.LZ22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein.This interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal degradation.LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway.Moreover,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal metastasis.Importantly,LZ22 administration in tumor-bearing mice did not manifest notable side effects.The findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.

关键词： LZ22 Wild-type p53 p53 Reactivator Snail-driven EMT Tumor growth and metastasis

Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

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Chinese Chemical Letters 2024年第2期35卷 352-357页

作者： Yingli Zhu Jie Qian Kunqian Yu Jing Hou Yeshuo Ma Fei Chen Jie Dong Wenbin Zeng xiangya school of pharmaceutical sciences Central South UniversityChangsha 410083China National Engineering Research Center of Rice and Byproduct Deep Processing School of Food Science and EngineeringCentral South University of Forestry and TechnologyChangsha 410004China State Key Laboratory of Drug Research Drug Discovery and Design CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Geriatrics Third Xiangya HospitalCentral South UniversityChangsha 410013China

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development,disease diagnosis,and basic theoretical research.Aminopeptidase N(APN),as a representative tumor biomarker with anti-tumor potential,still lacks a high-precision theranostic probe specifically targeting it.In this study,a novel quaternity design strategy for APN theranostic probe was developed.This proposed strategy utilizes advanced machine learning and molecular dynamics simulations,and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional fragments.Through this strategy,a unique“Off-On”theranostic probe,ABTP-DPTB,was ingeniously constructed to light up APN through fluorescence restoration,relying on conformation-induced effects and solvent restriction.Differ from the common diagnostic probes,the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ imaging.The fabricated probe was used for detecting and inhibiting APN in various environments,with a better in vitro inhibitory than golden-standard drug bestatin.

关键词： Theranostic probe Artificial intelligence Conformational restriction Fluorescence restoration Design strategy

In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence

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Asian Journal of pharmaceutical sciences 2024年第2期19卷 102-119页

作者： Shengnan Huang Chenyang Zhou Chengzhi Song Xiali Zhu Mingsan Miao Chunming Li Shaofeng Duan Yurong Hu Academy of Chinese Medical sciences Henan University of Chinese MedicineZhengzhou 450046China school of pharmaceutical sciences Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou UniversityZhengzhou 450001China Center for Quantitative Biology Peking UniversityBeijing 100871China school of pharmaceutical sciences Henan University of Chinese MedicineZhengzhou 450046China Department of Pharmacy Chongqing University Cancer HospitalChongqing 400030China school of pharmaceutical sciences Henan UniversityZhengzhou 450046China

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

关键词： Post-sur gical tumor recurrence In situl hydrogel Immunotherapy Tumor micr oenvir onment Manganese(Ⅱ) Nitic oxide

Effects of Maillard reaction and its product AGEs on aging and age-related diseases

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Food Science and Human Wellness 2024年第3期13卷 1118-1134页

作者： Huan Peng Yuqi Gao Chenye Zeng Rui Hua Yannan Guo Yida Wang Zhao Wang Protein Science Key Laboratory of the Ministry of Education School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China

Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.

关键词： Maillard reaction Advanced glycation end products Physiologic aging Pathological aging Drug intervention

Genetic association analysis-based networks and classification of human UCP1 polymorphisms

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Genes & Diseases 2024年第3期11卷 63-65页

作者： Donghai Li State Key Laboratory of pharmaceutical Biotechnology School of Life SciencesNanjing UniversityJiangsu 210023China

Uncoupling protein 1(UCP1,also known as thermogenin or SLC25A7)plays an important role in the uncoupling of oxidative phosphorylation and adaptive non-shivering thermogenesis(NST).The genomic location for UCP1 is chromosome 4 q31.1:140,555,770--140,568,961(GRCh38/hg38)and its size is 13,192 bases split into 6 exons.In dbSNP,3650 short genetic variations of human UCP1 are documented.In this study,UCP1 serves as an example to construct polymorphism-trait networks and enable a func-tional classification.

关键词： classification. UCP1 networks

Sigmatropic rearrangements of B(MIDA)-propargylic alcohols towards the diverse synthesis of α-functionalized organoborons

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Science China Chemistry 2024年第2期67卷 568-575页

作者： Jiasheng Qian Li-Cai Liu Zhi-Hao Chen Yuan Liu Yin Li Qingjiang Li Honggen Wang Guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou510006China

α-Functionalized organoborons are useful building blocks and key structural elements in functional molecules.Their previous synthesis relied on the famous Matteson reaction or the late-stage borylative modification of alkynes or alkenes.Recently,the synthetic transformation of borylated building blocks offers another useful strategy and is currently actively explored.We report herein that B(MIDA)-propargylic alcohols(BPAs) are a useful type of borylated building blocks.Bearing two complementary functional group handles(alkyne and hydroxyl) in close proximity,the redox-neutral [3,3] and [2,3] sigmatropic rearrangements of BPAs allow the efficient synthesis of several types of α-functionalized boronates,including α,β-unsaturated acylborons,α-S/P-substituted allenylborons,boryl-substituted thiazoles and a borylated α,β-unsaturated hydrazine,some of which are otherwise challenging targets using other synthetic methods.

关键词： organoboron diverse synthesis sigmatropic rearrangement heteroarene amide

Therapeutic potential and pharmacological mechanism of visnagin

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Journal of Integrative Medicine 2024年第4期22卷 399-412页

作者： Poonam Yadav Sumeet Kumar Singh Sayantap Datta Saloni Verma Aarti Verma Arnab Rakshit Anjana Bali Jasvinder Singh Bhatti Amit Khurana Umashanker Navik Department of Pharmacology School of Health SciencesCentral University of Punjab Department of Pharmacological and pharmaceutical sciences College of PharmacyUniversity of Houston Department of Human Genetics and Molecular Medicine School of Health SciencesCentral University of Punjab

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga (L.) Lam (a synonym of Visnaga daucoides Gaertn.) plant,which is used to cure various ailments.Many investigations into the bioactive properties of visnagin have been studied to date.The literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal diseases.Moreover,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates apoptosis.Thus,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical needs.The current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of action.The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

关键词： Ammi visnaga L. Anti-inflammatory Cancer Phytochemical Visnaga daucoides Gaertn Visnagin

Bionic immunoactivator copresenting autophagy promoting and costimulatory molecules for synergistic cancer immunotherapy

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Nano Research 2024年第3期17卷 1710-1724页

作者： Yiwei Peng Yiliang Yang Zhenzhen Yang Datong Gao Jiajia Li Qi Sun Yitian Du Meng Lin Xianrong Qi Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune boosters.PLT-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor microenvironment.PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive environment.PLT-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold vs.control group)in mouse tumor model after intravenous or subcutaneous administration.Also,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and PD-L1.Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication.All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.

关键词： in situ bionic immunoactivator autophagy glucocorticoid-induced tumor necrosis factor receptor(GITR)agonist platelets and platelet microparticles cancer immunotherapy