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A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2

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Chinese Chemical Letters 2024年第8期35卷 201-204页

作者： Yang Liu Yan Liu Kaiyin Yang Zhiruo Zhang Wenbo Zhang Bingyou Yang Hua Li Lixia Chen Wuya college of Innovation Key Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Basic and Application Research of Beiyao Ministry of EducationHeilongjiang University of Chinese MedicineHarbin 150006China Institute of Structural Pharmacology&TCM Chemical Biology College of PharmacyFujian University of Traditional Chinese MedicineFuzhou 350122China Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Hexokinase 2(HK2)is the rate-limiting enzyme in the first step of glycolysis,catalyzing glucose to glucose-6-phosphate,and overexpressed in most cancer ***2 also binds to voltage-dependent anion channel(VDAC)to stabilize the mitochondrial outer membrane,which inhibits cancer cell ***,HK2 has become a potential target for cancer *** targeting chimeras(PROTACs)are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted *** potent and specific PROTACs targeting dissimilar targets have been *** this study,an HK2 PROTAC,4H-5P-M,was developed and induced the degradation of HK2 relying on the ubiquitin-proteasome *** was found that 4H-5P-M as an effective HK2 degrader induced HK2 degradation in a dose-and time-dependent manner and suppressed the growth of SW480 cells.4H-5P-M selectively induced HK2 degradation at a lower concentration than other hexokinase ***,it could suppress glycolysis and accelerate the apoptosis of cancer ***,it provided a new insight into the development of anti-tumor drugs.

关键词： HK2 PROTACs Degrader Anti-tumor SW480

The Influence of Depression on Different Age and Gender Groups in Bahawalpur

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Journal of Clinical and Nursing Research 2024年第7期8卷 196-207页

作者： Mehran Khan Muhammad Shahbaz Tooba Waris Shoaib Yaseen Iqra Afzal Emaan Khadim Sawera Usman Muhammad Ismail Shah Sulaiman Aslam Zafar Iqbal Bahawalpur college of pharmacy BMDC Complex63100PunjabPakistan

In Bahawalpur,a cross-sectional study assessed depression prevalence across age and gender groups,involving 442 participants from diverse socioeconomic backgrounds and *** the PHQ9 questionnaire,84%were found to meet depression *** findings revealed a higher incidence in females(88%)than males(79%),with the greatest disparity among young adults,particularly young women,due to factors like academic pressure and financial *** children had the lowest depression rates(68%),possibly due to better *** individuals exhibited more severe depression,likely related to aging and domestic *** study’s findings highlight a significant variation in depression severity across different demographic groups,with an overall higher incidence in *** research underscores the necessity for targeted mental health resources and interventions tailored to the specific needs of each demographic *** also points to the importance of addressing academic and socioeconomic stressors to mitigate depression,particularly among young *** the study provides valuable insights,it relies on self-reported data,which may introduce ***,future research should include clinical assessments to validate these findings and ensure a more accurate representation of depression within the community.

关键词： Influence Depression Different age Gender groups Bahawalpur

UV,five wavelengths fusion and electrochemical fingerprints combined with antioxidant activity for quality control of antiviral mixture

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Asian Journal of Traditional Medicines 2024年第3期19卷 119-136,151页

作者： Kaining Zhou Zini Tang Guoxiang Sun Ping Guo Lili Lan college of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Aiming to ensure the consistency of quality control of Traditional Chinese Medicines(TCMs),a combination method of high-performance liquid chromatography(HPLC),ultraviolet(UV),electrochemical(EC)was developed in this study to comprehensively evaluate the quality of Antiviral Mixture(AM),and Comprehensive Linear Quantification Fingerprint Method(CLQFM)was used to process the *** analysis of three active substances in TCM was conducted.A fivewavelength fusion fingerprint(FWFF)was developed,using second-order derivatives of UV spectral data to differentiate sample levels *** combination of HPLC and UV spectrophotometry,along with electrochemical fingerprinting(ECFP),successfully evaluated total active ***,a multidimensional profiling analytical system for TCM was developed.

关键词： TCM antiviral mixture five-wavelength fusion fingerprint(FWFF) Comprehensive Linear Quantification Fingerprint Method(CLQFM) quantization fingerprint antioxidant activity profilling

Innovative hydrogel-based delivery systems for immunotherapy:A review of pre-clinical progress

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Nano Research 2024年第10期17卷 9031-9043页

作者： Narsimha Mamidi Michael Poellmann Kaila Javius-Jones KiChang Nam Seungpyo Hong Wisconsin Center for NanoBioSystems University of Wisconsin-MadisonMadisonWI 53705USA Pharmaceutical Sciences Division School of PharmacyUniversity of Wisconsin-MadisonMadisonWI 53705USA Department of Medical Engineering College of MedicineDongguk UniversityGoyang 10326Republic of Korea Department of pharmacy Yonsei UniversityIncheon 21983Republic of Korea Lachman Institute for Pharmaceutical Development University of Wisconsin-MadisonMadisonWI 53705USA

Immunotherapy has markedly reinvented how we treat cancer,as shown by numerous Food and Drug Administration(FDA)drug approvals that have made significant clinical impact and ongoing clinical ***,undesirable side effects,such as autoimmunity and inflammation,and inconsistent clinical outcomes remain a major *** response rates across various immunotherapeutic reagents is imperative to enhance overall effectiveness and reduce adverse side *** address this challenge,interdisciplinary approaches have been explored by incorporating immunotherapies into hydrogels,enabling finecontrolled delivery to target *** review focuses on recent progress in the utilization of hydrogel-based delivery systems for cancer immunotherapy and their potential to further enhance treatment response ***,recent preclinical advances in hydrogels implemented with immune checkpoint inhibitors,combination therapies,and vaccines,along with selfassembled peptide hydrogels,are *** also discuss technological advances and drawbacks in this area and provide insights to ultimately realize the clinical application of hydrogels in cancer immunotherapy.

关键词： cancer immunotherapy drug delivery hydrogels immunotherapeutic agents immune modulation clinical outcomes

Single-cell transcriptomics reveals T-cell heterogeneity and immunomodulatory role of CD4+T native cells in Candida albicans infection

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BIOCELL 2024年第9期48卷 1355-1368页

作者： KERAN JIA YANHAO ZHANG MENGYU JIANG MENGGE CUI JIA WANG JIAJIA ZHANG HUIHAI ZHAO MENGYAN LI HUA WANG QUANMING ZOU HAO ZENG National Engineering Research Center of Immunological Products Department of Microbiology and Biochemical PharmacyCollege of PharmacyArmy Medical UniversityChongqing400038China Department of Clinical Laboratory The 980th Hospital of PLA Joint Logistics Support Force(Bethune International Peace Hospital)Shijiazhuang050082China

Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi *** the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal ***:The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics,fluorescence quantitative PCR,and Western *** investigated intergroup differences in the dynamics of immune cell subpopulation infiltration,pathway enrichment,and differentiation during Candida albicans ***:Our findings indicate that infiltration of CD4^(+)naive cells,regulatory T(Treg)cells,and Microtubules(MT)-associated cells increased after infection,along with impaired T cell ***,CD4^(+)T cells and plasma cells were enhanced after infection,suggesting that antibody production is dependent on T *** addition,we screened 6 hub genes,transcription factor forkhead box protein 3(Foxp3),cytotoxic T-lymphocyte associated protein 4(CTLA4),Interleukin 2 Receptor Subunit Beta(Il2rb),Cd28,C-C Motif Chemokine Ligand 5(Ccl5),and Cd27 for alterations associated with CD4^(+)T cell ***:These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.

关键词： Candida albicans Single-cell transcriptomics Immune microenvironment Fungal infections Hub gene

Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4001-4013页

作者： Ziqi Huang Kun Zhang Yurui Jiang Mengmeng Wang Mei Li Yuda Guo Ruolin Gao Ning Li Chenyang Wang Jia Chen Jiefu Wang Ning Liu Xiang Liu Shuangwei Liu Mingming Wei Cheng Yang Guang Yang The State Key Laboratory of Medicinal Chemical Biology College of Life SciencesCollege of PharmacyNankai UniversityTianjin 300071China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

Cancer stem cells(CSCs)play a pivotal role in tumor initiation,proliferation,metastasis,drug resistance,and ***,targeting CSCs has emerged as a promising avenue for cancer ***,3-phosphoglycerate dehydrogenase(PHGDH)has been identified as being intricately associated with the regulation of numerous cancer stem ***,reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are *** this study,the novel“molecular glue”LXH-3-71 was identified,and it robustly induced degradation of PHGDH,thereby modulating the stemness of colorectal cancer cells(CRCs)both in vitro and in ***,LXH-3-71 was observed to form a dynamic chimera,between PHGDH and the DDB1-CRL E3 *** insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH ***,compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase,facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

关键词： Molecular glue Targeted protein degradation PHGDH Cancer stem cells PROTACs

Characterization of the spoilage strength of Aeromonas app. to collagen-rich chilled meat: comparative analysis

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Food Science and Human Wellness 2024年

作者： Junming Gong Liangting Shao Silu Liu Xinglian Xu Huhu Wang State Key Laboratory of Meat Quality Control and Cultured Meat Development， college of Food Science and Technology， Nanjing Agricultural University college of Food Science and pharmacy， Xinjiang Agricultural University

Aeromonas spp. are commonly found in spoilage of chilled meat. Aeromonas salmonicida NCM 29 and Aeromonas salmonicida NCM 57 have been discovered the spoilage heterogeneity in degrading myofibrillar protein. In this study， the two strains were tested to uncover the discrepancy of meat spoilage in collagen-rich chilled meat and extracted collagen. The results revealed that chicken claws， riched in collagen， inoculated with NCM 29 showed higher values of total viable counts (TVC)， total volatile basic nitrogen (TVB-N)， pH， adhered cells， TCA-soluble peptides， and protease activity compared to those inoculated with NCM 57. Furthermore， NCM 29 generated higher quantity of volatile organic compounds related to meat spoilage. The collagenase (hemagglutinin protease， Hap) secreted by NCM 29 has been identified as the key factor responsible for the observed discrepancies in spoilage， which gradually degraded collagen into peptides and hydroxyproline. The capacity of Hap to degrade type I collagen in vitro indicated that it has apparent proteolytic activity， which could reduce the average particle size and alter secondary structure of collagen. SDS-PAGE further confirmed the degradation of the β chain in collagen. These findings not only provide a theoretical basis for in-depth investigation of the meat spoilage mechanisms of Aeromonas spp.， but also encourage us to take measures to avoid the spoilage of related bacteria such as Aeromonas spp. during the preservation process.

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A distinct“repair”role of regulatory T cells in fracture healing

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Frontiers of Medicine 2024年第3期18卷 516-537页

作者： Tingting Wu Lulu Wang Chen Jian Zhenhe Zhang Ruiyin Zeng Bobin Mi Guohui Liu Yu Zhang Chen Shi Department of pharmacy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Hubei Province Clinical Research Center for Precision Medicine for Critical Illness Wuhan430022China Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Regulatory T cells(Tregs)suppress immune responses and ***,we described the distinct nonimmunological role of Tregs in fracture *** recruitment from the circulation pool,peripheral induction,and local expansion rapidly enriched Tregs in the injured *** Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid *** depletion of Tregs compromised the fracture healing process,which leads to increased bone *** addition,bone callus Tregs showed unique T-cell receptor *** was the most overexpressed protein in bone callus Tregs,and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling *** results of loss-and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg *** also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic *** findings indicate the distinct and nonredundant role of Tregs in fracture healing,which will provide a new therapeutic target and strategy in the clinical treatment of fractures.

关键词： regulatory T cells fracture healing amphiregulin non-union osteogenesis

Tb^(3+)-nucleic acid probe-based label-free and rapid detection of mercury pollution in food

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Food Science and Human Wellness 2024年第2期13卷 993-998页

作者： Xuhan Xia Chenxi Zhou Yulin Zhu Yi Dong Qiang He Mohammad Rizwan Khan Yuanlong Chi Rosa Busquets Ruijie Deng Yao Ren college of Biomass Science and Engineering Healthy Food Evaluation Research CenterSichuan UniversityChengdu 610065China Department of Chemistry College of ScienceKing Saud UniversityRiyadh 11451Saudi Arabia School of Life Sciences Pharmacy and ChemistryKingston University LondonKingston Upon Thames KT12EEUK

Mercury is a threatening pollutant in food,herein,we developed a Tb^(3+)-nucleic acid probe-based label-free assay for mix-and-read,rapid detection of mercury *** assay utilized the feature of light-up fluorescence of terbium ions(Tb^(3+))via binding with single-strand *** ion,Hg^(2+)induced thymine(T)-rich DNA strand to form a double-strand structure(T-Hg^(2+)-T),thus leading to fluorescence *** on the principle,Hg^(2+)can be quantified based on the fluorescence of Tb^(3+),the limit of detection was 0.0689μmol/L and the linear range was 0.1-6.0μmol/*** to the specificity of T-Hg^(2+)-T artificial base pair,the assay could distinguish Hg^(2+)from other metal *** recovery rate was ranged in 98.71%-101.34%for detecting mercury pollution in three food *** assay is low-cost,separation-free and mix-to-read,thus was a competitive tool for detection of mercury pollution to ensure food safety.

关键词： Mercury pollution Food safety Nucleic acid probe Label-free Terbium