摘要：
Peptides exhibit various biological activities, including biorecognition, cell targeting, and tumor penetration, and can stimulate immune cells to elicit immune responses for tumor immunotherapy. Peptide self-assemblies and peptide-functionalized nanocarriers can reduce the effect of various biological barriers and the degradation by peptidases, enhancing the efficiency of peptide delivery and improving antitumor immune responses. To date, the design and development of peptides with various functionalities have been extensively reviewed for enhanced chemotherapy; however, peptide-mediated tumor immunotherapy using peptides acting on different immune cells, to the knowledge, has not yet been summarized. Thus, this work provides a review of this emerging subject of research, focusing on immunomodulatory anticancer peptides. This review introduces the role of peptides in the immunomodulation of innate and adaptive immune cells, followed by a link between peptides in the innate and adaptive immune systems. The peptides are discussed in detail, following a classification according to their effects on different innate and adaptive immune cells, as well as immune checkpoints. Subsequently, two delivery strategies for peptides as drugs are presented: peptide self-assemblies and peptide-functionalized nanocarriers. The concluding remarks regarding the challenges and potential solutions of peptides for tumor immunotherapy are presented. This work introduces the role of peptides in immune regulation of innate and adaptive immune cells, as well as immune checkpoints. Then this work introduces two strategies for delivering polypeptides: peptide self-assemblies, and peptide-functionalized nanocarriers. Finally, the challenges and prospects of peptides in tumor immunotherapy are summarized. image
摘要：
Microcystin-LR (MC-LR) is a toxin that causes hepatic steatosis. Our previous study found that exposure to 60 μg/L MC-LR for 9 months resulted in liver lipid accumulation, but the underlying mechanisms remain elusive. Herein, for the first time, fatty acid-targeted metabolome and RNA-seq were combined to probe the effect and mechanism of chronic (12-month) MC-LR treatment on mice lipid metabolism at environmental-related levels (1, 60, and 120 μg/L). It was found that MC-LR dose-dependently raised serum and liver lipid levels. The total cholesterol (TC) levels in the liver were significantly increased following treatment with 1 μg/L MC-LR (equivalent to 0.004 μ/L in human). Treatment with 60 and 120 μg/L MC-LR significantly elevated TC and triglyceride (TG) levels in both serum and liver. Serum fatty acid-targeted metabolome analysis demonstrated that exposure to 1, 60, and 120 μg/L MC-LR caused significant alterations in the fatty acid profile. Chronic 1, 60, and 120 μg/L MC-LR treatment significantly increased serum polyunsaturated fatty acids (PUFAs), including conjugated linoleic acid and eicosapentaenoic acid, which positively correlated with serum or liver TG levels. Chronic exposure to 120 μg/L MC-LR led to a significant decrease in the accumulation of saturated fatty acids, including citramalic acid, pentadecanoic acid, and docosanoic acid, which were negatively correlated with serum or liver lipid levels. These findings suggested that 1 μg/L MC-LR exposure caused mild lipid metabolism disruption, while 60 and 120 μg/L MC-LR treatment resulted in pronounced hepatic steatosis in mice. Transcriptome analysis revealed that chronic environmental MC-LR treatment regulated the expression of genes involved in the phosphatidylinositol 3-kinase (PI3K) complex and fatty acid metabolism. Western blotting and RT-qPCR confirmed that chronic environmental MC-LR exposure activated the PI3K/AKT/mTOR signaling pathway, the downstream of fads3 gene that participates in fatty acid desaturation was upregulated, fatty acid degradation-related genes, including acsl1, acsl4, and ehhadh were inhibited, and lipid transport-related genes, including slc27a4 and apol7a, were promoted. Thus, chronic environmental MC-LR exposure boosts hepatic steatosis. Our work indicated that the limit concentration of 1 μg/L MC-LR in human drinking water for safety needs to be discussed. The study provides the first evidence of the fatty acid profile and gene changes and gains new insights into the mechanisms of chronic environmental MC-LR treatment-induced hepatic steatosis.
作者机构：
[Jiawen Deng; Xu Yao] Institute of Pharmacy and Pharmacology, Hengyang Medicinal School, University of South China, Hengyang, Hunan 421001, China;[Yahan Zhang; Jin-Hong Lin; Ji-Chang Xiao] State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China;[Jun Zhang] Department of Pharmacy, Hunan Vocational College of Science and Technology, Third Zhongyi Shan Road, Changsha, Hunan, 410004, China;[Lukang Lin] College of Chemical Engineering, Nanjing University of Science & Technology 200 Xiaolingwei, Nanjing 210094, China;[Wenbin Yi] Institute of Pharmacy and Pharmacology, Hengyang Medicinal School, University of South China, Hengyang, Hunan 421001, China<&wdkj&>College of Chemical Engineering, Nanjing University of Science & Technology 200 Xiaolingwei, Nanjing 210094, China
通讯机构：
[Jin-Hong Lin; Ji-Chang Xiao] S;[Wenbin Yi; Xing Zheng] I;State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hengyang Medicinal School, University of South China, Hengyang, Hunan 421001, China<&wdkj&>College of Chemical Engineering, Nanjing University of Science & Technology 200 Xiaolingwei, Nanjing 210094, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hengyang Medicinal School, University of South China, Hengyang, Hunan 421001, China<&wdkj&>Department of Pharmacy, Hunan Vocational College of Science and Technology, Third Zhongyi Shan Road, Changsha, Hunan, 410004, China
摘要：
Two types of 5-trifluoromethyl tetrazole-based energetic salts were successfully synthesized from trifluoroacetamide and sodium azide. The synthetic approach is characterized by its simplicity and safety. The X-ray diffraction analysis reveals the presence of both intermolecular and intramolecular hydrogen bonding within the crystal lattice of energetic salts. The synthesized compound 4 demonstrated notable physical properties, including high densities (1.64 g cm -3 ), great thermal stability (with decomposition temperatures of 167 °C), and excellent insensitivity (impact sensitivity exceeding 40 J). These attributes suggest that the compound 4 possess promising energetic performance and is potential candidates for use as insensitive high-energy materials.
Two types of 5-trifluoromethyl tetrazole-based energetic salts were successfully synthesized from trifluoroacetamide and sodium azide. The synthetic approach is characterized by its simplicity and safety. The X-ray diffraction analysis reveals the presence of both intermolecular and intramolecular hydrogen bonding within the crystal lattice of energetic salts. The synthesized compound 4 demonstrated notable physical properties, including high densities (1.64 g cm -3 ), great thermal stability (with decomposition temperatures of 167 °C), and excellent insensitivity (impact sensitivity exceeding 40 J). These attributes suggest that the compound 4 possess promising energetic performance and is potential candidates for use as insensitive high-energy materials.
通讯机构：
[Tan, XF; Yang, QL ; Chen, GD; Wu, GL] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
摘要：
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
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作者机构：
[Dai, Miao; Yan, Jialong; Xu, Si; Xi, Hanqing; Ou, Guifang; Li, Xiaoxue; Xue, Wen; Chen, Guang; Tang, Yonghong; Wang, Jiwu; Liu, Xuelian] Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;[Dai, Miao; Xu, Si; Xi, Hanqing; Ou, Guifang; Tang, Yonghong] Department of Neurology, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;[Li, Xiaoxue] Institute of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang 421002, China;[Luo, Si; Wei, Ping] Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
作者机构：
[Su, Bo; Jiang, Jinhuan; Liu, Jiyuan; Jiang, JH; Fan, Hui; Hu, Xiangyan] Univ South China, Inst Pharm & Pharmacol, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Su, Bo; Jiang, Jinhuan; Jiang, JH] Univ South China, Sch Pharmaceut Sci, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang, Hunan, Peoples R China.;[Cai, Jiye] Jinan Univ, Dept Chem, Guangzhou 510632, Peoples R China.
通讯机构：
[Jiang, JH ] U;Univ South China, Inst Pharm & Pharmacol, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;Univ South China, Sch Pharmaceut Sci, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang, Hunan, Peoples R China.
关键词：
XIAP;Tumor;XIAP inhibitor;Apoptotic
摘要：
X-linked inhibitor of apoptosis protein (XIAP) is the most potent endogenous member of the inhibitor of apoptosis protein family. XIAP exerts its anti-apoptotic effects by inhibiting both the death receptor pathway and mitochondrial pathway of apoptosis through various mechanisms such as directly binding to caspases, activating the nuclear factor kappa B (NF-κB) pathway, and other signaling pathways. These processes are closely related to tumor development and progression, making XIAP a therapeutic target for various types of cancer. This article will first review the structural characteristics and biological functions of XIAP, followed by its effects on tumors and an overview of XIAP-targeted inhibitors.
期刊：
JOURNAL OF ORGANIC CHEMISTRY,2025年90(4):1656-1662 ISSN：0022-3263
通讯作者：
Lei, Zhengwen;Wang, Zhen;Zeng, YF;Wang, Z
作者机构：
[Shen, Lixian] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm,Hunan Prov Key Lab Basic & Clin Pharmac, Hengyang 421001, Hunan, Peoples R China.;[Shen, Lixian; Liu, Jie; Wang, Zhen; Peng, Xue; Lei, Zhengwen; Zeng, Yao-Fu; Lei, ZW] Univ South China, Affiliated Hosp 1, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Wang, Zhen] Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Wang, Zhen] Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China.
通讯机构：
[Wang, Z; Zeng, YF ; Wang, Z ; Lei, ZW] U;Univ South China, Affiliated Hosp 1, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China.
摘要：
We report a photoredox-catalyzed three-component sulfonaminoalkynylation of alkenes with N -aminopyridine salts and potassium alkynyltrifluoroborate salts. This aminoalkylation reaction underwent a radial/polar crossover mechanism, which was distinguished from the previous reports. A variety of β-alkynylated sulfonamides were obtained in moderate to excellent yields. The versatility of this method was further evidenced by its successful application in modifying biological molecules in advanced stages of development.
We report a photoredox-catalyzed three-component sulfonaminoalkynylation of alkenes with N -aminopyridine salts and potassium alkynyltrifluoroborate salts. This aminoalkylation reaction underwent a radial/polar crossover mechanism, which was distinguished from the previous reports. A variety of β-alkynylated sulfonamides were obtained in moderate to excellent yields. The versatility of this method was further evidenced by its successful application in modifying biological molecules in advanced stages of development.
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摘要：
The monocyte adhesion to vascular endothelial cells constitutes a key step in atherosclerosis pathogenesis. We previously found that ROS-autophagy pathway participated in the monocyte-endothelial cell adhesion induced by angiotensin domain type 1 receptor-associated proteins (APJ) and its endogenous ligand apelin-13. In this study, we investigated what specific type of autophagy apelin-13 regulated in this process. By conducting full-scale transcriptomic analysis in apelin-13-treated human umbilical vein endothelial cells (HUVECs), we found that the transcription levels of ER-phagy receptor protein SEC62 were significantly elevated. Importantly, SEC62 was also upregulated in human atherosclerotic lesions. Thus, we investigated the effects of SEC62-dependent ER-phagy on apelin-13-induced monocyte-endothelial cell adhesion and atherosclerosis pathogenesis. We demonstrated that Apelin-13 (0.001-1 μM) dose-dependently upregulated SEC62 expression thereby inducing ER-phagy in HUVECs. This effect was reversed by autophagy inhibitor 3MA (10 mM) and endoplasmic reticulum stress inhibitor salubrinal (10 μM). The siRNA-Sec62, 3MA (10 mM), and salubrinal (10 μM) all inhibited apelin-13-induced monocyte-endothelial cells adhesion, whereas vascular endothelial cells specific SEC62 deletion alleviated atherosclerotic plaques area, intercellular adhesion molecules expression and lesional macrophages in apelin-13-treated APOE(-/-) mice with high-fat and high-cholesterol diet. Moreover, we demonstrated that ubiquitin-like modification of ALDH1L1 was involved in SEC62-dependent ER-phagy in apelin-13-treated HUVECs: apelin-13 upregulated small ubiquitin-like protein UBL4A, which mediated the ubiquitination-like modification of ALDH1L1 at 812-lysine site. This, in turn, promoted insertion of ALDH1L1 into ER membrane and led to SEC62-dependent ER-phagy. We showed that siRNA-UBL4A, siRNA-ALDH1L1, siRNA-ASNA1, and the mutant of 812 lysine site of ALDH1L1 all decreased apelin-13-induced monocyte-endothelial cell adhesion. We conclude that apelin-13 induces SEC62-dependent ER-phagy to promote monocyte-endothelial cell adhesion and atherosclerosis. This study reveals new mechanisms underlying atherosclerosis and identifies a potential therapeutic target.
摘要：
Empagliflozin is a highly selective sodium-glucose cotransporter 2 inhibitor and an effective medication for treating diabetes. This study aimed to assess the pharmacokinetics and bioequivalence of two 10-mg empagliflozin tablets in healthy Chinese subjects and examine food's effect on absorption. The research was conducted as a single-center, randomized, open-label, single-dose, 2-way crossover study involving 47 subjects (fasting: n = 23, fed: n = 24). Subjects received either the test or reference drug and switched to the alternative after a 7-day washout period. Blood samples were collected before administration and up to 48 hours after dosing, analyzed using validated liquid chromatography-tandem mass spectrometry techniques to determine empagliflozin levels. In both studies, all 23 subjects completed the study phases under fasting and fed conditions. In both scenarios, when comparing the test and reference formulations, the 90% confidence intervals for the geometric mean ratios of maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence threshold of 80%-125%, confirming their acceptability. The study found that a high-fat meal slightly reduced drug exposure and slightly accelerated absorption. No serious adverse events were observed. This research confirmed the pharmacokinetic similarity of the 2 empagliflozin formulations and demonstrated their good tolerance under fasting and fed conditions.
作者机构：
[Liu, Ying; Deng, Min; Zhai, Zibo; He, Longwei; Wang, Peipei; Li, Songjiao; Cheng, Dan; He, LW] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch,Dept Gastroenterol, Hengyang 421002, Peoples R China.;[He, LW; He, Longwei] Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
通讯机构：
[He, LW ] H;[Li, SJ ; He, LW] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
摘要：
Revealing changes in the tumor microenvironment is crucial for understanding cancer and developing sensitive methods for precise cancer imaging and diagnosis. Intracellular hydrogen peroxide (H(2)O(2)) and microenvironmental factors (e.g., viscosity and polarity) are closely linked to various physiological and pathological processes, making them potential biomarkers for cancer. However, a triple-response theranostic probe for precise tumor imaging and therapy has not yet been achieved due to the lack of effective tools. Herein, we present a mitochondria-targeting near-infrared (NIR) fluorescent probe, VPH-5DF, capable of simultaneously monitoring H(2)O(2), viscosity, and polarity through dual NIR channels. The probe specifically detects H(2)O(2) via NIR emission (λ(em) = 650 nm) and shows high sensitivity to microenvironmental viscosity/polarity in the deep NIR channel (λ(em) ≈ 750 nm). Furthermore, the probe not only monitors mitochondrial polarity, viscosity, and fluctuations in endogenous/exogenous H(2)O(2) levels but also distinguishes cancer cells from normal cells through multiple parameters. Additionally, VPH-5DF can be employed to monitor alterations in H(2)O(2) levels, as well as changes in viscosity and polarity, during drug-induced pyroptosis in living cells. After treatment with VPH-5DF, chemotherapy-induced oxidative damage to the mitochondria in tumor cells activated the pyroptosis pathway, leading to a robust antitumor response, as evidenced in xenograft tumor models. Thus, this triple-response theranostic prodrug offers a new platform for precise in vivo cancer diagnosis and anticancer chemotherapy.
摘要：
This study systematically investigated the antioxidant activities and phytochemical profiles of petroleum ether (PE), ethyl acetate (EtOAc), n-butanol (n-BuOH) and aqueous fractions of edible (tubers) and non-edible portions (peels) of Pachyrhizus erosus. The results showed that both the tubers and peels from P. erosus were rich in polyphenols and flavonoids, whereas the EtOAc fraction of peels had the highest polyphenol content, and the PE fraction of peels had the highest total flavonoid content. ABTS, DPPH, and FRAP assays revealed that both the EtOAc fraction of tubers and peels from P. erosus showed significant antioxidant activity, whereas the EtOAc fraction of peels possessed better antioxidant activity than that of tubers. UPLC-Orbitrap-MS/MS analysis indicated that thirty compounds were identified from the EtOAc fractions of peels and tubers, including twenty-one flavonoids, six phenolics, two coumarins, and one lignan, some of which have previously been revealed to display significant antioxidant and anti-inflammatory effects via the Nrf2-Keap1 and NF-kappa B signaling pathways. These findings provide robust scientific evidence for the health-promoting properties and pharmaceutical potential of P. erosus, and its non-edible portion (peels) has great potential for use as a natural antioxidant in the food, cosmetic, and pharmaceutical industries.
作者机构：
[Xie, Zhizhong; Zou, Wei; Wang, Jiaying] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Sch Pharm, Hengyang 421001, Peoples R China.;[Gao, Yinhuang; Liu, Menghua; Miao, Zhishuo] Southern Med Univ, Sch Pharmaceut Sci, Key Lab Drug Metab Res & Evaluat State Drug Adm, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China.
通讯机构：
[Liu, MH ] S;[Zou, W ] U;Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Sch Pharm, Hengyang 421001, Peoples R China.;Southern Med Univ, Sch Pharmaceut Sci, Key Lab Drug Metab Res & Evaluat State Drug Adm, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China.
摘要：
Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor with seven transmembrane domains, widely distributed in human cells. It plays a crucial role in inflammation-related diseases. Known for its "double-edged sword" nature, FPR2 can bind a variety of exogenous and endogenous ligands, mediating both pro-inflammatory and anti-inflammatory responses in tissues such as eyes, liver, joints, lungs, nerves, and blood vessels. FPR2's bioactivities are regulated by a complex network of genes and signaling pathways. However, the precise regulatory mechanisms governing its functions in different inflammatory conditions are still not well understood. This review summarizes the FPR2's activities in various inflammation-related diseases and looks into its potential as a therapeutic target. This review highlights recent advances in developing exogenous agonists for FPR2 and discusses receptor expression across species to support nonclinical research. Overall, this review aims to clarify FPR2's role in inflammation and provide insights for the development of new drugs against inflammatory diseases.
期刊：
Drug Design, Development and Therapy,2025年19:1655-1668 ISSN：1177-8881
通讯作者：
Long, MH;Xie, N
作者机构：
[Yan, Ting; Fu, Yilan; Zhang, Jiwen; Long, Minghui; Chen, Yun; Long, MH; Liao, Dehua] Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Xiangya Sch Med,Dept Pahrm, Changsha, Peoples R China.;[Zhang, Jiwen] Univ South China, Sch Pharm, Hengyang 421001, Peoples R China.;[Xie, Ning] Cent South Univ, Hunan Canc Hosp, Med Dept Breast Canc, Affiliated Canc Hosp,Xiangya Sch Med, Changsha, Peoples R China.
通讯机构：
[Long, MH ; Xie, N ] C;Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Xiangya Sch Med,Dept Pahrm, Changsha, Peoples R China.;Cent South Univ, Hunan Canc Hosp, Med Dept Breast Canc, Affiliated Canc Hosp,Xiangya Sch Med, Changsha, Peoples R China.
关键词：
T-DXd;AEs;ILD/pneumonitis;HER2;ADC
摘要：
Trastuzumab deruxtecan (T-DXd) has been approved to treat various tumors. While most adverse events (AEs) associated with T-DXd are manageable, interstitial lung disease (ILD)/pneumonitis is a notable AE of special concern. This review describes the incidence, severity, and management of T-DXd-induced ILD/pneumonitis across different tumors. We conducted a systematic search of PubMed, Embase, Cochrane Library, and Web of Science for literature published up to 13 September 2024, regarding the use of T-DXd in the treatment of HER2-positive tumors. Studies included were clinical trials involving HER2-positive tumors with reported ILD/pneumonitis cases.The main data extracted from the full-text articles included the incidence and severity of T-DXd-induced ILD. 18 studies involving 3380 patients with various advanced solid malignancies were included in our review. The overall incidence of adjudicated drug-related ILD/pneumonitis was 12.40%. Although most ILD/pneumonitis cases were low-grade, the risk of ILD/pneumonitis-related death should not be overlooked. Given the prolonged exposure to the drug, careful monitoring and management of T-DXd-induced ILD/pneumonitis are critical. Management strategies include dose reduction, treatment interruption, discontinuation, corticosteroids, and supportive care. Further research is needed to clarify the risk factors and mechanisms underlying T-DXd-induced ILD/pneumonitis. This review highlights critical gaps in understanding the risk factors and mechanisms of T-DXd-induced ILD, underscoring the need for further research.
摘要：
Therapeutic challenges of chronic pulmonary infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa ) biofilms due to significantly enhanced antibiotic resistance. This resistance is driven by reduced outer membrane permeability, biofilm barriers, and excessive secretion of virulence factors. Thickened mucus in the airways exacerbates the problem by impeding antibiotic penetration, providing a breeding ground for biofilms, consequently aggravating infection. Moreover, biofilms recruit numerous immune cells, resulting in chronic inflammation and lung tissue damage. In turn, damaged airway further facilitates bacterial colonization and elevated mucus production. To thoroughly disintegrate the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation” and address drug resistance, tailored multilayer nanoparticles (NPVC/PBIP NPs) were developed. NPVC/PBIP NPs were engineered through self-assembly of vanillin-chitosan amphiphilic polymer loading polymyxin B-linoleic acid ion pairs in. Then polyaspartic acid and N -acetylcysteine-ε-poly- l -lysine were coated by layer-by-layer on the surface of vanillin-chitosan NPs via electrostatic interactions. As expected, the NAC units on NPVC/PBIP NPs effectively thinned human clinical sputum and porcine sputum, resulting in rapid sputum penetration followed by biofilm permeation. NPVC/PBIP NPs achieved over 99 % eradication of mature biofilms in vitro . Furthermore, they effectively inhibited virulence factors production and bacteria re-adhesion (biofilm reformation) while exhibiting superior anti-inflammatory and antioxidant activities. In a chronic pulmonary infection model, NPVC/PBIP NPs remarkably thinned airway mucus, reduced bacterial burden by 99.7 %, alleviated inflammatory cell infiltration, and minimized lung tissue damage. In summary, the NPVC/PBIP NPs represent a novel and promising strategy to manage MDR P. aeruginosa biofilms associated infections by disintegrating the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation”.
Therapeutic challenges of chronic pulmonary infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa ) biofilms due to significantly enhanced antibiotic resistance. This resistance is driven by reduced outer membrane permeability, biofilm barriers, and excessive secretion of virulence factors. Thickened mucus in the airways exacerbates the problem by impeding antibiotic penetration, providing a breeding ground for biofilms, consequently aggravating infection. Moreover, biofilms recruit numerous immune cells, resulting in chronic inflammation and lung tissue damage. In turn, damaged airway further facilitates bacterial colonization and elevated mucus production. To thoroughly disintegrate the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation” and address drug resistance, tailored multilayer nanoparticles (NPVC/PBIP NPs) were developed. NPVC/PBIP NPs were engineered through self-assembly of vanillin-chitosan amphiphilic polymer loading polymyxin B-linoleic acid ion pairs in. Then polyaspartic acid and N -acetylcysteine-ε-poly- l -lysine were coated by layer-by-layer on the surface of vanillin-chitosan NPs via electrostatic interactions. As expected, the NAC units on NPVC/PBIP NPs effectively thinned human clinical sputum and porcine sputum, resulting in rapid sputum penetration followed by biofilm permeation. NPVC/PBIP NPs achieved over 99 % eradication of mature biofilms in vitro . Furthermore, they effectively inhibited virulence factors production and bacteria re-adhesion (biofilm reformation) while exhibiting superior anti-inflammatory and antioxidant activities. In a chronic pulmonary infection model, NPVC/PBIP NPs remarkably thinned airway mucus, reduced bacterial burden by 99.7 %, alleviated inflammatory cell infiltration, and minimized lung tissue damage. In summary, the NPVC/PBIP NPs represent a novel and promising strategy to manage MDR P. aeruginosa biofilms associated infections by disintegrating the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation”.
通讯机构：
[Yu, CY; Wei, H ] U;[Yu, CY ] Z;Zhejiang Univ, Dept Chem, Hangzhou 310027, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Peoples R China.;Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
enzyme-responsive;GSH-responsive;cross-linked shells;unimolecular micelles;anticancer drug delivery
摘要：
Cross-linked polymeric micelles capable of undergoing de-cross-linking triggered by tumor microenvironment (TME) provide a solution to the extracellular stability vs intracellular destabilization dilemma of nanomedicine. Herein, we reported a simple yet effective strategy for the one-pot construction of enzyme and glutathione (GSH) dual-responsive zwitterionic copolymer micelles consisting of hydrophobic enzyme-degradable polytyrosine (PTyr) cores and cross-linked zwitterionic poly(oligo(ethylene glycol)monomethyl ether methacrylate- co -sulfobetaine methacrylate- co -disulfide dimethacrylate) ( P (OEGMA- co -SBMA- co -DSDMA)) shells. Notably, the development of unimolecular zwitterionic copolymer micelles could be achieved simultaneously in the polymer synthesis process via regulating the feed ratio of a functionalized monomer, DSDMA, as a cross-linker. The optimized polymer construct could form stable unimolecular micelles with a drug-loading content (DLC) of 14.9% and an entrapment efficiency (EE) of 87.7% for DOX, along with promoted in vitro drug release and tumor inhibition ratio (TIR). The simple synthetic strategy developed herein provides a widespread approach for the production of multifunctional cross-linked polymeric delivery systems for efficient anticancer drug transportation.
摘要：
BACKGROUND: Proteus spp. have long been recognized for their role in urinary tract infections, while recent evidence disclosed their implications in gastrointestinal diseases. Despite this, the taxonomy of clinically-derived Proteus spp., particularly those from gastrointestinal samples, remains understudied and is frequently mis-assigned, which limits our understanding of infections caused by these species. RESULTS: Four Proteus strains (i.e., DFP240708, LHD240705, TSJ240517 and WDL240414) were isolated from the appendiceal pus of patients with acute appendicitis, whole-genome average nucleotide identity (ANI) analysis identified all of them as Proteus genomosp. 6, different from that identified using the automated bacterial identification instrument (VITEK(®)-32). Based on ANI and the core-genomic phylogenetic tree, we found that 87.5% of clinically-related strains previously identified as P. columbae should be re-classified as Proteus genomosp. 6. Additionally, the Proteus genomosp. 6 genomes all carry one or more beta-lactam resistance genes, but none carry aminoglycoside resistance genes, and antibiotic susceptibility testing conducted on the four strains isolated in this study confirmed these findings. Among the genomes analyzed, only four (two from this study (TSJ240517 and WDL240414)) carried virulence genes, specifically the hlyA, hlyB, and hlyD genes encoding hemolysin. CONCLUSION: Our study highlights inaccuracies in the taxa classification of Proteus species under clinical settings, underscoring the necessity of using genomic-based taxonomic assignment methods. We revealed that the prevalence of Proteus genomosp. 6 in clinical infections has likely been underestimated. Furthermore, given the resistance-gene absence and their sensitivity to aminoglycosides, aminoglycosides may serve as a promising first-line treatment option for infections caused by this species.
作者机构：
[Yuan, Peng-Xiang; Wang, Li-Li; Wang, Yu-Ping; Du, Fangfang] School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China;[Du, Fangfang] Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Emergency and Trauma, Ministry of Education, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, Hainan, China;[Yang, Liu-Pan] School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: yanglp@usc.edu.cn;[Wang, Li-Li] Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: wangll@usc.edu.cn
通讯机构：
[Li-Li Wang] S;School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China<&wdkj&>Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
摘要：
As widely used antibiotics, tetracycline residues exist in food and environmental media, which pose certain hidden dangers and negative effects on public health. Therefore, the sensing and discrimination of tetracycline analogs (TCs) have great significance for improving food safety and preventing environmental pollution. Herein, a 7-hydroxycoumarin-3-carboxylic acid-embedded Eu-MOF (HC@Eu-MOF) material was constructed and then developed for the detection of TCs. Upon addition of TCs, the synthesized sensor displays opposite fluorescence changes at two different wavelengths due to the simultaneous presence of the inner filter effect (IFE) and the antenna effect (AE), and achieves a stable ratio signal response within 90s. In addition, six important tetracycline analogs, including chlortetracycline (CTC), oxytetracycline (OTC), tetracycline (TC), metacycline (MC), doxycycline (DC) and demeclocycline (DMC) can be discriminated with 100% accuracy through the principal component analysis even in extremely complicated mixtures. Further, a smartphone-assisted portable device was applied for visual sensing of TCs. The as-developed platform possessed the characteristics of simple synthesis, fast response, high sensitivity, and high stability, which further lays a further foundation for the on-site visual detection and discrimination of TCs in real samples.
摘要：
Cardiovascular diseases (CVDs), the leading cause of human death worldwide, are diseases that affect the heart and blood vessels and include arrhythmias, coronary atherosclerotic heart disease, hypertension, and so on. Resveratrol (RSV) is a natural nonflavonoid phenolic compound with antioxidant, anti-inflammatory, anticancer, and cardiovascular protection functions. RSV has shown significant protective effects against CVD. However, RSV's clinical application is limited by its tendency to be oxidized and metabolized easily. Therefore, it is necessary to optimize the RSV structure. This review will introduce the activity, synthesis, and structure-activity relationships of RSV derivatives, and the mechanism of the action of RSV in CVDs in recent years.
