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1.
Food Microbiol ; 120: 104466, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38431318

RESUMO

In this study, we evaluated the histomorphology, reactive oxygen species (ROS), protein degradation, and iron metabolism characteristics and differential expression analysis of genes for siderophores synthesis and protease secretion in prepared beef steaks inoculated alone or co-inoculated with P. weihenstephanensis, B. thermotrichothrix and M. caseolyticus at 4 °C for 12 days. The results showed that the P. weihenstephanensis was the key bacteria that degraded protein in the process of prepared beef steaks spoilage, which led to protein oxidation by promoting ferritin degradation to release free iron and inducing ROS accumulation. The highest expression of FpvA and AprE was detected in the P. weihenstephanensis group by comparing qRT-PCR of the different inoculation groups. Both qRT-PCR and Western blot revealed that ferritin heavy polypeptide and ferritin light chain polypeptide gene and protein expressions were significantly higher in the P. weihenstephanensis inoculation group compared to the other inoculation groups. Results suggested that FpvA and AprE might play roles in meat spoilage and were potential positional, physiological and functional candidate genes for improving the quality traits of prepared beef steaks. This work may provide insights on controlling food quality and safety by intervening in spoilage pathways targeting iron carrier biosynthesis or protease secretion genes.


Assuntos
Carne , Peptídeo Hidrolases , Pseudomonas , Animais , Bovinos , Espécies Reativas de Oxigênio , Carne/microbiologia , Ferritinas/genética , Peptídeos
2.
Food Chem ; 441: 138287, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38218141

RESUMO

While calpain's role in myofibrillar protein degradation is well-established, its impact on post-mortem apoptosis remains fully elucidated. This study aimed to examine how calpain influences the mitochondrial apoptotic pathway in post-mortem muscle cells and assess its potential impact on chicken tenderness. The findings indicate that the calpain inhibitor treatment could decelerate the rate of lysosome destruction in post-mortem chicken, which is a crucial factor in delaying the mitochondrial apoptotic pathway. Subsequently, this inhibition enhanced the mitochondrial membrane's stability and suppressed the apoptosis-inducing factor Cyt c release into the sarcoplasm. The Western blot results in a greater myofibrillar protein degradation degree in the caspase inhibitor samples compared to the calpain inhibitor samples. Interestingly, the two groups had no significant difference in shear force. Based on these reasons, a novel perspective was introduced in this paper: Calpain could affect the change in meat tenderness by regulating mitochondrial apoptosis in the post-mortem period.


Assuntos
Calpaína , Carne , Animais , Calpaína/metabolismo , Proteólise , Carne/análise , Apoptose , Galinhas/metabolismo , Mudanças Depois da Morte
3.
J Agric Food Chem ; 71(49): 19221-19239, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37947813

RESUMO

Cryopreservation, one of the most effective preservation methods, is essential for maintaining the safety and quality of food. However, there is no denying the fact that the quality of muscle food deteriorates as a result of the unavoidable production of ice. Advancements in cryoregulatory materials and techniques have effectively mitigated the adverse impacts of ice, thereby enhancing the standard of freezing preservation. The first part of this overview explains how ice forms, including the theoretical foundations of nucleation, growth, and recrystallization as well as the key influencing factors that affect each process. Subsequently, the impact of ice formation on the eating quality and nutritional value of muscle food is delineated. A systematic explanation of cutting-edge strategies based on nucleation intervention, growth control, and recrystallization inhibition is offered. These methods include antifreeze proteins, ice-nucleating proteins, antifreeze peptides, natural deep eutectic solvents, polysaccharides, amino acids, and their derivatives. Furthermore, advanced physical techniques such as electrostatic fields, magnetic fields, acoustic fields, liquid nitrogen, and supercooling preservation techniques are expounded upon, which effectively hinder the formation of ice crystals during cryopreservation. The paper outlines the difficulties and potential directions in ice inhibition for effective cryopreservation.


Assuntos
Criopreservação , Gelo , Congelamento , Criopreservação/métodos , Alimentos , Proteínas Anticongelantes/química , Músculos/metabolismo
4.
J Agric Food Chem ; 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37921432

RESUMO

This study aimed to effectively identify anti-inflammatory peptides in Jinhua ham, a dry-cured meat product made from the hind legs of pigs by curing and fermenting processes, and elucidate their anti-inflammatory mechanism. The investigation involved a combination of chromatographic purification, in silico screening, and in vitro validation. The first peak of JHP (JHP-P1) was purified using two-part exchange chromatography, in which 3350 peptides were identified by nano-HPLC-MS/MS, among which QLEELKR and EAEERADIAESQVNKLR showed significant anti-inflammatory potential (prediction scores: 0.759 and 0.841). In molecular docking and in vitro RAW264.7 cell experiments, these peptides displayed a strong affinity for Toll-like receptor 4-myeloid differentiation-2 (TLR4-MD-2), specifically binding around Arg 380, Lys 475, His 401, Gln 423, Asp 426, etc. This binding inhibited TLR4 expression and prevented trimer formation about TLR4-MD-2 and lipopolysaccharide (LPS), strongly inhibiting the inflammatory cascade. JHP suppressed LPS-induced cytokine overproduction and partially inhibited the phosphorylation of proteins in the MAPK/NF-κB pathway. These results demonstrated that combining in silico methods (activity prediction and molecular docking) is an effective strategy for screening anti-inflammatory peptides. This study provided a theoretical basis for identifying more anti-inflammatory peptides and applying them in functional foods.

5.
Int J Mol Sci ; 24(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37894822

RESUMO

Chemotherapy is commonly used clinically to treat colorectal cancer, but it is usually prone to drug resistance, so novel drugs need to be developed continuously to treat colorectal cancer. Neocryptolepine derivatives have attracted a lot of attention because of their good cytotoxic activity; however, cytotoxicity studies on colorectal cancer cells are scarce. In this study, the cytotoxicity of 8-methoxy-2,5-dimethyl-5H-indolo[2,3-b] quinoline (MMNC) in colorectal cells was evaluated. The results showed that MMNC inhibits the proliferation of HCT116 and Caco-2 cells, blocks the cell cycle in the G2/M phase, decreases the cell mitochondrial membrane potential and induces apoptosis. In addition, the results of western blot experiments suggest that MMNC exerts cytotoxicity by inhibiting the expression of PI3K/AKT/mTOR signaling pathway-related proteins. Based on these results, MMNC is a promising lead compound for anticancer activity in the treatment of human colorectal cancer.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Quinolinas , Humanos , Antineoplásicos/farmacologia , Apoptose , Células CACO-2 , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolinas/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
6.
Food Chem ; 428: 136786, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37429235

RESUMO

This study investigated the impact of low-voltage electrostatic field-assisted freezing on the water-holding capacity of beef steaks. The enhances mechanism of water-holding capacity by electrostatic field was elucidated through the detection of dynamic changes in the myofilament lattice and the construction of an in vitro myosin filaments model. The findings demonstrated that the disorder of the myofilament array, resulted from the aggregation of myosin filaments during freezing, is a crucial factor responsible for the water loss. The intervention of the electrostatic field can effectively reduce the myofibril density by 18.7%, while maintaining a regular lattice array by modulating electrostatic and hydrophobic interactions between myofibrils. Moreover, the electrostatic field significantly inhibited the migration of immobilized water to free water, thus resulting in an increase in the water-holding capacity of myofibrils by 36%. This work provides insights into the underlying mechanisms of water loss in frozen steaks and its regulation.


Assuntos
Miofibrilas , Água , Animais , Bovinos , Miofibrilas/química , Congelamento , Água/análise , Eletricidade Estática , Miosinas/química
7.
Food Res Int ; 171: 112985, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37330841

RESUMO

This study aims to elucidate the mechanism behind the deterioration in the gel properties of collagen gel resulting from high-temperature treatment. The results show that the high level of triple-helix junction zones and related lateral stacking contribute to the dense and orderly collagen gel network with high gel strength and storage modulus. The analysis of the molecular properties of heated collagen shows that high-temperature treatment leads to serious denaturation and degradation of collagen, resulting in the formation of gel precursor solutions composed of low-molecular-weight peptides. The short chains in the precursor solution are not easy to nucleation and can limit the growth of triple-helix cores. To conclude, the decrease in triple-helix renaturation and crystallization abilities of peptide components is the reason for the deterioration in the gel properties of collagen gel induced by high temperature. The findings presented in this study add the understanding of texture deterioration in high-temperature processed collagen-based meat products and related products, and provide a theoretical basis for establishing methods to overcome the production dilemma faced by these products.


Assuntos
Colágeno , Temperatura Alta , Temperatura , Colágeno/química , Peptídeos/química , Peso Molecular
8.
Food Chem ; 417: 135901, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36933425

RESUMO

Although the relationship between myofibrillar protein status and cooked meat quality is well documented, its underlying mechanism still need to be clarified. In this study, the effect of calpain-induced myofibrillar degradation on the cooked chicken quality was discussed by comparing the difference in muscle fiber's heat shrinkage state. In early postmortem, the protein around Z-line was degraded, which would cause the unstable Z-line and released into the sarcoplasm, according to WB results. This phenomenon will aggravate the lateral contraction of muscle fragments during the heating process. Then along comes a higher cooking loss and lower texture properties of meat. Above findings indicate that the Z-line dissociation caused by calpain in the early postmortem period is an essential reason for the quality difference of mature chicken. This study provided a fresh light on the mechanism underlying the impact of myofibril degradation in the early postmortem on the quality of cooked chicken.


Assuntos
Calpaína , Galinhas , Animais , Proteólise , Calpaína/metabolismo , Galinhas/metabolismo , Calefação , Culinária/métodos , Carne/análise , Mudanças Depois da Morte , Músculo Esquelético/metabolismo
9.
Eur J Pharmacol ; 938: 175408, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36442620

RESUMO

Gastric cancer is highly heterogeneous and there is still a lack of efficient, low-toxicity small molecule compounds for the treatment of gastric cancer. Natural products are important sources for the development of antitumor compounds. Therefore, it is promising strategy to find the lead compound of anti-gastric cancer agents by structural modification of natural products. The aim of this study was to synthesize a novel neocryptolepine derivative CFNC and explore its potential anti-gastric cancer effect and molecular mechanism. The MTT assay showed that the IC50 of CFNC on AGS cells reached 148 nM. CFNC arrested AGS cells in the G2/M phase of the cell cycle. Furthermore, CFNC inhibited cell proliferation and migration, leading to the loss of membrane potential by causing mitochondrial dysfunction, which induced the apoptosis of AGS cells. Western blot assay suggested that CFNC could inhibit the expression of important proteins in the PI3K/AKT/mTOR signaling pathway. These results showed that CFNC exhibited strong cytotoxic activity in gastric cancer cell lines by regulating the PI3K/AKT/mTOR signaling pathway. Taken together, CFNC could be a promising lead compound for the clinical treatment of gastric cancer.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Apoptose , Proliferação de Células , Antineoplásicos/uso terapêutico , Produtos Biológicos/farmacologia
10.
J Texture Stud ; 54(2): 258-267, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36450611

RESUMO

The effects of thermal processing on the texture and collagen properties of ready-to-eat chicken claws were investigated and the relationship between the texture of chicken claws and the collagen properties of connective tissue was further discussed. The texture, sensory and collagen characteristics (content, solubility, and structure), and the degradation of insoluble collagen of chicken claws underwent thermal processing at 90°C/30 min, 100°C/30 min, 115°C/15 min, and 121°C/10 min were measured. The results showed that thermal processing significantly reduced the textural parameters (hardness, springiness, cohesiveness, chewiness, and resilience) of chicken claws, and the textural deterioration intensified with the increase in temperature. Thermal processing aggravated the degradation of collagen fibers in cooked chicken claws, resulting in decreased insoluble collagen content and increased collagen solubility. Moreover, higher thermal processing temperature produced more soluble collagen components composed of low-molecular weight peptides. The textural deterioration of chicken claws caused by thermal processing was related to the decrease of insoluble collagen content and the increase of content of soluble collagen composed of low-molecular weight peptides. On the one hand, the decreased of insoluble collagen content led to the weakening of connective tissue. On the other hand, low-molecular weight peptides hindered the cooling renaturation of soluble collagen, leading to the formation of gels with poor mechanical properties.


Assuntos
Culinária , Temperatura Alta , Culinária/métodos , Temperatura , Solubilidade , Colágeno
11.
Sensors (Basel) ; 22(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36433202

RESUMO

Binocular stereoscopic matching is an essential method in computer vision, imitating human binocular technology to obtain distance information. Among plentiful stereo matching algorithms, Semi-Global Matching (SGM) is recognized as one of the most popular vision algorithms due to its relatively low power consumption and high accuracy, resulting in many excellent SGM-based hardware accelerators. However, vision algorithms, including SGM, are still somewhat inaccurate in actual long-range applications. Therefore, this paper proposes a disparity improvement strategy based on subpixel interpolation and disparity optimization post-processing using an area optimization strategy, hardware-friendly divider, split look-up table, and the clock alignment multi-directional disparity occlusion filling, and depth acquisition based on floating-point operations. The hardware architecture based on optimization algorithms is on the Stratix-IV platform. It consumes about 5.6 K LUTs, 12.8 K registers, and 2.5 M bits of on-chip memory. Meanwhile, the non-occlusion error rate of only 4.61% is about 1% better than the state-of-the-art works in the KITTI2015 dataset. The maximum working frequency can reach up to 98.28 MHz for the 640 × 480 resolution video and 128 disparity range with the power dissipation of 1.459 W and 320 frames per second processing speed.

12.
Int J Mol Sci ; 23(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36233226

RESUMO

Natural products play an important role in drug development and lead compound synthesis. Neocryptolepine is a polycyclic quinoline compound isolated from Cryptolepis sanguinolent. The cytotoxicity of neocryptolepine to gastric cancer cells AGS, MKN45, HGC27, and SGC7901 was not very strong, and it also had certain toxicity to gastric mucosa cells GES-1. Therefore, a series of neocryptolepine derivatives were synthesized by the modification of the structure of neocryptolepine, and their cytotoxicity was evaluated. The results showed that compounds C5 and C8 exhibited strong cytotoxicity to AGS cells. The cell colony formation and cell migration experiments suggested that compounds C5 and C8 could inhibit the proliferation and cell migration of AGS and HGC27 cells. Cell cycle and apoptosis experiments showed that compounds C5 and C8 did not cause the apoptosis of AGS and HGC27 cells but, mainly, caused cell necrosis. Compound C5 had no significant effect on AGS and HGC27 cell cycles at low concentration. After treatment with AGS cells for 24 h at high concentration, compound C5 could significantly arrest the AGS cell cycle in the G2/M phase. Compound C8 had no significant effect on the AGS and HGC27 cell cycles. The results of molecular docking and Western blot showed that compounds C5 and C8 might induce cytotoxicity through the PI3K/AKT signaling pathway. Therefore, compounds C5 and C8 may be promising lead compounds for the treatment of gastric cancer.


Assuntos
Antineoplásicos , Produtos Biológicos , Quinolinas , Neoplasias Gástricas , Alcaloides , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo
13.
Int J Mol Sci ; 23(14)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35887375

RESUMO

Isaindigotone is an alkaloid containing a pyrrolo-[2,1-b]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Isatis indigotca Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC50) of 1.45 µM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD50 (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer.


Assuntos
Alcaloides , Antineoplásicos , Neoplasias Gástricas , Alcaloides/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Quinazolinas/farmacologia , Transdução de Sinais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo
14.
Curr Microbiol ; 79(9): 270, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881202

RESUMO

Serofluid dish is a traditional fermented food that contains rich microbial populations. To gain insight into the environmental variables shaping the microbial diversity patterns, serofluid dish samples were collected from different areas, and 16S rRNA sequencing was performed. Analyses revealed both species and community diversity, including phylotype richness, Shannon index and phylogenetic diversity, were mostly influenced by pH. Additionally, such effects were corroborated by the Mantel test of pairwise UniFrac distances and variable selection of multiple linear regression models. Eventually, correlations between dominant lineages and the pH of serofluid dish other than geographical distance explained a large portion of the changes in microbial composition and diversity. Lactobacillus and related genera, Pediococcus and Acetobacter were largely driven by the variability of pH, and higher richness was observed under moderate pH ranges. Collectively, the results demonstrated that a microbial diversity pattern in serofluid dish is predictable by natural environmental variation and can be better understood through pH conditions.


Assuntos
Alimentos Fermentados , Verduras , China , Filogenia , RNA Ribossômico 16S/genética
15.
Front Bioeng Biotechnol ; 10: 898240, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677304

RESUMO

Cancer is second only to heart disease as a cause of death, despite improvements in its early diagnosis and precision medicine. Due to the limitations of commonly used anticancer methods such as surgery, radiotherapy and chemotherapy, biological therapy, especially probiotics such as lactic acid bacteria, has received widespread attention. Lactobacillus has been proven to inhibit the proliferation of a variety of cancer cells. In this work, the effects of the cell-free culture supernatant of serofluid dish (CCS1) and the cell-free culture supernatant of Lactiplantibacillus plantarum YT013 (CCS2) isolated from serofluid dish on AGS, HCT116, HepG2 and PANC-1 cells were investigated. Based on the CCK-8 assay, CCS1 and CCS2 were shown to suppress the growth of cancer cells in a concentration-dependent manner. The IC50 values of CCS2 of AGS, HCT116, HepG2 and PANC-1 cells were 346.51 ± 35.28, 1207.69 ± 333.18, 650.94 ± 123.78 and 808.96 ± 126.27 µg/ml, respectively. In addition, the results of fluorescence microscopy showed that CCS2 changed cell morphology and treated with CCS2 (200, 400 and 800 µg/ml) for 48 h, AGS cell apoptosis was quantitatively surveyed by flow cytometry, showing 25.0, 34.1, and 42.6% total apoptotic cells. Moreover, western blotting confirmed that BAX, BAD and Caspase-3/8/9 were significantly upregulated and that BCL-2 was significantly downregulated in AGS cells treated with CCS2. These results indicated that CCS2 might lead to apoptosis via the endogenous mitochondrial apoptotic pathway. In summary, Lactiplantibacillus plantarum YT013 may be considered a good candidate for anticancer therapies.

16.
Appl Environ Microbiol ; 88(14): e0048022, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35762790

RESUMO

Over 300 essential genes are predicted using transposon sequencing in the genome of Pseudomonas aeruginosa. However, methods for reverse genetic analysis of essential genes are scarce. To address this issue, we developed a three-step protocol consisting of integration of deletion plasmid, introduction of temperature-sensitive rescue plasmid, and excision of integrated-deletion plasmid to construct the plasmid-based temperature-sensitive allele of essential genes. Using PA0006 as an example, we showed that PA0006(Ts) exhibited wild-type cell morphology at permissive temperature but filamentous form at restrictive temperatures. We further showed that the glycerol-mannoheptose-bisphosphate phosphatase GmhB in Escherichia coli shared 32.4% identity with that of PA0006p and functionally complemented the defect of PA0006(Ts) at 42°C. SDS-PAGE and Western blotting indicated the presence and absence of the complete core lipopolysaccharide (LPS) and B-band O-antigen in PA0006(Ts) at 30 and 42°C, respectively. An isolated suppressor sup displayed wild-type-like cell morphology but no complete core LPS or O-antigen. Genome resequencing together with comparative transcriptomic profiling identified a candidate suppressor fructose-bisphosphate phosphatase in which the promoter harbored a SNP and the transcription level was not downregulated at 42°C compared to 30°C in sup. It was further validated that fbp overexpression suppressed the lethality of PA0006(Ts) at 42°C. Taken together, our results demonstrate that PA0006 plays a role in regulation of cell morphology and biosynthesis of core LPS. This three-step protocol for construction of conditional lethal allele in P. aeruginosa should be widely applicable for genetic analysis of other essential genes of interest, including analysis of bypass suppressibility. IMPORTANCE Microbial essential genes encode nondispensable function for cell growth and therefore are ideal targets for the development of new drugs. Essential genes are readily identified using transposon-sequencing technology at the genome scale. However, genetic analysis of essential genes of interest was hampered by limited methodologies. To address this issue, we developed a three-step protocol for construction of conditional allele of essential genes in the opportunistic pathogen Pseudomonas aeruginosa. Using PA0006 as an example, we demonstrated that the plasmid-based PA0006(Ts) mutant exhibited defects in regulation of cell morphology, formation of intact core LPS, and attachment of the O-antigen at restrictive temperatures but not at permissive temperatures. A suppressor of PA0006(Ts) was isolated through spontaneous mutations and showed restored cell morphology but not core oligosaccharide or O-antigen. This method should be widely applicable for phenotype and suppressibility analyses of other essential genes of interest in P. aeruginosa.


Assuntos
Lipopolissacarídeos , Pseudomonas aeruginosa , Alelos , Escherichia coli/genética , Antígenos O , Monoéster Fosfórico Hidrolases/genética , Plasmídeos/genética , Pseudomonas aeruginosa/genética
17.
Eur J Pharmacol ; 928: 175120, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35753402

RESUMO

1H-imidazole [4,5-f][1,10] phenanthroline is a promising chemical structure for cancer treatment. Herein, we synthesized a novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative named IPM714 and found it exhibited selectively colorectal cancer (CRC) cells inhibitory activities, with half maximal inhibitory concentration (IC50) of 1.74 µM and 2 µM in HCT116 cells and SW480 cells, respectively. The present study is intended to explore the cytotoxicity of IPM714 in cancer cells of various types and its anticancer mechanism in vitro. Cellular functional analyses indicated IPM714 can arrest HCT116 cell cycle in S phase and induce apoptosis in HCT116 and SW480 cells. Western blot and molecular docking showed that IPM714 may suppress PI3K/AKT/mTOR pathway to inhibit cell proliferation and regulate cell cycle as well as apoptosis. This study proved IPM714 to be a promising drug in CRC therapy.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Células HCT116 , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Simulação de Acoplamento Molecular , Fenantrolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo
18.
J Enzyme Inhib Med Chem ; 37(1): 1212-1226, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35450499

RESUMO

A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1-26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 µM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Humanos , Alcaloides , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Quinazolinas , Neoplasias Gástricas/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo
19.
Front Pharmacol ; 13: 841918, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308221

RESUMO

Colorectal cancer (CRC) is a common clinical malignant tumor and closely related to intestinal microbiome disorders. Especially, Fusobacterium nucleatum (F. nucleatum) is one of the most prevalent pathogens in CRC. However, its change in CRC patients of Northwest China, an area with a high incidence of gastrointestinal tumors, is unclear, and therapeutic strategies targeting F. nucleatum remain unresolved. Here, fecal samples of healthy people and CRC patients were studied using 16S rRNA sequencing to explore microbial community alterations. Additionally, vanillin derivate (IPM711 and IPM712) intervention by coculture with CRC cells and potential mechanism were investigated. Results showed that intestinal microbial homeostasis was gradually dysregulated, and the abundance of Fusobacterium was higher in CRC patients. Moreover, IPM711 and IPM712 showed better anti-F. nucleatum activity than vanillin by increasing cell membrane permeability and destroying bacterial integrity. In addition, IPM711 and IPM712 could downregulate the expression of E-cadherin and ß-catenin, thus, suppressing the migration of HCT116. Collectively, IPM711 and IPM712 have both anticolorectal cancer and anti-F. nucleatum activities, providing potential natural product drug candidates for microbe-targeted strategies for the treatment of CRC.

20.
J Nat Prod ; 85(4): 963-971, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35191714

RESUMO

Neocryptolepine derivatives have attracted great interest because of their unique cytotoxic activity. 8-Fluoroneocryptolepine (8FNC) was synthesized, and its cytotoxicity was evaluated by MTT assay in AGS gastric cancer cells and gastric mucosa GES-1 cells. 8-Fluoroneocryptolepine showed greater selectivity and cytotoxicity to AGS cells than the cisplatin (CIS) and fluorouracil (5-Fu) commonly used in clinical treatment of gastric cancer. Most importantly, we significantly improved the cytotoxic effect of 8FNC against AGS cells by structural modification and reduced the cytotoxicity against GES-1 cells compared with neocryptolepine. We further evaluated the activity of 8FNC against AGS cells in vitro. Our results indicate that 8FNC arrests the AGS cell cycle in the G2/M phase, reduces the mitochondrial membrane potential of AGS cells, and drives the initiation of apoptotic body formation in 8FNC-induced apoptosis. Moreover, 8FNC exhibits strong inhibitory effects on AGS cell migration. Studies on the molecular mechanisms of the cytotoxic activities of 8FNC revealed that it may play a significant role in the inhibitory effect on AGS human gastric cancer cells through the PI3K/AKT signaling pathway. In conclusion, 8FNC may become a promising lead compound in the development of potential clinical drug candidates for the treatment of gastric cancer.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Fluoruracila/farmacologia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Gástricas/tratamento farmacológico
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