Dendrimer-conjugated podophyllotoxin suppresses DENA-induced HCC progression by modulation of inflammatory and fibrogenic factors

Sharma, Supriya; Mehak,; Chhimwal, Jyoti; Patial, Vikram; Sk, Ugir Hossain

doi:10.1039/c9tx00103d

Cited by 15 publications

(13 citation statements)

References 39 publications

(48 reference statements)

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“…The sections were analyzed using a bright-field microscope, and the quantification of fibrous tissue was done with ImageJ software (ImageJ 1.52j) . 16…”

Section: Methodsmentioning

confidence: 99%

“…The stained slides were evaluated under microscope and quantification of the expression was done using ImageJ software. 16…”

Section: Methodsmentioning

confidence: 99%

“…The RNA pellet then washed with 70% ethanol, air-dried, and suspended in RNase free water. 16 Nanodrop (Thermo Fisher Scientific) was used to measure the quantity and purity of RNA.…”

Section: Methodsmentioning

confidence: 99%

“…The stained slides were evaluated under microscope and quantification of the expression was done using ImageJ software. 16 Total RNA isolation and RT-qPCR Total RNA was isolated using trizol reagent from the liver tissues stored at À80 C. Liver tissues were (100 mg) homogenized in 1 ml of trizol reagent. Chloroform (0.2 ml) per ml of trizol was added and centrifuged (12,000 Â g; 15 min; 4 C) to separate the nucleic acids into the aqueous phase.…”

Section: Picrosirius Stainmentioning

confidence: 99%

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Crocin attenuates CCl₄-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats

et al. 2020

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Background: Liver fibrosis is a chronic pathological condition with a leading cause of liver-related mortality worldwide. In the present study, we have evaluated the antifibrotic effect of crocin, a carotenoid present in the stigma of Crocus sativus, and also explored its putative mechanism of action. Methods: Liver fibrosis was induced by intraperitoneal administration of 30% carbon tetrachloride (CCl4). The crocin was administered orally at 20, 40 and 80 mg/kg body weight along with CCl4 up to 8 weeks. Results: Chronic exposure to CCl4 resulted in elevated levels of liver enzymes and reduced cytochrome P450 2E1 (CYP2E1) activity in the liver. The liver tissue showed cellular swelling, vacuolization, necrosis, infiltration of inflammatory cells and fibrotic changes. The crocin treatment significantly lowered the levels of liver enzymes in serum and improved the liver CYP2E1 mRNA levels. The pathological changes in the liver were also lowered by crocin treatment. The level of pro-inflammatory cytokines, nuclear factor-kappa B, interleukin-6 and tumor necrosis factor α and fibrogenic factor, transforming growth factor β, and α-smooth muscle actin were elevated by the CCl4 in the liver tissue. However, crocin treatment at different doses significantly reduced the expression of these factors. The increased caspase 3/7 activity was also lowered by crocin. CCl4 administration decreased the expression of peroxisome proliferator-activated receptor γ (PPAR-γ) in liver tissue. The improved PPAR-γ expression in the liver by crocin treatment indicates its role in the therapeutic effect of crocin. Conclusions: Crocin attenuated the various events in the progression of liver fibrosis via PPAR-γ mediated modulation of inflammatory and fibrogenic pathways.

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“…The sections were analyzed using a bright-field microscope, and the quantification of fibrous tissue was done with ImageJ software (ImageJ 1.52j) . 16…”

Section: Methodsmentioning

confidence: 99%

“…The stained slides were evaluated under microscope and quantification of the expression was done using ImageJ software. 16…”

Section: Methodsmentioning

confidence: 99%

“…The RNA pellet then washed with 70% ethanol, air-dried, and suspended in RNase free water. 16 Nanodrop (Thermo Fisher Scientific) was used to measure the quantity and purity of RNA.…”

Section: Methodsmentioning

confidence: 99%

Section: Picrosirius Stainmentioning

confidence: 99%

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Crocin attenuates CCl₄-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats

et al. 2020

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“…It is also well known that inflammation causes many cancers, especially liver cancer 9,10 . HCC is closely related to inflammation and usually occurs on the basis of chronic liver injury 11,12 .…”

Section: Introductionmentioning

confidence: 99%

Differential expression and diagnostic significance of P53, MutS homologs 2, tropomyosin‐4 in alpha‐fetoprotein‐negative hepatocellular carcinoma

Gong

Huang

2020

Clinical Laboratory Analysis

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Background Current study aimed to explore the value of P53, MutS homologs 2 (MSH2), and tropomyosin‐4 (Tm‐4) combined with inflammatory factors, life‐history traits in the differential diagnosis of alpha‐fetoprotein‐negative hepatocellular carcinoma (AFP‐Negative HCC). Methods A testing cohort including 280 AFP‐Negative HCC patients and 300 controls was included. Three external validation cohorts from 3 centers were used to assess the novel logistic regression model including 400 AFP‐Negative HCC patients and 400 controls. Results Compared with the control group, the levels of P53, MSH2, and Tm‐4 protein in si‐P53 group, si‐MSH2 group, and si‐Tm‐4 group were significantly reduced ( P < .05). The P53, MSH2, Tm‐4, neutrophil to lymphocyte ratio (NLR), monocytes to lymphocyte ratio (MLR), hypersensitive C‐reactive protein (hs‐CRP), tumor necrosis factor‐α (TNF‐α), interleukin 6 (IL‐6) levels, and the smoking, drinking, and occupational exposure to chemicals rates in patients were significantly higher than those in controls ( P < .05). ROC analyses showed that the area under curve (AUC) of NLR, MLR, hs‐CRP, TNF‐α, IL‐6, P53, MSH2, Tm‐4, drinking, smoking, and occupational exposure to chemicals were 0.798, 0.803, 0.560, 0.644, 0.808, 0.681, 0.830, 0.694, 0.582, 0.581, and 0.567, respectively. A novel logistic regression model was built and has a high value in identifying AFP‐Negative HCC with AUC of 0.917, sensitivity of 85.2%, and specificity of 88.3%. In the validation cohorts, this model also showed good diagnostic efficiency (AUC = 0.898 with Dazu Branch cohort, AUC = 0.924 with Jinshan Branch cohort, and AUC = 0.907 with Liangping Branch cohort). Conclusion Current model has potential significance for the noninvasive diagnosis of AFP‐Negative HCC.

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Targeting transforming growth factor‐ß signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin

Tewari

Priya

Bishayee³

et al. 2022

Clinical & Translational Med

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Background Cancer is the world's second leading cause of death, but a significant advancement in cancer treatment has been achieved within the last few decades. However, major adverse effects and drug resistance associated with standard chemotherapy have led towards targeted treatment options. Objectives Transforming growth factor‐β (TGF‐β) signaling plays a key role in cell proliferation, differentiation, morphogenesis, regeneration, and tissue homeostasis. The prime objective of this review is to decipher the role of TGF‐β in oncogenesis and to evaluate the potential of various natural and synthetic agents to target this dysregulated pathway to confer cancer preventive and anticancer therapeutic effects. Methods Various authentic and scholarly databases were explored to search and obtain primary literature for this study. The Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) criteria was followed for the review. Results Here we provide a comprehensive and critical review of recent advances on our understanding of the effect of various bioactive natural molecules on the TGF‐β signaling pathway to evaluate their full potential for cancer prevention and therapy. Conclusion Based on emerging evidence as presented in this work, TGF‐β‐targeting bioactive compounds from natural sources can serve as potential therapeutic agents for prevention and treatment of various human malignancies.

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Dendrimer-conjugated podophyllotoxin suppresses DENA-induced HCC progression by modulation of inflammatory and fibrogenic factors

Abstract: Podophyllotoxin has been explored as an anticancer, antiviral, and antibacterial agent; however, its low water solubility and toxicity limit its use.

Cited by 15 publications

References 39 publications

Crocin attenuates CCl₄-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats

Crocin attenuates CCl₄-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats

Differential expression and diagnostic significance of P53, MutS homologs 2, tropomyosin‐4 in alpha‐fetoprotein‐negative hepatocellular carcinoma

Targeting transforming growth factor‐ß signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin

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Dendrimer-conjugated podophyllotoxin suppresses DENA-induced HCC progression by modulation of inflammatory and fibrogenic factors

Abstract: Podophyllotoxin has been explored as an anticancer, antiviral, and antibacterial agent; however, its low water solubility and toxicity limit its use.

Cited by 15 publications

References 39 publications

Crocin attenuates CCl4-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats

Crocin attenuates CCl4-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats

Differential expression and diagnostic significance of P53, MutS homologs 2, tropomyosin‐4 in alpha‐fetoprotein‐negative hepatocellular carcinoma

Targeting transforming growth factor‐ß signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin

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Crocin attenuates CCl₄-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats

Crocin attenuates CCl₄-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats