• Book : 211(1)
• Pub. Date : 2025
• Page : pp.66-78
• Keyword :

• Book : 30(1)
• Pub. Date : 2025
• Page : pp.363-363
• Keyword :

ABSTRACT

Berberine, an isoquinoline alkaloid derived from various medicinal plants, emerges as a potential therapeutic agent against diverse human diseases. It has particularly shown notable anticancer efficacy against breast, colorectal, lung, prostate, and liver cancer. Berberine results in inhibition of cancer cell proliferation, induction of apoptosis, and suppressing angiogenesis, positioning it as a versatile, multitargeted therapeutic tool against cancer. Notably, berberine enhances the effectiveness of conventional chemotherapeutic drugs, mitigating associated drug resistance. Mechanistically, it has been shown to exert its efficacy by targeting molecules like nuclear factor‐kappa B (NF‐κB), mitogen‐activated protein kinases (MAPKs), and phosphoinositide 3‐kinase (PI3K)/Akt, thereby inhibiting survival pathways and promoting apoptosis of cancer cells. Moreover, berberine influences the expression of tumor suppressor genes, curtails cancer cell migration and invasion, and modulates the tumour microenvironment. Despite promising preclinical evidence, further research is essential to comprehensively elucidate its mechanisms of action and evaluate its safety and efficacy in clinical settings. In the present review, we have highlighted the pharmacokinetics, biosynthesis, and recent research work done pertaining to berberine's strong anticancer activity. We have also emphasised on the research being done on nanoformulations of berberine, which aim to improve its stability and bioavailability.

• Book : 39(1)
• Pub. Date : 2025
• Page : pp.e70073
• Keyword :

Abstract

Chronic obstructive pulmonary disease (COPD) is a pervasive and incapacitating respiratory condition, distinguished by airway inflammation and the remodeling of the lower respiratory tract. Central to its pathogenesis is an intricate inflammatory process, wherein macrophages exert significant regulatory functions, and High mobility group box 1 (HMGB1) emerges as a pivotal inflammatory mediator potentially driving COPD progression. This study explores the hypothesis that HMGB1, within macrophages, modulates COPD through inflammatory mechanisms, focusing on its influence on macrophage polarization. Our investigation uncovered that HMGB1 is upregulated in the context of COPD, associated with an enhanced proinflammatory M1 macrophage polarization induced by cigarette smoke. This polarization is linked to suppressed cell proliferation and induced apoptosis, indicative of HMGB1's role in the disease's inflammatory trajectory. The study further implicates HMGB1 in the activation of the Nuclear factor kappa‐B (NF‐κB) signaling pathway and chemokine signaling within macrophages, which are likely to amplify the inflammatory response characteristic of COPD. The findings underscore HMGB1's critical involvement in COPD pathogenesis, presenting it as a significant target for therapeutic intervention aimed at modulating macrophage polarization and inflammation.

• Book : 49(1)
• Pub. Date : 2025
• Page : pp.79-91
• Keyword :

Abstract

Background

The E‐cadherin, α‐ and β‐Catenin interaction at the cell adherens junction plays a key role in cell adhesion; alteration in the expression and function of these genes are associated with disease progression in several solid tumors including prostate cancer. The membranous β‐Catenin is dynamically linked to the cellular cytoskeleton through interaction with α‐Catenin at amino acid positions threonine 120 (T120) to 151 of β‐Catenin. Nuclear presence of α‐Catenin modulates the sensitivity of cells to DNA damage. The objective of this study is to determine the role of α‐Catenin and protein kinase D1 (PrKD1) in DNA damage response.

Methods

Prostate cancer cells; LNCaP, LNCaP (Sh‐PrKD1; silenced PrKD1), C4‐2 and C4‐2 PrKD1 were used for various sets of experiments to determine the role of DNA damage in PrKD1 overexpression and silencing cells. These cells were treated with compound‐10 (100 nM) and Etoposide (30 µM), total cell lysates, cytosolic and nuclear fractions were prepared to observe various protein expressions. We performed single cell gel electrophoresis (COMET assay) to determine the etoposide induce DNA damage in C4‐2 and C4‐2 PrKD1 cells. The animal experiments were carried out to determine the tolerability of compound‐10 by mice and generate preliminary data on efficacy of compound‐10 in modulating the α‐Catenin and PrKD1 expressions in inhibiting tumor progression.

Results

PrKD1, a novel serine threonine kinase, phosphorylates β‐Catenin T120. In silico analysis, confirmed that T120 phosphorylation alters β‐ to α‐Catenin binding. Forced expression of PrKD1 in prostate cancer cells increased β‐ and α‐Catenin protein levels associated with reduced etoposide induced DNA damage. Downregulation of α‐Catenin abrogates the PrKD1 mitigation of DNA damage. The in vitro results were corroborated in vivo using mouse prostate cancer patient derived xenograft model by inhibition of PrKD1 kinase activity with compound‐10, a selective PrKD inhibitor, demonstrating decreased total β‐ and α‐Catenin protein levels, and β‐Catenin T120 phosphorylation.

Conclusions

Alteration in DNA damage response pathways play major role in prostate cancer progression. The study identifies a novel mechanism of α‐Catenin dependent DNA damage mitigation role for PrKD1 in prostate cancer.

• Book : 85(2)
• Pub. Date : 2025
• Page : pp.156-164
• Keyword :

The consequence of nanoparticle aggregation and convective boundary condition on the nanofluid stream past the co-axial cylinder with radiation impact is investigated in the present examination. The influence of linear, nonlinear, and quadratic thermal radiation on the nanofluid flow is analyzed. The outer cylinder stays stable, while the inner cylinder deforms horizontally in the axial direction, allowing fluid to flow. By using similarity variables, the governing equations are transformed into ordinary differential equations (ODEs). Subsequently, the Runge-Kutta-Fehlberg fourth-fifth order (RKF-45) method is employed to solve the reduced ODEs. The upshot of several nondimensional terms on the temperature and velocity profiles is displayed with graphical representation. The comparison of linear, quadratic, and nonlinear thermal radiation on the thermal profile is illustrated. The upsurge in curvature parameter increases velocity and thermal profile. The increase in radiation parameter intensifies the temperature profile. The thermal profile improves with a rise in the values of radiation parameter. The radiation parameter generates thermal energy in the flow zone, which is why the temperature field has improved. The thermal Biot number exhibits an increasing response with temperature and thermal boundary layer thickness. The linear thermal radiation shows better heat transfer compared to quadratic and nonlinear thermal radiation.

• Book : 39(1)
• Pub. Date : 2025
• Page : pp.2450361
• Keyword :

• Book : 860()
• Pub. Date : 2025
• Page : pp.139186
• Keyword :

• Book : 213()
• Pub. Date : 2025
• Page : pp.111079
• Keyword :

• Book : 227()
• Pub. Date : 2025
• Page : pp.459-471
• Keyword :

• Book : 217()
• Pub. Date : 2025
• Page : pp.111634
• Keyword :