Glaucoma is a leading cause of irreversible blindness worldwide. A substantial proportion of patients experience disease progression despite adequate IOP control, which is the most significant modifiable risk factor. This indicates the involvement of additional pathogenic mechanisms. One such mechanism is neuroinflammation within the retina and optic nerve head, spearheaded by resident glial cells. These activated glial cells initiate a cascade of proinflammatory cytokines that drives oxidative stress, excitotoxic injury, and ultimately apoptosis in retinal ganglion cells (RGCs), the cells that are responsible for vision. Given the central role of cytokines in mediating this neuroinflammatory damage, several genetic association studies have checked whether functional variants in the cytokine genes modify disease susceptibility to primary glaucoma. In this review, we critically compare and assess the strength of these associations in both open-angle and angle-closure glaucoma, highlighting the inconsistencies and population-specific variability, while also evaluating the limitations of current association studies and how to overcome these challenges. Second, we address a critical mechanistic gap—how cytokine gene variants may influence glial activation, and contribute to the inflammatory ocular microenvironment that may drive disease progression. Finally, we discuss if oxidative stress–driven epigenetic modifications may modulate cytokine gene expression and amplify inflammatory responses in individuals who might be genetically predisposed to develop primary glaucoma.
The present study aimed to phytofabricate silver nanoparticles using the aqueous leaf extract of Rubus ellipticus through an eco-friendly green synthesis approach and evaluate their anticancer potential against triple-negative breast cancer (TNBC). Triple-negative breast cancer (TNBC) is an aggressive and therapeutically challenging subtype of breast cancer, highlighting the need for safer and effective treatment alternatives. Formation of Rubus ellipticus Sm. derived silver nanoparticles (REAgNPs) was confirmed by a visible color change and a characteristic surface plasmon resonance peak at 422 nm in UV–Vis spectroscopy. Comprehensive characterization using FTIR, SEM, EDX, TEM, SAED, AFM, XRD and zeta potential analysis revealed stable, spherical, crystalline nanoparticles with an average particle size of 10–30 nm and a negative surface charge (-22mV) indicating colloidal stability. REAgNPs exhibited a potential antioxidant activity in DPPH and hydrogen peroxide scavenging assays. In vitro cytotoxicity studies demonstrated a concentration-dependent antiproliferative effect against MDA-MB-231 TNBC cells, with an IC50 value of 30.12 µg/mL, comparable to the standard chemotherapeutic drug 5-fluorouracil. Mechanistic investigations revealed that REAgNPs-induced cytotoxicity involved mitochondrial membrane depolarization, nuclear and DNA damage, phosphatidylserine externalization, G0/G1 phase cell cycle arrest and caspase-3 activation, confirming apoptosis via the intrinsic pathway. This study highlights Rubus ellipticus derived silver nanoparticles as promising eco-friendly nanotherapeutic candidates for triple-negative breast cancer, warranting further in vivo validation and safety evaluation.
This study examines how advertising spending influences firm performance and investigates whether internationalization shapes this relationship. Using fixed-effects regression, we analyze a balanced panel of 185 listed Indian manufacturing firms over the period 2006-2024. The findings indicate a non-linear, concave-down relationship between advertising spending and firm performance, suggesting diminishing returns to advertising beyond a certain level. Importantly, the results show that internationalization significantly moderates this relationship. Firms with greater international exposure benefit more from advertising at lower levels of spending; however, at higher levels, internationalization intensifies the adverse effects of excessive advertising on sales. By integrating internationalization into the advertising-performance nexus through a contingency theory perspective, this study offers new empirical evidence that firm-specific strategic context plays a crucial role in determining advertising effectiveness. The findings contribute to the literature by highlighting internationalization as a key boundary condition that explains when and how advertising spending enhances firm performance.
Introduction Open-source software (OSS) projects thrive on collaborative communities, forming a critical backbone of modern technology. Despite community contributions shaping open-source development, a gap remains in understanding how community interactions impact project longevity. To address this, our study investigates how discussion volume (as a measure of engagement), sentiment expressed in discussions, issue resolution time, and issue characteristics influence both the resolution process and, crucially, OSS project lifespan.Methods Using a comprehensive GitHub issue dataset, we applied robust statistical analyses and effect size measures across various project lifecycle stages.Results Our findings reveal that while discussion volume weakly correlates with resolution time and sentiment's practical impact is negligible, a counter-intuitive pattern emerges: longer-lived projects consistently exhibit extended median issue resolution times, in contrast to faster initial resolutions observed in shorter-lived projects. Analysis of issue labels suggests this is because shorter-lived projects tend to address beginner-friendly issues, whereas enduring projects confront more complex, core development tasks. These findings emphasize that OSS project longevity depends less on rapid initial issue resolution and more on structured, sustained engagement with increasingly complex contributions-underscoring the vital role of qualitative communication and the nature of work in fostering robust communities.
Green synthesis of silver nanoparticles (AgNPs) is environmentally friendly, simple, and cost-effective and due to their unique physical and chemical properties, they have gained much attention in biomedical applications. The use of an aqueous plant extract that serves as both a reducing and stabilizing agent for AgNPs is considered natural and reliable method of treating diseases. In this study we have produced AgNPs using an aqueous extract of Tragopogon dubius, a medicinal herb traditionally used to treat rheumatism and burns, heal wounds, and prevent stomach ulcers, bleeding, strengthen the stomach wall and used in improvement of fatty liver with no evident side effects etc. The synthesized silver nanoparticles from Tragopogon dubius (AQTd-AgNPs) through UV-VIS spectroscopy and XRD analysis indicated suitable nucleation, stable absorbance peak, and appropriate reduction into nanoparticle formation. Dynamic Light Scattering (DLS) confirmed hydrodynamic diameter size distribution of 184.95 nm in colloidal solution with a polydispersity index below 0.253 while average zeta potential was recorded as -16.9 mV indicating a negatively charged surface. FESEM analysis revealed spherical shaped particles with average particle sizes of 16.86 nm. The HRTEM images using ImageJ software, yielding an average size of 14.48 nm. The investigations for cytotoxicity towards cancer cell lines demonstrated that AQTd-AgNPs possess potent anticancer properties towards MCF-7 (GI50 = 75.69 µg/mL), HCT-116 (GI50 = 61.71 µg/mL), and HeLa (GI50 = 52.75 µg/mL) respectively. The fluorescence microscopy observations indicated that AQTd-AgNPs induced apoptotic effects by disrupting nuclear integrity and mitochondrial membrane potential of cancer cells.The findings presented the first reports for systematically synthesizing silver nanoparticles from T. dubius aqueous extract with controlled optimization parameters for reproducible nanoparticle formation and demonstration of anticancer activity across different cancer cell lines revealed possible broad therapeutic potential of biogenic silver nanoparticles of Tragopogon dubius in cancer chemoprevention.
