Introduction: Cervical cancer is primarily caused by the human papilloma virus (HPV), which transforms normal cervical cells into cancerous cells that are highly resistant to radiation and chemotherapy. Induction of a...Introduction: Cervical cancer is primarily caused by the human papilloma virus (HPV), which transforms normal cervical cells into cancerous cells that are highly resistant to radiation and chemotherapy. Induction of apoptosis in transformed cells is a key strategy in successfully treating HPV-induced cervical cancer. TRAIL (tumor necrosis factor related apoptosis-inducing ligand) has been shown to selectively induce apoptosis in cancer cells by binding to death receptors and activating extrinsic pathways for apoptosis. However, certain cervical cancers—such as the cultured cell line SiHa—are remarkably resistant to TRAIL. In this study, SiHa cells were sensitized to TRAIL by using sanguinarine—derived from the plant Sanguinaria Canadensis—which is known to induce oxidative stress and lead to the upregulation of receptors for TRAIL. Methods: Cultured SiHa cells were exposed to sub-lethal doses of sanguinarine in combination with TRAIL. Cell viability changes as well as the production of reactive oxygen species (ROS) were assessed. The induction of apoptosis was investigated by assays for caspase activation. Flow cytometry was performed to analyze expression of death receptors 4/5. Results: Treatment of SiHa cells with a combination of sanguinarine and TRAIL led to a significant reduction in cell viability. Significant increase in ROS was observed and caspase activation assays confirmed the induction of apoptosis. Conclusions: The observed synergistic effect of sanguinarine and TRAIL on SiHa cells is promising for the treatment of cervical, and possibly other, HPV-induced cancers. Oxidative stress caused by sanguinarine seems to play a central role in this synergy. The precise link between reactive oxygen species and the possible upregulation of death receptors needs further investigation. This knowledge will enable us to devise more effective treatments for those who suffer from this devastating disease.展开更多
Retinal ganglion cells(RGCs)are essential in transmitting visual information from the retina to the brain,and their impairment has been linked to glaucoma and various neuro-ophthalmic diseases.In vivo imaging of RGC m...Retinal ganglion cells(RGCs)are essential in transmitting visual information from the retina to the brain,and their impairment has been linked to glaucoma and various neuro-ophthalmic diseases.In vivo imaging of RGC morphology and functionality is crucial for understanding the pathophysiology of retinal disease caused by RGC degeneration and their responses to treatments.This review provides a comprehensive overview of optical technologies suitable for in vivo RGC imaging.First,we compare scanning laser ophthalmoscopy,optical coherence tomography,and two-photon imaging and discuss their effectiveness in quantifying RGC damage in retinal disorders.Then,we discuss how functional vascular imaging techniques and specialized fluorophores,such as capQ and GCaMP,can be exploited to provide deeper insights into the physiology of RGCs.Lastly,we highlight the clinical translation of these imaging modalities,emphasizing handheld devices and clinical workflows to improve the image acquisition process.We also highlight the emerging role of machine learning,which automates tasks such as segmentation and disease classification to improve the efficiency of large data analysis.展开更多
文摘Introduction: Cervical cancer is primarily caused by the human papilloma virus (HPV), which transforms normal cervical cells into cancerous cells that are highly resistant to radiation and chemotherapy. Induction of apoptosis in transformed cells is a key strategy in successfully treating HPV-induced cervical cancer. TRAIL (tumor necrosis factor related apoptosis-inducing ligand) has been shown to selectively induce apoptosis in cancer cells by binding to death receptors and activating extrinsic pathways for apoptosis. However, certain cervical cancers—such as the cultured cell line SiHa—are remarkably resistant to TRAIL. In this study, SiHa cells were sensitized to TRAIL by using sanguinarine—derived from the plant Sanguinaria Canadensis—which is known to induce oxidative stress and lead to the upregulation of receptors for TRAIL. Methods: Cultured SiHa cells were exposed to sub-lethal doses of sanguinarine in combination with TRAIL. Cell viability changes as well as the production of reactive oxygen species (ROS) were assessed. The induction of apoptosis was investigated by assays for caspase activation. Flow cytometry was performed to analyze expression of death receptors 4/5. Results: Treatment of SiHa cells with a combination of sanguinarine and TRAIL led to a significant reduction in cell viability. Significant increase in ROS was observed and caspase activation assays confirmed the induction of apoptosis. Conclusions: The observed synergistic effect of sanguinarine and TRAIL on SiHa cells is promising for the treatment of cervical, and possibly other, HPV-induced cancers. Oxidative stress caused by sanguinarine seems to play a central role in this synergy. The precise link between reactive oxygen species and the possible upregulation of death receptors needs further investigation. This knowledge will enable us to devise more effective treatments for those who suffer from this devastating disease.
基金supported by the National Institutes of Health R01EY034353,U01EY033001,and R01EY034740the American Heart Association Predoctoral Fellowship 24PRE1177917.
文摘Retinal ganglion cells(RGCs)are essential in transmitting visual information from the retina to the brain,and their impairment has been linked to glaucoma and various neuro-ophthalmic diseases.In vivo imaging of RGC morphology and functionality is crucial for understanding the pathophysiology of retinal disease caused by RGC degeneration and their responses to treatments.This review provides a comprehensive overview of optical technologies suitable for in vivo RGC imaging.First,we compare scanning laser ophthalmoscopy,optical coherence tomography,and two-photon imaging and discuss their effectiveness in quantifying RGC damage in retinal disorders.Then,we discuss how functional vascular imaging techniques and specialized fluorophores,such as capQ and GCaMP,can be exploited to provide deeper insights into the physiology of RGCs.Lastly,we highlight the clinical translation of these imaging modalities,emphasizing handheld devices and clinical workflows to improve the image acquisition process.We also highlight the emerging role of machine learning,which automates tasks such as segmentation and disease classification to improve the efficiency of large data analysis.
