Discovering the anti-cancer phytochemical rutin against breast cancer through the methodical platform based on traditional medicinal knowledge.

A number of therapeutic drugs have been developed from functional chemicals found in plants. Knowledge of plants used for medicinal purposes has historically been transmitted by word of mouth or through literature. The aim of the present study is to provide a systemic platform for the development of lead compounds against breast cancer based on a traditional medical text. To verify our systematic approach, integrating processes consisted of text mining of traditional medical texts, 3-D virtual docking screening, and in vitro and in vivo experimental validations were demonstrated. Our text analysis system identified rutin as a specific phytochemical traditionally used for cancer treatment. 3-D virtual screening predicted that rutin could block EGFR signaling. Thus, we validated significant anticancer effects of rutin against breast cancer cells through blockade of EGFR signaling pathway in vitro. We also demonstrated in vivo anti-cancer effects of rutin using the breast cancer recurrence in vivo models. In summary, our innovative approach might be proper for discovering new phytochemical lead compounds designing for blockade of malignant neoplasm including breast cancer. [BMB Reports 2023; 56(11): 594-599].

The emerging role of exosomes as novel therapeutics: Biology, technologies, clinical applications, and the next.

The extracellular vesicles (EVs) research area has grown rapidly because of their pivotal roles in intercellular communications and maintaining homeostasis of individual organism. As a subtype of EVs, exosomes are made via unique biogenesis pathway and exhibit disparate functional and phenotypic characteristics. Functionally, exosomes transfer biological messages from donor cell to recipient cell, which makes exosomes as a novel therapeutic platform delivering therapeutic materials to the target tissue/cell. Currently, both academia and industry try to develop exosome platform-based therapeutics for disease management, some of which are already in clinical trials. In this review, we will discuss focusing on therapeutic values of exosomes, recent advances in therapeutic exosome platform development, and late development of exosome therapeutics in diverse therapeutic areas.

Evaluation of drug-targetable genes by defining modes of abnormality in gene expression.

In the post-genomic era, many researchers have taken a systematic approach to identifying abnormal genes associated with various diseases. However, the gold standard has not been established, and most of these abnormalities are difficult to be rehabilitated in real clinical settings. In addition to identifying abnormal genes, for a practical purpose, it is necessary to investigate abnormality diversity. In this context, this study is aimed to demonstrate simply restorable genes as useful drug targets. We devised the concept of "drug targetability" to evaluate several different modes of abnormal genes by predicting events after drug treatment. As a representative example, we applied our method to breast cancer. Computationally, PTPRF, PRKAR2B, MAP4K3, and RICTOR were calculated as highly drug-targetable genes for breast cancer. After knockdown of these top-ranked genes (i.e., high drug targetability) using siRNA, our predictions were validated by cell death and migration assays. Moreover, inhibition of RICTOR or PTPRF was expected to prolong lifespan of breast cancer patients according to patient information annotated in microarray data. We anticipate that our method can be widely applied to elaborate selection of novel drug targets, and, ultimately, to improve the efficacy of disease treatment.

Application of dynamic indocyanine green perfusion imaging for evaluation of vasoactive effect of acupuncture: a preliminary follow-up study on normal healthy volunteers.

BACKGROUND: Even though acupuncture has long been used for alleviating symptoms related to vascular insufficiency, the clinical effect of acupuncture on peripheral circulation has not been fully confirmed. In this study, we investigated whether a near-infrared optical imaging-based method can be used to evaluate the efficacy of the acupuncture procedure to induce changes in peripheral tissue perfusion. METHODS: Two normal, healthy controls were treated with acupuncture on two acupoints (LI-4 and SI-3) three times within 1 week. At the first and third visits, participants were examined using indocyanine green (ICG) perfusion imaging before and 10 minutes after the acupuncture procedure. Blood perfusion of the hands was determined after intravenous bolus injection of ICG and dynamic analysis of the fluorescence signals by near-infrared imaging system. RESULTS: The blood perfusion rates of the hands were markedly increased immediately after acupuncture at the first trial in both cases. The baseline perfusion rates of the hands measured at the third visit were higher compared to the original basal level in one case; there was no difference in baseline perfusion rates of both hands in another case. In both cases, there was no acute effect of acupuncture on hand perfusion at the third trial. CONCLUSIONS: These results collectively suggest a potential of the ICG perfusion imaging as an effective evaluation tool to validate the vasoactive effect of acupuncture.

Effects of delayed and extended antioxidant treatment on acute acoustic trauma.

OBJECTIVE: Hair cell death caused by acute acoustic trauma (AAT) reaches a secondary maximum at 7-10 days after noise exposure due to a second oxidative stress. Therefore, this study tested the effects of a combination of hydroxylated alpha-phenyl-tert-butylnitrone (4-OHPBN), N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) on AAT when the duration of treatment was extended over the period of 7-10 days after noise exposure as well as when the initial treatment was delayed 24 to 48 h after noise exposure. METHODS: Thirty chinchilla were exposed to a 105 dB octave-band noise centred at 4 kHz for 6 h and received the following treatments: (1) noise + saline (2-5) 4-OHPBN (20 mg/kg) + NAC (50 mg/kg) + ALCAR (20 mg/kg) intraperitoneally injected beginning 24 or 48 h after noise exposure twice daily for the next 2, 8 or 9 days. Auditory brainstem response (ABR) threshold shifts, outer hair cell (OHC) counts and organ of Corti immunohistochemistry were analyzed. RESULTS: The combination administration decreased ABR threshold shifts, inhibited OHC loss and reduced 4-hydroxynonenal (4-HNE) immunostaining. Significant decreases in the threshold shifts and reduction in OHC loss were observed with a shorter delay before starting treatment (24 h) and longer duration (9 days) treatment. CONCLUSIONS: These results demonstrate that the administration of antioxidant drugs extended up to 10 days after noise exposure can effectively treat AAT in a chinchilla model. This may provide significant and potentially clinically important information about the effective therapeutic window for AAT treatment.

Aqueous extract of the medicinal plant Patrinia villosa Juss. induces angiogenesis via activation of focal adhesion kinase.

Patrinia villosa, a Chinese medicinal herb, is known for its anti-inflammatory effects. In the present study, we tested the pro-angiogenic efficacy of an aqueous extract of Patrinia villosa (PVE) in vitro and in vivo. Treatment with PVE significantly enhanced cell proliferation, migration, and the capillary-like structure forming activity of cultured human umbilical vein endothelial cells (HUVECs). Western blot analysis demonstrated that PVE treatment induced a time-dependent phosphorylation of FAK and Akt in HUVECs. Preincubation with a FAK inhibitor, SC203950, abolished PVE-induced proliferation of HUVECs, indicating a role for FAK in PVE-induced angiogenesis. The proangiogenic activity of PVE was confirmed by an ex vivo mouse aortic ring assay and an in vivo murine hindlimb ischemia model. Further analysis using fractions of PVE partitioned by n-hexane, EtOAc, n-BuOH, and water residue revealed that the EtOAc fraction contains the bioactive components responsible for PVE-induced migration, endothelial cord formation, FAK phosphorylation, and aortic ring sprouting. Our results provide a rationale for the use of PVE in the treatment of peripheral vascular insufficiency; they indicate the need to identify the novel pro-angiogenic chemicals in the fractions of PVE.

Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury.

Vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor (PDGF) play an important role in the development of atherosclerosis and restenosis. Recent evidence indicates that PDGF increases intracellular levels of reactive oxygen species in VSMCs and that both PDGF-induced VSMC proliferation and migration are reactive oxygen species-dependent. Danshen is a representative oriental medicine used for the treatment of vascular disease. Previously, we reported that magnesium lithospermate B, an active component of Danshen, is a potent antioxidant. Thus we investigated the therapeutic potential of magnesium lithospermate B in neointimal formation after carotid artery injury in rats along with its effects on the PDGF signaling pathway for stimulating VSMC proliferation and migration in vitro. PDGF is dimeric glycoprotein composed of two A or two B chains. In this study, we used PDGF-BB, which is one of the isoforms of PDGF (i.e., PDGF-AA, PDGF-BB, and PDGF-AB). Our results demonstrated that magnesium lithospermate B directly scavenged reactive oxygen species in a xanthine/xanthine oxidase system and reduced PDGF-BB-induced intracellular reactive oxygen species generation in VSMCs. In a rat carotid artery balloon injury model, magnesium lithospermate B treatment (10 mg/kg/day, i.p) showed a significant effect on the prevention of neointimal formation compared with vehicle treatment. In cultured VSMCs, magnesium lithospermate B significantly attenuated PDGF-BB-induced cell proliferation and migration as measured by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and transwell migration assays, respectively. Further, magnesium lithospermate B inhibited PDGF-BB-induced phosphorylation of phospatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways by scavenging reactive oxygen species. Together, these data indicated that magnesium lithospermate B, a potent reactive oxygen species scavenger, prevented both injury-induced neointimal formation in vivo and PDGF-BB-induced VSMC proliferation and migration in vitro, suggesting that magnesium lithospermate B may be a promising agent to prevent atherosclerosis and restenosis following angioplasty.

Laser irradiation of the guinea pig basilar membrane.

BACKGROUND AND OBJECTIVES: The cochlea is the part of the inner ear that transduces sound waves into neural signals. The basilar membrane, a connective tissue sheet within the cochlea, is tonotopically tuned based on the spatial variation of its mass, stiffness, and damping. These biophysical properties are mainly defined by its constituent collagen fibers. We sought to assess the effect of laser irradiation on collagen within the basilar membrane using histological analysis. STUDY DESIGN/MATERIALS AND METHODS: Four excised guinea pig cochleae were stained with trypan blue. From these, two were irradiated with a 600 nm pulsed dye laser and two were used as controls. Collagen organization was visualized using polarization microscopy. RESULTS: Laser irradiation reduced the birefringence within the basilar membrane as well as within other stained collagen-containing structures. Larger reductions in birefringence were measured when more laser pulses were given. The effects were similar across all turns of each cochlea. CONCLUSIONS: Laser irradiation causes immediate alterations in collagen organization within the cochlea that can be visualized with polarization microscopy. These alterations may affect cochlear tuning. Ongoing research is aimed at analyzing the effect of laser irradiation on cochlear function. It is conceivable that this technique may have therapeutic benefits for patients with high-frequency sensorineural hearing loss.