Recent progress in development of new sonosensitizers for sonodynamic cancer therapy.

The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy-sonodynamic therapy, ultrasound-mediated chemotherapy, ultrasound-mediated gene delivery and anti-vascular ultrasound therapy-was reviewed. Each technique consistently resulted in the death of cancer cells, and the bio-effects of ultrasound were attributed primarily to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform that can monitor the success of anti-cancer therapy. Little attention, however, has been given either to the direct assessment of the mechanisms underlying the observed bio-effects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data, there could be prompt application of a therapy technique in the treatment of cancer patients.

A review of low-intensity ultrasound for cancer therapy.

Sonodynamic therapy (SDT) is a promising non-invasive therapeutic modality. Compared to photo-inspired therapy, SDT provides many opportunities and benefits, including deeper tissue penetration, high precision, less side effects, and good patient compliance. Thanks to the facile engineerable nature of nanotechnology, nanoparticles-based sonosensitizers exhibit predominant advantages, such as increased SDT efficacy, binding avidity, and targeting specificity. This review aims to summarize the possible mechanisms of SDT, which can be expected to provide the theoretical basis for SDT development in the future. We also extensively discuss nanoparticle-assisted sonosensitizers to enhance the outcome of SDT. Additionally, we focus on the potential strategy of combinational SDT with other therapeutic modalities and discuss the limitations and challenges of SDT toward clinical applications.

Sonodynamic therapy (SDT): a novel strategy for cancer nanotheranostics.

BACKGROUND
Early detection of premalignant/malignant lesions in the oral cavity can certainly improve the patient's prognosis. This study presents fluorescence imaging with the topical application of 5-aminolevulinic as a way to improve detection of various oral tissue pathologies. This procedure depends mainly on comparing the intensity of red and green fluorescence emitted from tissues during examination.


MATERIALS AND METHODS
Seventy-one patients who presented with clinically suspicious oral leukoplakia were recruited for this study. Each of the patients was required to have 5-aminolevulinic acid in the form of mouth rinse prior to fluorescence imaging. Following this a surgical biopsy was acquired from the exact examination site. The results of the fluorescence spectroscopy have been compared with histopathology.


RESULTS
A Student's t-test was applied to test the viability of the ratio between red and green fluorescence. The red-to-green ratio was found to increase significantly when the lesion was identified as dysplastic or carcinoma in situ. By applying a threshold line to discriminate between normal and dysplastic lesions; a sensitivity of 83-90% and specificity of 79-89% were obtained.


CONCLUSION
Fluorescence spectroscopy combined with 5-aminolevulinic acid-induced protoporphyrin IX was found as a valuable tool in the diagnosis of oral premalignancy. This technique offers the potential to be advantageous over other non-optical techniques in terms of providing real-time diagnosis, in situ monitoring, cost effectiveness and more tolerated by patient compared to surgical biopsy.

Fluorescence spectroscopy combined with 5-aminolevulinic acid induced protoporphyrin IX fluorescence in detecting oral premalignancy

Purpose
Sonodynamic therapy (SDT) is a new method for treating cancer by inducing cell necrosis and/or apoptosis. However, the molecular mechanisms of cell apoptosis after SDT treatment remain unclear. In this study we investigated the apoptotic effect and mechanisms of SDT mediated by hematoporphyrin monomethyl ether (HMME) on C6 glioma cells in vitro.

Apoptotic effect of sonodynamic therapy mediated by hematoporphyrin monomethyl ether on C6 glioma cells in vitro

This study was to investigate whether the apoptosis in isolate sarcoma 180 (S180) cells could be enhanced by ultrasound in the presence of protoporphyrin IX (PPIX) and also to evaluate the underlying biologic mechanism. S180 cells were exposed to ultrasound for 30 seconds' duration, at the frequency of 2.2 MHz and an acoustical power of 3 W/cm2 with 120 μM of PPIX. Cell apoptosis was evaluated based on the morphologic changes at different incubation times after sonication. Our results showed that the apoptosis in S180 tumor cells were induced by exposure, and the rate of apoptosis rose gradually with a longer incubation time. Our results also showed that changes in Fas protein expression were correlated with the development of apoptosis. The activities of caspase-8 and -3 were apparently upregulated by apoptosis, and the death substrate (PARP) was cleaved to active segments in a time-dependent manner. These results indicated that PPIX-mediated sonodynamic effect could exert its antitumor effect by trigger...

Enhancement of apoptosis by sonodynamic therapy with protoporphyrin IX in isolate sarcoma 180 cells.

Abstract Sophoridine is a natural quinolizidine alkaloid and a bioactive ingredient that can be isolated and identified from certain herbs, including Sophora flavescens Alt, Sophora alopecuroides L, and Sophora viciifolia Hance. In recent years, this quinolizidine alkaloid has gained widespread attention because of its unique structure and minimal side effects. Modern pharmacological investigations have uncovered sophoridine’s multiple wide range biological activities, such as anti-cancer, anti-inflammatory, anti-viral, anti-arrhythmia, and analgesic functions, among others. These pharmacological activities and beneficial effects point to sophoridine as a strong potential therapeutic candidate for the treatment of various diseases, including several cancer types, hepatitis B virus, enterovirus 71, coxsackievirus B3, cerebral edema, cancer pain, heart failure, acute myocardial ischemia, arrhythmia, inflammation, acute lung injury, and osteoporosis. The data showed that sophoridine had adverse reactions, including hepatotoxicity and neurotoxicity. Additionally, analyses of sophoridine’s safety, bioavailability, and pharmacokinetic parameters in animal models of research have been limited, especially in the clinic, as have been investigations on its structure-activity relationship. In this article, we comprehensively summarize the biological activities, toxicity, and pharmacokinetic characteristics of sophoridine and its derivatives, as currently reported in publications, as we attempt to provide an overall perspective on sophoridine analogs and the prospects of its application clinically.

https://www.dovepress.com/getfile.php?fileID=77667

Research Progress in the Pharmacological Activities, Toxicities, and Pharmacokinetics of Sophoridine and Its Derivatives

Fengreqing oral liquid (FOL), a Chinese patent drug frequently used in clinical practice in China, is effective in treating inflammatory diseases of the upper respiratory tract such as colds and flu. However, its anti-inflammatory effects and mechanisms remain to be elucidated. In this study, the anti-inflammatory effects of FOL and its mechanisms on PI3K/AKT and NF-κB signaling pathways in LPS-induced RAW264.7 cells were explored, as well as the regulatory effect of FOL on apoptosis. In addition, the potential of FOL for the treatment of acute lung injury was explored in LPS-induced ALI mice. The results showed that treatment with FOL significantly reduced the levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), nitric oxide (NO), and tumor necrosis factor α (TNF-α) in the supernatant of LPS-induced RAW264.7 cells, and also significantly reduced the phosphorylated protein levels of PI3K and AKT in the PI3K/AKT signaling pathway and also protein levels of NF-κB p50, phosphorylated NF-κB p65, and IκBα in the NF-κB signaling pathway. In addition, the results showed that FOL induced apoptosis in LPS-induced RAW264.7 cells at the level of 80%–90%, and significantly increased the protein expression levels of the pro-apoptotic Bax and cleaved-caspase-3. In LPS-induced ALI mice, FOL administration showed inhibition of IL-1β, IL-6, and TNF-α in Bronchoalveolar lavage fluid (BALF) and decreased protein expression levels of PI3K, AKT, NF-κB p50, and NF-κB p65, and elevated protein expression levels of Bax and cleaved-caspase-3 significantly. These results suggest that FOL may exert anti-inflammatory effects by inhibiting the PI3K/AKT signaling pathway to promote apoptosis and leading to attenuated activation of the NF-κB signaling pathway.

Fengreqing Oral Liquid Exerts Anti-Inflammatory Effects by Promoting Apoptosis and Inhibiting PI3K/AKT and NF-κB Signaling Pathways

*These authors contributed equally to this work Abstract: Sophoridine is a natural quinolizidine alkaloid and a bioactive ingredient that can be isolated and identified from certain herbs, including Sophora flavescens Alt, Sophora alopecuroides L, and Sophora viciifolia Hance. In recent years, this quinolizidine alkaloid has gained widespread attention because of its unique structure and minimal side effects. Modern pharmacological investigations have uncovered sophoridine’s multiple wide range biological activities, such as anti-cancer, anti-inflammatory, anti-viral, anti-arrhythmia, and analgesic functions, among others. These pharmacological activities and beneficial effects point to sophoridine as a strong potential therapeutic candidate for the treatment of various diseases, including several cancer types, hepatitis B virus, enterovirus 71, coxsackievirus B3, cerebral edema, cancer pain, heart failure, acute myocardial ischemia, arrhythmia, inflammation, acute lung injury, and osteoporosis. The data showed that sophoridine had adverse reactions, including hepatotoxicity and neurotoxicity. Additionally, analyses of sophoridine’s safety, bioavailability, and pharmacokinetic parameters in animal models of research have been limited, especially in the clinic, as have been investigations on its structure-activity relationship. In this article, we comprehensively summarize the biological activities, toxicity, and pharmacokinetic characteristics of sophoridine and its derivatives, as currently reported in publications, as we attempt to provide an overall perspective on sophoridine analogs and the prospects of its application clinically.

Dddt_a_339555 191..212

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and important human pathogen capable of causing significant clinical diseases ranging from skin damage to encephalitis, particularly in immunocompromised and neonatal hosts. Currently, widely used nucleoside analogs, including acyclovir and penciclovir, have some limitations in their use due to side effects and drug resistance. Herein, we report sophoridine's (SRI) dramatic inhibition of HSV-1 replication in vitro. SRI exhibited a remarkable inhibitory influence on HSV-1 virus-induced cytopathic effect and plaque formation, as well as on progeny viruses in Vero and HeLa cells, with selection indexes (SI) of 38.96 and 22.62, respectively. Moreover, SRI also considerably suppressed HSV-1 replication by hindering the expression of viral immediate-early (ICP0 and ICP22), early (ICP8 and TK), and late (gB and gD) genes and the expression of viral proteins ICP0, gB, and gD. We suggest that SRI can directly inactivate viral particles and block some stages in the life cycle of HSV-1 after adsorption. Further experiments showed that SRI downregulated the cellular PI3K/Akt signaling pathway and obstructed HSV-1 replication even more. Most importantly, SRI markedly repressed HSV-1-induced p38 MAPK pathway activation. Collectively, this natural bioactive alkaloid could be a promising therapeutic candidate against HSV-1 via the modulation of cellular PI3K/Akt and p38 MAPK pathways.

Sophoridine Suppresses Herpes Simplex Virus Type 1 Infection by Blocking the Activation of Cellular PI3K/Akt and p38 MAPK Pathways

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