RESUMO
Platelet hyper-reactivity and neutrophil extracellular trap (NET) formation contribute to the development of thromboembolic diseases for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the pathophysiological effects of SARS-CoV-2 surface protein components and the viral double-stranded RNA (dsRNA) on platelet aggregation and NET formation. Traditional Chinese medicine (TCM) with anti-viral effects was also delineated. The treatment of human washed platelets with SARS-CoV-2 spike protein S1 or the ectodomain S1 + S2 regions neither caused platelet aggregation nor enhanced agonists-stimulated platelet aggregation. Moreover, NET formation can be induced by polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of viral dsRNA, but not by the pseudovirus composed of SARS-CoV-2 spike, envelope, and membrane proteins. To search for TCM with anti-NET activity, the plant Melastoma malabathricum L. which has anticoagulant activity was partially purified by fractionation. One of the fractions inhibited poly(I:C)-induced NET formation in a dose-dependent manner. This study implicates that SARS-CoV-2 structural proteins alone are not sufficient to promote NET and platelet activation. Instead, dsRNA formed during viral replication stimulates NET formation. This study also sheds new insight into using the active components of Melastoma malabathricum L. with anti-NET activity in the battle of thromboembolic diseases associated with SARS-CoV-2 infection.
RESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive cancer whose 5-year survival rate remains poor. San-Zhong-Kui-Jian-Tang (SZKJT), a Chinese herbal formula, has long been used in clinical practice as adjuvant therapy in cancers. However, its therapeutic effects and molecular mechanisms in OSCC remain unclear. METHODS: We investigated the potential therapeutic effects and molecular mechanism of SZKJT in OSCC in tumor cell lines and in tumor xenograft mice and evaluated combined SZKJT and cisplatin treatment efficacy. In vitro-cultured OSCC cells were administered SZKJT at different doses or SZKJT plus cisplatin, and cell proliferation, colony formation assays, and cell cycle analysis were used to assess the effects on cancer cell proliferation and apoptosis. We also analyzed the effects of SZKJT on oral cancer cell line migration, the regulation of mitogen-activated protein kinase (MAPK) signaling, and epithelial-mesenchymal transition (EMT)-associated genes. The antitumor effects of SZKJT plus cisplatin were also tested in vivo using a tumor-bearing NOD/SCID mice model. RESULTS: The results showed that SZKJT effectively inhibited OSCC cell proliferation, induced cell cycle S phase arrest, and induced cell apoptosis. SZKJT also inhibited cell migration by modulating the MAPK signaling and epithelial-mesenchymal transition (EMT) pathway. Further exploration suggested that SZKJT affects OSCC by modulating ERK pathway; downregulating vimentin, fibronectin, and Oct-4; and upregulating E-cadherin. In vivo, SZKJT significantly inhibited tumor growth, and SZKJT and cisplatin exerted synergistic antitumor effects in model animals. CONCLUSIONS: SZKJT exerts antitumor effects in OSCC cells. Additionally, SZKJT and cisplatin exhibit synergy in OSCC treatment. These findings support the clinical usage of Chinese herbal formulas as adjuvant therapy with chemotherapy in cancer treatment.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Camundongos , Animais , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Transição Epitelial-Mesenquimal , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cisplatino/farmacologia , Camundongos SCID , Camundongos Endogâmicos NOD , Proliferação de CélulasRESUMO
Polycystic ovary syndrome (PCOS) is a common endocrine disease of reproductive-age women, accounting for about 9% to 18% of all women in this age group. Hyperandrogenemia, oligomenorrhea, or amenorrhea or anovulation, and polycystic ovary morphology are the 3 main criteria used to diagnose PCOS currently. Substantial scientific evidence and consensus on treating Taiwanese PCOS was lacking. The aim of this study is to investigate the characteristics and utilization of traditional Chinese medicine (TCM) among Taiwanese women with PCOS.The data used in this study were derived from the Longitudinal Health Insurance Database (LHID 2000 and LHID 2005). Demographic characteristics, TCM usage, the frequency, as well as average daily dose of Chinese herbal formulas and the single herbs prescribed for patients with PCOS, were analyzed. Chinese herbal formulas and the single herbs prescribed for PCOS women during 1999 to 2013 were extracted to build up Chinese Herbal Medicine prescription database.In our study, 66.43% (nâ=â8205) women sought TCM treatment because of PCOS for infertility or menstrual disorders. The most commonly prescribed Chinese herbal formula was Jia-wei-xiao-yao-san (Supplemented Free Wanderer Powder). The most commonly prescribed single herb was Yi-mu-cao (Leonuri herba). Among top 20 Chinese herbal formulas, Si-wu-tang has the largest average daily dosage (9.60âg).Our study identified the characteristics and prescription patterns of TCM for patients with PCOS in Taiwan. We may need do further longitudinal research for TCM and its long-term response for improvement of pregnancy rate and reduction of metabolic disease rate.