The effect of black and green-tea extracts on dental-plaque forming Streptococci

زمینه و هدف: چای از پرمصرف‌ترین نوشیدنی‌ها در ایران است. اثرات ضد میکربی چای روی میکروارگانیسم‌های متعددی به اثبات رسیده است و یافتن فرآورده های طبیعی مانند مشتقات چای، که فاقد مخاطرات بر سلامت انسان باشند جهت کاهش ارگانیسم های پاتوژن ضروری بنظر می رسد. لذا این پژوهش با هدف بررسی اثر عصاره چای سیاه و سبز ایرانی بر استرپتوکوک‌های دهانی (استرپتوکوکوس موتانس، استرپتوکوکوس میتیس و استرپتوکوکوس سنگوییس) و اثر بازدارندگی آنها از تشکیل بیوفیلم، روی عوامل ایجاد کنندۀ پلاک‌های دندانی و پوسیدگی دندان انجام شد. روش بررسی: در این مطالعه تجربی پس از عصاره گیری نمونه ها با حلال متانول50 و جدا نمودن مجدد در فاز اتیل استـــات، عصاره ها توسط فیلتر 44/0 میکرون استریل شده و در 4 درجۀ سانتیگراد نگهداری شدند. از روش تهیۀ رقت های متوالی در محیط مایع برای محاسبۀ حداقل غلظت بازدارندگی و با تلقیح باکتری‌ها به درون ارلن های حاوی لام‌های شیشه‌ای برای سنجش تشکیل بیوفیلم استفاده شد. تشکیل بیوفیلم با کشت نمونه از روی لام ها و شمارش کلنی‌ها و همچنین مقایسۀ آنها در زیر میکروسکوپ فاز کنتراست با نمونۀ شاهد (محیط های تیمار نشده) مقایسه گردید. میانگین اندازه گیری‌ها در سه بار تکرار بیان و خطاها در هر نمونه با استفاده از آزمون آماری استاندارد (ANOVA) تعیین گردید. یافته ها: میکروسکوپ فاز کنتراست کاهش فوق العاده ای را در چسبیدن میکروارگانیسم های تیمار شده به یکدیگر در مقایسه با نمونۀ شاهد نشان داد. در غلظت 1 میلی گرم در میلی لیتر از عصارۀ چای سیاه بیوفیلم تشکیل نشد و غلظت 5/1 میلی گرم در میلی لیتر از عصارۀ چای سبز نیز بازدارندۀ کامل تشکیل بیوفیلم بود. عصاره های چای سیاه و سبز، به ترتیب در غلظت 5/2 و 3 میلی گرم در میلی لیتر اثر باکتریسایدی روی استرپتوکوکوس موتانس، استرپتوکوکوس میتیس و استرپتوکوکوس سنگوییس داشتند. نتیجه گیری: عصاره های چای به هر دو صورت چای سیاه و سبز خاصیت باکتریسایدی داشتند و اثر ضد میکربی چای سیاه بر روی استرپتوکوک های دهانی و ممانعت از تشکیل بیوفیلم توسط آنها بیشتر از چای سبز است

A bibliometric review of oncolytic virus research as a novel approach for cancer therapy

Background In recent years, oncolytic viruses (OVs) have drawn attention as a novel therapy to various types of cancers, both in clinical and preclinical cancer studies all around the world. Consequently, researchers have been actively working on enhancing cancer therapy since the early twentieth century. This study presents a systematic review of the literature on OVs, discusses underlying research clusters and, presents future directions of OVs research. Methods A total of 1626 published articles related to OVs as cancer therapy were obtained from the Web of Science (WoS) database published between January 2000 and March 2020. Various aspects of OVs research, including the countries/territories, institutions, journals, authors, citations, research areas, and content analysis to find trending and emerging topics, were analysed using the bibliometrix package in the R-software. Results In terms of the number of publications, the USA based researchers were the most productive (n = 611) followed by Chinese (n = 197), and Canadian (n = 153) researchers. The Molecular Therapy journal ranked first both in terms of the number of publications (n = 133) and local citations (n = 1384). The most prominent institution was Mayo Clinic from the USA (n = 117) followed by the University of Ottawa from Canada (n = 72), and the University of Helsinki from Finland (n = 63). The most impactful author was Bell J.C with the highest number of articles (n = 67) and total local citations (n = 885). The most impactful article was published in the Cell journal. In addition, the latest OVs research mainly builds on four research clusters. Conclusion The domain of OVs research has increased at a rapid rate from 2000 to 2020. Based on the synthesis of reviewed studies, adenovirus, herpes simplex virus, reovirus, and Newcastle disease virus have shown potent anti-cancer activity. Developed countries such as the USA, Canada, the UK, and Finland were the most productive, hence, contributed most to this field. Further collaboration will help improve the clinical research translation of this therapy and bring benefits to cancer patients worldwide.publishedVersio

Automatic sleep apnea detection using fuzzy logic

The obstructive sleep apnea (OSA) is one of the most important sleep disorders characterized by obstruction of the respiratory tract and cessation in respiratory flow level. Currently, apnea diagnosis is mainly based on the Polysomnography (PSG) testing during sleeping hours, however, recording the entire signals during nights is a very costly, time-consuming and difficult task. The goal of this study is to provide and validate an automatic algorithm to analyze four PSG-recordings and detect the occurrence of sleep apnea by noninvasive features. Four PSG signals were extracted from oxygen saturation (SaO2), Transitional air flow (Air Flow), abdominal movements during breathing (Abdomen mov.) and movements of the chest (Thoracic mov.). We describe a fuzzy algorithm to compensate the imprecise information about the range of signal loss, regarding the expert opinions. Signal classification is implemented minute-by-minute and for 30 labeled samples of MIT/BIH data sets (acquired from PhysioNet). The obtained data from 18 apnea subjects (11 males and 7 females, mean age 43 years) were categorized in three output signals of apnea, hypopnea and normal breathing. The proposed algorithm shows proficiency in diagnosing OSA with acceptable sensitivity and specificity, respectively 86% and 87%

Recombinant λ-phage nanobioparticles for tumor therapy in mice models

Lambda phages have considerable potential as gene delivery vehicles due to their genetic tractability, low cost, safety and physical characteristics in comparison to other nanocarriers and gene porters. Little is known concerning lambda phage-mediated gene transfer and expression in mammalian hosts. We therefore performed experiments to evaluate lambda-ZAP bacteriophage-mediated gene transfer and expression in vitro. For this purpose, we constructed recombinant λ-phage nanobioparticles containing a mammalian expression cassette encoding enhanced green fluorescent protein (EGFP) and E7 gene of human papillomavirus type 16 (λ-HPV-16 E7) using Lambda ZAP- CMV XR vector. Four cell lines (COS-7, CHO, TC-1 and HEK-239) were transduced with the nanobioparticles. We also characterized the therapeutic anti-tumor effects of the recombinant λ-HPV-16 E7 phage in C57BL/6 tumor mice model as a cancer vaccine. Obtained results showed that delivery and expression of these genes in fibroblastic cells (COS-7 and CHO) are more efficient than epithelial cells (TC-1 and HEK-239) using these nanobioparticles. Despite the same phage M.O.I entry, the internalizing titers of COS-7 and CHO cells were more than TC-1 and HEK-293 cells, respectively. Mice vaccinated with λ-HPV-16 E7 are able to generate potent therapeutic antitumor effects against challenge with E7- expressing tumor cell line, TC-1 compared to group treated with the wild phage. The results demonstrated that the recombinant λ-phages, due to their capabilities in transducing mammalian cells, can also be considered in design and construction of novel and safe phage-based nanomedicines

The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways

Hepatocellular carcinoma (HCC) is a significant global health issue, with a high prevalence in many regions. There are variations in the etiology of HCC in different regions, but most cases are due to long-term infection with viral hepatitis. Hepatitis B virus (HBV) is responsible for more than 50% of virus-related HCC, which highlights the importance of HBV in pathogenesis of the disease. The development and progression of HBV-related HCC is a complex multistep process that can involve host, viral, and environmental factors. Several studies have suggested that some HBV genome mutations as well as HBV proteins can dysregulate cell signaling pathways involved in the development of HCC. Furthermore, it seems that the pathogenicity, progression of liver diseases, response to treatment and also viral replication are different among HBV mutants. Understanding the relationship between HBV genome variations and host signaling pathway alteration will improve our understanding of the molecular pathogenesis of HBV-related HCC. Furthermore, investigating commonly dysregulated pathways in HBV-related HCC is necessary to discover more specific therapeutic targets and develop more effective strategies for HCC treatment. The objective of this review is to address the role of HBV in the HCC progression and primarily focus on the impacts of HBV genome variations on HCC-related signaling pathways

Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant = Avaliação da potência terapêutica da vacina de DNA do papilomavírus humano-16 E7 isolada e com interleucina-18 como adjuvante genético

OBJETIVOS: Apesar da existência de vacinas preventivas eficazes contra o papilomavírus humano (HPV), são necessárias vacinas terapêuticas que desencadeiem respostas imunes mediadas por células para tratar infecções e malignidades estabelecidas. O objetivo deste estudo foi avaliar a potência terapêutica da vacina de ácido desoxirribonucleico (DNA) HPV-16 E7 isolada e com interleucina (IL)-18. MÉTODOS: Expressões in vitro de IL-18 foram realizadas em células renais embrionárias humanas 293 e confirmadas por Western blotting. A vacina de DNA foi disponibilizada em um estudo anterior. Um total de 45 camundongos fêmeas C57BL/6 divididos em cinco grupos (vacina de DNA, vacina de DNA adjuvada com IL-18, pcDNA3. 1 e solução salina tamponada com fosfato) e foram inoculados com linhagem murina-1 de carcinoma relacionado ao HPV, expressando antígenos E6 / E7 do HPV-16. Os animais foram então imunizados por via subcutânea duas vezes no intervalo de sete dias. A imunidade antitumoral e antígeno-celular específica foi avaliada pela proliferação de linfócitos (ensaio de brometo de 3- [4,5-dimetiltiazol-2-il] -2,5-difeniltetrazólio: MTT), ensaio de liberação de lactato desidrogenase, ensaio de IL-4 e ensaio de interferon-gama [IFN-γ]. O tamanho do tumor foi seguido por 62 dias. RESULTADOS: O ensaio MTT, que mede a proliferação de linfócitos em resposta ao antígeno específico, aumentou nos grupos de coadministração e de vacina de DNA em comparação aos grupos controle e adjuvante genético (p <0,001). Os camundongos imunizados com a coadministração geraram significativamente mais IFN-γ e IL-4 do que os outros camundongos imunizados (p<0,001) A redução do tamanho do tumor nos grupos de coadministração e de vacina de DNA foi significativamente mais acentuada do que nos grupos controle e adjuvante genético (p<0,001), mas não houve nenhuma diferença estatisticamente significativa entre os grupos vacina de DNA e coadministração (p=0,15). CONCLUSÕES: A IL-18 como adjuvante genético e a vacina de DNA E7 aumentaram as respostas imunes em sistemas modelo de camundongos contra o câncer cervical. No entanto, o uso de IL-18 como adjuvante genético com a vacina de DNA E7 não teve efeito sinérgico significativo nas respostas imunes in viv

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. Methods For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. Results A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. Conclusion The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines’ low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies