The Combination of 5-FU and Resveratrol Can Suppress the Growth of Glioblastoma Cells Through Downregulation of TRPM2 and ß-Catenin.

Glioblastoma multiforme (GBM) is the most common as well as the most fatal primary malignant tumor of the central nervous system (CNS), which still lacks a definitive cure. 5-FU is an anti-metabolite anti-cancer agent which has shown promising results for GBM treatment. Resveratrol (Res) is a phytochemical anti-oxidant that has also been effective in suppressing the progression of GBM. The combination of 5-FU and Res has been studied in a variety of cancers, but no study has assessed this combination in GBM. In this study, we investigated how 5-FU and Res, in combination and alone, may affect the growth and apoptosis of GBM cells and also the potential of TRPM2 and ß-catenin as the mediator of their effects. U87 cells were cultured as the in vitro model. MTT assay was used for measuring cellular growth, and RT-qPCR was used to measure the level of caspase-3, TRPM2, and ß-catenin; caspase-3 level served as the indicator of apoptotic rate. 5-FU and Res, in combination and alone, suppressed the growth while promoting the apoptosis of U87 cells; these effects were significantly greater when they were used in combination. RT-qPCR showed downregulation of TRPM-2 and ß-catenin in response to this combination, which suggested that these two molecules may mediate the cited anti-oncogenic effects. In conclusion, our study confirmed the synergism between 5-FU and Res in suppressing the progression of GBM and suggested the putative axis of TRPM2/ ß-catenin as the downstream mediator of this therapeutic regime. Future studies may be able to approve the eligibility of this therapeutic regime for GBM treatment and also the underlying mechanism.

Triggering of Endoplasmic Reticulum Stress by Tannic Acid Inhibits the Proliferation and Migration of Colorectal Cancer Cells.

INTRODUCTION: Due to the pivotal role of endoplasmic reticulum (ER) stress in cancers, interfering with its function can cause the accumulation of unfolded proteins, which ultimately leads to the activation of the unfolded protein response (UPR) signaling pathway and apoptosis. Therefore, the use of plant compounds such as tannic acid with UPR-inducing properties can be proposed as a possible treatment method for cancer. In this study, we investigated the effect of tannic acid on cell migration, colony formation, growth, and UPR-induced apoptosis in the SW48 colorectal cancer cell line. METHODS: The MTT assay was performed to investigate the cytotoxic effect of tannic acid. We performed the qPCR method to elucidate the effect of tannic acid on the expression of Bim, MMP-9, Bcl-xL, cyclin D1, CHOP, and ATF4 genes. We also used the colony formation and migration experiments to investigate the effect of this compound on the colony formation and migration ability of tumor cells. Finally, we used Hoechst staining to measure cell apoptosis. RESULTS: Tannic acid inhibited the cell survival, clonogenic, and migration of colon cancer cells. This compound increased the expression of ER stress-mediated UPR genes, ATF4 and CHOP. Moreover; tannic acid increased the expression of pro-apoptotic proteins like Bim, while at the same time causing a sharp decline in the expression of anti-apoptotic protein Bcl-xL. A decline in MMP-9 expression confirmed the anti-metastatic role of this compound. CONCLUSION: Taken together, tannic acid can induce apoptosis via ER stress-mediated UPR pathway, and has a suppressive effect on cell viability, growth, migration, colony formation, and metastasis, suggesting it may be a potential drug in colorectal cancer treatment.

LncRNA FTH1P3: A new biomarker for cancer-related therapeutic development.

Cancer is a persistent and urgent health problem that affects the entire world. Not long ago, regulatory biomolecules referred to as long noncoding RNAs (lncRNAs) might have value for their innate abundance and stability. These single-stranded RNAs potentially interfere with several physiological and biochemical cellular processes involved in many human pathological situations, particularly cancer diseases. Ferritin heavy chain1 pseudogene 3 (FTH1P3), a lncRNA that is ubiquitously transcribed and belongs to the ferritin heavy chain (FHC) family, represents a novel class of lncRNAs primarily found in oral squamous cell carcinoma. Further research has shown that FTH1P3 is involved in other malignancies such as uveal melanoma, glioma, esophageal squamous cell carcinoma, non-small cell lung cancer, breast cancer, laryngeal squamous cell carcinoma, and cervical cancer. Accordingly, FTH1P3 significantly enhances cancer symptoms, including cell proliferation, invasion, metastasis, chemoresistance, and inhibition of apoptosis through many specific mechanisms. Notably, the clinical data significantly demonstrated the association of FTH1P3 overexpression with poor prognosis and poor overall survival within the examined samples. Here, we summarize all the research published to date (13 articles) on FTH1P3, focusing on the biological function underlying the regulatory mechanism and its possible clinical relevance.

Exosomal microRNAs: A Diagnostic and Therapeutic Small Bio-molecule in Esophageal Cancer.

Esophageal cancer (EC) is one of the major causes of cancer-related death worldwide. EC is usually diagnosed at a late stage, and despite aggressive therapy, the five-year survival rate of patients remains poor. Exosomes play important roles in cancer biology. Indeed, exosomes are implicated in tumor proliferation, angiogenesis, and invasion. They contain bioactive molecules such as lipids, proteins, and non-coding RNAs. Exosome research has recently concentrated on microRNAs, which are tiny noncoding endogenous RNAs that can alter gene expression and are linked to nearly all physiological and pathological processes, including cancer. It is suggested that deregulation of miRNAs results in cancer progression and directly induces tumor initiation. In esophageal cancer, miRNA dysregulation plays an important role in cancer prognosis and patients' responsiveness to therapy, indicating that miRNAs are important in tumorigenesis. In this review, we summarize the impact of exosomal miRNAs on esophageal cancer pathogenesis and their potential applications for EC diagnosis and therapy.

A designed peptide-based vaccine to combat Brucella melitensis, B. suis and B. abortus: Harnessing an epitope mapping and immunoinformatics approach.

Vaccines against Brucella abortus, B. melitensis and B. suis have been based on weakened or killed bacteria, however there is no recombinant vaccine for disease prevention or therapy. This study attempted to predict IFN-γ epitopes, T cell cytotoxicity, and T lymphocytes in order to produce a multiepitope vaccine based on BtpA, Omp16, Omp28, virB10, Omp25, and Omp31 antigens against B. melitensis, B. abortus, and B. suis. AAY, GPGPG, and EAAAK peptides were used as epitope linkers, while the PADRE sequence was used as a Toll-like receptor 2 (TLR2) and TLR4 agonist. The final construct included 389 amino acids, and was a soluble protein with a molecular weight of 41.3 kDa, and nonallergenic and antigenic properties. Based on molecular docking studies, molecular dynamics simulations such as Gyration, RMSF, and RMSD, as well as tertiary structure validation methods, the modeled protein had a stable structure capable of interacting with TLR2/4. As a result, this novel vaccine may stimulate immune responses in B and T cells, and could prevent infection by B. suis, B. abortus, and B. melitensis.

Circular RNAs in neuroblastoma: Pathogenesis, potential biomarker, and therapeutic target.

Neuroblastoma (NB) is a common cancer in childhood responsible for 15 % of fatalities by pediatric cancers. Epigenetic factors play an important role in the pathogenesis of NB. Recently, it has been demonstrated that circular RNAs (circRNAs, ciRNAs), a newly identified class of non-coding RNAs, are also dysregulated in NB. CircRNAs mediate their functions by regulating gene expression mainly through microRNA (miRNA) sponging. The dysregulation (abnormal upregulation or downregulation) of circRNAs is involved in tumorigenesis of a variety of tumors including NB. It seems that the expression of some circRNAs is correlated with NB prognosis and clinical features. CircRNAs might be favorable as a diagnostic/prognostic biomarker and therapeutic target. However, due to the lack of studies, it is difficult to make a conclusion regarding the clinical benefits of circRNAs. In this review, we discussed the circRNAs that experimentally have been proved to be dysregulated in NB tissues and cancer cells.

Biosynthesis of Zn-doped CuFe2O4 nanoparticles and their cytotoxic activity.

Zn-doped CuFe2O4 nanoparticles (NPs) were eco-friendly synthesized using plant extract. These nanoparticles were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy and thermal gravimetric analysis (TGA). SEM image showed spherical NPs with size range less than 30 nm. In the EDS diagram, the elements of zinc, copper, iron, and oxygen are shown. The cytotoxicity and anticancer properties of Zn-doped CuFe2O4 NPs were evaluated on macrophage normal cells and A549 lung cancer cells. The cytotoxic effects of Zn-doped CuFe2O4 and CuFe2O4 NPs on A549 cancer cell lines were analyzed. The Zn-doped CuFe2O4 and CuFe2O4 NPs demonstrated IC50 values 95.8 and 278.4 µg/mL on A549 cancer cell, respectively. Additionally, Zn-doped CuFe2O4 and CuFe2O4 NPs had IC80 values of 8.31 and 16.1 µg/mL on A549 cancer cell, respectively. Notably, doping Zn on CuFe2O4 NPs displayed better cytotoxic effects on A549 cancer cells compared with the CuFe2O4 NPs alone. Also spinel nanocrystals of Zn-doped CuFe2O4 (~ 13 nm) had a minimum toxicity (CC50 = 136.6 µg/mL) on macrophages J774 Cell Line.

Oncogenic viruses and chemoresistance: What do we know?

Chemoresistance is often referred to as a major leading reason for cancer therapy failure, causing cancer relapse and further metastasis. As a result, an urgent need has been raised to reach a full comprehension of chemoresistance-associated molecular pathways, thereby designing new therapy methods. Many of metastatic tumor masses are found to be related with a viral cause. Although combined therapy is perceived as the model role therapy in such cases, chemoresistant features, which is more common in viral carcinogenesis, often get into way of this kind of therapy, minimizing the chance of survival. Some investigations indicate that the infecting virus dominates other leading factors, i.e., genetic alternations and tumor microenvironment, in development of cancer cell chemoresistance. Herein, we have gathered the available evidence on the mechanisms under which oncogenic viruses cause drug-resistance in chemotherapy.

Atezolizumab and granzyme B as immunotoxin against PD-L1 antigen; an insilico study.

CD274 gene encodes programmed death-ligand 1 (PD-L1) protein, also known as B7 homolog 1 (B7-H1), which is a crucial hallmark for highly proliferation cells including cancer cells. PD-1 and PD-L1 interaction is assumed as a negative regulator for immune response which can inhibit the T cell growth and cytokine secretion and supports tumor cells evasion from immune system. therefore, PD-L1 could be assumed as a candidate target for immune-therapy. The predicted structure of PD-L1 indicates (Gly4Ser) 3 linker-based chains links. In that line, different simulation softwares applied to explore the structure of granzyme B (GrB), a serine protease in cytotoxic lymphocytes granules as an apoptosis mediator, was attached to its specific antibody structure (atezolizumab) via an adaptor sequence. Evaluation of accuracy, energy minimization and characterization of biological properties of the final processed structure were performed and our computational outcomes indicated that the employed method for structure prediction has been successfully managed to design the immunotoxin structure. It is necessary to mention that, the precise and accurate design of the immune-therapeutic agents against cancer cells can be confirmed by employment of in-silico approaches. Consequently, based on this approach we could introduce a capable immunotoxin which specifically targeting PD-L1 in an accurate orientation and initiates cancer cell destruction by its toxin domain. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00076-z.

Therapeutic Measures for the Novel Coronavirus: A Review of Current Status and Future Perspective.

The coronavirus disease 19 (COVID-19) is a highly pathogenic and transmissible viral disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in the city of Wuhan, Hubei Province, Central China and spread quickly around the world. The genome sequence of SARSCoV- 2 is phylogenetically related to bat-derived severe acute respiratory syndrome-like (SARS-like) coronaviruses; therefore bats could be the possible primary reservoirs. At present, there are no clinically approved vaccines or specific antiviral drugs for COVID- 19. However, several broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical studies and resulted in the improvement of patients. In this regard, other therapies such as antiviral drugs, antibodies, stem cells and plasma therapy are being studied. In the current study, we reviewed the emergence, pathogenicity and the genome structure of COVID-19 infection. The main focus of this study is on the therapeutic approaches that may be effective against SARS-CoV-2.

Evaluation of the Effect of the Intensity and Occurrence of Postoperative Pain of Resin-Based and Bioceramic Root Canal Sealers: A Systematic Review and Meta-Analysis of Randomized Controlled Trial Studies

ABSTRACT Objective: To evaluate resin- and bioceramic root canal sealers affect postoperative intensity and pain occurrence. Material and Methods: From the electronic databases, PubMed, Cochrane Library, Embase, ISI have been used to perform systematic literature until September 2020. Electronic titles were managed using the Endnote X8 software. They performed searches with mesh terms. Two reviewers blindly and independently extracted data from studies that included data for data extraction. Results: A total of 186 potentially relevant titles and abstracts were found. Finally, four studies were included. Pain score was (RR = -0.20; 95% CI -1.09-0.68; p= 0.65). This result showed no statistically significant difference for the resin-based and bioceramic root canal sealers after 24 hours between the VAS scores. Conclusion: Postoperative pain was low in Patients requiring root canal retreatment and obturated with resin-based or bioceramic-based sealers without extrusion beyond the apex. No differences were observed between postoperative pain in resin-based and bioceramic root canal sealers 24 and 48 hours postoperatively.

Therapeutic role of curcumin and its novel formulations in gynecological cancers.

Gynecological cancers are among the leading causes of cancer-associated mortality worldwide. While the number of cases are rising, current therapeutic approaches are not efficient enough. There are considerable side-effects as well as treatment resistant types. In addition, which all make the treatment complicated for afflicted cases. Therefore, in order to improve efficacy of the treatment process and patients' quality of life, searching for novel adjuvant treatments is highly warranted. Curcumin, a promising natural compound, is endowed with numerous therapeutic potentials including significant anticancer effects. Recently, various investigations have demonstrated the anticancer effects of curcumin and its novel analogues on gynecological cancers. Moreover, novel formulations of curcumin have resulted in further propitious effects. This review discusses these studies and highlights the possible underlying mechanisms of the observed effects.

Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer.

Pancreatic cancer is the most lethal malignancy of the gastrointestinal tract. Due to its propensity for early local and distant spread, affected patients possess extremely poor prognosis. Currently applied treatments are not effective enough to eradicate all cancer cells, and minimize their migration. Besides, these treatments are associated with adverse effects on normal cells and organs. These therapies are not able to increase the overall survival rate of patients; hence, finding novel adjuvants or alternatives is so essential. Up to now, medicinal herbs were utilized for therapeutic goals. Herbal-based medicine, as traditional biotherapeutics, were employed for cancer treatment. Of them, apigenin, as a bioactive flavonoid that possesses numerous biological properties (e.g., anti-inflammatory and anti-oxidant effects), has shown substantial anticancer activity. It seems that apigenin is capable of suppressing the proliferation of cancer cells via the induction of cell cycle arrest and apoptosis. Besides, apigenin inhibits metastasis via down-regulation of matrix metalloproteinases and the Akt signaling pathway. In pancreatic cancer cells, apigenin sensitizes cells in chemotherapy, and affects molecular pathways such as the hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1). Herein, the biotherapeutic activity of apigenin and its mechanisms toward cancer cells are presented in the current review to shed some light on anti-tumor activity of apigenin in different cancers, with an emphasis on pancreatic cancer.

The therapeutic potential of resveratrol in a mouse model of melanoma lung metastasis.

Resveratrol is an anticancer phytochemical polyphenol isolated from a natural origin, without any significant side effects. Resveratrol was investigated in immunocompetent mice with regards to its possible effect on lung cancer metastasis. Cytotoxicity was assessed in three melanoma cell lines (B16F10, B6, and A375) by administration of 20 and 40 µM resveratrol. B16F10 cells were transfected with pT-tdTomato vector to express red fluorescent protein (RFP). RFP-B16F10 cells were injected IV into 3 groups of 20 C57BL/6 mice (ten for tests and others for survival). The three groups include PBS, no treatment, and resveratrol 40 mg/kg IP (4X/week for 3 weeks). Lung tissues were analyzed by TUNEL assay, Western blot, and immunohistochemistry. The in vitro growth of all melanoma cell lines was significantly suppressed by 40 µM resveratrol for 3 days. The mean survival rate of mice was enhanced and the lung tumor growth was inhibited by in vivo IP injection of 40 mg/kg resveratrol. Increased CXCL10 and IFN-γ levels and decreased angiogenesis and less tumor infiltration by Tregs were found in the lung tumors. In conclusion, lung metastasis of melanoma was effectively inhibited by resveratrol treatment.

The Effect of Brief Supportive Psychotherapy on Prevention of Psychiatric Morbidity in Women with Miscarriage: A Randomized Controlled Trial about the First 24-hours of Hospitalization.

OBJECTIVES: Miscarriage is a common pregnancy complication causing substantial psychiatric complications. This study was designed to investigate whether the administration of brief supportive psychotherapy (BSP) is effective on the management of women with miscarriage when conducted in the first 24 hours of hospitalization in order to prevent symptoms of anxiety, depression, and grief at four-months post-miscarriage. METHODS: We conducted a randomized clinical trial on 79 women with miscarriage hospitalized in Ayatollah Rohani teaching hospital. The women were randomly assigned into two groups (39 in the experimental group and 40 in the control group). All interventions were implemented for two study groups during the first 24 hours of hospitalization in a private room in the hospital. The experimental group received a two-hour BSP. The objective outcomes were assessed using Hospital Anxiety and Depression Scale and Perinatal Grief Scale (PGS), which has three subscales (active grief, difficulty coping, and despair) and were measured before the intervention and at four-months post-miscarriage. RESULTS: The results of pre-tests in the follow-up of the trial suggested that the participants who received BSP reported significant reductions in the mean scores of active grief (-34.2±9.7 vs. 28.1±-6.9), difficulty coping (27.1±6.4 vs. 23.3±4.3), despair (28.0±8.4 vs. 22.8±5.2), and total PGS (89.6±23.1 vs. 74.4±15.3), in contrast to participants in the control group who did not report such results. Further, the results of generalized estimating equations models revealed that brief supportive psychotherapy caused a significant decrease in the level of factors including active grief, difficulty coping, despair, total perinatal grief, anxiety symptoms, and depressive symptoms in subjects in the experimental group compared to those in the control group after miscarriage. Also, the frequency of anxiety symptoms (13.5% vs. 60.5%), depressive symptoms (32.4% vs. 71.1%), and grief symptoms (10.8% vs. 65.8%) was found to be significantly lower in the group receiving psychotherapy than in the control group at four-months follow-up. CONCLUSIONS: Administration of BSP session during the first 24 hours of hospitalization for women with miscarriage can be considered a reliable method to prevent anxiety symptoms, depression symptoms, and perinatal grief at four-months follow-up.

Management of the maxillary sinus complications after dental implantation: a systematic review and meta-analysis / Tratamento das complicações do seio maxilar após cirurgia de implante dentário: Revisão Sistemática e Meta-Análise

Background and aim: Endoscopic sinus surgery owing to its satisfactory prognosis and low complication is considered as the first line of surgical procedure. Implant failure is often reported despite efforts in recent years. The purpose of this study was to review the factors leading to side effects in dental implantation of the maxillary sinus. Material and Methods: The systematic search was performed on electronic databases of MEDLINE, PubMed, Cochrane Library, Embase, ISI, Google scholar to find corresponding articles regarding dental literature during 2010 to 2019. Electronic title management was carried out by Endnote X9 software. Searches were based on the keywords of "dental implants", "Implants"," dental"," maxilla", "sinusitis". Results: The searched potentially relevant titles and abstracts were related to 294 articles, 104 of which were excluded due to lack of study inclusion criteria. At last, 11 articles were included into the final analysis. Postoperative sinusitis was found in 78 patients within 9 articles among 1195 patients. The implant failure was reported in 136 cases and the sinus membrane perforation in 185 sinuses within 11 articles among 1372 sinus lift procedures. Conclusion: The findings showed that the risk factors of sinusitis after implant surgery were Schneiderian membrane rupture and preoperative sinusitis, as well as smoking and residual bone height were the parameters elevating the dental implant failure risk. (AU)

Justificativa e objetivo: A cirurgia endoscópica do seio maxilar, devido ao seu prognóstico satisfatório e baixa complicação, é considerada a primeira opção cirúrgica. A falha do implante é frequentemente relatada, apesar dos esforços realizados nos últimos anos. O objetivo deste estudo foi revisar os fatores que levaram a efeitos colaterais no implante dentário do seio maxilar. Material e Métodos: A busca sistemática foi realizada nas bases de dados eletrônicas do MEDLINE, PubMed, Cochrane Library, Embase, ISI, Google Scholar para encontrar artigos correspondentes sobre literatura odontológica no período de 2010 a 2019. O gerenciamento eletrônico de títulos foi realizado pelo software Endnote X9. As pesquisas foram baseadas nas palavras-chave "implantes dentários", "implantes", "dentário", "maxila", "sinusite". Resultados: Os títulos e resumos potencialmente relevantes pesquisados foram relacionados a 294 artigos, 104 dos quais foram excluídos por falta de critérios de inclusão no estudo. Por fim, 11 artigos foram incluídos na análise final. Sinusite pós-operatória foi encontrada em 78 pacientes em 9 artigos entre 1195 pacientes. A falha do implante foi relatada em 136 casos e a perfuração da membrana sinusal em 185 seios, em 11 artigos, entre 1372 procedimentos de elevação sinusal. Conclusão: Os achados mostraram que os fatores de risco para sinusite após cirurgia de implante foram ruptura da membrana Schneideriana e sinusite pré-operatória, assim como tabagismo e altura óssea residual, os quais foram considerados parâmetros que elevaram o risco de falha do implante dentário. (AU)

Hyalinization and Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review and Meta-Analysis

Abstract Objective: To systematically review the hyalinization of experimental tooth movement in humans and animals. Material and Methods: The electronic databases of MEDLINE, PubMed, Cochrane Library, Embase, Institute for Scientific Information, and Google Scholar were searched for performing a systematic review of the related literature published until 2019. Moreover, Endnote X9 software was utilized to manage electronic titles. The searches were fulfilled using keywords of "hyalinization," "orthodontic tooth movement" OR "OTM" AND "periodontal ligament" OR "PDL," "molecular pathways," AND "mechanical cell." Therefore, this systematic review was conducted based on the key consideration of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Forces ranged between 2.3 and 50 CN had been applied. According to the research design, incisors had been included in two experiments, whereas maxillary molars had been displaced by tipping forces in another rat examination. However, a majority of investigations had stated that hyalinization had firstly appeared within the first 24 hours. Moreover, the amount of prostaglandin-end peroxide synthase 2 (PTGS2) had been positively related to force term and size utilizing Western blotching. As PTGS2 had been included in the prostaglandin E2 (PGE2) metabolism, the up-regulation of PTGS2 gene expression could be connected with that of PGE2 emission. Conclusion: Gene expression in connection with force term and size and also the first signalling pathways were recognized utilizing protein-protein interactions (PPIs).

The Using Virtual Computer-Assisted Planning in Orthognathic Surgery: A Systematic Review and Meta-Analysis

Abstract Objective: To use virtual computer-assisted planning in orthognathic surgeries through meta-analysis and systematic review. Material and Methods: This search took place between 2010 and 2019. The databases searched in this domain included MEDLINE, PubMed, Cochrane Library, Embase, ISI, and Google scholar. Accordingly, the abstracts of the articles were initially reviewed and the ones that had the most coordination with the study objectives were selected. Then, the full texts of the articles were examined; and finally, five studies were selected. In addition to reviewing the related literature, the results were extracted and entered into the meta-analyzer Stata V.14 to summarize the final results. Results: The sample size in this study was at a range from 6 to 28 patients and a total number of 85 patients had participated in the given investigations. As well, CT and CBCT were selected as imaging methods. Clinical imaging and analysis were also employed in computer-assisted planning in all five studies. Subsequently, surgical planning was performed and the virtual splint was designed while the planning time was 225 minutes and 145 minutes in two studies. Conclusion: The present results supported computer-assisted planning and the quality of scientific evidence.