Assessment of a combined mouthwash on pain relief in pericoronitis: a randomized clinical study.

BACKGROUND: Pericoronitis, an inflammation near wisdom teeth, often occurs when they are partially emerged, especially in the lower jaw. Commonly, the gingiva partially envelops the tooth. Treatments vary from gingival surgery to extraction. This study assessed the efficacy of a mouthwash with Chlorhexidine, Benzydamine, Nanosilver, Amoxicillin, and Metronidazole for pain reduction and enhancement of maximum mouth opening in acute pericoronitis cases. MATERIALS AND METHODS: In this randomized controlled clinical trial conducted at the Gorgan Dental Faculty, 48 pericoronitis patients were randomized into two groups. The control group used a 0.12% chlorhexidine mouthwash, while the case group used a mouthwash containing Chlorhexidine, Benzydamine, Nanosilver, Amoxicillin, and Metronidazole. The study recorded Visual Analog Scale (VAS) scores for 7 days, and Maximum mouth opening (MMO) was measured at the start and after 7 days. The analysis was performed using SPSS v20. RESULTS: In this study, we compared the effects of a combined mouthwash with those of a chlorhexidine mouthwash on pericoronitis in 48 patients, with an average age of 21.56 years. No significant difference in pain reduction was observed between the groups; however, both groups exhibited decreased pain and improved MMO post-treatment. The gender distribution was balanced across both groups. CONCLUSION: The results indicate that both chlorhexidine mouthwash and combined mouthwash significantly improved maximum mouth opening. Nonetheless, there were no notable differences in efficacy between the two groups. These findings suggest that these mouthwashes may be beneficial for oral hygiene, warranting further in-depth research. TRIAL REGISTRATION: Registered on 12/03/2023, registration number IRCT20230104057046N1.

RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin-RGD interactions.

RGD peptide can be found in cell adhesion and signaling proteins, such as fibronectin, vitronectin, and fibrinogen. RGD peptides' principal function is to facilitate cell adhesion by interacting with integrin receptors on the cell surface. They have been intensively researched for use in biotechnology and medicine, including incorporation into biomaterials, conjugation to medicinal molecules or nanoparticles, and labeling with imaging agents. RGD peptides can be utilized to specifically target cancer cells and the tumor vasculature by engaging with these integrins, improving drug delivery efficiency and minimizing adverse effects on healthy tissues. RGD-functionalized drug carriers are a viable option for cancer therapy as this focused approach has demonstrated promise in the future. Writing a review on the RGD peptide can significantly influence how drugs are developed in the future by improving our understanding of the peptide, finding knowledge gaps, fostering innovation, and making drug design easier.

The role of viruses in cancer development versus cancer therapy: An oncological perspective.

Despite great medical advances, oncological research is still looking for novel therapeutic approaches due to the limitation of conventional therapeutic agents. Virotherapy is one of these new emerging therapeutic approaches that attract attention with their widespread applications. Virotherapy use lives oncolytic viruses or genetically engineered viruses that selectively infect the tumor cells, replicate, and disrupt the cancerous cells that also induce their anticancer activity by stimulating the host antitumor immune response. Moreover, viruses are widely used as target delivery vectors for specifically delivering different genes, therapeutic agents, and immune-stimulating agents. In addition to having antitumor activity by themselves in combination with conventional therapeutic agents like immune therapy and chemotherapy, Virotherapy agents also elicit promising outcomes. Therefore, in addition to their promising result in monotherapy use, virotherapy agents can also be used in combination with conventional cancer therapy, epigenetic modulators, and even microRNAs without any cross-resistance, which allows the patient not to be deprived of her routine medicine. Still, this combination therapy reduces the adverse effect of the conventional therapies. All together suggest that virotherapy agents as novel potential agents in the field of cancer therapy.

Strategy of targeting the tumor microenvironment via inhibition of fibroblast/fibrosis remodeling new era to cancer chemo-immunotherapy resistance.

The use of repurposing drugs that may have neoplastic and anticancer effects increases the efficiency and decrease resistance to chemotherapy drugs through a biochemical and mechanical transduction mechanisms through modulation of fibroblast/fibrosis remodeling in tumor microenvironment (TME). Interestingly, fibroblast/fibrosis remodeling plays a vital role in mediating cancer metastasis and drug resistance after immune chemotherapy. The most essential hypothesis for induction of chemo-immunotherapy resistance is via activation of fibroblast/fibrosis remodeling and preventing the infiltration of T cells after is mainly due to the interference between cytoskeleton, mechanical, biochemical, metabolic, vascular, and remodeling signaling pathways in TME. The structural components of the tumor that can be targeted in the fibroblast/fibrosis remodeling include the depletion of the TME components, targeting the cancer-associated fibroblasts and tumor associated macrophages, alleviating the mechanical stress within the ECM, and normalizing the blood vessels. It has also been found that during immune-chemotherapy, TME injury and fibroblast/fibrosis remodeling causes the up-regulation of inhibitory signals and down-regulation of activated signals, which results in immune escape or chemo-resistance of the tumor. In this regard, repurposing or neo-adjuvant drugs with various transduction signaling mechanisms, including anti-fibrotic effects, are used to target the TME and fibroblast/fibrosis signaling pathway such as angiotensin 2, transforming growth factor-beta, physical barriers of the TME, cytokines and metabolic factors which finally led to the reverse of the chemo-resistance. Consistent to many repurposing drugs such as pirfenidone, metformin, losartan, tranilast, dexamethasone and pentoxifylline are used to decrease immune-suppression by abrogation of TME inhibitory signal that stimulates the immune system and increases efficiency and reduces resistance to chemotherapy drugs. To overcome immunosuppression based on fibroblast/fibrosis remodeling, in this review, we focus on inhibitory signal transduction, which is the physical barrier, alleviates mechanical stress and prevents mechano-metabolic activation.

Innovative targets of the lncRNA-miR-mRNA network in response to low-dose aspirin in breast cancer patients.

This study aimed to investigate innovative targets in breast cancer patients by considering the interaction of the lncRNA-miR-mRNA network in response to low-dose aspirin. The candidate miRs were first taken from the GEO and TCGA databases. Then, the candidate network was constructed using the high-throughput sequencing data. The expression levels of candidate targets were finally measured using Real-Time PCR in luminal A breast cancer patients undergoing aspirin (80 mg daily for three months) and non-aspirin groups during chemotherapy after surgery. The expression levels of TGFß, IL-17, IFNγ, and IL-ß proteins were measured using the ELISA technique. 5 lncRNAs, 12 miRs, and 10 genes were obtained in the bioinformatic phase. A significant expression increase of the candidate tumor suppressor lncRNAs, miRs, and genes and a substantial expression decrease of the candidate onco-lncRNAs, oncomiRs, and oncogenes were achieved after the aspirin consumption. Unlike the non-aspirin group, the expression levels of TGFß, IL-17, IFNγ, and IL-ß proteins were significantly decreased following aspirin consumption. The Kaplan-Meier analysis indicated a longer overall survival rate in the patients after aspirin consumption. Our results showed that the lncRNA-miR-mRNA network might be a significant target for aspirin; their expression changes may be a new strategy with potential efficacy for cancer therapy or prevention.

Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs); where do they stand in tumorigenesis and how they can change the face of cancer therapy?

The tumor microenvironment (TME) and its components have recently attracted tremendous attention in cancer treatment strategies, as alongside the genetic and epigenetic alterations in tumor cells, TME could also provide a fertile background for malignant cells to survive and proliferate. Interestingly, TME plays a vital role in the mediation of cancer metastasis and drug resistance even against immunotherapeutic agents. Among different cells that are presenting in TME, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) have shown to have significant value in the regulation of angiogenesis, tumor metastasis, and drug-resistance through manipulating the composition as well as the organization of extracellular matrix (ECM). Evidence has shown that the presence of both TAMs and CAFs in TME is associated with poor prognosis and failure of chemotherapeutic agents. It seems that these cells together with ECM form a shield around tumor cells to protect them from the toxic agents and even the adaptive arm of the immune system, which is responsible for tumor surveillance. Given this, targeting TAMs and CAFs seems to be an essential approach to potentiate the cytotoxic effects of anti-cancer agents, either conventional chemotherapeutic drugs or immunotherapies. In the present review, we aimed to take a deep look at the mechanobiology of CAFs and TAMs in tumor progression and to discuss the available therapeutic approaches for harnessing these cells in TME.

The Use of Bio-Active Compounds of Citrus Fruits as Chemopreventive Agents and Inhibitor of Cancer Cells Viability.

Common therapy of cancer, such as chemotherapy, has various side effects for the patients. In recent studies, new therapeutic approaches in cancer treatment are adjuvant therapy, along with a reduction in side effects of chemotherapy drugs. Treatment by herbal medicines may have some advantages over treatment with single purified chemicals, also in terms of side effects, the use of plants in cancer treatment is a more secure method. Citrus fruits are one of the most consumed natural products in the world due to the presence of various metabolites and bioactive compounds, such as phenols, flavonoids and, carotenoids. Bioactive compounds of citrus modulate signaling pathways and interact with signaling molecules such as apoptotic and cell cycle (P53, P21, etc.) and thus have a wide range of pharmacological activities, including anti-inflammatory, anti-cancer and oxidative stress. The findings discussed in this review strongly support their potential as anti-cancer agents. Therefore, the purpose of this review was to examine the effects of active compounds in citrus as a therapy agent in cancer treatment.

Dual effects of atorvastatin on angiogenesis pathways in the differentiation of mesenchymal stem cells.

Atorvastatin (ATO) can improve the transplantation efficacy of mesenchymal stem cells (MSCs) after acute myocardial infarction. The present study aimed at ATO effects on the angiogenesis-signaling pathways from MSCs' differentiation to tissue angiogenesis. MSCs were first prepared from BALB/c mouse bone marrow. MTT assay was then done for the biodegradability of MSCs with the extracellular matrix. After that, the differentiation of cells into the bone and fat tissues was confirmed by Alizarin and Oil Red O staining. The extracellular matrix was then combined with the cells to the implant. Animals were intraperitoneally treated with ATO (2 and 40 mg/kg, daily) three days before cell transplantation to one week after. Finally, the assays were carried out by electron microscopy, immunocytochemistry, ELISA, Western blot, and RT-qPCR techniques. A phase-contrast microscope confirmed the morphology of cells. The cell differentiation into bone and fat tissues was confirmed by Alizarin red staining and flow cytometry, and the cell proliferation was confirmed by MTT assay. Unlike ATO 40 mg/kg group, ATO 2 mg/kg was significantly increased the CD31, eNOS, podocalyxin, von Willibrand factor, and alpha-smooth muscle actin proteins levels compared to the control group in vitro experiment. The expression of CD31 and VEGF proteins, as angiogenesis markers, and Ki-67 protein, as a proliferation marker, was significantly higher in a low dose of ATO (2 mg/kg) than that of the control group in vivo experiment. Unlike ATO 40 mg/kg, the expression levels of ERK, AKT, NF-ҝB, Rho, STAT3, Ets-1, HIF-1α, and VEGF proteins and genes were significantly increased in ATO 2 mg/kg compared to the control. A low dose of ATO can be a beneficial tool in the function of MSCs and their differentiation to tissue angiogenesis.

Gamma-radiated immunosuppressed tumor xenograft mice can be a new ideal model in cancer research.

Tumor xenograft models can create a high capacity to study human tumors and discover efficient therapeutic approaches. Here, we aimed to develop the gamma-radiated immunosuppressed (GIS) mice as a new kind of tumor xenograft model for biomedical studies. First, 144 mice were divided into the control and treated groups exposed by a medical Cobalt-60 apparatus in 3, 4, and 5 Gy based on the system outputs. Then, 144 BALB/c mice were divided into four groups; healthy, xenograft, radiation, and radiation + xenograft groups. The animals in the xenograft and radiation + xenograft groups have subcutaneously received 3 × 106 MCF-7 cells 24 h post-radiation. On 3, 7, 14, and 21 days after cell injection, the animals were sacrificed. Then, the blood samples and the spleen and tumor tissues were removed for the cellular and molecular analyses. The whole-body gamma radiation had a high immunosuppressive effect on the BALB/c mice from 1 to 21 days post-radiation. The macroscopic and histopathological observations have proved that the created clusters' tumor structure resulted in the xenograft breast tumor. There was a significant increase in tumor size after cell injection until the end of the study. Except for Treg, the spleen level of CD4, CD8, CD19, and Ly6G was significantly decreased in Xen + Rad compared to the Xen alone group on 3 and 7 days. Unlike IL-4 and IL-10, the spleen level of TGF-ß, INF-γ, IL-12, and IL-17 was considerably decreased in the Xen + Rad than the Xen alone group on 3 and 7 days. The spleen expressions of the VEGF, Ki67, and Bax/Bcl-2 ratio were dramatically increased in the Xen + Rad group compared to the Xen alone on 3, 7, 14, and 21 days. Our results could confirm a new tumor xenograft model via an efficient immune-suppressive potential of the whole-body gamma radiation in mice.

Protective and anticancer effects of orange peel extract and naringin in doxorubicin treated esophageal cancer stem cell xenograft tumor mouse model.

BACKGROUND: chemotherapy drugs are the common therapy for cancer cells with side effects. Recent studies reported that natural products may contribute to decreasing the side effects of chemotherapy drugs. Here, we aimed to investigate the effects of orange peel extract (OPE) and its main compound; naringin (NR) to protect the side effects of doxorubicin (Dox) in esophageal cancer stem cells (CSCs) derived tumors in vivo. METHODS: for this purpose, Esophageal cancer cell (YM1) derived spheres were treated in vitro with OPE, NR, Dox, Dox in combination with OPE or NR. The cell viability was assessed by XTT and the apoptosis was measured using Annexin/7-AAD and the cell cycle was also quantified by using PI staining method. The pluripotency related genes expression was carried out using qRT-PCR The protective effects of OPE and NR were evaluated by body weight evaluation and oxidative stress factors: malondialdehyde (MDA), total antioxidant capacity (TAC) and superoxide dismutase (SOD) measurement in xenograft mice tumor model injected with Dox. RESULTS: ESCC CSCs overexpress SOX2 and OCT4 pluripotency genes. OPE or NR can protect the cellular toxicity of Dox in vitro mainly by decreasing cellular apoptosis of ESCC CSCs however S-phase cell cycle arrest has not been affected significantly. In vivo experiments revealed that the use of Dox simultaneously with OPE or NR not only can reduce the tumor size but also the body weight of the treated nude mice were maintained in comparison to Dox alone. In contrast to Dox alone, Dox in combination with OPE or NR showed less systemic toxicity and decreased oxidative stress fraction circulation, however, OPE seemed as more protective. CONCLUSION: The results suggest that these natural compounds can be used as adjuvant therapy to lower systemic toxicity of chemotherapeutic agents like DOX in ESCC cancer stem cells treatment.

Selective Inhibition of Esophageal Cancer Stem-like Cells with Salinomycin.

BACKGROUND: Targeting Cancer Stem-Like Cells (CSLCs) can provide promising new therapeutic strategies to inhibit cancer progression, metastasis and recurrence. Salinomycin (Sal), an antibacterial ionophore, has been shown to inhibit CSCs specifically. Recently, it has been reported that Sal can destabilize TAZ, the hypo pathway transducer in CSLCs. OBJECTIVES: Here, in the current study, we aimed to assess the differential toxicity of Sal in esophageal CSLCs and its relation to TAZ gene expression. METHODS: The esophageal cancer cell line, KYSE-30, was used for the enrichment of CSLCs. The expression of TAZ was knocked down using specific siRNA transfection and then the cytotoxicity of Sal was measured using XTT assay. The qRT-PCR method was used for gene expression assessment and the sphere formation ability was monitored using light microscopy. RESULTS: Our findings showed that esophageal CSLCs over-express stemness-associated genes, including SOX2, OCT4 as well as TAZ (~14 fold, P value=0.02) transcription coactivator. We found Sal can selectively inhibit KYSE-30 CSLCs viability and sphere formation ability; however, TAZ knockdown does not change its differential toxicity. CONCLUSION: Overall, our results indicated that Sal can selectively decrease the viability of esophageal CSLCs in a TAZ-independent manner.