Therapeutic potential of Phycocyanin in gastrointestinal cancers and related disorders.

Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/ß-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.

The role of aquaporin 4 in brain tumors: implications for pathophysiology, diagnosis and therapy.

Primary brain tumors are a heterogeneous group of tumors that arise from cells intrinsic to the central nervous system (CNS). Aquaporin-4 (AQP4) has been implicated in the pathogenesis of brain tumors. Previous reports have documented a relationship between AQP4 and several molecular pathways associated with the etiology of brain tumors, such as apoptosis, invasion and cell migration. AQP4 affects apoptosis via cytochrome C, Bad and Bcl-2, as well as invasion and migration via IDO1/TDO-Kyn-AhR axis, lncRNA LINC00461, miR-216a, miRNA-320a and MMPs. In addition, inhibition of AQP4 mitigates the progression of brain tumors. This review summarizes current knowledge and evidence regarding the relationship between AQP4 and brain tumors, and the mechanisms involved.

Therapeutic Potential of Berberine in the Treatment of Glioma: Insights into Its Regulatory Mechanisms.

Glioma is known as one of the most common primary intracranial tumors accounting for four-fifths of malignant brain tumors. There are several biological pathways that play a synergistic, pathophysiological role in glioma, including apoptosis, autophagy, oxidative stress, and cell cycle arrest. According to previous rese arches, the drugs used in the treatment of glioma have been associated with significant limitations. Therefore, improved and/or new therapeutic platforms are required. In this regard, multiple flavonoids and alkaloids have been extensively studied in the treatment of glioma. Berberine is a protoberberine alkaloid with wide range of pharmacological activities, applicable to various pathological conditions. Few studies have reported beneficial roles of berberine in glioma. Berberine exerts its pharmacological functions in glioma by controlling different molecular and cellular pathways. We reviewed the existing knowledge supporting the use of berberine in the treatment of glioma and its effects on molecular and cellular mechanisms.

New trends in glioma cancer therapy: Targeting Na+ /H + exchangers.

Glioma is the oneof the most prevalent primarybrain tumors. There is a variety of oxidative stresses, inflammatory pathways, apoptosis signaling, and Na+ /H + exchangers (NHEs) involved in the pathophysiology of glioma. Previous studies have indicated a relationship between NHEs and some molecular pathways in glioma. NHEs, including NHE1, NHE5, and NHE9 affect apoptosis, tumor-associated macrophage inflammatory pathways, matrix metalloproteinases, cancer-cell growth, invasion, and migration of glioma. Also, inhibition of NHEs contributes to increased survival in animal models of glioma. Limited studies, however, have assessed the relationship between NHEs and molecular pathways in glioma. This review summarizes current knowledge and evidence regarding the relationship between NHEs and glioma, and the mechanisms involved.

PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers.

Glioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are associated with the initiation and progression of gliomas. Studies have shown that PIWI-interacting RNAs (piRNAs) and PIWI proteins are involved in tumorigenesis by epigenetic mechanisms. Hence, it seems that piRNAs and PIWI proteins may be potential prognostic, diagnostic or therapeutic biomarkers in the treatment of glioma. Previous studies have demonstrated a relationship between piRNAs and PIWI proteins and some of the molecular and cellular pathways in glioma. Here, we summarize recent evidence and evaluate the molecular mechanisms by which piRNAs and PIWI proteins are involved in glioma. Video abstract.

Aquaporin 4: A key player in Parkinson's disease.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases which occur in aged people worldwide. Given that a sequence of cellular and molecular mechanisms, including oxidative stresses, apoptosis, inflammatory pathways, microglia, astrocyte activation, and aquaporin 4 (AQP4) are associated with initiation and the progression of PD. AQP4 may affect various pathways (i.e., α-synuclein, inflammatory pathways, and microglia and astrocyte activation). Few reports have evaluated the relationship between AQP4 and PD-related cellular and molecular pathways. Here, for the first time, we highlighted the relationship between AQP4 and molecular mechanisms involved in PD pathogenesis.

The investigation of relevancy between PIAS1 and PIAS2 gene expression and disease severity of multiple sclerosis.

Introduction: PIAS1 and PIAS2 (protein inhibitor of activated STAT 1,2) play key roles in the pathogenesis of autoimmune and inflammatory diseases. This study aims to evaluate the gene expression of these factors in multiple sclerosis (MS) patients compared to healthy individuals and correlate them with the severity of MS. Materials and methods: Sixty participants, including 30 patients with MS and 30 healthy controls were studied. The expression of PIAS1 and PIAS2 genes in peripheral blood samples of all participants was measured by real-time PCR. The severity of MS was evaluated using the Expanded Disability Status Scale (EDSS). Finally, we evaluated the correlation between the expression of PIAS1 and PIAS2 genes with disease severity. Results: The expression of PIAS1 gene was increased in patients with MS compared to healthy subjects (P value<.001). Also, there was a significant correlation between the expression of PIAS1 and PIAS2 genes with disease severity according to EDSS. Conclusion: Our study suggests the expression of PIAS1 and PIAS2 genes as a prognostic and diagnostic marker in MS disease.

Correlation of serum levels and gene expression of tumor necrosis factor-α-induced protein-8 like-2 with Parkinson disease severity.

Different immune-mediated mechanisms involved in the pathogenesis of Parkinson disease (PD) as a neurodegenerative and inflammatory disease. According to our knowledge, there is no report evaluating Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a cytokine maintaining immune homeostasis, in PD. We analyzed the correlation of the serum levels and circulatory gene expression of TIPE2 with severity of PD. In this case-control study, 43 patients with PD and 40 healthy subjects were enrolled. The diagnosis of PD was performed byclinical diagnostic criteria of the UK Parkinson's Disease Society Brain Bank. The severity of PD was evaluated by modified Hoehn and Yahr (H and Y) scale. Serum levels and gene expression of TIPE2 were assessed by Elisa and real time PCR, respectively. The mean serum levels and gene expression of TIPE2 in patients with PD did not have significant difference compared to healthy subjects. Linear multiple regression analysis showed that increased serum levels of TIPE2 are positively related to age and severity of PD (P ≤ 0.0001). In addition, the gene expression of TIPE2 was found to be associated with age (P < 0.0001). Our study showed that the serum levels of TIPE2 and its gene expression might be important prognostic biomarkers of PD.

Optimal query-based relevance feedback in medical image retrieval using score fusion-based classification.

In this paper, a new content-based medical image retrieval (CBMIR) framework using an effective classification method and a novel relevance feedback (RF) approach are proposed. For a large-scale database with diverse collection of different modalities, query image classification is inevitable due to firstly, reducing the computational complexity and secondly, increasing influence of data fusion by removing unimportant data and focus on the more valuable information. Hence, we find probability distribution of classes in the database using Gaussian mixture model (GMM) for each feature descriptor and then using the fusion of obtained scores from the dependency probabilities, the most relevant clusters are identified for a given query. Afterwards, visual similarity of query image and images in relevant clusters are calculated. This method is performed separately on all feature descriptors, and then the results are fused together using feature similarity ranking level fusion algorithm. In the RF level, we propose a new approach to find the optimal queries based on relevant images. The main idea is based on density function estimation of positive images and strategy of moving toward the aggregation of estimated density function. The proposed framework has been evaluated on ImageCLEF 2005 database consisting of 10,000 medical X-ray images of 57 semantic classes. The experimental results show that compared with the existing CBMIR systems, our framework obtains the acceptable performance both in the image classification and in the image retrieval by RF.

The effects of combined and independent low-level laser and mesenchymal stem cell therapy on induced knee osteoarthritis: An animal study.

BACKGROUND: Mesenchymal stem cell (MSC) injection has emerged as a novel treatment for knee osteoarthritis (OA). In addition, low-level laser therapy (LLLT) has been reported to delay the progression of OA. Thus, the current study on animal models of OA investigated the effectiveness of these methods when administered independently and combined. METHODS: Twenty-five guinea pig models of OA were randomly sorted into five study groups. The test groups received intra-articular MSC, LLLT, and a combination of these therapeutics for 8 weeks. Radiological and histopathologic evaluations were carried out for the test groups and the control after the completion of treatments. RESULTS: The MSC-treated groups showed better outcomes in terms of all radiological and histological indexes compared with the control, apart from subchondral bone (P < 0.05). Similarly, but to a different extent, the LLLT-treated group showed better results than the controls (P < 0.05). The combination of MSC therapy and LLLT improved the cartilage, surface, matrix, space width, osteophytes, and radiologic OA scores more effectively than each of these methods alone (P < 0.05). CONCLUSIONS: According to our results, the combination of intra-articular MSC and LLLT can effectively improve OA in animal models. Further preclinical and clinical studies are recommended to assess the effectiveness of these therapeutics alone and in combination.

Melanoma Cancer Therapy Using PEGylated Nanoparticles and Semiconductor Laser.

Purpose: Photothermal therapy (PTT) is a procedure that converts laser beam energy to heat so can disturb tumor cells. Carbon nanotubes (CNTs) have unique properties in absorption optical energy and could change optical power into heat in PTT procedures. Additionally, titanium dioxide (TiO2) nanoparticles (NPs) have a unique feature in absorbing and scattering light. Therefore, these mentioned NPs could play a synergistic role in the PTT method. Methods: CNTs and TiO2 NPs were injected into the melanoma tumor sites of cancerous mice. Then sites were excited using the laser beam (λ = 808 nm, P = 2 W, and I = 4 W/cm2). Injected NPs caused hyperthermia in solid tumors. Tumor size assay, statistical analysis, and histopathological study of the treated cases were performed to assess the role of mentioned NPs in PTT of murine melanoma cancer. Results: The results showed that CNTs performed better than TiO2 NPs in destroying murine melanoma cancer cells in animals. Conclusion: The present study compared the photothermal activity of excited CNTs and TiO2 NPs in cancer therapy at the near-infrared spectrum of light. Tumors were destroyed selectively because of their weakened heat resistance versus normal tissue. PTT of malignant melanoma through CNTs caused remarkable necrosis into the tumor tissues versus TiO2 NPs.

PEGylated Carbon Nanotubes Decorated with Silver Nanoparticles: Fabrication, Cell Cytotoxicity and Application in Photo Thermal Therapy.

A new technique for cancer therapy is Photo Thermal Therapy (PTT). In the PTT technique, photon energy is converted into heat via various operations to destroy malignant tumors. Carbon nanotubes (CNTs) have good optical absorption in the near-infrared (NIR) spectrum and could transform optical energy into heat to induce hyperthermia in the PTT method. In this study, CNTs were firstly oxidized (O-CNT) and then decorated with silver nanoparticles (Ag NPs). Polyethylene glycol (PEG) was utilized for wrapping the surface of CNTs (O-CNT/Ag-PEG). Coating of CNTs with Ag NPs and PEG was confirmed by XRD, FESEM, and TEM techniques. Results demonstrated that noble metal could increase optical absorption of CNTs and concurrently improve the efficacy of the PTT technique. Cell cytotoxicity study showed that O-CNT/Ag NPs were less cytotoxic than O-CNTs, and O-CNT/Ag-PEG had the lowest toxicity against HeLa, HepG2, and PC3 human cell lines. The efficacy of O-CNT/Ag-PEG NPs in destroying malignant melanoma tumors was evaluated through the PTT technique. A continuous wave NIR laser diode (λ = 808 nm, P = 2 W, and I = 2 W/cm2) irradiated the tumor sites for 8 min once in the period of the treatment. The tumors in cases receiving O-CNT/Ag-PEG were shrunk efficiently compared to laser treatment ones. Results of in-vivo studies demonstrated that O-CNT/Ag-PEG was a puissant candidate in extirpating malignant tumors in PTT method.

The correlation of helios and neuropilin-1 frequencies with parkinson disease severity.

OBJECTIVES: Parkinson disease (PD), a neurodegenerative disease, has also some immunologic basis in which several regulatory factors, like Helios and Neuropilin-1 (NRP-1) may show some roles in its pathogenesis. We aimed to evaluate the circulatory frequency of T regulatory cells (Tregs) expressing Helios and NRP-1 in PD. PATIENTS AND METHODS: In this case-control study, 83 patients with PD and 83 healthy controls were enrolled. The diagnosis of PD was accomplished in accordance with clinical diagnostic criteria of the UK Parkinson Disease Society Brain Bank. The modified Hoehn and Yahr (H and Y) were used to measure the severity of PD. Flow cytometry was used to evaluate the circulatory frequency of CD4+CD25+Foxp3+Tregs expressing and Helios and NRP-1 in all participants. Also, correlation of H and Y with such frequencies was evaluated. RESULTS: Our findings showed that frequency of CD4+CD25+Foxp3+Tregs expressing NRP-1 (P = 0.04) and Helios (P = 0.01) in patients with PD was significantly higher than those in healthy subjects. The frequency of Tregs expressing Helios and NRP-1 showed a negative correlation with H and Y criteria and disease duration. Multiple linear regression analysis indicated that the severity of PD is the only effective factor on the frequency of CD4+CD25+Foxp3+NRP-1+Tregs (P = 0.012) and CD4+CD25+FoxP3+ Helios + Tregs (P = 0.038). CONCLUSION: Our study showed that the increased frequency of Tregs expressing Helios and NRP-1 is associated with the severity of PD.

The Therapeutic Potential of Quercetin in Parkinson's Disease: Insights into its Molecular and Cellular Regulation.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). PD is a multifactorial disorder, with several different factors being suggested to play a synergistic pathophysiological role, including oxidative stress, autophagy, underlying pro-inflammatory events and neurotransmitters abnormalities. Overall, PD can be viewed as the product of a complex interaction of environmental factors acting on a given genetic background. The importance of this subject has gained more attention to discover novel therapies to prevent as well as treat PD. According to previous research, drugs used to treat PD have indicated significant limitations. Therefore, the role of flavonoids has been extensively studied in PD treatment. Quercetin, a plant flavonol from the flavonoid group, has been considered as a supplemental therapy for PD. Quercetin has pharmacological functions in PD by controlling different molecular pathways. Although few studies intended to evaluate the basis for the use of quercetin in the context of PD have been conducted so far, at present, there is very little evidence available addressing the underlying mechanisms of action. Various principal aspects of these treatment procedures remain unknown. Here, currently existing knowledge supporting the use of quercetin for the clinical management of PD has been reviewed.

Benign prostatic hyperplasia treatment using plasmonic nanoparticles irradiated by laser in a rat model.

OBJECTIVE: In the current study we have stimulated the efficacy of plasmonic nanoparticles (NPs) by laser hyperthermia to achieve a less invasive method for tumor photothermal therapy of benign prostatic hyperplasia (BPH). METHODS: The levels of apoptosis on induced BPH in rats were assessed after treatment and revealed and recorded by various assayed. Moreover, the expression of caspases was considered to demonstrate the apoptotic pathways due to laser induced plasmonic NPs. RESULTS: In the Laser + NPs group prostate size of induced BPH decreased. Laser + NPs also decreased prostate specific antigen in comparison with the BPH groups. Furthermore, Laser + NPs attenuated BPH histopathologic indices in the rats. Laser + NPs induced apoptosis in prostatic epithelial cells via caspase-1 pathway. CONCLUSIONS: Altogether, the approach and findings from this study can be applied to introduce the laser irritated NPs method as a novel and less invasive therapy for patients suffering from BPH.

The application of titanium dioxide (TiO2) nanoparticles in the photo-thermal therapy of melanoma cancer model.

OBJECTIVES: Photo-thermal therapy (PTT) is a therapeutic method in which photon energy is converted into heat to induce hyperthermia in malignant tumor cells. In this method, energy conversion is performed by nanoparticles (NPs) to enhance induced heat efficacy. The low-cytotoxicity and high optical absorbance of NPs used in this technique are very important. In the present study, titanium dioxide (TiO2) NPs were used as agents for PTT. For increasing water dispersibility and biocompatibility, polyethylene glycol (PEG)-TiO2 NPs (PEGylated TiO2 NPs) were synthesized and the effect of these NPs on reducing melanoma tumor size after PTT was experimentally assessed. MATERIALS AND METHODS: To improve the dispersibility of TiO2 NPs in water, PEG was used for wrapping the surface of TiO2 NPs. The formation of a thin layer of PEG around the TiO2 NPs was confirmed through thermo-gravimetric analysis and transmission electron microscopy techniques. Forty female cancerous mice were divided into four equal groups and received treatment with NPs and a laser diode (λ = 808 nm, P = 2 W & I = 2 W/cm2) for seven min once in the period of the treatment. RESULTS: Compared to the mice receiving only the laser therapy, the average tumor size in the mice receiving TiO2-PEG NPs with laser excitation treatment sharply decreased. CONCLUSION: The results of animal studies showed that PEGylated TiO2 NPs were exceptionally potent in destroying solid tumors in the PTT technique.

Increased serum levels of TNF-α and decreased serum levels of IL-27 in patients with Parkinson disease and their correlation with disease severity.

OBJECTIVES: Immunological basis of neurodegenerative diseases including Alzheimer and Parkinson disease (PD) has some important roles in their pathogenesis. There are conflicting studies to serum level of TNF-α in PD. Also, according to our finding there is no report evaluating serum level of IL-27 in PD. This study correlates the serum level of those factors with severity of PD. PATIENTS AND METHODS: In this case-control study, 83 patients with PD and 83 healthy volunteers were enrolled. The diagnosis was fulfilled in accordance with clinical diagnostic criteria of the UK Parkinson's Disease Society Brain Bank by two neurologists. The modified Hoehn and Yahr (H and Y) scale was used to evaluate the severity of PD. Serum levels of TNF-α and IL-27 were measured by Elisa. Correlation of H and Y scale with serum levels of these cytokines was evaluated. RESULTS: The serum levels of TNF-α were increased and serum levels of IL-27 were decreased in patients with PD compared to those in healthy subjects (P < 0.0001). There was a significant correlation between serum levels of TNF-α and IL-27 with H and Y scale. CONCLUSION: Our study showed that the serum levels of TNF-α and IL-27 may be important prognostic biomarkers of PD.

Novel Combination of Silver Nanoparticles and Carbon Nanotubes for Plasmonic Photo Thermal Therapy in Melanoma Cancer Model.

Purpose: Plasmonic photo thermal therapy (PPTT) is a therapeutic method in which the photon energy is rapidly transformed into heat via a series of radiative and non-radiative phenomena to ablate cancer. Plasmonic NPs, such as silver NPs (Ag NPs), have considerable properties in optical absorbance. Furthermore, good thermal conductivity and cell penetration ability of carbon nanotubes (CNTs) could improve the efficacy of Ag NPs for PPTT. Decoration of the multi-walled carbon nanotubes (MWCNTs) with silver has been developed to enhance thermal conductivity of the MWCNT particles. Methods: The Ag NPs were decorated on the CNTs and the ability of these particles (CNT/Ag NPs) in reduction of melanoma tumor size after PTT was evaluated experimentally. For comparison, the PTT of silver nanorods (Ag NRs) and CNTs were investigated. The melanoma tumor was induced by injection of B16/F10 cell line to the inbred mice. Different NPs were injected into the tumors and then irradiated via laser diode (λ=670 nm, P=500 mW, and I= 3.5 W/cm2) at scheduled time. Results: Monitoring of tumor sizes showed that integration of CNTs with silver could enhance the optical absorption of CNTs and improve tumor destruction in PPTT technique. Conclusion: The CNT/Ag NPs could act as a potent agent in PPTT method in curing solid tumors.

Photothermal therapy of melanoma tumor using multiwalled carbon nanotubes.

Photothermal therapy (PTT) is a therapeutic method in which photon energy is transformed into heat rapidly via different operations to extirpate cancer. Nanoparticles, such as carbon nanotubes (CNTs) have exceptional optical absorbance in visible and near infrared spectra. Therefore, they could be a good converter to induce hyperthermia in PTT technique. In our study, for improving the dispersibility of multiwalled CNTs in water, the CNTs were oxidized (O-CNTs) and then polyethylene glycol (PEG) was used for wrapping the surface of nanotubes. The formation of a thin layer of PEG around the nanotubes was confirmed through Fourier transform infrared, thermogravimetric analysis, and field emission scanning electron microscopy techniques. Results of thermogravimetric analysis showed that the amount of PEG component in the O-CNT-PEG was approximately 80% (w/w). Cell cytotoxicity study showed that O-CNT was less cytotoxic than pristine multiwalled nanotubes, and O-CNT-PEG had the lowest toxicity against HeLa and HepG2 cell lines. The effect of O-CNT-PEG in reduction of melanoma tumor size after PTT was evaluated. Cancerous mice were exposed to a continuous-wave near infrared laser diode (λ=808 nm, P=2 W and I=8 W/cm2) for 10 minutes once in the period of the treatment. The average size of tumor in mice receiving O-CNT-PEG decreased sharply in comparison with those that received laser therapy alone. Results of animal studies indicate that O-CNT-PEG is a powerful candidate for eradicating solid tumors in PTT technique.