The therapeutic potential of immunotherapy in the treatment of breast cancer: Rational strategies and recent progress.

The second leading cause of cancer death in women worldwide is breast cancer (BC), and despite significant advances in BC therapies, a significant proportion of patients develop metastasis and disease recurrence. Currently used treatments, like radiotherapy, chemotherapy, and hormone replacement therapy, result in poor responses and high recurrence rates. Alternative therapies are therefore needed for this type of cancer. Cancer patients may benefit from immunotherapy, a novel treatment strategy in cancer treatment. Even though immunotherapy has been successful in many cases, some patients do not respond to the treatment or those who do respond relapse or progress. The purpose of this review is to discuss several different immunotherapy approaches approved for the treatment of BC, as well as different strategies for immunotherapy for the treatment of BC.

The effect of continuous positive airway pressure on total antioxidant capacity in obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA), a sleep-related disorder with high prevalence, is associated with an imbalance in oxidative stress and is linked to cardiovascular disease. There are conflicting reports regarding the effectiveness of continuous positive airway pressure (CPAP) therapy on oxidative stress/antioxidant markers in patients with OSA. This review was performed to evaluate the influence of therapy with CPAP on serum/plasma total antioxidant capacity (TAC) in patients with OSA. METHODS: The Cochrane Library, Web of Science, Scopus, Embase, and PubMed were searched through June 2022 to obtain studies evaluating CPAP treatment on TAC in patients with OSA. Overall results were tested using standardized mean difference (SMD) with a 95% confidence interval (CI). Comprehensive Meta-Analysis V2 software was employed to perform analyses. RESULTS: Ten studies with 12 effect sizes were eligible for inclusion in this analysis. The overall SMD revealed that CPAP therapy significantly increased TAC [SMD 0.497; 95% CI: 0.21 to 0.77; p: 0.00] in OSA. Analyses based on subgroups showed that the effect of CPAP therapy was significant in all subgroups according to therapy duration, age, BMI, and AHI. Whereas the meta-regression results indicated that the impact of therapy with CPAP on TAC is associated with AHI, BMI, and age in patients with OSA. CONCLUSIONS: The finding of this meta-analysis demonstrated a favorable impact of CPAP therapy on TAC levels in patients suffering from OSA.

Bio-synthesized selenium nanoparticles ameliorate Brain oxidative stress in Parkinson disease rat models.

AIM: Parkinson disease (PD) is a prevalent central nervous system degenerative condition that impacts elderly people. Recent clinical and experimental study findings have established oxidative stress as one of the main pathogeneses of PD. Selenium, a trace metals with antioxidant effects, might reverse the neurobehavioral impairments and oxidative stress in rats. Thus, the goal of this study was to ascertain if Selenium Nano Particles (SeNPs) are also effective to protect brain cells from oxidative stress or not. MAIN METHODS: SeNPs were synthesized utilizing Ascorbic acid and chitosan as a reducing and stabilizing agent. Next, eight groups (N: 6) of male Wistar rats were randomly assigned and injected by different dosage (0.1, 0,2, and 0.3 mg/kg) of Se and SeNP. Finally, to ascertain the protective benefits of SeNP on PD rats, behavioral evaluation, clinical symptoms, antioxidant activity, and oxidant levels were examined. KEY FINDINGS: According to the findings, PD rats' motor functions had developed by SeNP injection. Higher MDA levels and inhibited antioxidant activities (SOD, CAT, and GPX) in lesion group are highlighting the significant role of oxidative stress in dopaminergic neuron death and neurobehavioral abnormalities. SeNP also protect against oxidative stress as compared to the lesion group. The levels of MDA had greatly reduced while the activities of enzymes, TAC, and SeNP both had significantly increased. SIGNIFICANCE: By enhancing antioxidant activity, administration of SeNP can reduce the hazardous consequences of oxidative stress.

Curcumin loaded ß-cyclodextrin-magnetic graphene oxide nanoparticles decorated with folic acid receptors as a new theranostic agent to improve prostate cancer treatment.

This article presents a novel approach to treating prostate cancer using a nanocarrier composed of folic acid (FA), ß-cyclodextrin (ß-CD), and magnetic graphene oxide (MGO) as a theranostic agent. The carrier is designed to improve the solubility and bioavailability of curcumin, a potential therapeutic substance against prostate cancer. Folic acid receptors overexpressed on the surface of solid tumors, including prostate cancer, may facilitate targeted drug delivery to tumor cells while avoiding nonspecific effects on healthy tissues. The anticancer efficacy of Folic acid-curcumin@ß-CD-MGO in vitro was also examined on LNCaP (an androgen-dependent) and PC3 (an androgen-independent) prostate cancer cells. The relaxivity of nanoparticles in MRI images was also investigated as a diagnostic factor. The results showed a concentration-dependent inhibitory effect on cell proliferation, induction of oxidative damage, and apoptotic effects. Also, nanoparticle relaxometry shows that this agent can be used as a negative contrast agent in MRI images. Overall, this study represents a promising theranostic agent to improve the delivery and trace of curcumin and enhance its therapeutic potential in the treatment of prostate cancer.

Investigating the anticancer effects of chitosan-NLC-folate nanohybrid loaded with auraptene on A2780 ovarian cancer cells.

The significant fatality rate associated with ovarian cancer underscores the urgent need for novel therapeutic interventions in this area. The focus of this study was to assess the cytotoxic impact of auraptene nanohybrid chitosan folate on A2780 ovarian cancer cells. A combination of liquid and solid lipids were used to create auraptene-nanostructured lipid carriers. Folic acid was conjugated to chitosan in order to modify the surface. The nanoparticles containing methylene blue were dissolved in deionized distilled water to attach the chitosan-folic acid to the nanoparticles. The resazurin cell viability assay was employed to gauge the cytotoxicity of auraptene on the cells. Real-time PCR was utilized to quantify the expression levels of Bcl-2, Bax, and P53 genes. DLS analysis exposed a spheroidal particle with an approximate diameter of 211 nm. The auraptene nanoparticles did not revealed inhibitory effect on normal cell line (HFF-1) at the concentrations that it was toxic for cancerous cells (A2780). In vitro trials suggested that auraptene nanoparticles trigger apoptosis in A2780 cells in a dose-responsive manner by promoting the expression of pro-apoptotic genes (Bax and P53), while suppressing the expression of the anti-apoptotic gene (Bcl-2). Furthermore, auraptene nanoparticles also heightened the production of reactive oxygen species within the cancerous cells. The notable cytotoxic and lethal influence of auraptene nanoparticles on human ovarian cancer may be attributed to their capacity to generate oxidative stress conditions and induce apoptosis.

The protective effects of hesperidin as an antioxidant against quinolinic acid-induced toxicity on oligodendroglia cells: An in vitro study.

INTRODUCTION: Multiple sclerosis (MS) is a complex central nervous system disorder, marked by neurodegenerative and inflammatory processes, where overproduction of reactive oxygen species (ROS) is a key factor in demyelination and neurodegeneration. The current study aims to investigate the effect of hesperidin and Quinolinic acid (QA) on ROS and antioxidant levels, and cell viability of OLN-93 cells. METHODS: OLN-93 cell lines were treated with hesperidin and QA. OLN-93 cells were cultured in Dulbecco's modified Eagle's medium under controlled conditions. Cell viability assays were performed using resazurin to assess the toxicity of hesperidin and QA. Additionally, ROS levels were measured using DCFDA, and malondialdehyde (MDA) levels were determined to evaluate oxidative stress. Superoxide dismutase (SOD) activity and cell viability were assessed by trypan blue staining after exposure to hesperidin and QA. RESULTS: The results of the current study showed that co-administration of 8 mM QA with 50, 100, and 200 µM hesperidin significantly reduced both ROS and MDA levels, demonstrating a substantial attenuation in comparison to the elevated ROS and MDA levels induced by 8 mM QA (p-value < 0.01). Furthermore, 8 mM QA + 50, 100, and 200 µM hesperidin significantly increased SOD levels compared with QA alone (p-value < 0.01). In addition, treatment of OLN cells with 8 mM QA + 50, 100, and 200 µM hesperidin led to higher cell viability compared to QA alone (p value <0.0001). CONCLUSION: The current study demonstrated the antioxidant effect of hesperidin on OLN-93 cells suggesting new insights into the clinical application of hesperidin as an effective treatment for patients with MS. Future in vivo studies, focusing on cellular mechanisms are recommended.

The Combinational Effect of Inulin and Resveratrol on the Oxidative Stress and Inflammation Level in a Rat Model of Diabetic Nephropathy.

Background: Using inulin can enhance resveratrol's effects by improving the intestinal microbiome and the stability of resveratrol. Objectives: We aimed to investigate the effect of therapeutic intervention with combined inulin and resveratrol on kidney function in diabetic rats. Methods: Diabetic model was induced by intraperitoneal injection of streptozotocin. Afterward, rats were divided into 6 groups: control, diabetic without treatment, diabetic treated with insulin, diabetic treated with resveratrol, diabetic treated with inulin, and diabetic treated with a combination of inulin and resveratrol. After 10 wk, the creatinine, urea, insulin, urinary proteins, and inflammatory and oxidative stress markers were evaluated. Pathologic changes were examined in kidney tissues. Results: Renal dysfunction, accompanied by increased inflammation and oxidative stress, was observed. Our results showed that treatment with resveratrol and inulin had antidiabetic effects and was associated with reduced renal dysfunction, oxidative stress, and kidney inflammation. In addition, it was observed that combined treatment with inulin and resveratrol outperformed monotherapies in improving kidney function and reducing oxidative stress and inflammation. Conclusions: Treatment with resveratrol and inulin can have renoprotective effects by improving oxidative stress and inflammation in kidney tissues. Therefore, employing these 2 compounds is suggested as an inexpensive and available method for diabetic nephropathy.

Quantifying microstructures of earth materials using higher-order spatial correlations and deep generative adversarial networks.

The key to most subsurface processes is to determine how structural and topological features at small length scales, i.e., the microstructure, control the effective and macroscopic properties of earth materials. Recent progress in imaging technology has enabled us to visualise and characterise microstructures at different length scales and dimensions. However, one limitation of these technologies is the trade-off between resolution and sample size (or representativeness). A promising approach to this problem is image reconstruction which aims to generate statistically equivalent microstructures but at a larger scale and/or additional dimension. In this work, a stochastic method and three generative adversarial networks (GANs), namely deep convolutional GAN (DCGAN), Wasserstein GAN with gradient penalty (WGAN-GP), and StyleGAN2 with adaptive discriminator augmentation (ADA), are used to reconstruct two-dimensional images of two hydrothermally rocks with varying degrees of complexity. For the first time, we evaluate and compare the performance of these methods using multi-point spatial correlation functions-known as statistical microstructural descriptors (SMDs)-ultimately used as external tools to the loss functions. Our findings suggest that a well-trained GAN can reconstruct higher-order, spatially-correlated patterns of complex earth materials, capturing underlying structural and morphological properties. Comparing our results with a stochastic reconstruction method based on a two-point correlation function, we show the importance of coupling training/assessment of GANs with higher-order SMDs, especially in the case of complex microstructures. More importantly, by quantifying original and reconstructed microstructures via different GANs, we highlight the interpretability of these SMDs and show how they can provide valuable insights into the spatial patterns in the synthetic images, allowing us to detect common artefacts and failure cases in training GANs.

Sol-gel synthesis and cytotoxicity evaluation of selenium-doped cerium oxide nanoparticles for biomedical applications.

Over the past few years, ovarian cancer is the second most commonly diagnosed cancer among women. Despite the widespread knowledge of its prevalence, the curative measures and survival rates for ovarian cancer have not improved significantly, making it a challenging condition. Nanotechnology has become increasingly prominent in the field of cancer treatment. Previous studies showed both cerium oxide nanoparticles (CONPs) and selenium (Se) had anti-cancer. Therefore, doping selenium into CONPs may exhibit a more significant anti-cancer effect on ovarian cancer cells. Cerium nitrate hexahydrate, sodium selenite, and gelatin were employed for the production of CONPs and Se-doped CONPs. The EDX, XRD, and TEM/PSA imaging were employed to investigate the structural characteristics and morphology of the synthesized Se-doped CONPs. The reactive oxygen species (ROS) level and TNF, IL-6, and IL-1B gene expression were evaluated after inoculating A2780 human epithelial ovarian carcinoma (HEOC) with Se-doped CONP. Statistical analysis was conducted using ANOVA, followed by Bonferroni's t-test for multiple group comparisons. Se-doped CONPs had IC50 of 113 and 49 PPM after 24 and 48 h, respectively. In addition, Se-doped CONPs with concentrations of 50 and 100 PPM significantly reduced to ROS levels in the HEOC cell line. Also, 50 and 100 PPM Se-doped CONPs lead to significantly reduced TNF, IL-6, and IL-1B gene expression compared to the control group in the HEOC cell line. Our study showed the potential anti-cancer effects of Se-doped CONPs on ovarian cancer cell lines.

PEGylated Lecithin-Chitosan-Folic Acid Nanoparticles as Nanocarriers of Allicin for In Vitro Controlled Release and Anticancer Effects.

In this study, chitosan-lecithin nanoparticles modified with polyethylene glycol (PEG) and folic acid (FA) were used to deliver allicin (AC) to colon cancer cells. AC-loaded polyethylene glycol (PEG) and folic acid (FA)-modified chitosan-lecithin nanoparticles (AC-PLCF-NPs) were fabricated via self-assembling procedure. HPLC for AC encapsulation and FA binding, MTT for viability assay, ABTS and DPPH for antioxidant capacity, disc diffusion, MIC and MBC for antibacterial assay, qPCR and AO/PI staining for apoptotic, and CAM assay for angiogenesis effects of AC-PLCF-NPs were used. AC-PLCF-NPs (113.55 nm) were synthesized as single dispersed (PDI: 0.28) and stable (ZP: + 33.18 mV) with 81% AC encapsulation and 48% FA binding. The antioxidant power of AC-PLCF-NPs was confirmed by inhibiting free radicals ABTS (74.25 µg/mL) and DPPH (366.214 µg/mL) and its antibacterial capacity with very high inhibitory effects against gram-negative bacterial strains. MTT results showed higher toxicity of AC-PLCF-NPs (68.06 µg/mL) compared to AC (171.45 µg/mL). Increased expression of caspase 3 and 9 genes showed activation of the intrinsic apoptosis pathway in treated cells, and on the other hand, reduction of vascular and embryonic growth factors in CAM model confirmed the anti-angiogenesis effects of AC-PLCF-NPs. AC-PLCF-NPs can be suggested as a promising therapeutic agent for studies in the field of colon cancer treatment.

Anti-inflammatory effects of resveratrol in patients with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic inflammation is one of the most important factors involved in the development and progression of cardiovascular disease (CVDs). Accumulating evidence has described the effect of resveratrol, a natural polyphenolic compound, on biomarkers of inflammation among patients with CVDs; however, findings are controversial. Here we performed a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of resveratrol supplements on TNF-α, IL-6, and CRP levels in CVDs patients. METHODS: Online research was conducted in the following database: MEDLINE, EMBASE, Cochrane Library, Web of Science databases, and Scopus. This systematic review and meta-analysis were conducted to investigate the effects of resveratrol supplements on inflammatory biomarkers among patients with CVDs. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. RESULTS: Six RCTs met the inclusion criteria and were selected for the current meta-analysis. Our results demonstrated that resveratrol significantly decreases serum levels of CRP (MD = -0.63, 95 % CI: -0.1.13, -0.12; p = 0.01), and TNF-α (MD = -0.55, 95 % CI: -1.04, -0.06; p = 0.02), however, resveratrol had not significant effect on serum concentration of IL-6 (MD = -0.12, 95 % CI: -0.52, 0.27; p = 0.53), in patients with CVDs. CONCLUSION: Our results suggest that resveratrol can be used as a potential treatment in patients with CVD by reducing inflammatory conditions.

Acetyl-11-Keto-ß-Boswellic Acid (AKBA) Prevents Lipopolysaccharide-Induced Inflammation and Cytotoxicity on H9C2 Cells.

Acetyl-11-keto-beta-boswellic acid (AKBA), the major component of Boswellia serrata, exhibits anti-inflammatory activities. This in vitro study investigated the protective effects of AKBA against lipopolysaccharide (LPS)-induced cardiac dysfunction. In this study, the H9C2 cardiomyocytes were pretreated with AKBA (2.5, 5, and 10 µM for 24 h), and then cotreated with LPS for another 24 h. The MTT assay, ELISA test kits, and quantitative real-time PCR analysis assessed the cell viability, levels of proinflammatory factors (IL-ß, IL-6, TNF- α, and PGE2), and the gene expression of IL-ß, IL-6, TNF- α, iNOS, and COX-2, respectively. The nitric oxide (NO) and thiol levels were also measured using a biochemical assay. The results indicated that LPS exposure markedly reduced cell viability and total thiol content, but increased the inflammatory cytokines, NO metabolites, and gene expression of proinflammatory mediators in H9C2 cells. AKBA pretreatment significantly altered the mentioned factors induced by LPS. Our results demonstrated that AKBA might be a promising therapeutic agent for treating sepsis-related cardiac dysfunction in the future.

Carbon nanotubes in microfluidic lab-on-a-chip technology: current trends and future perspectives.

Advanced nanomaterials such as carbon nano-tubes (CNTs) display unprecedented properties such as strength, electrical conductance, thermal stability, and intriguing optical properties. These properties of CNT allow construction of small microfluidic devices leading to miniaturization of analyses previously conducted on a laboratory bench. With dimensions of only millimeters to a few square centimeters, these devices are called lab-on-a-chip (LOC). A LOC device requires a multidisciplinary contribution from different fields and offers automation, portability, and high-throughput screening along with a significant reduction in reagent consumption. Today, CNT can play a vital role in many parts of a LOC such as membrane channels, sensors and channel walls. This review paper provides an overview of recent trends in the use of CNT in LOC devices and covers challenges and recent advances in the field. CNTs are also reviewed in terms of synthesis, integration techniques, functionalization and superhydrophobicity. In addition, the toxicity of these nanomaterials is reviewed as a major challenge and recent approaches addressing this issue are discussed.

Low and high CD8 positive T cells in multiple sclerosis patients.

Cumulating evidence points to a key role for CD8+ T cells in the pathogenesis of multiple sclerosis.CD8 expression level was believed to be present constantly on the surface of human peripheral blood T cells. However, it was shown that peripheral blood lymphocytes may be divided by the level of CD8 expression, into CD8+high and CD8+low T cells. Now it is well established that the CD8low population of CD8+ T cells demonstrates an activated effector phenotype while the CD8+high T cells have been reported to have regulatory function. In this report we used a flow cytometric assay to compare the frequency of these two subsets in multiple sclerosis patients (n=31) with healthy age- and gender-matched controls (n=18). We found that CD8+ T cells and CD8+low T cells significantly increased in secondary progressive (SP) and primary progressive multiple sclerosis (PPMS) patients in comparison to controls (p<0.0002 and p<0.004 respectively) and also RRMS (p<0.005 and p<0.017 respectively). These results demonstrated the role of CD8low T cells in progressive form of multiple sclerosis.