The effect of propolis supplementation on cardiovascular risk factors in women with rheumatoid arthritis: A double-blind, placebo, controlled randomized clinical trial.

Propolis has gained popularity in recent years because of its beneficial properties, which make it a possible preventative and therapeutic agent as well as a valuable food and cosmetic ingredient. The objective of this study was to evaluate the effects of propolis supplementation on cardiovascular risk factors in women with rheumatoid arthritis. This randomized, double-blind, placebo-controlled clinical trial was performed among 48 patients diagnosed with rheumatoid arthritis. Subjects were randomly assigned to placebo and intervention groups, supplemented with 1000 mg/day of propolis for 12 weeks. Cardiovascular risk factors including, high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein (MCP-1), Nitric oxide, blood pressure, and lipid profile were assessed pre-and post-intervention. The atherogenic index of plasma value, as well as total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C, and non-HDL-C/HDL-C ratios, were significantly reduced in the intervention group, compared with the placebo group post-intervention (p < 0.05). Moreover, there was a significant reduction in the serum level of hs-CRP in the intervention group when compared with the placebo group (p = 0.001). Furthermore, propolis supplementation could marginally reduce MCP-1 (p = 0.051). These data indicate that propolis supplementation may be a promising treatment strategy for cardiovascular complications among rheumatoid arthritis patients.

Use of antioxidant nanoparticles to reduce oxidative stress in blood storage.

Oxidative damage by free radicals has a negative effect on blood quality during storage. Antioxidant nanoparticles can prevent oxidative stress. We use SOD-CAT-Alb-PEG-PLGA- nanoparticles to reduce the effects of oxidative stress in blood storage. Electrospray was employed to prepare nanoparticles. Nanoparticles entered the test bags and were kept for 35 days from the time of donation under standard conditions. On target days, experiments were performed on the samples taken. The examination included blood smear, red blood cells count, hemoglobin, hematocrit, K, Fe, glutathione peroxidase, glutathion reductase, glucose-6-phosphate dehydrogenase, prooxidant-antioxidant balance, malondialdehyde, and flow cytometric assay for phosphatidylserine. The repeated measures analysis was performed on samples every week. Morphological changes were less in the test group compared to the control. The quantitative hemolysis profile test showed significant changes in the test and control groups (p < 0.05) in consecutive weeks except for K and Fe. Oxidative stress parameters too showed a significant change during the target days of the examination (p < 0.05). Also, the phosphatidylserine expression was increased in control groups more than test in consecutive weeks (p < 0.05). It seems that the use of antioxidant nanoparticles improves the quality of stored red blood cells and can prevent posttransfusion complications and blood loss by reducing oxidative stress.

Biological and pharmacological effects and nutritional impact of phytosterols: A comprehensive review.

Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low-density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health-promoting effects of PSs include anti-obesity, anti-diabetic, anti-microbial, anti-inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol-rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.

Resveratrol: Mechanistic and therapeutic perspectives in pulmonary arterial hypertension.

Resveratrol, trans 3,5,4'-trihydroxystilbene, is a stilbenoid polyphenol with a wide range of properties including antioxidant, neuroprotective, cardioprotective, anti-inflammatory and anticancer activities. It is found in the skins of grape (50-100 µg/mL), red wine, peanuts, bilberries, blueberries and cranberries. The most important effects of resveratrol have been found in cardiovascular disease, with pulmonary arterial hypertension (PAH) being a major severe and progressive component. Many factors are involved in the pathogenesis of PAH, including enzymes, transcription factors, proteins, chemokines, cytokines, hypoxia, oxidative stress and others. Resveratrol treats PAH through its actions on various signaling pathways. These signaling pathways are mainly suppressed SphK1-mediated NF-κB activation, BMP/SMAD signaling pathway, miR-638 and NR4A3/cyclin D1 pathway, SIRT1 pathway, Nrf-2, HIF-1 α expression, MAPK/ERK1 and PI3K/AKT pathways, and RhoA-ROCK signaling pathway. Resveratrol efficiently inhibits the proliferation of pulmonary arterial smooth muscle cells and right ventricular remodeling, which are underlying processes leading to enhanced PAH. While supportive evidence from randomized controlled trials is yet to be available, current in vitro and in vivo studies seem to be convincing and suggest a therapeutic promise for the use of resveratrol in PAH.

Evaluating the mechanism underlying antitumor effect of interleukin 27 on B cells of chronic lymphocytic leukemia patients.

Chronic lymphocyte leukemia (CLL) is a B-cell malignancy resisted to apoptosis. Recently, some studies indicated that cytokines such as interleukin 27 (IL-27) can reduce B-cell proliferation. The aim of this study is to evaluate the mechanism underlying the proapoptotic effect of IL-27 on B cells of patients with CLL in comparison with B cells of normal subjects. The effect of IL-27 on the antitumor activity of natural killer (NK) and T cells was also evaluated. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CLL and 15 normal subjects. B cells and PBMCs were cocultured with IL-27 and B cells apoptosis to evaluate proliferation. Both messenger RNA and protein expression of IL-27 and IL-27 receptor were determined using flow cytometry and real-time polymerase chain reaction analysis. To evaluate the apoptotic effect of IL-27 on B cells of patients with CLL, Annexin V-FITC and 7-AAD (BioLegend) fluorescent dyes were used. In addition, the IL-27 effect on activation of T cell and NK cell was determined by determining CD96 molecule expression. IL-27 and IL-27 receptor expression in patients with CLL was significantly lower than that of normal subjects (p < .05). IL-27 enhanced apoptosis of B cells in patients with CLL (p < .05) but this effect was not significantly observed in B cells of normal subjects (p > .05). Consequently, IL-27 reduced the proliferation of B cells and enhanced NK cell activity (p < .05). IL-27, through inducing apoptosis, can exert an inhibitory effect on cancer B cells of CLL patients with minimal effect on normal B cells.

The Effects of Mouse Recombinant Resistin on mRNA Expression of Proinflammatory and Anti-Inflammatory Cytokines and Heat Shock Protein-70 in Experimental Stroke Model.

BACKGROUND: Our recent research showed that resistin has a neuroprotective effect against stroke-induced injury through suppressing apoptosis and oxidative stress. However, the molecular mechanism of neuroprotection of resistin is unclear. This work was designed to examine the effect of mouse recombinant resistin on mRNA expression of Tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-10 (IL-10), Transforming growth factor-ß1 (TGF- ß1), and Heat shock protein-70 (HSP-70) in mouse model of stroke. MATERIALS AND METHODS: Transient focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) in mice. TNF-α, IL-1ß, IL-10, TGF-ß1, and HSP-70 mRNA were detected at sham (0 hour), 3 hours, 6 hours, 12 hours, and 24 hours after MCAO using real-time QRT-PCR method. Moreover, animals were treated with resistin at the dose of 400ng/mouse at the commencement of MCAO, and mRNA expression of the cytokines and HSP-70 was measured 24 hours after MCAO. RESULTS: Tumor necrosis factor-α and IL-1ß mRNA expression markedly increased at 12-hour time point and then returned to the basal level at 24 hours after MCAO; but HSP-70 mRNA expression increased at 24-hour time point. Furthermore, resistin (400 ng/mouse) significantly increased TGF-ß1 and IL-10 and decreased HSP-70 gene expression at 24 hours after MCAO. CONCLUSIONS: Our findings revealed that a molecular mechanism of attenuating ischemic damage by resistin administration probably is increased mRNA expression of anti-inflammatory cytokines. However, applying resistin in the clinical settings for the treatment of stroke deserves further researches in the future.

A comprehensive review on the role of T cell subsets and CAR-T cell therapy in Aspergillus fumigatus infection.

Understanding the immune response to Aspergillus fumigatus, a common cause of invasive fungal infections (IFIs) in immunocompromised individuals, is critical for developing effective treatments. Tcells play a critical role in the immune response to A. fumigatus, with different subsets having distinct functions. Th1 cells are important for controlling fungal growth, while Th2 cells can exacerbate infection. Th17 cells promote the clearance of fungi indirectly by stimulating the production of various antimicrobial peptides from epithelial cells and directly by recruiting and activating neutrophils. Regulatory T cells have varied functions in A.fumigatus infection. They expand after exposure to A. fumigatus conidia and prevent organ injury and fungal sepsis by downregulating inflammation and inhibiting neutrophils or suppressing Th17 cells. Regulatory T cells also block Th2 cells to stop aspergillosis allergies. Immunotherapy with CAR T cells is a promising treatment for fungal infections, including A. fumigatus infections, especially in immunocompromised individuals. However, further research is needed to fully understand the mechanisms underlying the immune response to A. fumigatus and to develop effective immunotherapies with CAR-T cells for this infection. This literature review explores the role of Tcell subsets in A.fumigatus infection, and the effects of CAR-T cell therapy on this fungal infection.

The protection role of human growth hormone on skin cells following ultraviolet B exposure.

BACKGROUND: Ultraviolet-B (UVB) radiation is the leading environmental cause of skin damage and photoaging. The epidermis and dermis layers of the skin mainly absorb UVB. UVB stimulates apoptosis, cell cycle arrest, generation of reactive oxygen species, and degradation of collagen and elastin fibers. OBJECTIVE: This study investigated the potential of human growth hormone (hGH) in protecting the skin fibroblasts and keratinocytes (HFFF-2 and HaCaT cell lines) from UVB-induced damage. METHODS: The MTT assay was performed to evaluate UVB-induced mitochondrial damage via assessing the mitochondrial dehydrogenase activity, and flow cytometry was carried out to investigate the effects of UVB and hGH on the cell cycle and apoptosis of UVB-irradiated cells. In addition, the fold change mRNA expression levels of Type I collagen and elastin in HFFF-2 cells were evaluated using the qRT-PCR method following UVB exposure. RESULTS: We observed that treatment of cells with hGH before UVB exposure inhibited UVB-induced loss of mitochondrial dehydrogenase activity, apoptosis, and sub-G1 population formation in both cell lines. We also found that hGH-treated HFFF-2 cells showed up-regulated mRNA expression of Type I collagen, elastin, and IGF-1 in response to UVB irradiation. CONCLUSION: These findings suggest hGH as a potential anti-UVB compound that can protect skin cells from UVB-induced damage. Our findings merit further investigation and can be used to better understand the role of hGH in skin photoaging.

Intermittent fasting: A promising dietary intervention for autoimmune diseases.

Intermittent fasting, which includes periods of fasting and nutrition, has been considered a dietary approach for weight loss and metabolic health improvement. However, its potential benefits in autoimmune diseases have not been widely studied. This study aims to review the existing studies on the role and effects of intermittent fasting on autoimmune diseases. A comprehensive search was conducted on electronic databases such as PubMed, Scopus, Embase, and Web of Science, and relevant studies were included based on inclusion criteria. Studies show that intermittent fasting may have beneficial effects on various autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, by reducing inflammatory markers, modulating the immune system, altering and improving gut microbiota, and enhancing cellular repair mechanisms through autophagy. However, evidence regarding the effects of intermittent fasting on other autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, thyroid diseases, and psoriasis is limited and inconclusive. Nevertheless, further research is needed to determine optimal intermittent fasting guidelines and its long-term effects on autoimmune diseases. Overall, this literature review proves intermittent fasting may be a promising dietary intervention for managing autoimmune diseases.

Cladosporium tenuissimum-induced sinusitis in a woman with immune-deficiency disorder.

Fungal sinusitis is a widespread infection that affects both healthy and immunocompromised individuals. Reports of sinus fungal infections have increased due to recent advances in diagnosis. Furthermore, susceptible and immune-compromised patients play an important role in increasing the number of reported cases. Infections with lesser-known fungi have been reported infrequently around the world. This paper describes a Cladosporium tenuissimum infection caused by chronic fungal sinusitis in a woman who had traveled to several countries. We used morphological and molecular methods to confirm the infection. The infection is most likely caused by the use of sulfasalazine, which is related to the patient's rheumatism. Sulfasalazine inhibits neutrophilic chemoattractant lipid synthesis in neutrophils, which play a key role in antifungal immunity. The patient is also undergoing root canal therapy and has several upper jaw implants, which may have contributed to the development of sinusitis.

Cobalt ferrite nanoparticle for the elimination of CD133+CD44+ and CD44+CD24-, in breast and skin cancer stem cells, using non-ionizing treatments.

Background: Cancer stem cells (CSCs) are the most challenging issue in cancer treatment, because of their high resistance mechanisms, that can cause tumor recurrence after common cancer treatments such as drug and radiation based therapies, and the insufficient efficiency of common treatments in CSCs removal and the recurrence of tumors after these treatments, it is essential to consider other methods, including non-ionizing treatments likes light-based treatments and magnetic hyperthermia (MHT). Method and material: After synthesis, characterization and investigation, the toxicity of novel on A375 and MAD-MB-231 cell lines, magnetic hyperthermia and light-based treatments were applied. MTT assay and flow cytometry was employed to determine cell survival. the influence of combination therapy on CD44 + CD24-and CD133 + CD44+ cell population, Comparison and evaluation of combination treatments was done respectively using Combination Indices (CIs). Result: The final nanoparticle has a high efficiency in producing hydroxyl radicals and generating heat in MHT. According to CIs, we can conclude that combined using of light-based treatment and MHT in the presence of final synthesized nanoparticle have synergistic effect and a high ability to reduce the population of stem cells in both cell lines compared to single treatments. Conclusion: In this study a novel multi-functional nanoplatform acted well in dual and triple combined treatments, and showed a good performance in the eradication of CSCs, in A375 and MAD-MB-231 cell lines.

Dysregulated balance in Th17/Treg axis of Pristane-induced lupus mouse model, are mesenchymal stem cells therapeutic?

BACKGROUND: Despite advances in general and targeted immunosuppressive therapies, limiting all mainstay treatment options in refractory systemic lupus erythematosus (SLE) cases has necessitated the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have recently emerged with unique properties, including a solid propensity to reduce inflammation, exert immunomodulatory effects, and repair injured tissues. METHODS: An animal model of acquired SLE mice was induced via intraperitoneal immunization with Pristane and affirmed by measuring specific biomarkers. Bone marrow (BM) MSCs were isolated from healthy BALB/c mice and cultured in vitro, then were identified and confirmed by flow cytometry and cytodifferentiation. Systemic MSCs transplantation was performed and then several parameters were analyzed and compared, including specific cytokines (IL-17, IL-4, IFN-É£, TGF-ß) at the serum level, the percentage of Th cell subsets (Treg/Th17, Th1/Th2) in splenocytes, and also the relief of lupus nephritis, respectively by enzyme-linked immunosorbent assay (ELISA), flow cytometry analysis and by hematoxylin & eosin staining and also immunofluorescence assessment. Experiments were carried out with different initiation treatment time points (early and late stages of disease). Analysis of variance (ANOVA) followed by post hoc Tukey's test was used for multiple comparisons. RESULTS: The rate of proteinuria, anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies, and serum creatinine levels decreased with BM-MSCs transplantation. These results were associated with attenuated lupus renal pathology in terms of reducing IgG and C3 deposition and lymphocyte infiltration. Our findings suggested that TGF-ß (associated with lupus microenvironment) can contribute to MSC-based immunotherapy by modulating the population of TCD4+ cell subsets. Obtained results indicated that MSCs-based cytotherapy could negatively affect the progression of induced SLE by recovering the function of Treg cells, suppressing Th1, Th2, and Th17 lymphocyte function, and downregulating their pro-inflammatory cytokines. CONCLUSION: MSC-based immunotherapy showed a delayed effect on the progression of acquired SLE in a lupus microenvironment-dependent manner. Allogenic MSCs transplantation revealed the ability to re-establish the balance of Th17/Treg, Th1/Th2 and restore the plasma cytokines network in a pattern dependent on disease conditions. The conflicting results of early versus advanced therapy suggest that MSCs may produce different effects depending on when they are administered and their activation status.

The effects of Chlorella vulgaris on cardiovascular risk factors: A comprehensive review on putative molecular mechanisms.

High incidence rate of cardiovascular disease (CVD) make this condition as an important public health concern. The use of natural products in treating this chronic condition has increased in recent years one of which is the single-celled green alga Chlorella. Chlorella vulgaris (CV) has been studied for its potential benefits to human health due to its biological and pharmacological features. CV contains a variety of macro and micronutrients, including proteins, omega-3, polysaccharides, vitamins, and minerals. Some studies have indicated that taking CV as a dietary supplement can help reduce inflammation and oxidative stress. In some studies, cardiovascular risk factors that are based on hematological indices did not show these benefits, and no molecular mechanisms have been identified. This comprehensive review summarized the research on the cardio-protective benefits of chlorella supplementation and the underlying molecular processes.

Animal and plant-based proteins have different postprandial effects on energy expenditure, glycemia, insulinemia, and lipemia: A review of controlled clinical trials.

Dietary proteins have been shown to stimulate thermogenesis, increase satiety, and improve insulin sensitivity in the short and long term. Animal-based proteins (AP) and plant-based proteins (PP) have different amino acid profiles, bioavailability, and digestibility, so it seems to have various short- and long-term effects on metabolic responses. This review aimed to compare the findings of controlled clinical trials on postprandial effects of dietary Aps versus PPs on energy expenditure (EE), lipemia, glycemia, and insulinemia. Data are inconclusive regarding the postprandial effects of APs and PPs. However, there is some evidence indicating that APs increase postprandial EE, DIT, and SO more than PPs. With lipemia and glycemia, most studies showed that APs reduce or delay postprandial glycemia and lipemia and increase insulinemia more than PPs. The difference in amino acid composition, digestion and absorption rate, and gastric emptying rate between APs and PPs explains this difference.

A review of PD-1/PD-L1 siRNA delivery systems in immune T cells and cancer cells.

OBJECTIVES: Programmed cell death 1 (PD-1) is a member of the CD28/CTLA-4 family of inhibitory immunological checkpoint receptors that's also widely produced by exhausted T lymphocytes in an immunosuppressive tumor microenvironment. PD-1 binds to programmed death ligand (PD-L1) and suppresses anti-cancer activity of T lymphocytes. We examined the current literature on how siRNA delivery systems can be used to target PD-1 and PD-L1, as well as the anti-cancer mechanisms and challenges associated with siRNA molecules. We look at studies that use program death 1 siRNA or program death 1 ligand siRNA to treat cancer. Several databases have been used for this purpose, including NCBI, Scopus, and Google Scholar. KEY FINDINGS: This study looked at several methods for delivering siRNA to immune cells and cancer cells. According to these findings, suppressing PD-1 in T cells increases T lymphocyte activity. PD-L1 suppression in DCs improves antigen presentation and co-stimulatory signals on their surface, resulting in T cell activation. Chemotherapy resistance and cancer cell suppression of T cells are reduced when PD-L1/2 is suppressed in cancer cells. CONCLUSION: The findings of this study indicated that several strategies for siRNA transfection to immune and cancer cells have been evaluated in recent decades, some of which effectively transfect siRNA to target cells, and defined PD-1 siRNA as a promising strategy for cancer treatment.

CD73 downregulation by EGFR-targeted liposomal CD73 siRNA potentiates antitumor effect of liposomal doxorubicin in 4T1 tumor-bearing mice.

Blocking CD73 ectonucleotidase has been proposed as a potential therapeutic approach for cancer treatment. The present study aimed to investigate the antitumor effect of a novel EGFR-Targeted liposomal CD73 siRNA formulation in combination therapy with liposomal doxorubicin in the 4T1 mouse model. CD73 siRNA was encapsulated into nanoliposomes by the ethanol injection method. After preparation, characterization, morphology, and stability evaluation of formulations, the toxicity was measured by MTT assay. Uptake assay and efficiency of the liposomal formulations were investigated on the 4T1 cell line. The liposomal formulation containing CD73 siRNA was targeted with GE11 peptide for in vivo evaluations. Following biodistribution analysis, the antitumor activity of prepared formulations in combination with liposomal doxorubicin was studied in mice bearing 4T1 metastatic breast cancer cells. Finally, the induction of immune response of formulations in concomitant treatment with liposomal doxorubicin was evaluated in the tumor microenvironment of a mouse model of breast cancer. The size of prepared liposomal formulations at N/P = 16 for the liposomal CD73 siRNA and GE11-liposomal CD73 siRNA groups were 89 nm ± 4.4 and 95 nm ± 6.6, respectively. The nanoparticle's PDI was less than 0.3 and their surface charge was below 10 mV. The results demonstrated that N/P = 16 yielded the best encapsulation efficiency which was 94% ± 3.3. AFM results showed that the liposomes were spherical in shape and were less than 100 nm in size. The results of the MTT assay showed significant toxicity of the liposomes containing CD73 siRNA during the 48-h cell culture. Real-time PCR and flow cytometry results showed that liposomes containing CD73 siRNA could effectively downregulate CD73 expression. Liposomal formulations were able to significantly downregulate CD73 gene expression, in vivo. However, CD73 downregulation efficiency was significantly higher for the targeted form compared to the non-targeted formulation (P value < 0.01). The combination showed maximum tumor growth delay with remarkable survival improvement compared to the control group. Studying the immune responses in the treatment groups which received doxorubicin, showed decreased number of lymphocytes in the tumor environment. However, this decrease was lower in the combination therapy group. Finally, our results clearly showed that CD73 downregulation increases the activity of CD8+ lymphocytes (IFN-ℽ production) and also significantly decreases the Foxp3 in the CD25+ lymphocytes compared to the control group. GE11-Lipo CD73 siRNA formulation can efficiently knockdown CD73 ectonucleotidase. Also, the efficacy of liposomal doxorubicin is significantly enhanced via the downregulation of CD73 ectonucleotidase.

Pegylated liposomal encapsulation improves the antitumor efficacy of combretastatin A4 in murine 4T1 triple-negative breast cancer model.

Combretastatin A4 (CA4), a vascular disrupting agent has been recently proposed as an anticancer agent. However, its low water solubility and low bioavailability limited its clinical efficacy. Overcomingthis issue requires developing new delivery strategies to enhance its anticancer effects. Here, we prepared various PEGylated liposomal formulations containing CA4 composed of different molar ratios of HSPC/DSPE-mPEG2000/Cholesterol/CA4 (F1: 80:5:10:5; F2: 75:5:15:5; F3: 70:5:20:5; F4: 60:5:30:5 and F5: 50:5:40:5) by the thin-film hydration method plus sonication and extrusion. All formulations had a particle diameter of 100-150 nm, a monomodal distribution with low polydispersity index and a negative zeta potential. Among the formulations only F1, F2, and F3 showed a high CA4 encapsulation efficiency; so their anticancer effects on triple-negative breast cancer (TNBC) were investigated in vitro and in vivo. The release study showed that F3 liposomes had significantly lower CA4 release compared to the F1 and F2 liposomes in different pH of 5.5, 6.5, and 7.4. We found that, CA4-loaded liposomes effectively inhibited both proliferation and migration of 4T1 and MDA-MB-231 TNBC cell lines by inducing cell cycle arrest at the G2/M phase and decreasing MMP-2 and MMP-9 expression and activity. In vivo studies revealed that F3 liposomes were highly accumulated at the tumor site and more effectively delayed tumor growth andprolonged the overall survival than other groups in 4T1 breast tumor-bearing mice. Taken together, encapsulation of CA4 in PEGylated F3 liposomes enhances its anti-tumor activity and may be serve as a promising approach for TNBC treatment and merits further investigation.

Enhanced antitumor immune response in melanoma tumor model by anti-PD-1 small interference RNA encapsulated in nanoliposomes.

Programmed cell death protein-1 (PD-1), as an immune checkpoint molecule, attenuates T-cell activity and induces T-cell exhaustion. Although siRNA has a great potential in cancer immunotherapy, its delivery to target cells is the main limitation of using siRNA. This study aimed to prepare a liposomal formulation as a siRNA carrier to silence PD-1 expression in T cells and investigate it's in vivo antitumor efficacy. The liposomal siRNA was prepared and characterized by size, zeta potential, and biodistribution. Following that, the uptake assay and mRNA silencing were evaluated in vitro at mRNA and protein levels. siRNA-PD-1 (siPD-1)-loaded liposome nanoparticles were injected into B16F0 tumor-bearing mice to evaluate tumor growth, tumor-infiltrating lymphocytes, and survival rate. Liposomal siPD-1 efficiently silenced PD-1 mRNA expression in T cells (P < 0.0001), and siPD-1-loaded liposomal nanoparticles enhanced the infiltration of T-helper 1 (Th 1) and cytotoxic T lymphocytes into the tumor tissue (P < 0.0001). Liposome-PD-1 siRNA monotherapy and PD-1 siRNA-Doxil (liposomal doxorubicin) combination therapy improved the survival significantly, compared to the control treatment (P < 0.001). Overall, these findings suggest that immunotherapy with siPD-1-loaded liposomes by enhancing T-cell-mediated antitumor immune responses could be considered as a promising strategy for the treatment of melanoma cancer.

A review on liposome-based therapeutic approaches against malignant melanoma.

Melanoma is a highly aggressive form of skin cancer with a very poor prognosis and excessive resistance to current conventional treatments. Recently, the application of the liposomal delivery system in the management of skin melanoma has been widely investigated. Liposomal nanocarriers are biocompatible and less toxic to host cells, enabling the efficient and safe delivery of different therapeutic agents into the tumor site and further promoting their antitumor activities. Therefore, the liposomal delivery system effectively increases the success of current melanoma therapies and overcomes resistance. In this review, we present an overview of liposome-based targeted drug delivery methods and highlight recent advances towards the development of liposome-based carriers for therapeutic genes. We also discuss the new insights regarding the efficacy and clinical significance of combinatorial treatment of liposomal formulations with immunotherapy and conventional therapies in melanoma patients for a better understanding and successfully managing cancer.

Exercise and crocin prevent adolescent-stress induced impairment of spatial navigation and dendritic retraction in the hippocampal CA3 area in adult male rats.

Adolescent chronic stress has been shown to induce functional, biochemical and morphological modifications of the hippocampus, leading to stress-related disorders in adulthood. The present study investigated the effects of exercise, crocin and their combination on spatial learning and memory impairment and dendritic retraction of the CA3 pyramidal neurons induced by chronic adolescent stress in adult male rats. Rats were exposed to restraint stress 2 h/day for 10 days during postnatal days (PNDs) 30-40. Following this period, separate groups of animals were treated with crocin (25 and 50 mg/kg), exposed to running wheel, and or received the combined treatment during PNDs 41-55. Following the interventions, plasma levels of corticosterone, spatial learning and memory, apical dendritic length of CA3 pyramidal neurons and BDNF levels in the CA3 area were assessed. Findings showed that adolescent stress significantly increased corticosterone levels and caused a tendency to reduce CA3 BDNF levels. Adolescent stress also impaired spatial learning and memory, and retracted apical dendritic length of CA3 pyramidal neurons. Crocin, voluntary exercise, and their combination recovered stress-induced spatial learning and impairment and CA3 pyramidal neurons dendritic length retraction. All treatments also reduced significantly corticosterone levels and enhanced CA3 BDNF levels in the stress groups. Finally, these treatments even increased apical dendritic length of CA3 pyramidal neurons in the non-stress groups. These findings indicate that detrimental effects of adolescent stress on cognitive function and hippocampal morphology in adulthood could be restored by early interventions with physical activity and crocin treatment during adolescent period.