Human umbilical cord mesenchymal stem cell-derived exosomes alleviate the severity of experimental autoimmune encephalomyelitis and enhance lag-3 expression on foxp3 + CD4 + T cells.

BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease that affects the central nervous system, causing inflammation, demyelination, and neurodegeneration. Understanding the dysregulation of Tregs, dynamic cells involved in autoimmunity, is crucial in comprehending diseases like MS. However, the role of lymphocyte-activation gene 3 (Lag-3) in MS remains unclear. METHODS: In this study, we explore the potential of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSCs-Exs) as an immune modulator in experimental autoimmune encephalomyelitis (EAE), a model for MS. RESULTS: Using flow cytometry, our research findings indicate that groups receiving treatment with hUMSC-Exs revealed a significant increase in Lag-3 expression on Foxp3 + CD4 + T cells. Furthermore, cell proliferation conducted on spleen tissue samples from EAE mice using the CFSE method exposed to hUMSC-Exs yielded relevant results. CONCLUSIONS: These results suggest that hUMSCs-Exs could be a promising anti-inflammatory agent to regulate T-cell responses in EAE and other autoimmune diseases. However, further research is necessary to fully understand the underlying mechanisms and Lag-3's precise role in these conditions.

Exosomal miRNAs in osteoarthritis.

Exosomes, as lipid nanostructure, are secreted by approximately all cell types within the body and actively involved in either short or long distances cell-cell communication in an autocrine and paracrine manner. Recently, exosomes are widely used as a nanocarrier for delivery of various nucleotide- or protein passed molecules including miRNA, and drugs into various cells, as a therapeutic strategy in a broad range of diseases including osteoarthritis. Osteoarthritis is one of the most common debilitating chronic musculoskeletal disorders with a multifaceted condition and an increasing impact on the quality of life. Therefore, this review aims to focus on the current knowledge of the exosomal miRNAs in the osteoarthritis to address their potential therapeutic application.

Synergistic Antiproliferative Effects of Co-nanoencapsulated Curcumin and Chrysin on MDA-MB-231 Breast Cancer Cells Through Upregulating miR-132 and miR-502c.

In this study, we explored whether co-nanoencapsulated Curcumin (Cur) and Chrysin (Chr), natural herbal compounds with antitumor activities, regulate miR-132 and miR-502c and their downstream targets, leading to the synergistic growth inhibition in MDA-MB-231 breast cancer cells. For this purpose, Cur and Chr were co-encapsulated into PLGA-PEG nanoparticles (NPs) and characterized through DLS, FTIR and FE-SEM. MTT assay and cell cycle arrest analysis revealed that CurChr-loaded NPs had a considerable synergistic cytotoxicity against MDA-MB-231 cells with more cell accumulation in G2/M phase compared to the other groups. In addition, highest percentage of cell apoptosis was acquired in cells treated with CurChr-loaded NPs according to apoptosis analysis. Real-time PCR findings revealed that co-encapsulated form of Cur and Chr than free combination could further upregulate miR-132 and miR-502c expression (P < 0.001). Also, the strong reduction was detected in the protein levels of HN1 and P65 at the cells co-nanodelivered with Cur and Chr. These findings demonstrated that the co-nanodelivery of Cur and Chr through targeting miR-132 and miR-205c might be a novel strategy for the treatment of breast cancer.

In vitro study of the scolicidal effects of Echinometra mathaei spine and shell extracts on hydatid cyst protoscolices.

Hydatid cyst is a zoonotic parasitic infection caused by the tapeworm Echinococcus granulosus. Such infections are of considerable public health and economic concern, and new effective treatments are intensely sought. Sea urchin (Salmacis virgulata) shell extracts have potent antimicrobial and antioxidant activity, and spines of several species of echinoderms also show antimicrobial activity. In the present in vitro study, we investigated the scolicidal effect of spines and shells extractions from Echinometra mathaei obtained from the Persian Gulf. Spines and shells from the sea urchin, Echinometra mathaei were used in the tests. Spines and shells from 800 specimens were extracted with dibasic sodium phosphate buffer (pH 7.5). Procedures used protoscolices of E. granulosus were obtained aseptically from hydatid cyst in naturally infected sheep's liver and goats and viable protoscolices exposed with spine and shell extractions. The apoptosis was assessed by measuring the caspase 3 activity of the extract-treated protoscolices, using ELISA-based commercial kits to determine caspase activity. The scolicidal effects of shells were also showed, 20 µg/ml of shell extracts after 60 min exposure, the viability of protoscolices were 21.99 ±â€¯0.01. The results showed that 20 µg/ml of spines gave maximum scolicidal activity (p < 0.05). This study represents the first attempt at combatting echinoid parasites by natural compounds with high efficiency, and may provide a base for future treatment of hydatid cysts.

Association of circulating omentin-1 level with lung cancer in smokers.

Background: Omentin has recently been considered as an adipokine secreted from visceral fat and is expressed in the lungs, heart, ovary etc. Various studies have shown that omentin may have an anti-inflammatory role in the inflammatory process and the amount of omentin alters in some cancers, such as colorectal, prostate and renal cells cancers, changes. The serum level of omentin, however, remains unknown in non-patient smokers and the smokers afflicted with lung cancer. Therefore, this study examines the serum levels of omentin in smokers suffering from lung cancer. Methods: The amount of serum omentin was measured in 45 patients with lung cancer and 61 age - and sex - matched controls (30 smokers and 31 non-smokers) using enzyme-linked immunosorbent assay (ELISA) kit. Data were analyzed using SPSS-16, and oneway analysis of variance and Scheffe post hoc test were used to determine and compare the serum levels of omentin in different types of lung malignancies. Significance level was set at p≤0.05. Results: The amount of circulating omentin for healthy non-smokers and non-patient smokers was 3.55±0.57 ng/l and 5.43±1.95 ng/l, respectively (p<0.001). The serum level of omentin was 3.63±0.70 ng/l for smokers afflicted with cancer (p<0.001 compared with nonpatient smokers: 5.43±1.95). Conclusion: The meaningful decrease in omentin levels in smokers with lung cancer can be considered as a risk factor in smokers and can use as a significant factor in the prognosis of lung cancer in these people.

Cooperative Treatment of Gastric Cancer Using B7-H7 siRNA and Docetaxel; How Could They Modify Their Effectiveness?

Purpose: Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemosensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with docetaxel on GC cells. Methods: MTT test was applied to determine the IC50 of docetaxel and the combined effect of B7-H7 siRNA and docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony-forming ability, wound healing assay and colony formation test were employed, respectively. Results: B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and docetaxel in MKN-45 GC cells. Also, B7-H7 suppression alongside docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes. Conclusion: B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with docetaxel, may be a promising therapeutic approach in treating GC.

Long-Term Clinical Outcomes of Keratolimbal Allograft Alone or in Combination With Keratoplasty in Chronic and Delayed-Onset Mustard Gas Keratopathy.

PURPOSE: The purpose of this study was to investigate the long-term clinical outcome of keratolimbal allograft (KLAL) alone or in combination with keratoplasty, in the management of patients with chronic and delayed-onset mustard gas keratopathy (MGK). METHODS: Patients who had KLAL for MGK with or without corneal transplantation between 2002 and 2016 were recalled to be enrolled in this retrospective interventional case series. The primary outcome was the success rate of the KLAL demonstrated by Kaplan-Meier cumulative survival analysis. The secondary outcomes were postoperative BCVA and the need for further surgery. RESULTS: A total of 108 eyes of 68 patients with MGK underwent KLAL. All patients were male with an average age of 54 ± 6 years with an average follow-up duration of 81.9 ± 38.4 months. Sectoral KLAL alone was performed in 62 eyes (57.4%), combined with lamellar keratoplasty (LKP) in 40 eyes (37%) and combined with penetrating keratoplasty in 6 eyes (5.6%). The cumulative probability of success was 75% within the follow-up duration. The mean duration of successful KLAL survival was 80.6 ± 38 months. 88.1% of these eyes needed only 1 operation to stabilize the ocular surface. Average BCVA did not improve significantly after KLAL alone, except in those accompanied by keratoplasty. KLAL combined with LKP achieved the superior clinical outcome compared with KLAL alone. Infectious keratitis occurred in 6 eyes (5.5%). No adverse event due to postoperative systemic immunosuppression was observed. CONCLUSIONS: KLAL alone or combined with LKP is effective, durable, and visually acceptable in the reconstruction of ocular surface in patients with limbal stem cell deficiency secondary to MGK.

Serum Levels of Interleukin-1ß and Disease Progression in Multiple Myeloma Patients: A Case and Control Study.

OBJECTIVE: Multiple myeloma  (MM) is known as an incurable heterogeneous plasma cell malignancy that presents with a variety of clinical manifestations. Inflammation plays an important role in this disease. Cytokines and Chemokines cause the progression of the disease. One of them is interleukin-1ß (IL-1ß), which may be involved in the pathogenesis of MM. Other markers such as calcium, albumin, creatinine, globulins, and total protein are also used to diagnose and prognosis patients. The main purpose of this study was to evaluate the serum level of IL-1ß and various forms of calcium (total calcium, ionized calcium, and corrected calcium), albumin, creatinine, globulin, and total protein on stage-I of MM patients and healthy controls. METHODS: Serum samples from 30 stage-I MM patients and 30 healthy subjects as controls were examined in this study. The protein concentrations of serum IL-1ß was assessed by enzyme-linked immunosorbent assay (ELISA), total calcium, albumin, creatinine, total protein, and globulin Measured by auto analyzer BT3000, an electrolyte analyzer was used to measure ionized calcium (Ca++) and a special equation was used to calculate the corrected calcium. RESULT: The mean level of IL-1ß was significantly elevated in stage-I MM. The mean levels of IL-1ß were 7.04±1.15 ng/ml in stage-I MM and 3.12± 0.90 ng/ml in controls (p<0.001). The mean levels of total calcium (total Ca) were 9.45±0.56 mg/dl in stage-I MM and 9.09±0.43mg/dl in controls (p=0.008). The mean levels of ionized calcium (Ca++) was 4.65±0.28mg/dl in stage-I MM and 4.75±0.33mg/dl in controls (p=0.2). The mean ratio of serum ionized calcium to total calcium (Ca++/ total Ca) was 0.49±0.054 in stage-I MM and 0.52±0.047 in controls (p=0.02). The mean ratio of serum ionized calcium to corrected calcium (Ca++/corrected Ca) was 0.42±0.033 in stage-I MM and the Mean ratio of serum ionized calcium to calcium total (Ca++/ total Ca) was 0.52±0.047 in controls, Comparison of the mean of the two groups shows a significant difference (p<0.001). The mean level of albumin was 1.72±0.35 g/dl in stage-I MM and4.32±0.41g/dl in controls (p<0.001). The mean level of total protein was 12.65±0.81g/dl in stage-I MM and 7.07±0.4 g/dl in controls (p<0.001). The mean level of globulin was 11.00±0.96 mg/dl in stage-I MM and 2.85±0.77 mg/dl in controls (p<0.001). The mean level of creatinine was 1.15±0.25 mg/dl in stage-I MM and 0.96±0.15 mg/dl in controls (p=0.001). CONCLUSION: The results of the study indicate the possible involvement of IL-1ß at stage-I MM and it can indicate the role of chemokines in the disease process, especially in the early stages. Changes in the chemical profiles mentioned can help in the diagnosis and prognosis of the disease.

Exosomes and COVID-19: challenges and opportunities.

Coronavirus disease 2019 or COVID-19, starting from Wuhan, China, in December 2019, is a pandemic situation affecting millions worldwide and has exerted a huge burden on healthcare infrastructure. Therefore, there is an urgent need to understand the molecular mechanisms underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and design novel effective therapeutic strategies for combating this pandemic. In this regard, special attention has been paid to the exosomes. These nanoparticles are extracellular vesicles with critical function in the pathogenesis of several diseases including viral sepsis. Therefore, they may be involved in the pathogenesis of COVID-19 infection and also may be a way for transferring viral components and infecting other neighbor cells. Exosomes also can be considered as a therapeutic strategy for treating COVID-19 patients or used as a carrier for delivering effective therapeutic agents. Therefore, in this review, we discussed the biogenesis and contents of exosomes, their function in viral infection, and their potential as a therapeutic candidate in treating COVID-19.

The role of histone deacetylase 3 in breast cancer.

It has been recently revealed that Histone Deacetylase (HDAC) 3, a unique member of the HDACs family, can trigger and progress cancers by alternation in genes expression and proteins activity. Epigenetic modifications by HDACs have been studied well in various cancer cells. Recent studies have focused on the HDAC enzymes as a possible target in cancer therapy. There are significant documents on upregulation of HDAC3 in breast cancer (BC) cells which suggest an oncogenic role for this enzyme. Interestingly, some studies showed that HDAC3 inhibition could be considered as a promising target in breast cancer therapy, and thus far, several inhibitors from different nature have been introduced. In this review, we discussed the function and highlight the existing inhibitors of HDAC3 in BC pathogenesis and therapy.

Lupeol synergizes with doxorubicin to induce anti-proliferative and apoptotic effects on breast cancer cells.

PURPOSE: Anti-cancer and anti-migration effects of lupeol as a biological pentacyclic triterpenoid were investigated individually and in combination with Doxorubicin (DOX) on MCF-7 and MDA-MB-231 breast cancer cells and human foreskin fibroblasts. METHODS: To uncover the anticancer effect of lupeol and the impact of its combination with DOX, cell viability and scratch assays and dual acridine-orange apoptotic staining were performed. Moreover, the expression of proapoptotic caspase-3 and metastasis-related MMP-9 at the mRNA and protein levels was analyzed using qPCR and western blot techniques. RESULTS: Lupeol synergistically increased the anti-proliferative effect of DOX with IC50 values of 42.55, 62.24 and 65.9 µM on MCF-7, MDA-MB-231 and HFF cells, respectively. Lupeol reduced the cell migration and lowered the DOX-induced cell migration, significantly (p < 0.05). The number of apoptotic cells elevated significantly (p < 0.05) when cancer cells were treated with the combination of lupeol and DOX. Lupeol individually and in combination with DOX up-regulated the expression of caspase-3. The proposed combination therapy synergized (3-4 fold) the down-regulation of MMP-9 expression in MCF-7 and MDA-MB-231 cells. CONCLUSION: Our results indicate that lupeol could be considered as an anticancer agent and anticancer adjuvant in breast cancer-therapy. The anticancer properties of lupeol attribute to its antiproliferative, antimigrative and apoptotic effects.

miR-589-5p Inhibits Cell Proliferation by Targeting Histone Deacetylase 3 in Triple Negative Breast Cancer.

BACKGROUND: Histone deacetylase 3 (HDAC3) is a potential oncogene that is significantly up-regulated in patients with breast cancer. MicroRNAs (miRs) are a group of small non-coding and regulatory RNAs which have recently been proposed as promising molecules for breast cancer target therapy. In the current study, we investigated the impact of miR-589-5p/ HDAC3 axis on cancer cell development in triple negative breast cancer (TNBC) cells. METHODS: In-silico analysis determined that miR-589-5p potentially targets HDAC3. We evaluated the HDAC3 and mir-589-5p expression levels in clinical samples and breast cancer cell lines including MDA-MB-231, MDA-MB-468, MCF-7 and MCF-10A. HDAC3 was knocked out to investigate its role on cancer cell progression. Anti-cancerous role of the miR-589-5p was assessed using an expression vector. We evaluated possible alteration in the cell cycle progression, cell viability and cell proliferation, after transient transfection. RESULTS: HDAC3 was over-expressed in TNBC clinical samples and breast cancer cell lines compared to non-cancerous controls while miR-589-5p was down regulated in cancer cells. Suppression of HDAC3 decreased the cell viability, cell proliferation and colony formation. Similar results were observed after over-expression of the miR-589-5p. Dual-Luciferase reporter assay confirmed the direct targeting of HDAC3 by miR-589-5p. CONCLUSION: Our results showed that miR-589-5p mediates its anti-proliferative effects on breast cancer cells via targeting HDAC3. These findings suggest that the miR-589-5p/ HDAC3 axis could be considered as a possible therapeutic strategy in TNBC.

Elevated levels of urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in esophageal squamous cell carcinoma.

AIMS: To measure oxidative DNA and lipid damages, urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostane in esophageal squamous cell carcinoma (SCC) patients and compare the values with that in controls. MATERIALS AND METHODS: The urinary concentrations of 8-OHdG and 8-isoprostane were measured in 32 SCC patients (13 female/19 male; mean age: 61.4 ± 10.5 years) and 45 controls (22 female/23 male; mean age: 58.1 ± 8.3 years). RESULTS: Squamous cell carcinoma patients showed significantly higher levels of urinary 8-OHdG (15.6 ± 5.1 ng/mg creatinine) than controls (5.8 ± 2.1 ng/mg creatinine) (P<.001). Increased urinary concentrations of 8-isoprostane were also detected in SCC patients (35.4 ± 6.5 ng/mmol creatinine) as compared to the controls (16.9 ± 4.0 ng/mmol creatinine) (P<.001). CONCLUSIONS: Our results show the presence of oxidative DNA and lipid damage in the SCC patients. This may have a connection to carcinogenesis in the esophagus.

A comprehensive review of anticancer mechanisms of action of Alantolactone.

Cancer is considered as the main challenge of human communities, and it annually imposes a significant economic burden on society. Natural products have been used for treatment of many diseases including inflammation, infections, neurological disorders, atherosclerosis, asthma and cancer for many years. Sesquiterpene lactones (STLs) refers to a group of natural products with different biological activities. A type of STL that has recently attracted much attention is Alantolactone (ALT). In recent years, many studies have investigated the molecular mechanism of this compound affecting cancer cells and results suggest that this compound exerts its anticancer effects by providing free radicals and inhibiting some of the signaling pathways that are effective in progression of cancer cells. The present study is aimed to introduce the latest molecular mechanisms of ALT proposed by researchers in recent years.

Therapeutic potential of quercetin in an animal model of PCOS: Possible involvement of AMPK/SIRT-1 axis.

Polycystic ovary syndrome is a common endocrine disorder worldwide. Recently, quercetin has been extensively investigated as a therapeutic option in patients with PCOS. Therefore, this study aimed to investigate the mechanisms underlying quercetin's positive effects by modulating key components of energy homeostasis and adipose tissue hormones in rats with letrozole-induced PCOS. Eighteen female Wistar rats were divided into three groups including control group (received carboxy methylcellulose (CMC 0.5%)), letrozole-induced PCOS ± quercetin group (received 1 mg/kg letrozole in CMC 0.5%), and letrozole-induced PCOS +/+ quercetin group (received same dose of letrozole + 100 mg/kg quercetin in CMC 0.5%). The estrous cycle, biochemical and hormonal parameters, as well as insulin resistance (IR) were evaluated in all groups. Western blotting was used to assess the expression levels of sirtuin-1 (SIRT-1), 5' AMP-activated protein kinase (AMPK), and adiponectin in target tissues of rats. The expression levels of visfatin and resistin were also evaluated through Real-time polymerase chain reaction (PCR). Treatment with quercetin improved the PCOS related disturbances in estrous cycle, lipid profile, serum levels of testosterone, estradiol and progesterone, and IR. Besides, the expression levels of AMPK and SIRT-1 in ovarian tissue were upregulated in the rats which received quercetin. Quercetin also reversed the PCOS-induced alteration in adipose tissue levels of adiponectin, visfatin, and resistin. Modulation of energy homeostasis through key components involved in this axis, as well as regulation of hormones releasing from adipose tissue may be the main underlying mechanisms for positive effects of quercetin in PCOS.

Ameliorative effects of fisetin in letrozole-induced rat model of polycystic ovary syndrome.

BACKGROUND: The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS). METHODOLOGY: Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method. RESULTS: Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS. CONCLUSION: Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.

Polyphenols: Natural compounds with promising potential in treating polycystic ovary syndrome.

Polyphenols are natural compounds used by plants as a defense system against various stresses. In recent years, the importance of these polyhydroxyphenols has extensively increased due to their potent cardioprotection, anti-carcinogenic, anti-oxidant, anti-apoptotic, and anti-inflammatory properties. Therefore, various studies have reported promising results from the studies investigating their efficacy as a therapeutic strategy in various disorders such as human malignancies, cardiovascular diseases, nervous system impairments, diabetes, metabolic syndrome, aging, and inflammation-associated disorders, as well as a polycystic ovarian syndrome (PCOS). Since oxidative stress, hormonal, metabolic, and endocrine disturbances have been shown to play a crucial role in the initiation/progression of PCOS, polyphenols are suggested to be an effective treatment for this disorder. Therefore, this study aimed to discuss the therapeutic potential of multiple polyphenols in PCOS.

The effects of nanocurcumin supplementation on inflammation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Serum levels of several pro-inflammatory cytokines are higher in hemodialysis patients compared to healthy people. Curcumin has been shown to be able to decrease cytokines levels in nonuremic subjects. Our goal was to evaluate the effect of nanocurcumin administration on cytokines levels in hemodialysis patients. METHODS: The study was performed over a 3 months period on 54 hemodialysis patients who had been randomized to receive either nanocurcumin or placebo. Serum levels and gene expressions of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were evaluated using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). FINDINGS: Serum levels of IL-6 and TNF-α were similar in the two groups at baseline but were lower after 12 weeks of treatment with nanocurcumin compared to placebo (P = 0.024 for IL-6 and 0.02 for TNF). In the group given nanocurcumin, serum levels of both cytokines decreased substantially (P < 0.001 for each), whereas they were unchanged in the group given placebo. Gene expression for each cytokine in peripheral blood mononuclear cells (PBMCs) was reduced at 12 weeks vs. baseline in the group given nanocurcumin, and changes in gene expression correlated with changes in serum level for each of the two cytokines. DISCUSSION: The results indicate that nanocurcumin supplementation reduces both serum levels and gene expression of IL-6 and TNF-α in hemodialysis patients. The feasibility and potential clinical benefits of nanocurcumin treatment to reduce inflammation in hemodialysis patients warrant further study.

Serum level of Xanthine oxidase, Uric Acid, and NADPH oxidase1 in Stage I of Multiple Myeloma.

OBJECTIVE: The etiology of multiple myeloma (MM) is not known. Enzymes such as xanthine oxidase (XO) and NADPH oxidase 1 (NOX1) as relevant sources of reactive oxygen species (ROS) production may play a crucial role in the incidence and progress of MM. Uric acid generated by XO has a controversial dual role in both the prevention and promotion of cancer. We conducted a case-control study and selected patients with stage I MM to investigate the status of XO, NOX1, and uric acid in the patients and controls. METHODS: We used a sample of 33 patients with stage I MM and 30 healthy controls. The enzyme-linked immunosorbent assay (ELISA) measured the enzyme concentration of XO and NOX1, and the colorimetric method measured the serum level of uric acid. RESULTS: Mean serum levels for XO in patients and controls were 6.17±0.83 ng/ml and 4.12±0.57 ng/ml (P<0.001). serum levels of NOX1 were 4.35±1.03 ng/ml in patients and 3.54±0.91 ng/ml in controls (P<0.001). Evaluating the levels of XO and NOX1 in male and female populations showed a significant difference in the male population (NOX1 P=0.002; XO P<0.001) and female population (NOX1 P=0.002; XO P<0.001). Also, a significant correlation was observed between the two enzymes only in the female population (Pearson correlation=0.5; P=0.006). A significant inverse correlation found between albumin and XO (Pearson correlation=-0.7, P<0.001) and NOX1 (Pearson correlation=-0.5, P<0.001). XO was correlated with B2-m (Pearson correlation=0.37, P=0.003). There was no significant difference in uric acid between patients (6.2±1.2 mg/dl) and controls (5.7±1 mg/dl) (P=0.2), and no correlation was found with XO. CONCLUSION: The present study indicates the possible role of XO and NOX 1 in the etiology of MM. Although we found no correlation between uric acid and XO, further studies will help clarify the function of uric acid in the pathogenesis of MM.
.

Alantolactone inhibits stem-like cell phenotype, chemoresistance and metastasis in PC3 cells through STAT3 signaling pathway.

BACKGROUND AND PURPOSE: Cancer stem cells (CSCs), as the subpopulation of cancer cells, are associated with carcinogenesis, chemoresistance, and metastasis in malignancies. Also, CSCs are considered as the major reason for treatment failure in prostate cancer (PCa). Alantolactone (ALT), exerts anticancer activity in different types of cancers. In the present study, the relationship between ALT and CSCs in PCa metastasis and the molecular mechanisms involved in the progression of PCa were investigated. EXPERIMENTAL APPROACH: In this study, to evaluate cell viability, MTT assay was performed. Then, PC3 cells were treated with nontoxic concentrations of ALT and after this step wound-healing assay, colony-formation assay and chemosensitization assay were applied to determine cell migration, the ability of colony formation, and chemoresistance, respectively. Also, real-time polymerase chain reaction and western blotting were used for the determination of genes and protein expression, respectively. FINDINGS/RESULTS: Our finding showed that ALT at nontoxic concentrations (0.01 and 0.1 µM) for 72 h suppressed the STAT3 phosphorylation and signaling pathway. Also, ALT was able to modulate the stemness of PCa cells through downregulation of expression of SOX2, Oct-4, Nanog, CD133, CD44, and upregulation of p53 expression. On the other hand, we further found that ALT in nontoxic concentrations sensitized PCa cells to cisplatin. CONCLUSION AND IMPLICATIONS: ALT combated the stemness of cancer cells and metastasis by antagonizing of STAT3 signaling pathway. In addition, ALT exhibited anti-metastatic properties and may have potential as a new chemotherapy agent for the reduction of PCa metastasis.