LncRNAs orchestration of gastric cancer - particular emphasis on the etiology, diagnosis, and treatment resistance.

Gastric cancer (GC) remains a major public health challenge worldwide. Long non-coding RNAs (lncRNAs) play important roles in the development, progression, and resistance to the treatment of GC, as shown by recent developments in molecular characterization. Still, an in-depth investigation of the lncRNA landscape in GC is absent. However, The objective of this systematic review is to evaluate our present understanding of the role that lncRNA dysregulation plays in the etiology of GC and treatment resistance, with a focus on the underlying mechanisms and clinical implications. Research that described the functions of lncRNA in angiogenesis, stemness, epigenetics, metastasis, apoptosis, development, and resistance to key treatments was given priority. In GC, it has been discovered that a large number of lncRNAs, including MALAT1, HOTAIR, H19, and ANRIL, are aberrantly expressed and are connected with disease-related outcomes. Through various methods such as chromatin remodeling, signal transduction pathways, and microRNA sponging, they modulate hallmark cancer capabilities. Through the activation of stemness programs, epithelial-mesenchymal transition (EMT), and survival signaling, LncRNAs also control resistance to immunotherapy, chemotherapy, and targeted therapies. By clarifying their molecular roles further, we may be able to identify new treatment targets and ways to overcome resistance. This article aims to explore the interplay between lncRNAs, and GC. Specifically, the focus is on understanding how lncRNAs contribute to the etiology of GC and influence treatment resistance in patients with this disease.

Preparation and in vivo evaluation of nano sized cubosomal dispersion loaded with Ruta graveolens extracts as a novel approach to reduce asthma-mediated lung inflammation.

Asthma is a chronic disease affecting people of all ages. Asthma medications are associated with adverse effects restricting their long-term usage, demanding newer alternative therapies. This study aimed to investigate the anti-asthmatic properties of Ruta graveolens extract and its prepared nano-cubosomal dispersion (Ruta-ND). Firstly, the R. graveolens methanolic extract exhibited higher anti-inflammatory activity on Lipopolysaccharide (LPS)-activated BEAS-2B cells. To ensure best bioavailability and hence best cellular uptake, R. graveolens extract was loaded in nano-cubosomal dispersion (ND). Then, the anti-asthmatic effects of Ruta extract and ND were simultaneously evaluated in rats' model with ovalbumin-induced allergic asthma. R. graveolens extract and Ruta-ND subsided asthma score and improved lung function by restoring FEV1/FVC ratio to the expected values in control rats. Also, it showed strong antioxidant and anti-inflammatory activities manifested by lowering levels of malondialdehyde (MDA), IL-4, IL-7, TGF-ß, and Ig-E, and increasing levels of superoxide dismutase (SOD) and INF-γ in bronchoalveolar lavage fluid. Our research findings also indicate autophagy induction and apoptosis inhibition by Ruta extract and Ruta-ND. Finally, the HPLC MS/MS phytochemical profiling of R. graveolens extract evident production of various alkaloids, flavonoids, coumarins, and other phenolics with reported pharmacological properties corresponding to/emphasize our study findings. In conclusion, R. graveolens exhibited promise in managing Ova-induced allergic asthma and could be developed as an alternative anti-allergic asthma drug.

Acovenoside A as a novel therapeutic approach to boost taxol and carboplatin apoptotic and antiproliferative activities in NSCLC: Interplay of miR-630/miR-181a and apoptosis genes.

The aim of the present study is to explore the potential anticancer effect of the cardenolide; acovenoside A against non-small cell lung cancer (NSCLC), understand its molecular mechanism in inducing apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the synergistic effect. The triple combination showed the best growth inhibition efficiency where the number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The combination also showed the most remarkable increase in gene expression of Bax and p53 and the least level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell lines treated with the combination. The present study has proven that the underlying mechanism of acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present study is the first to address the valuable effect of using acovenoside A together with carboplatin and taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic effects..

Chondroprotection of fruit peels in a monosodium iodoacetate-induced osteoarthritis rat model via downregulation of Col1A1.

The potential of the fruit peels of mango, orange, cantaloupe, and pomegranate in the treatment of osteoarthritis (OA) was evaluated in a rat model. Their metabolic profiles were characterized using ultrahigh-performance liquid chromatography (UPLC)-electrospray ionization-mass spectroscopy and 66 albino rats were intra-articularly injected with monosodium iodoacetate in the knee joints. The extracts were orally administered at doses of 200 and 400 mg/kg for 28 days. Serum levels of IL-6 and tissue levels of cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor-gamma (PPARγ), and alpha-smooth muscle actin (α-SMA) were measured using ELISA. COL1A1 expression was measured by quantitative polymerase chain reaction. Histopathological changes in the joints were examined. In the extracts, 85 metabolites were annotated, and the levels of interleukin (IL)-6, COX-2, α-SMA, malondialdehyde, and nitric oxide were significantly reduced, while PPARγ and glutathione levels were significantly raised in all treated groups compared to the OA group. All extracts downregulated the cartilage mRNA expressions for COL1A1 dose-dependently. Mango peel extract exhibited the best chondroprotective effect. The in silico study showed the link between mango extract metabolites and COX-2.

Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation.

A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage.

Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line.

Despite advances in treatment, breast cancer remains the widest spread disease among females with a high mortality rate. We investigated the potential effects of gallic acid (GA) as supportive therapy in the management of breast cancer. Anti-cancer activity with GA alone or in combination with paclitaxel and/or carboplatin was assessed by MTT assay and flow cytometry using annexin V/propidium iodide. The mechanism underlying the antiproliferative effects was investigated by measuring the expression of the pro-apoptotic marker (Bax), CASP-3, anti-apoptotic (Bcl-2), and, tumor suppressor (p53) by real-time polymerase chain reaction (RT-PCR) and western blot analysis. Cell cycle analysis was performed for the MCF-7 breast cancer cell line. GA, paclitaxel, and carboplatin alone or in combination arrested cell cycle progression at the G2/M phase and induced Pre-G1 apoptosis. RT-PCR showed that the triplet combination significantly raised P53, Bax, and CASP-3 mRNA expression (20.1 ± 1.41, 16.6 ± 0.43, and 20.04 ± 1.61, respectively) in MCF-7 cells when compared to single or combined treatment (p < .0001) while anti-apoptotic Bcl-2 mRNA levels were decreased in all treated groups compared to untreated cells. Western blot data of tested apoptotic factors were consistent with RT-PCR results. For the first time, we show that a minimum non-toxic concentration of GA increased the efficacy of paclitaxel- and carboplatin-induced MCF-7 apoptotic cell death.

Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats.

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 µg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

Design, synthesis, and biological evaluation of new pyrazoloquinazoline derivatives as dual COX-2/5-LOX inhibitors.

A new series of pyrazoloquinazoline derivatives equipped with different chalcones was designed, synthesized, and identified through 1 H nuclear magnetic resonance (NMR), 13 C NMR, and infrared spectroscopic techniques. Our design strategy of the quinazolinone-privileged scaffold as a new scaffold was based on merging pharmacophores previously reported to exhibit cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LOX) inhibitory activity. All the newly synthesized derivatives were biologically evaluated for COX and 5-LOX inhibitory activity and COX-2 selectivity, using celecoxib and zileuton as reference drugs, as they exhibited promising anti-inflammatory activity. Compound 3j was found to be the most promising derivative, with IC50 values of 667 and 47 nM against COX-1 and COX-2, respectively, which are superior to that of celecoxib (IC50 value against COX-2 = 95 nM), showing an SI of 14.2 that was much better than celecoxib. Compounds 3f and 3h exhibited COX-1 inhibition, with IC50 values of 1,485 and 684 nM, respectively. The synthesized compounds showed a significant inhibitory activity against 5-LOX, with IC50 values ranging from 0.6 to 4.3 µM, where compounds 3f and 3h were found to be the most potent derivatives, with IC50 values of 0.6 and 1.0 µM, respectively, in comparison with that of zileuton (IC50 = 0.8 µM). These promising derivatives, 3f, 3h, and 3j, were further investigated in vivo for anti-inflammatory, gastric ulcerogenic effects, and prostaglandin production (PGE2) in rat serum. The molecular docking studies concerning the binding sites of COX-2 and 5-LOX revealed similar orientation, compared with reported inhibitors, which encouraged us to design new leads targeting COX-2 and 5-LOX as dual inhibitors, as a new avenue in anti-inflammatory therapy.

Effect of Gallic acid in potentiating chemotherapeutic effect of Paclitaxel in HeLa cervical cancer cells.

BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. Paclitaxel/Carboplatin is one of the most commonly prescribed regimens in cervical cancer treatment. Although chemotherapeutic drugs are very effective, severe side effects and development of drug resistance limits the use of these drugs. The use of natural products with anticancer activity may help to partially overcome these issues. METHODS: In the present study, we investigated the ability of Gallic acid, to potentiate the anti-cancer effects of Paclitaxel, Carboplatin and Paclitaxel/Carboplatin combination in human HeLa cells by performing MTT assay, cell cycle analysis and RT-PCR assay and Western blotting for some apoptotic markers. RESULTS: Our results revealed that the highest cytotoxic effect, the highest induction of apoptosis and significant elevation in P53 and Caspase 3 levels was seen in Paclitaxel/Gallic acid combination. CONCLUSION: These results indicate that Gallic acid potentiates Paclitaxel effect and that Paclitaxel/Gallic acid combination could represent a promising alternative with lower side effects-for Paclitaxel/Carboplatin combination in treatment of cervical cancer treatment.

IL-10 and TGF-ß: Roles in chondroprotective effects of Glucosamine in experimental Osteoarthritis?

OBJECTIVE: Osteoarthritis (OA) is a complex disease of the whole joint. Glucosamine (GlcN) treatment may have a chondroprotective effect on OA. We investigated the mechanism of action of glucosamine treatment through interleukin-10 (Il-10) and transforming growth factor ß-1 (TGF ß-1). METHODS: Thirty male albino rats were used. A single intraarticular (i.a.) injection of 2mg of Monosodium Iodoacetate (MIA) was injected into the knee joint of anesthetized rats. GlcN (50 or 100mg/kg/day, p.o. for 2 month) was administered orally. Serum levels of Il-10 and TGF-ß1 were determined by ELISA. Histopathological changes in treated and control joints were examined using hematoxylin-eosin (H & E) staining. RESULTS: The mean serum level of IL-10 significantly decreased in the OA group compared to control group (P value<0.0001). On the other hand, mean serum level of IL-10 significantly increased in GlcN treated groups when compared to the OA group (P value<0.0001). Serum level of TGF ß-1 was significantly elevated in OA group compared to control group (P value<0.0001). On the other hand, the mean serum level of TGF ß-1 was significantly decreased in the GlcN treated groups when compared to the OA group (P value<0.0001). Histopathological evaluation of GlcN treated groups showed different grades of healing, according to Osteoarthritis Research Society International (OARSI) grading system. CONCLUSION: Our results showed that IL-10 and TGF-ß1 possibly mediate GlcN chondroprotective effects in OA. Both serum biomarkers can be useful in the follow-up of articular cartilage damage in clinical settings.

A putative Chondroprotective role for IL-1ß and MPO in herbal treatment of experimental osteoarthritis.

BACKGROUND: Herbal treatment may have a chondroprotective and therapeutic effect on Osteoarthritis (OA). We investigated the mechanism of action of ginger and curcumin rhizomes cultivated in Egypt in treatment of OA in rat model. METHODS: Thirty-five albino rats were intra-articularly injected with Monosodium Iodoacetate in the knee joint. Ginger and curcumin was orally administered at doses of 200 and 400 mg/kg (F200 and F400). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), malondialdehyde (MDA), myeloperoxidase (MPO), Interleukin-1 beta (IL-1ß) and superoxide dismutase activity (SOD) were measured using ELISA. The composition of the herbal formula hydro-ethanolic extract was characterized using UPLC-ESI-MS. Histopathological changes in injected joints was examined using routine histopathology. Statistical analysis was performed using one-way ANOVA. RESULTS: Serum levels of COMP, HA, MPO, MDA, and IL-1ß were significantly decreased in F 200, F 400 and V groups when compared to OA group (P value <0.0001). On the other hand SOD levels were significantly elevated in treated groups compared to OA groups (P value <0.0001). CONCLUSIONS: The ginger/curcumin at 1:1 had chondroprotective effect via anti-inflammatory and antioxidant effect in rat OA model. Further pharmacological and clinical studies are needed to evaluate this effect.

Resistin mediates tomato and broccoli extract effects on glucose homeostasis in high fat diet-induced obesity in rats.

BACKGROUND: Resistin is an adipocyte hormone that regulates glucose metabolism. Elevated levels of resistin may cause insulin resistance. This may link obesity, and increased fat mass to type II diabetes and insulin resistance. We hypothesized that treatment with tomato and broccoli extracts regulates glucose homeostasis via modulation of resistin levels in high fat diet-induced obesity rats (HFD). METHODS: Forty-eight male albino rats were divided into 8 groups as follows: control, HFD, stop fat diet (SD), Tomato 200 mg/kg (T200), Tomato 400 mg/kg (T400), Broccoli 200 mg/kg (B200), Broccoli 400 mg/kg (B400), and Chromax (CX). Treatment continued for 1 month. Serum levels of resistin, leptin, adiponectin, glucose and insulin were measured using ELISA and spectrophotometry. RESULTS: Serum levels of resistin were significantly reduced in the T 200, T 400, B 200, B 400 and CX groups to: 4.13 ± 0.22 ng/ml, 1.51 ± 0.04 ng/ml, 4.13 ± 0.22 ng/ml, 2.32 ± 0.15 ng/ml and 1.37 ± 0.03 ng/ml, respectively, compared to HFD group and SD group (P value < 0.0001). Non-significant differences were found between T 400, B 400 and CX groups. Serum levels of leptin were significantly reduced in the T 400 (22.7 ± 0.84 pg/ml) group compared to the B 400 (41 ± 2.45 Pg/ml) and CX groups (45.7 ± 2.91 Pg/ml), P value < 0.001. Serum levels of adiponectin were significantly increased in the T 400 group (131 ± 3.84 pg/ml) compared to the CX group (112 ± 4.77 pg/ml), P value < 0.01. CONCLUSIONS: Our results demonstrate that tomato and broccoli extract treatment regulates glucose homeostasis via reduction of serum resistin and may be a useful non-pharmacological therapy for obesity.

An approach for an enhanced anticancer activity of ferulic acid-loaded polymeric micelles via MicroRNA-221 mediated activation of TP53INP1 in caco-2 cell line.

Ferulic acid (FA) has powerful antioxidant and antitumor activities, but it has low bioavailability owing to its poor water solubility. Our aim is to formulate polymeric mixed micelles loaded with FA to overcome its poor solubility and investigate its potential anticancer activity via miRNA-221/TP53INP1 axis-mediated autophagy in colon cancer. A D-optimal design with three factors was used for the optimization of polymeric mixed micelles by studying the effects of each of total Pluronics mixture (mg), Pluronic P123 percentage (%w/w), and drug amount (mg) on both entrapment efficiency (EE%) and particle size. The anticancer activity of FA and Tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles formula (O2) was assessed by MTT and flow cytometry. O2 showed an EE% of 99.89%, a particle size of 13.86 nm, and a zeta potential of - 6.02 mv. In-vitro drug release studies showed a notable increase in the release rate of FA from O2, as compared to the free FA. The (IC50) values for FA from O2 and free FA were calculated against different cell lines showing a prominent IC50 against Caco-2 (17.1 µg/ml, 191 µg/ml respectively). Flow cytometry showed that FA caused cell cycle arrest at the G2/M phase in Caco-2. RT-PCR showed that O2 significantly increased the mRNA expression level of Bax and CASP-3 (4.72 ± 0.17, 3.67 ± 0.14), respectively when compared to free FA (2.59 ± 0.13, 2.14 ± 0.15), while miRNA 221 levels were decreased by the treatment with O2 (0.58 ± 0.02) when compared to free FA treatment (0.79 ± 0.03). The gene expression of TP53INP1 was increased by the treatment with O2 compared to FA at P < 0.0001. FA-loaded TPGS mixed micelles showed promising results for enhancing the anticancer effect of FA against colorectal cancer, probably due to its enhanced solubility. Thus, FA-loaded TPGS mixed micelles could be a potential therapeutic agent for colorectal cancer by targeting miRNA-221/TP53INP1 axis-mediated autophagy.

Untargeted metabolomics-based molecular networking for chemical characterization of selected Apiaceae fruit extracts in relation to their antioxidant and anti-cellulite potentials.

Stress, obesity, hormonal changes, and aging have been connected to cellulite aggravation resulting in skin dimpled appearance, a very common painless skin disorder with a female preponderance. Several Apiaceae plants have been traditionally used for cosmetic applications. However, their screening for anti-cellulite potential has not been deeply investigated. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of nine Apiaceae fruits. Additionally, the extracts were screened for in vitro antioxidant and anti-cellulite activities. Apium graveolens and Petroselinum crispum revealed excellent free radical scavenging activity, remarkably increased lipolysis, and decreased adipogenesis. Furthermore, apigenin and its glycosides were identified to be the major components in both extracts, which might be responsible for the antioxidant activity and anti-cellulite potential. Conclusively, these results signify the potent antioxidant and anti-cellulite properties of A. graveolens and P. crispum fruit extracts, holding potential for the development of plant derived products for cellulite management.

A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line.

Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus. Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic effects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their significant effect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA significantly downregulated miRNA-21 expression. Meanwhile, the three compounds caused significant overexpression of Let-7 miRNA. This is the first report on the anti-cancer activity of acetoxy-lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and differentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer.

Association of XIST/miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti-phospholipid syndrome and its effect on cell adhesion molecules and inflammatory mediators.

Anti-phospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis and miscarriage events. Still, the molecular mechanisms underlying APS, which predisposes to a wide spectrum of complications, are being explored. Seventy patients with primary and secondary APS were recruited, in addition to 35 healthy subjects. Among APS groups, the gene expression levels of XIST, Gab2, and TAK1 were higher along with declined miRNA155 level compared with controls. Moreover, the sera levels of ICAM-1, VCAM-1, IL-1ꞵ, and TNF-α were highly elevated among APS groups either primary or secondary compared with controls. The lncRNA XIST was directly correlated with Gab2, TAK1, VCAM-1, ICAM-1, IL-1ꞵ, and TNF-α. The miRNA155 was inversely correlated with XIST, Gab2, and TAK1. Moreover, ROC curve analyses subscribed the predictive power of the lncRNA XIST and miRNA155, to differentiate between primary and secondary APS from control subjects. The lncRNA XIST and miRNA155 are the upstream regulators of the Gab2/TAK1 axis among APS patients via influencing the levels of VCAM-1, ICAM-1, IL1ꞵ, and TNF-α which propagates further inflammatory and immunological streams. Interestingly, the study addressed that XIST and miRNA155 may be responsible for the thrombotic and miscarriage events associated with APS and provides new noninvasive molecular biomarkers for diagnosing the disease and tracking its progression.

Nanotechnology in leukemia: diagnosis, efficient-targeted drug delivery, and clinical trials.

Leukemia is a group of malignant disorders which affect the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Many types of leukemia exist; thus, their diagnosis and treatment are somewhat complicated. The use of conventional strategies for treatment such as chemotherapy and radiotherapy may develop many side effects and toxicity. Hence, modern research is concerned with the development of specific nano-formulations for targeted delivery of anti-leukemic drugs avoiding toxic effects on normal cells. Nanostructures can be applied not only in treatment but also in diagnosis. In this article, types of leukemia, its causes, diagnosis as well as conventional treatment of leukemia shall be reviewed. Then, the use of nanoparticles in diagnosis of leukemia and synthesis of nanocarriers for efficient delivery of anti-leukemia drugs being investigated in in vivo and clinical studies. Therefore, it may contribute to the discovery of novel and emerging nanoparticles for targeted treatment of leukemia with less side effects and toxicities.

Circular SERPINA3 and its target microRNA-944 as potential biomarkers in hepatitis C virus-induced hepatocellular carcinoma in Egyptian population.

Background: The most prevalent cancer in Egypt is hepatocellular carcinoma (HCC) mainly due to the infection with the hepatitis C virus. So it is critical to find sensitive biomarkers for early diagnosis of HCC and avoid post-operation tumor recurrence. Therefore, this research was designed to demonstrate the circSERPINA3 role in the regulation of microRNA-944 gene expression in HCV-related HCC cases and compare these results with circSERPINA3 and microRNA-944 gene expression levels in HCV-infected patients. Methodology: Study participants were divided into three groups: healthy controls, HCV- infected, and HCV-induced HCC patients. The gene expression levels of circSERPINA3 and microRNA-944 were evaluated using Real-Time qPCR. Then the immunoblotting procedure was applied to measure the serum levels of MDM2 and E-cadherin besides, the serum concentration levels of glypican-3 and alpha-fetoprotein were measured by sandwich ELISA. Results: The gene expression level of circSERPINA3 was significantly upregulated in both HCV-infected and HCC patients causing suppression of the antitumor effect of miR-944 and showing a lower 1-year survival rate than the participants who had low circSERPINA3 gene expression levels. Subsequently, the miR-944 downstream protein, MDM2 was remarkably upregulated, exaggerating the metastasis and oxidative stress in HCC cases. Additionally, the results confirmed the downregulation of microRNA-944 improved the progression of viral hepatitis C cases to hepatocarcinogenesis through the significantly increased serum level of the metastatic marker, E-cadherin. Although alpha-fetoprotein is a common diagnostic marker used in the diagnosis of HCC, our results showed that glypican-3 had greater sensitivity and specificity and positively correlated to the IGF-1 signaling pathway of HCC cases. Moreover, the gene expression levels of circSERPINA3 and E-cadherin in both the HCV and HCV-induced HCC were significantly positively correlated. Conclusion: circSERPINA3 and miR-944 were sensitive molecular markers for early diagnosis of HCC and could be prospective treatment targets for HCV-infected patients to avoid tumor recurrence in HCC cases.

Metabolomics driven analysis of Nigella sativa seeds identifies the impact of roasting on the chemical composition and immunomodulatory activity.

Nigella sativa L. seeds (NS) are known as one of the most traditional immunomodulatory and nutritive food additives. NS can, furthermore, be roasted to give curries, breads, and other dishes a smoky, nutty flavor. This study evaluated the effect of roasting NS on the metabolic profile and immunomodulatory activity. Non-targeted metabolomics analysis was conducted using several analytical platforms, including GC-MS and UPLC-MS. A total of 197 metabolites were identified, belonging to different classes such as saponins, alkaloids, flavonoids, and lipids. In vitro immunomodulatory activity on the differentiated monocytic cell line THP-1 was assessed, revealing that the roasted seeds showed significantly-decreased immunomodulatory activity. Furthermore, a molecular docking study, which was carried out against immunomodulation-related pathway protein (iNOS), revealed that compounds which showed the best binding scores were severely decreased by roasting. Conclusively, our results demonstrate that the roasting of NS results in severe losses in their bioactive metabolites and immunomodulatory activity.

Anti-Obesity Effect of a Tea Mixture Nano-Formulation on Rats Occurs via the Upregulation of AMP-Activated Protein Kinase/Sirtuin-1/Glucose Transporter Type 4 and Peroxisome Proliferator-Activated Receptor Gamma Pathways.

White, green, and oolong teas are produced from the tea plant (Camellia sinensis (L.) Kuntze) and are reported to have anti-obesity and hypolipidemic effects. The current study aims to investigate the anti-obesity effects of a tea mixture nano-formulation by targeting the AMPK/Sirt-1/GLUT-4 axis in rats. In vitro lipase and α-amylase inhibition assays were used to determine the active sample, which was then incorporated into a nanoparticle formulation subjected to in vivo anti-obesity testing in rats by measuring the expression level of different genes implicated in adipogenesis and inflammation using qRT-PCR. Moreover, metabolomic analysis was performed for each tea extract using LC/ESI MS/MS coupled to chemometrics in an attempt to find a correlation between the constituents of the extracts and their biological activity. The in vitro pancreatic lipase and α-amylase inhibition assays demonstrated more effective activity in the tea mixture than the standards, orlistat and acarbose, respectively, and each tea alone. Thus, the herbal tea mixture and its nanoparticle formulation were evaluated for their in vivo anti-obesity activity. Intriguingly, the tea mixture significantly decreased the serum levels of glucose and triglycerides and increased the mRNA expression of GLUT-4, P-AMPK, Sirt-1, and PPAR-γ, which induce lipolysis while also decreasing the mRNA expression of TNF-α and ADD1/SREBP-1c, thereby inhibiting the inflammation associated with obesity. Our study suggests that the tea mixture nano-formulation is a promising therapeutic agent in the treatment of obesity and may also be beneficial in other metabolic disorders by targeting the AMPK/Sirt-1/Glut-4 pathway.