Involvement of FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p in breast cancer.

BACKGROUND: FAM170B-AS1 is usually expressed low in all organs except for testicular tissues. No study was performed to explore its role in breast cancer (BC). Contradictory results were reported about hsa-miR-1202 and hsa-miR-146a-5p in BC. OBJECTIVE: The present study aimed to explore the involvement of FAM170B-AS1 in BC using bioinformatics predictive tools, followed by a practical validation besides exploring the impact of hsa-miR-1202 and hsa-miR-146a-5p in BC. METHODS: This study enrolled 96 female patients with BC, 30 patients with benign breast diseases (BBD), and 25 control subjects. The expressions of circulating FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p were quantified using qRT-PCR. These ncRNAs' associations, predictive, and diagnostic roles in BC were statistically tested. The underlying miRNA/mRNA targets of FAM170B-AS1 in BC were bioinformatically predicted followed by confirmation based on the GEPIA and TCGA databases. RESULTS: The expression of FAM170B-AS1 was upregulated in sera of BC patients and hsa-miR-1202 was upregulated in sera of BBD and BC patients while that of hsa-miR-146a-5p was downregulated in BC. These FAM170B-AS1 was significantly associated with BC when compared to BBD. FAM170B-AS1 and hsa-miR-1202 were statistically associated with the BC's stage, grade, and LN metastasis. FAM170B-AS1 and hsa-miR-146a-5p gave the highest specificity and sensitivity for BC. KRAS and EGFR were predicted to be targeted by FAM170B-AS1 through interaction with hsa-miR-143-3p and hsa-miR-7-5p, respectively. Based on the TCGA database, cancer patients having mutations in FAM170B show good overall survival. CONCLUSIONS: The present study reported that for the first time, FAM170B-AS1 may be a potential risk factor, predictive, and diagnostic marker for BC. In addition, FAM170B-AS1 might be involved in BC by interacting with hsa-miR-143-3p/KRAS and hsa-miR-7-5p/EGFR through enhancement or repression that may present a new therapeutic option for BC.

Ultrasound abnormalities of the major salivary glands in Egyptian patients with systemic sclerosis.

INTRODUCTION/OBJECTIVES: systemic sclerosis (SSc) is an autoimmune disorder with multiple organs destruction. This study aimed to identify the ultrasonographic changes of major salivary glands in Egyptian scleroderma patients and to detect their association to different disease manifestations. METHODS: Forty-seven SSc patients and 43 apparent healthy volunteers were enrolled. Demographics, inflammatory markers, and autoimmune status were recorded. Ultrasound evaluation of salivary glands was performed. Salivary gland changes' associations were statistically examined with SSc susceptibility and disease manifestations. RESULTS: Thirty-one SSc patients exhibited glandular pathology (p < 0.0001), compared to controls. Of these abnormalities, SSc patients showed a total parotid gray scale of 2, total submandibular gray scale of 2, total glandular gray scale of 4, and total glandular Doppler signal of 1 at p < 0.0001, compared to the control group. Patients with SSc and glandular pathology had a higher prevalence of arthritis (p = 0.029) and ESR (p = 0.002) than those with normal glandular ultrasound. Significant associations were reported between gray scale ultrasound (GSUS) of total parotid (odds ratio "OR" = 0.4), total submandibular (OR = 0.36), and total glandular (OR = 0.53) with susceptibility to SSc at p < 0.0001. Total glandular GSUS (p = 0.039) and total submandibular power Doppler (p = 0.044) correlated with the SSc duration. Total parotid GSUS (p = 0.008) and total glandular GSUS (p < 0.0001) correlated with Schirmer's test. CONCLUSIONS: Major salivary glands are affected in SSc. Hence, scanning these glands with ultrasound is an additive tool besides the current practice. Key Points • Major salivary gland changes, observed by ultrasonography, are new findings in Egyptian SSc patients. • Ultrasound changes of major salivary glands are associated with inflammatory markers and clinical manifestations of SSc. • Scleroderma ultrasonography scans of the main salivary glands could be added to the routine work.

Association study of HIF-1α rs11549465 and VEGF rs3025039 genetic variants with diabetic retinopathy in Egyptian patients: crosslinks with angiogenic, inflammatory, and anti-inflammatory markers.

BACKGROUND: Genetic factors are implicated in the progression of DR-a global cause of blindness. Hence, the current work investigated the association of HIF-1α rs11549465 and VEGF rs3025039 genetic variants with the different stages of retinopathy among T2DM Egyptian patients. The crosslinks of these variants were explored with angiogenesis (VEGF), inflammation (AGEP and VCAM-1), and anti-inflammation (CTRP3) markers. Two hundred eighty-eight subjects were recruited in this study: 72 served as controls and 216 were having T2DM and were divided into diabetics without retinopathy (DWR), diabetics with non-proliferative retinopathy (NPDR), and diabetics with proliferative retinopathy (PDR). The genetic variants were analyzed using PCR-RFLP and their associations with NPDR and PDR were statistically tested. The circulating levels of AGEP, VCAM-1, HIF-1α, VEGF, and CTRP3 were assayed followed by analyzing their associations statistically with the studied variants. RESULTS: Only HIF-1α rs11549465 genetic variant (recessive model) was significantly associated with the development of NPDR among T2DM patients (p < 0.025) with a significant correlation with the circulating HIF-1α level (p < 0.0001). However, this variant was not associated with PDR progression. Neither HIF-1α rs11549465 nor VEGF rs3025039 genetic variants were associated with the PDR progression. The circulating AGEP, VCAM-1, HIF-1α, and VEGF were significantly elevated (p < 0.0001) while the CTRP3 was significantly decreased (p < 0.0001) in NPDR and PDR groups. The HIF-1α rs11549465 CT and/or TT genotype carriers were significantly associated with AGEP and VCAM-1 levels in the NPDR group, while it showed a significant association with the CTRP3 level in the PDR group. The VEGF rs3025039 TT genotype carriers showed only a significant association with the CTRP3 level in the PDR group. CONCLUSION: The significant association of HIF-1α rs11549465 other than VEGF rs3025039 with the initiation of NPDR in T2DM Egyptian patients might protect them from progression to the proliferative stage via elevating circulating HIF-1α. However, this protective role was not enough to prevent the development of NPDR because of enhancing angiogenesis and inflammation together with suppressing anti-inflammation. The non-significant association of HIF-1α rs11549465 with PDR among T2DM patients could not make this variant a risk factor for PDR progression.

Impact of rs11024102 PLEKHA7, rs3753841 COL11A1 single nucleotide polymorphisms, and serum levels of oxidative stress markers on the risk of primary angle-closure glaucoma in Egyptians.

BACKGROUND: Primary angle-closure glaucoma (PACG) is one of the major causes of blindness in the Middle East with genetic loci and systemic oxidative stress as potential risk factors. The current case-control study aimed to investigate the associations of rs11024102 in Pleckstrin homology domain-containing family A member 7 (PLEKHA7), rs3753841 in collagen 11 A1 (COL11A1), and the systemic oxidative stress markers with PACG in Egyptian patients. Thirty-five control subjects and 64 PACG patients were enrolled in this study. The polymorphisms in PLEKHA7 and COL11A1 were analyzed using quantitative PCR, and their associations were statistically tested with PACG at homozygous, heterozygous, dominant, and recessive genetic models. The levels of malondialdehyde (MDA), advanced glycation-end product (AOPP), protein carbonyl (PC), and ischemia modified albumin (IMA) were quantitated colorimetrically, and their associations with PACG were analyzed statistically. The associations of MDA, AOPP, PC, and IMA with elevated intraocular pressure (IOP) were statistically tested. RESULTS: Neither significant difference in the genotype distribution nor allele frequency of PLEKHA7 11024102 T>C (p = 0.425 and 0.517, respectively) and COL11A1 rs3753841 G>A (p = 0.600 and 0.473, respectively) were recorded under any of the tested genetic models. Either rs11024102 PLEKHA7 or rs3753841 COL11A1 was not significantly (p > 0.025 after Bonferroni correction) associated with an increased risk of PACG in Egyptians. Egyptian patients with PACG showed significant elevations in the serum levels of MDA, AOPP, and PC either in patients with or without cases with diabetes mellites, hypertension, coronary vascular diseases, and smoking. Serum levels of MDA, AOPP, and PC were significantly associated with PACG in Egyptians (p < 0.013 after Bonferroni correction). However, MDA and PC only showed significant associations with the elevation in the IOP (p = 0.007 and 0.045, respectively) in PACG patients. CONCLUSION: Both rs11024102 and rs3753841 could not be considered as potential gene-dependent risk factors for PACG pathogenesis in Egyptians. On the other hand, serum levels of MDA, AOPP, and PC might be considered risk factors for PACG. Moreover, MDA and PC could serve as good predictors for the elevation of the IOP in PACG disease.

Telomerase activator-65 and pomegranate peel improved the health status of the liver in aged rats; multi-targets involved.

OBJECTIVES: This study was undertaken to investigate the efficacy of telomerase activator-65 (Ta-65) and pomegranate peel against aging-induced deteriorations in the liver. MATERIALS AND METHODS: The rats were divided into four groups: control, aged, aged rats treated with Ta-65, and pomegranate orally for two months. RESULTS: Aging significantly increased the serum levels of total protein, globulins, and protein carbonyl and reduced the insulin-like growth factor 1 (IGF-1). It also elevated the hepatic malondialdehyde and decreased the hepatic glutathione S-transferase (GST) activity. Aging elevated the expression of thioredoxin reductase1, telomerase reverse transcriptase, and cytochrome 3a1 in the liver; it increased the p53 protein level and elevated the activity of caspase-3 in the liver indicating the occurrence of apoptosis. The architecture of the liver deteriorated in the aged rats, as shown by both light and electron microscopy examinations. The liver of the aged rats had many apoptotic hepatocytes with shrunken nuclei. Many hepatocytes had dilated rough endoplasmic reticulum, many lysosomes, and many fat droplets. Administration of Ta-65 and pomegranate to the aged rats normalized most of the previous biochemical parameters and improved the liver architecture. CONCLUSION: Ta-65 and pomegranate have anti-aging activity through targeting multiple cellular pathways. It is also noteworthy that Ta-65 was superior to pomegranate in its alleviative effects.

Astragalus membranaceus and Punica granatum alleviate infertility and kidney dysfunction induced by aging in male rats.

By aging, male fertility and kidney function decline. Therefore, the investigation of health span-extending agents becomes more urgent to overcome aging-induced infertility and kidney dysfunction. The current research was undertaken to investigate the antiaging efficacy of Astragalus membranaceus telomerase activator-65 (Ta-65) and pomegranate supplements. Forty male Wistar rats were divided into young rats, aged rats, aged rats treated with Ta-65 (500mg/kg/day), and aged rats treated with pomegranate (250mg/kg/day). Testosterone, FSH, LH, and kidney functions were measured in serum. Sperm analysis as well as testicular histological examination was performed. Aging caused an imbalance in male sex hormones resulting in sperm abnormality and reductions in the sperm count and motility. Elevations in serum creatinine, uric acid, sodium, and potassium were reported in aged rats. Treatment with Ta-65 or pomegranate effectively ameliorated all the deteriorations induced by normal aging in male fertility and renal function. Ta-65 and pomegranate possessed strong antiaging activity by alleviating aging-induced male infertility through reestablishing the hormonal balance and testis architecture. They also alleviated the kidney dysfunction. On comparing Ta-65 with pomegranate, the improvement in FSH, LH, and sperm abnormalities caused by Ta-65 was much better than that caused by pomegranate.

Modulatory effect of Prosopis juliflora leaves on hepatic fibrogenic and fibrolytic alterations induced in rats by thioacetamide.

This study investigated the antifibrotic effect of Prosopis juliflora leaves crude methanolic extract (PJEL) against thioacetamide (TAA)-induced liver fibrosis. The phytochemical analysis of PJEL was performed via HPLC/MS in association with evaluating its free radical scavenging and cytotoxic activities. The antifibrotic activity of PJEL was assessed by dividing Wistar rats into 8 groups: normal control, PJEL1-administered rats (2 mg/ Kg b.w.), PJEL2-administered rats (4 mg/ Kg b.w.), PJEL3-administered rats (8 mg/Kg b.w.), TAA-induced hepatic fibrosis, TTA + PJEL1, TAA + PJEL2, and TAA + PJEL3. Results indicated that PJEL crude methanolic extract is rich in polyphenolic compounds and alkaloids. PJEL exerted free radical scavenging activity with IC50 of 123.5 µg/mL and cytotoxic activity against a well-differentiated hepatocellular cell line (IC50 = 11.1 µg/mL). PJEL at a dose of 4 mg/Kg b.w. ameliorated serum ALT activity and improved serum albumin level and hepatic hydroxyproline content in association with a reduction in the fibrosis stage. PJEL elevated hepatic tumor necrosis factor-α and interleukin-6 contents with less necrosis grade. PJEL post-therapy ameliorated the relative expression of Bcl-2, Col1A1, Mmp-9, and Mmp-2 genes in liver. CONCLUSION: PJEL possesses a good therapeutic activity against TAA-induced liver fibrosis via enhancing extracellular matrix removal and stimulating hepatic regeneration to decrease hepatic necrosis.

Ziziphus spina-christi leaves methanolic extract alleviates diethylnitrosamine-induced hepatocellular carcinoma in rats.

This study evaluated the antitumor activity of a methanolic extract from the leaves of Ziziphus spina-christi (ZSCL) against diethylnitrosamine (DENA)-induced hepatocarcinoma in rats. The phytochemical constituents, in vitro antioxidant and cytotoxic activities of ZSCL extract were investigated. Male Wistar rats were distributed among 6 groups: (i) normal control; (ii) ZSCL1-treated rats (100 mg/kg body mass; "b.m."); (iii) ZSCL2-treated rats (300 mg/kg b.m.); (iv) rats with DENA-induced hepatocarcinoma; (v and vi) rats with hepatocarcinoma that were treated with either (v) ZSCL1 or (vi) ZSCL2. Serum liver function and levels of oxidative stress were assayed. The expression of hepatocyte growth factor, insulin-like growth factor-1 receptor, B cell lymphoma-2, and matrix metalloproteinase-9 oncogenes were quantified in liver samples. Histological examination of the liver tissues was performed. The ZSCL was rich in essential fatty acids, phytol, and polyphenolic flavones (luteolin and quercetin) with strong free-radical and peroxide scavenging activities and cytotoxic activity. Administration of ZSCL1 and ZSCL2 to the rats produced no toxic effects. DENA induced hepatocellular carcinoma and cholangioma by producing oxidative stress and upregulating the expression of hepatic oncogenes. Treatment of DENA-induced hepatocarcinoma with ZSCL2 ameliorated all of the abnormalities induced by DENA except for cholangioma. In conclusion, the ZSCL (300 mg/kg b.m.) displayed strong therapeutic activity against DENA-induced hepatocellular carcinoma via targeting oxidative stress and oncogenes.

New Quinazoline-Sulfonylurea Conjugates: Design, Synthesis and Hypoglycemic Activity.

BACKGROUND: Sulphonylureas are the oldest and commonly used to treat diabetic patients, but its efficacy declines by time. It was reported that quinazoline nucleus exhibits a potent hypoglycemic effect in diabetic animal models. OBJECTIVE: The current study aimed to synthesize new quinazoline-sulfonylurea conjugates and evaluate their hypoglycemic effects in alloxan-induced diabetic rats. METHODS: The conjugates were synthesized by bioisosteric replacement of 5-chloro-2-methoxybenzamide moiety in glibenclamide or 1,3-dioxo-3,4-dihydroisoquinoline moiety in gliquidone with 6,7-dimethoxy-4-oxoquinazoline moiety (compounds 4a-4d, 9b-9c and 10b-10d). Diabetes was induced in rats by a single i.p. administration of alloxan, followed by treatment with the synthesized conjugates (5mg/kg Body weight). RESULTS: All conjugates showed hypoglycemic effects with different efficacy indicated by the reduction in blood glucose and elevation of insulin levels. Moreover, these conjugates up-regulated the expression of pancreatic glucose transporter 2, muscle glucose transporter 4, and insulin receptor substrate-1 genes, compared to the diabetic group. A normal pancreatic tissue pattern was noticed in diabetic rats treated with compounds 9b, 9c, and 10c. CONCLUSION: Conjugation of sulfonylurea with quinazoline (especially 9b, 9c, 10c) possessed a significant hypoglycemic effect through improving blood insulin level and insulin action and consequently increased the glucose uptake by the skeletal muscles.

Chemical Characteristics, Antimicrobial, and Cytotoxic Activities of the Essential Oil of Egyptian Cinnamomum glanduliferum Bark.

The essential oil isolated from the bark of Cinnamomum glanduliferum (Wall) Meissn grown in Egypt was screened for its composition as well as its biological activity for the first time. The chemical composition was analyzed by GC and GC/MS. The antimicrobial activity of the oil was assessed using agar-well diffusion method toward representatives for each of Gram-positive bacteria, Gram-negative bacteria, and fungi. The cytotoxic activity was checked using three human cancer cell lines. Twenty seven compounds were identified, representing 99.07% of the total detected components. The major constituents were eucalyptol (65.87%), terpinen-4-ol (7.57%), α-terpineol (7.39%). The essential oil possessed strong antimicrobial activities against Escherichia coli, with an activity index of one and minimum inhibitory concentration (MIC) equaling to 0.49 µg/ml. The essential oil possessed good antimicrobial activities against methicillin-resistant Staphylococcus aureus, Geotrichum candidum, Pseudomonas aeruginosa, Bacillus subtilis, Helicobacter pylori, Aspergillus fumigatus (MIC: 7.81, 1.95, 7.81, 0.98, 31.25, and 32.5 µg/ml, respectively). A considerable activity was reported against S. aureus and Mycobacterium tuberculosis (MIC; 32.5 and 31.25 µg/ml, respectively). The extracted oil was cytotoxic to colon (HCT-116), liver (HepG2), and breast (MCF-7) carcinoma cell lines with IC50 of 9.1, 42.4, and 57.3 µg/ml, respectively. These results revealed that Egyptian Cinnamomum glanduliferum bark oil exerts antimicrobial and cytotoxic activities mainly due to eucalyptol and other major compounds.