Paracetamol-Mediated Synthesis of Silver Nanoparticles and Their Functionalization with Ionic Liquid for the Colorimetric Biosensing of Ascorbic Acid.

Ascorbic acid is a vital biomolecule for human beings. When the body's level of ascorbic acid is abnormal, it can lead to a number of illnesses. Its appropriate concentration is necessary for the oxidation of prostaglandins and cyclic adenosine monophosphate, the production of dopamine, norepinephrine, epinephrine, and carnitine, and the expansion and durability of the collagen triple helix in humans. In the present work, silver nanoparticle synthesis was performed through a paracetamol-mediated approach. Different characterization techniques, such as X-ray diffractometry (XRD), energy dispersive X-ray (EDX), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM), were used to confirm the prepared nanoparticles. Subsequently, the prepared Ag NPs functionalized with an ionic liquid were used as a sensing platform for ascorbic acid in blood serum samples. To achieve the best possible results, the proposed biosensor was optimized with different parameters such as TMB concentration, time, amount of capped nanoparticles (NPs), and pH. The proposed biosensor offers a sensitive and straightforward method for ascorbic acid with a linear range from 2 × 10-9 to 3.22 × 10-7 M, an LOD of 1.3 × 10-8 M, an LOQ of 4.3 × 10-8 M, and an R2 of 0.9996, Moreover, applications of the proposed biosensor were successfully used for the detection of ascorbic acid in samples of human plasma, suggesting that Ag NPs with high peroxidase-like activity, high stability, and facile synthesis exhibited promising applications in biomedical fields.

Phytochemical profiling, in vitro biological activity, docking studies, and cytotoxicity assessments of Rondeletia odorata Jacquin: An unexplored plant of the coffee family.

Rondeletia odorata Jacquin is a flowering plant that belongs to the coffee family. As a rich source of polyphenols with significant antioxidant potential, R. odorata may have health benefits. Therefore, in the current work, ethanolic extract of aerial parts and its n-hexane, ethyl acetate, and n-butanol soluble fractions were analyzed for their antioxidant potential and various enzyme inhibition properties. The total phenolic and flavonoid contents of the crude ethanol extract (ROE) and its n-hexane (ROH), ethyl acetate (ROEA), and n-butanol (ROB) fractions were determined spectrophotometrically, while metabolic profiling was established through UHPLC-MS analysis, which revealed the presence of 58 phytochemicals. Total phenolic and flavonoid contents of ROE extract were measured as 51.92 mg GA.Eq./g of dry extract and 52.35 mg Qu.Eq./g of the dry extract, respectively. In the DPPH radical scavenging activity assay, ROE and ROEA showed the highest potential with values of 62.13 ± 0.62 and 76.31% ± 1.86%, respectively, comparable to quercetin (80.89% ± 0.54%). Similarly, in the FRAP assay, the same pattern of the activity was observed with ROE and ROEA, which displayed absorbance values of 1.32 ± 0.01 and 0.80 ± 0.02 at 700 nm, respectively, which are comparable (1.76 ± 0.02) with the reference compound quercetin, whereas the ROH showed maximum metal-chelating capacity (62.61% ± 1.01%) among all extracts and fractions. Antibacterial activity assay indicated that the ROEA fraction was the most active against Serratia marcescens, Stenotrophomonas maltophilia, Bacillus subtilis, Klebsiella pneumonia, and Staphylococcus aureus, while the rest of the fractions showed good to moderate activity. Enzyme inhibition assays showed that ROEA fraction exhibited the highest activity with IC50 values of 2.78 ± 0.42 and 3.95 ± 0.13 mg/mL against urease and carbonic anhydrase (CA), respectively. Furthermore, the docking studies of some of the major compounds identified in the extract revealed a strong correlation with their inhibitory activity. All extracts and fractions were also tested for their thrombolytic activity, and the ROB fraction showed a notable potential. Antiviral assay led to remarkable outcomes. Thus, it can be inferred that aerial parts of R. odorata are potential sources of bioactive components with several significant pharmacological activities.

The relationship between NTCP gene varieties and the progress of liver disease after HBV infection: an updated systematic review and meta-analysis.

BACKGROUND: The aim of this study was to analyze the relationship between sodium taurocholate cotransporting polypeptide (NTCP) gene varieties and hepatitis B virus (HBV) infection and the progress of HBV-related liver disease. METHODS: PubMed, EMBASE, Web of Science and Cochrane library were used to search eligible studies. STATA software was performed to combine results. Pooled odds ratios (OR) was used to assess the potential genetic relationships. RESULTS: A total of 18 eligible case-control studies with 24960 cases and 28342 controls were included in this meta-analysis. The A allele of rs2296651 polymorphism was found to be significantly linked to a protection of HBV infection in the whole combined analysis (P = 0.000). Meanwhile, this allele was significantly associated with a decreased risk of hepatocellular carcinoma (HCC) (A vs. G: OR = 0.668, 95% CI: 0.571-0.782, P = 0.000), and was significantly associated with HBV nature clearance (A vs. G: OR = 0.744, 95% CI: 0.585-0.946, P = 0.016; AA+GA vs. GG: OR = 0.775, 95% CI: 0.613-0.980, P = 0.033; GA vs. GG: OR = 0.748, 95% CI: 0.588-0.952, P = 0.018). However, rs4646287 genetic varieties had no statistical differences in all models with HBV infection or HBV-related disease progress, liver cirrhosis, acute-on-chronic liver failure and HCC, as well as rs7154439, rs4646285, rs4646296. CONCLUSIONS: Rs2296651 polymorphism (A allele) may protect from HBV infection and the progress of HBV-related disease (HBV-related HCC). Future research about other single nucleotide polymorphisms (SNPs) (rs4646287, rs7154439, rs4646285, rs4646296) of NTCP may be needed to clarify the relationship of NTCP gene varieties with HBV infection and HBV-related disease.

THRSP identified as a potential hepatocellular carcinoma marker by integrated bioinformatics analysis and experimental validation.

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with high mortality and poor prognosis worldwide. This study aimed to identify hub genes and investigate the underlying molecular mechanisms in HCC progression by integrated bioinformatics analysis and experimental validation. Based on the Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas (TCGA), 12 critical differential co-expression genes were identified between tumor and normal tissues. Via survival analysis, we found higher expression of LCAT, ACSM3, IGF1, SRD5A2, THRSP and ACADS was associated with better prognoses in HCC patients. Among which, THRSP was selected for the next investigations. We found that THRSP mRNA expression was negatively correlated with its methylation and closely associated with clinical characteristics in HCC patients. Moreover, THRSP expression had a negative correlation with the infiltration levels of several immune cells (e.g., B cells and CD4+ T cells). qRT-PCR verified that THRSP was lower expressed in HCC tissues and cell lines compared with control. Silencing of THRSP promoted the migration, invasion, proliferation, and inhibited cell apoptosis of HCCLM and Huh7 cell lines. Decreased expression of THRSP promoted HCC progression by NF-κB, ERK1/2, and p38 MAPK signaling pathways. In conclusion, THRSP might serve as a novel biomarker and therapeutic target of HCC.

AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics.

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis. Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC. Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs. Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

A Spellbinding Interplay Between Biological Barcoding and Nanotechnology.

Great scientific research with improved potential in probing biological locales has remained a giant stride. The use of bio-barcodes with the potential use of nanotechnology is a hallmark being developed among recent advanced techniques. Biobarcoding is a novel method used for screening biomolecules to identify and divulge ragbag biodiversity. It establishes successful barcoding projects in the field of nanomedical technology for massively testing disease diagnosis and treatment. Biobarcoding and nanotechnology are recently developed technologies that provide unique opportunities and challenges for multiplex detection such as DNAs, proteins and nucleic acids of animals, plants, viruses, and various other species. These technologies also clump drug delivery, gene delivery, and DNA sequencing. Bio-barcode amplification assay (BCA) is used at large for the detection and identification of proteins and DNAs. DNA barcoding combined with nanotechnology has been proven highly sensitive rendering fast uniplex and multiplex detection of pathogens in food, blood, and other specimens. This review takes a panoramic view of current advances in nano bio-barcodes which have been summarized to explore additional applications such as detection of cytokines, neurotransmitters, cancer markers, prostate-specific antigens, and allergens. In the future, it will also be possible to detect some fungi, algae, protozoa, and other pollutants in food, agriculture, and clinical samples. Using these technologies, specific and efficient sensors would possibly be developed that can perform swift detections of antigens, allergens, and other specimens.

Enhanced Efficacy of Direct-Acting Antivirals in Hepatitis C Patients by Coadministration of Black Cumin and Ascorbate as Antioxidant Adjuvants.

The widespread adaptation of a new generation of direct-acting antiviral agents (DAAs) unveils a superlative effect in the eradication of the hepatitis C virus (HCV). However, this therapy has been reported to exhibit vigorous side effects that pose a risk in fleet recovery. This study was conducted to investigate the efficacy of DAAs: sofosbuvir (SOF) and ribavirin (RBV), along with black cumin (BLC) and ascorbate (ASC), as adjuvants on hematological parameters; oxidative stress markers such as total antioxidant status (TAS), superoxide dismutase (SOD), reduced (GSH) and oxidized (GSSG) glutathione (GSH), gamma-glutamyl transferase (GGT), and malondialdehyde (MDA); liver function markers such as aspartate transaminase (AST), alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase (ALP); and viral load with determined genotypes. HCV-infected patients (n = 30) were randomly divided into two equal groups: control group (n = 15) and treatment group (n = 15). The control group was subjected only to SOF and RBV (400 mg each/day). Synergistically, the treatment group was administered with adjuvant therapy of BLC (250 mg/day) and ASC (1000 mg/day) along with DAAs (400 mg each/day) for 8 weeks. All selected patients were subjected to sampling at pre- and posttreatment stages for the assessment of defined parameters. The data revealed that the BLC/ASC adjuvant therapy boosted the efficacy of DAAs by reducing the elevated levels of liver markers such as AST, ALT, ALP, and bilirubin in the treatment group compared with those in the control group (P > 0.05). The adjuvant therapy synchronously showed an ameliorating effect on hematological parameters. The SOF/RBV with adjuvant therapy also demonstrated an increasing effect in the activity of SOD, TAS, and GSH and a decreasing effect for GSSG, GGT, and malondialdehyde (MDA; P > 0.05) followed by curtailing a RT-PCR-quantified viral load. Our findings provide evidence that systemic administration of BLC/ASC efficiently alleviates hematological, serological, and antioxidant markers as well as the viral load in hepatitis C patients. This highlights a potentially novel role of BLC and ASC in palliating hepatitis C.

Association of IL-6, IL-10 and TGF-ß1 gene polymorphisms with brucellosis: A systematic review with meta-analysis.

BACKGROUND: Brucellosis is one of the major public health problems worldwide. Several current studies have provided data that polymorphisms in the interleukin-6 (IL-6), interleukin-10 (IL-10) and transforming growth factor beta1(TGF-ß1) gene were associated with the susceptibility to human brucellosis, but the results remain inconsistent. OBJECTIVES: The aim of present study was to investigate the relationship between IL-6 (-174 G/C), IL-10 (-1082 A/G, -819C/T) and TGF-ß1 (codon 10, codon 25) gene polymorphisms and brucellosis. METHODS: We performed a comprehensive search of the PubMed, EMBASE, Web of Science, OVID-EBMR, and the Cochrane Library up to Oct. 30, 2018. The search was designed using the following key words: "brucellosis" or" "brucella melitensis", "IL-10" or "interleukin10" or "interleukin-10", "IL-6" or "interleukin6" or "interleukin-6", "TGF-ß1" or "TGF-beta1" or "transforming growth factor ß1", "polymorphism" and "single nucleotide polymorphism (SNP)". Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of association between TGF-ß1, IL-10 and IL-6 polymorphisms and brucellosis risk. All the statistical analyses were conducted by Review manager 5.3 software. RESULTS: A total of 8 studies involving 1308 cases and 902 controls met the inclusion criteria for IL-6, IL-10, TGF-ß1 polymorphisms and brucellosis risk. There was a slightly trend of increasing risk of brucellosis in individuals with the G allele compared with individuals with the C allele (OR = 1.07, 95% CI: 0.85-1.33, P = 0.57) in IL-6 polymorphism. However, statistical analysis showed that these differences are not significant. Our results suggested TGF-ß1 (codon 25 G/C) GG genotype may be considered as a risk factor for brucellosis (OR = 1.67, 95% CI: 1.12-2.50, P = 0.01). Herein, we failed to find any significant association between IL-10 (-1082 A/G, -819C/T), TGF-ß1 (codon 10C/T) gene polymorphism and susceptibility to brucellosis in all gene models. CONCLUSION: IL-6 (-174 G/C), IL-10 (-1082 A/G, -819C/T), and TGF-ß1 (codon 10C/T) polymorphisms is not a risk factor for brucellosis infection. TGF-ß1 codon 25 GG genotype may be considered as a risk factor for brucellosis.

Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis.

Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07-1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09-1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.