Corrosion inhibition study of 6061 aluminium alloy in the presence of ethyl 5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (NTE) in hydrochloric acid.

The inhibitory effect of an ethyl 5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (NTE) was investigated on the corrosion of Al (AA6061) alloy at different temperatures (303-333 K) by Electrochemical impedance spectroscopy (EIS), Potentiodynamic polarization (PDP), and weight loss techniques. It was found that NTE molecules protect the aluminium against corrosion and its ability increases with increasing concentrations, and temperature resulting in better inhibitory performance. At all concentrations and temperature ranges, NTE exhibited mixed inhibitor action and complied with the Langmuir isotherm. At 100 ppm and 333 K, NTE demonstrated the highest inhibition efficiency (94%). The EIS results and the PDP results had a good level of concordance. A suitable mechanism for the corrosion prevention of AA6061 alloy was proposed. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to confirm the adsorption of an inhibitor onto the aluminium alloy surface. The electrochemical results were validated by morphological examination, which demonstrated that NTE prevents uniform corrosion of aluminium alloy in acid chloride solutions. The activation energy and thermodynamic parameters were computed, and the results were discussed.

The role of p53 and ki67 in predicting clinical outcome in breast cancer patients.

Background: ">ki67 may be used as a proliferative index in addition to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) negative status. p53 gene expression is a well-known biomarker in breast cancer and its role in predicting clinical outcome remains unclear. The current study aimed to determine the relationship between p53 gene mutation and ki67 expression, their clinical characteristics, and overall survival (OS), and to differentiate the significance of p53 and ki67 as the prognostic value in breast cancer patients. Methods: ">In this study, 135 patients were enrolled in the study from December 2015 to May 2017. Medical records for all patients were reviewed prospectively. The inclusion criteria included age more than 18 years with histologically proven breast cancer and willingness to be enrolled in p53 genetic study. Exclusion criteria included dual malignancy, male breast cancer, with a loss to follow-up during the study. Results: ">The mean survival of patients with ki67 ≤20 index was 42.7 months (95% confidence interval [CI] 38.7-46.7) and 129 months (95% CI 101.3-157.2) in patients with ki67 >20. The mean OS was 145 months (95% CI 105.6-185.5) in the p53 wild-type group and 106 months (95% CI 78.0-133.0) in the p53 mutated group, as illustrated. Conclusion: ">Our results indicated that p53 mutational status and high ki67 might have an essential impact on overall survival, with p53 mutated patients having a poorer outcome than p53 wild type patients.

Effect of Hypochlorites on the Compressive Strength and Surface Hardness of Type V Dental Stone: An In Vitro Study.

AIM: The study aimed to evaluate the compressive strength and surface hardness of a type V dental stone after hypochlorite disinfection. MATERIALS AND METHODS: Two types of specimens were made according to the American Dental Association (ADA) specification no. 25 for each wet compressive strength, dry compressive strength, and surface hardness. The specimens were split into three groups with 30 samples each according to the type of disinfection. All specimens were immersed in their respective disinfecting solutions for 30 minutes at room temperature and after removal, they were left to dry for 24 hours at room temperature. Total five cycles of immersion and drying were followed. A compressive strength test was done using a universal testing machine. Wet compressive strength was tested one hour after the last cycle and dry compressive strength was tested 7 days after the last cycle. Surface hardness was measured after 48 hours using Vickers hardness test. The results were statistically analyzed. RESULTS: There was a statistical difference between the calcium hypochlorite and sodium hypochlorite groups for both dry and wet compressive strength. The mean wet compressive strength of calcium hypochlorite was higher when compared to the sodium hypochlorite group and it was statistically significant (p = 0.042). The results were similar and statistically significant (p = 0.003) for dry compressive strength. When the mean surface hardness of the sodium hypochlorite (As) group was compared to calcium hypochlorite the results were highly significant (p = 0.0001) with the mean surface hardness of the calcium hypochlorite group more than the sodium hypochlorite group. CONCLUSION: Calcium hypochlorite used as a disinfectant showed better compressive strength and surface hardness when compared to sodium hypochlorite as a disinfectant. CLINICAL SIGNIFICANCE: Dental casts poured in the contaminated impressions which might not be disinfected at all or properly. They also come in contact with the prosthesis that might be tried inside the patient's mouth and sent to a lab for corrections without disinfecting the cast causing cross-contamination between patients, dentists, and laboratory personnel. However, immersion disinfection with sodium or calcium hypochlorite might affect important properties of the cast. Any negative effect on the mechanical or physical properties of the cast will affect the final outcome of the prosthesis.

Infectious causes of acute encephalitis syndrome hospitalizations in Central India, 2018-20.

BACKGROUND: We enhanced surveillance of hospitalizations of all ages for acute encephalitis syndrome (AES) along with infectious aetiologies, including the Japanese encephalitis virus (JEV). METHODS: From October 2018 to September 2020, we screened neurological patients for AES in all age groups in Maharashtra and Telangana States. AES cases were enrolled at study hospitals along with other referrals and sampled with cerebrospinal fluid, acute and convalescent sera. We tested specimens for non-viral aetiologies viz. leptospirosis, typhoid, scrub typhus, malaria and acute bacterial meningitis, along with viruses - JEV, Dengue virus (DENV), Chikungunya virus (CHIKV), Chandipura virus (CHPV) and Herpes simplex virus (HSV). RESULTS: Among 4977 neurological hospitalizations at three study site hospitals over two years period, 857 (17.2%) were AES. However, only 287 (33.5%) AES cases were eligible. Among 278 (96.9%) enrolled AES cases, infectious aetiologies were identified in 115 (41.4%) cases, including non-viral in 17 (6.1%) cases - leptospirosis (8), scrub-typhus (3) and typhoid (6); and viral in 98 (35.3%) cases - JEV (58, 20.9%), HSV (22, 7.9%), DENV (15, 5.4%) and CHPV (3, 1.1%). JEV confirmation was significantly higher in enrolled cases than referred cases (10.2%) (p < 0.05). However, the contribution of JEV in AES cases was similar in both children and adults. JE was reported year-round and from adjacent non-endemic districts. CONCLUSIONS: The Japanese encephalitis virus continues to be the leading cause of acute encephalitis syndrome in central India despite vaccination among children. Surveillance needs to be strengthened along with advanced diagnostic testing for assessing the impact of vaccination.

Long-acting and extended-release implant and nanoformulations with a synergistic antiretroviral two-drug combination controls HIV-1 infection in a humanized mouse model.

The HIV pandemic has affected over 38 million people worldwide with close to 26 million currently accessing antiretroviral therapy (ART). A major challenge in the long-term treatment of HIV-1 infection is nonadherence to ART. Long-acting antiretroviral (LA-ARV) formulations, that reduce dosing frequency to less than once a day, are an urgent need that could tackle the adherence issue. Here, we have developed two LA-ART interventions, one an injectable nanoformulation, and the other, a removable implant, for the delivery of a synergistic two-drug ARV combination comprising a pre-clinical nonnucleoside reverse transcriptase inhibitor (NNRTI), Compound I, and the nucleoside reverse transcriptase inhibitor (NRTI), 4'-ethynyl-2-fluoro-2'-deoxyadenosine. The nanoformulation is poly(lactide-co-glycolide)-based and the implant is a copolymer of ω-pentadecalactone and p-dioxanone, poly(PDL-co-DO), a novel class of biocompatible, biodegradable materials. Both the interventions, packaged independently with each ARV, released sustained levels of the drugs, maintaining plasma therapeutic indices for over a month, and suppressed viremia in HIV-1-infected humanized mice for up to 42 days with maintenance of CD4+ T cells. These data suggest promise in the use of these new drugs as LA-ART formulations in subdermal implant and injectable mode.

The prominence of potential biomarkers in the diagnosis and management of hepatocellular carcinoma: Current scenario and future anticipation.

Hepatocellular carcinoma (HCC) is one of the most aggressive and truculent types of cancer. Early detection of HCC is a massive concern that can boost the overall survival rates of HCC patients. As a result, there is a continual quest for advancements in screening, diagnosis, and treatment strategies to enhance the prognosis at its early stages. However, the confluence of inflammation and cirrhosis hampers the early detection of HCC. The analysis of different types of biomarkers such as tissue biomarkers, serum biomarkers, protein biomarkers, autoantibody markers, and improved imaging techniques has played a vital role in ameliorating HCC monitoring responses. Therefore biomarkers that can identify HCC early with a high degree of sensitivity and specificity might be prodigiously serviceable in the diagnosis and treatment of this notorious disorder. This study offers an overview of the contemporary understanding of several types of biomarkers implicated in hepatocarcinogenesis and their applications in monitoring, diagnosis, and prognosis presage. In additament, we address the role of image techniques associated with HCC diagnosis.

Development of improved strain in species of Pleurotus by gamma irradiation.

The oyster mushroom (Pleurotus spp.) is the second important edible mushroom in the world, with 19 per cent contribution to total mushroom production (Sharma et al., Mushroom Res 26(2):111-120, 2017). The cultivated mushrooms face the problems like loss of genetic diversity and strain degeneration (Wang et al., Curr Microbiol 65(4):424-431, 2012). Thus to enhance the productivity within short duration, three species of Pleurotus namely Pleurotus djamor, Pleurotus florida and Pleurotus ostreatus were gamma irradiated at 20 and 25 Gy at 9.779 kGy/h and performance of mutants followed by three generation of selection in paddy straw substrate were observed. Biological efficiency (BE) of P. djamor mutants irradiated at 20 Gy was increased by 9.25 per cent. The number of days taken for primordial initiation was also reduced by 1 day compared to P. djamor. P. florida irradiated at 25 Gy recorded increase in sporocarp size over P. florida. The biological efficiency of P. ostreatus irradiated at 25 Gy was improved by 12.89 per cent and there was earliness in primordial initiation by 3 days compared to P. ostreatus. The polymorphism per cent was analysed by Random Amplified Polymorphic DNA (RAPD) and revealed that P. djamor, P. florida and P. ostreatus had 16.70%, 25% and 22% polymorphism with their respective improved strains.

Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir.

Small CD4-mimetic compounds (CD4mc) sensitize HIV-1-infected cells to antibody-dependent cellular cytotoxicity (ADCC) by facilitating antibody recognition of epitopes that are otherwise occluded on the unliganded viral envelope (Env). Combining CD4mc with two families of CD4-induced (CD4i) antibodies, which are frequently found in plasma of HIV-1-infected individuals, stabilizes Env in a conformation that is vulnerable to ADCC. We employed new-generation SRG-15 humanized mice, supporting natural killer (NK) cell and Fc-effector functions to demonstrate that brief treatment with CD4mc and CD4i-Abs significantly decreases HIV-1 replication, the virus reservoir and viral rebound after ART interruption. These effects required Fc-effector functions and NK cells, highlighting the importance of ADCC. Viral rebound was also suppressed in HIV-1+-donor cell-derived humanized mice supplemented with autologous HIV-1+-donor-derived plasma and CD4mc. These results indicate that CD4mc could have therapeutic utility in infected individuals for decreasing the size of the HIV-1 reservoir and/or achieving a functional cure.

Delaying clozapine: how long is too long?

BACKGROUND: Although clozapine is the most effective drug for treatment-resistant schizophrenia, its use remains restricted in clinical practice in India. The delay in initiating treatment with clozapine and its impact on disease outcome needs evaluation. AIM: To identify the implications of delaying clozapine initiation in clinical outcomes among people with treatment-resistant schizophrenia. METHODS: Subjects with treatment-resistant schizophrenia, stabilised on clozapine monotherapy, were recruited from the outpatient clinic of a general hospital psychiatry unit offering tertiary care services in Thrissur district, Kerala, India. A retrospective cohort design was employed, and information on duration of illness, total duration of treatment and duration of treatment with clozapine was collected. Present symptom status was measured using the Positive and Negative Syndrome Scale. Factors associated with higher symptom scores were analysed using an independent sample t test, Spearman correlation and multiple linear regression. RESULTS: Forty subjects stabilised on long-term clozapine therapy formed the study sample. The mean dose of clozapine used in the study population was 200 mg. The mean duration of antipsychotic treatment before starting clozapine was 89.3 months (7.4 years). The duration of treatment before starting clozapine was found to have a significant positive association with the total Positive and Negative Syndrome Scale score (correlation coefficient 0.40; p=0.01) and negative symptom score (correlation coefficient 0.33; p=0.04). The multiple regression analysis adjusting for covariates showed that the duration of treatment before starting clozapine was an independent factor associated with a higher negative symptom score in the Positive and Negative Syndrome Scale (slope ß=0.05; p=0.02; R2=0.27). CONCLUSION: Poor treatment outcomes in treatment-resistant schizophrenia could be secondary to a delay in initiating clozapine therapy.

Microwave-assisted synthesis, biological evaluation and molecular docking studies of new coumarin-based 1,2,3-triazoles.

Coumarin-based 1,4-disubstituted 1,2,3-triazole derivatives were synthesized using a highly efficient, eco-friendly protocol via a copper(i)-catalyzed click reaction between various substituted arylazides and terminal alkynes. The synthetic route was easy to access and gave excellent yields under microwave irradiation conditions compared to the conventional heating route. The structures of all the compounds were characterized by IR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. All the synthesized compounds were screened for their in vitro antimicrobial, antioxidant and anti-inflammatory activities; among all compounds, 8a, 8j, 8k and 8l exhibited better results with respect to standard drugs. Furthermore, molecular docking studies have been carried out with PDB IDs 2VCX (anti-inflammatory), 3VXI (antioxidant), 4GEE (antimicrobial) and 2XFH (antifungal) using the Glide module of the Schrödinger suite. The final compounds 8d, 8e, 8h, and 8k showed the highest hydrogen bond interactions with His-88 and Val-191 proteins and with water in all the proteins.

Needs and perceptions regarding healthy eating among people at risk of food insecurity: a qualitative analysis.

BACKGROUND: Healthy eating behaviour is an essential determinant of overall health. This behaviour is generally poor among people at risk of experiencing food insecurity, which may be caused by many factors including perceived higher costs of healthy foods, financial stress, inadequate nutritional knowledge, and inadequate skills required for healthy food preparation. Few studies have examined how these factors influence eating behaviour among people at risk of experiencing food insecurity. We therefore aimed to gain a better understanding of the needs and perceptions regarding healthy eating in this target group. METHODS: We conducted a qualitative exploration grounded in data using inductive analyses with 10 participants at risk of experiencing food insecurity. The analysis using an inductive approach identified four core factors influencing eating behaviour: Health related topics; Social and cultural influences; Influences by the physical environment; and Financial influences. RESULTS: Overall, participants showed adequate nutrition knowledge. However, eating behaviour was strongly influenced by both social factors (e.g. child food preferences and cultural food habits), and physical environmental factors (e.g. temptations in the local food environment). Perceived barriers for healthy eating behaviour included poor mental health, financial stress, and high food prices. Participants had a generally conscious attitude towards their financial situation, reflected in their strategies to cope with a limited budget. Food insecurity was mostly mentioned in reference to the past or to others and not to participants' own current experiences. Participants were familiar with several existing resources to reduce food-related financial strain (e.g. debt assistance) and generally had a positive attitude towards these resources. An exception was the Food Bank, of which the food parcel content was not well appreciated. Proposed interventions to reduce food-related financial strain included distributing free meals, facilitating social contacts, increasing healthy food supply in the neighbourhood, and lowering prices of healthy foods. CONCLUSION: The insights from this study increase understanding of factors influencing eating behaviour of people at risk of food insecurity. Therefore, this study could inform future development of potential interventions aiming at helping people at risk of experiencing food insecurity to improve healthy eating, thereby decreasing the risk of diet-related diseases.

Ru(II)-Catalyzed C-H Activation/Alkylation of 3-Formylbenzofurans with Conjugated Olefins: Product Divergence.

Ru-catalyzed alkylation of 3-formylbenzofuran with acrylates and acrylamides has been described. Branched selectivity with unsubstituted or ß-substituted acrylates/acrylamides and linear selectivity with α-substituted acrylates have been observed. However, in all of the cases, the intermediate alkylation products seem to undergo further reactions, either cycloannulation or deformylation, depending on the substrate employed. For example, with methyl acrylate, the intermediate branched alkylation product underwent cycloannulation with another molecule of methyl acrylate, resulting in a densely functionalized cyclohexene ring formation. On the other hand, in the case of N-monosubstituted acrylamides, the branched alkylation proceeded with intramolecular aldehyde-amide condensation, leading to pyridin-2-one ring annulation. However, with both methacrylate and crotonate, deformylation of the initially formed alkylation products was observed.

Development and application of genomic resources for comparative and translational genomics in legumes through leveraging genomic sequence of Medicago truncatula.

The expressed sequence tags (ESTs) of common bean were BLAST aligned with barred medic genome sequence and developed 1196 conserved intron spanning primers (CISPs) to facilitate genetic studies in legumes. Randomly selected 288 CISPs, representing loci on barrel medic genome, were tested on 10 selected members of legume family. On the source taxa, the highest single copy amplification success rates of 61.8% (barrel medic) and 56.2% (common bean) was obtained. The success rate of markers was 54.5% in cowpea followed by 53.5% in pigeonpea and chickpea, signifying cross taxon amplification and their potential use in comparative genomics. However, relatively low percentages of primer set amplified (40-43%) in soybean, urdbean and peanut. Further, these primers were tested on different varieties of chickpea, pigeonpea and cowpea. The PCR products were sequenced and aligned which resulted in detection of 26 SNPs and eight INDeLs in cowpea, seven SNPs and two INDeLs in chickpea and 27 SNPs and 14 INDeLs in pigeonpea. These SNPs were successfully converted in to size variation for gel-based genotyping. The CISP markers developed in this study are expected to aid in map saturation of legumes and in marker-assisted selection for accelerated crop improvement.

Flexural Strength of Surface-Treated Heat-Polymerized Acrylic Resin after Repair with Aluminum Oxide-Reinforced Autopolymerizing Acrylic Resin.

BACKGROUND: A fracture of denture base in situ often occurs through a fatigue mechanism, which over a period of time leads to the formation of small cracks, resulting in fracture. AIM AND OBJECTIVE: To evaluate the flexural strength of repaired heat-polymerized acrylic resin, with different percentage of aluminum oxide (Al2O3) added to the repair resin and effect of two different surface treatments on the flexural strength of repaired heat-polymerized acrylic resin and also to evaluate quantification of filler particles using scanning electron microscopy. MATERIALS AND METHODOLOGY: Fifty specimens of heat-polymerized acrylic resin were prepared according to the American Dental Association specification no. 12 (65 mm × 10 mm × 2.5 mm). Al2O3<50 nm particle size was silanized using metal alloy primer before incorporation in polymer. Two different percentages of Al2O3 nanoparticles, that is, 1% and 1.5% were added to autopolymerizing acrylic resin which was used as repairing material. RESULTS: The study showed that repair resin incorporated with 1.5% Al2O3 in the group surface treated with silicon carbide paper improved the flexural strength of denture base resin. A proper filler distribution and deep penetration within the polymer matrix were observed by scanning electron microscope in the same group.

Comparing the Efficiency of Two Different Extraction Techniques in Removal of Maxillary Third Molars: A Randomized Controlled Trial.

INTRODUCTION: Extractions are routine procedures in dental surgery. Traditional extraction techniques use a combination of severing the periodontal attachment, luxation with an elevator, and removal with forceps. A new technique of extraction of maxillary third molar is introduced in this study-Joedds technique, which is compared with the conventional technique. METHODS AND MATERIAL: One hundred people were included in the study, the people were divided into two groups by means of simple random sampling. In one group conventional technique of maxillary third molar extraction was used and on second Joedds technique was used. Statistical analysis was carried out with student's t test. RESULTS: Analysis of 100 patients based on parameters showed that the novel joedds technique had minimal trauma to surrounding tissues, less tuberosity and root fractures and the time taken for extraction was <2 min while compared to other group of patients. CONCLUSION: This novel technique has proved to be better than conventional third molar extraction technique, with minimal complications. If Proper selection of cases and right technique are used.

Erratum to: Comparing the Efficiency of Two Different Extraction Techniques in Removal of Maxillary Third Molars: A Randomized Controlled Trial.

[This corrects the article DOI: 10.1007/s12663-016-0935-1.].

Inhibition of Carbonyl Reductase 1 Safely Improves the Efficacy of Doxorubicin in Breast Cancer Treatment.

AIMS: Doxorubicin (DOX) is a chemotherapeutic drug that is used to treat many cancers, but its use is limited by cardiotoxic side effect. Carbonyl reductase 1 (CBR1) is an NADPH-dependent oxidoreductase that reduces DOX to doxorubicinol (DOXOL), a less potent derivative that is responsible for DOX cardiotoxicity. Thus, we aimed to demonstrate that inhibition of CBR1 enhances the chemotherapeutic efficacy of DOX and attenuates cardiotoxicity. RESULTS: Pharmacological or genetic inhibition of CBR1 improved the anticancer effects of DOX in preclinical models of breast cancer. RNA interference or chemical inhibition of CBR1 improved the anticancer effect of DOX in breast cancer. Moreover, CBR1 overexpression enabled breast cancer cells to obtain chemotherapeutic resistance to DOX treatment. Intriguingly, inhibition of CBR1 decreased DOX-induced cardiotoxicity in animal model. Innovation and Conclusions: Inhibition of CBR1 increases chemotherapeutic efficacy of DOX and reduces cardiotoxicity by blocking DOX reduction to DOXOL. Therefore, we offer preclinical proof-of-concept for a combination strategy to safely leverage the efficacy of doxorubicin by blunting its cardiotoxic effects that limit use of this cytotoxic agent used widely in the oncology clinic. Antioxid. Redox Signal. 26, 70-83.

A case of adrenoleukodystrophy presenting with manic symptoms in a patient on steroids for Addison's disease.

Adrenoleukodystrophy (ALD) is an X-linked disorder with diverse clinical presentations. A 30-year-old male, previously diagnosed with Addison's disease, on steroid supplementation for 18 years, presented to us with manic symptoms for 4 years. He was found to have white matter hypodensities in computed tomography head and had white matter signal changes in magnetic resonance imaging, and therefore a diagnosis of ALD was made.

Identification and introgression of QTLs implicated in resistance to sorghum downy mildew (Peronosclerospora sorghi (Weston and Uppal) C. G. Shaw) in maize through marker-assisted selection.

Sorghum downy mildew caused by Peronosclerospora sorghi is a major disease of maize and resistance is under the control of polygenes which necessitated identification of quantitative-trait loci (QTLs) for initiating marker-assisted introgression of resistant QTLs in elite susceptible inbred lines. In the present study, QTLs for sorghum downy mildew (SDM) resistance in maize were identified based on cosegregation with linked simple sequence repeats in 185 F2 progeny from a cross between susceptible (CM500-19) and resistant (MAI105) parents. F3 families were screened in the National Sorghum Downy Mildew Screening Nursery during 2010 and 2011. High heritability was observed for the disease reaction. The final map generated using 87 SSR markers had 10 linkage groups, spanning a length of 1210.3 cM. Although, we used only 87 SSR markers for mapping, the per cent of genome within 20 cM to the nearest marker was 88.5. Three putative QTLs for SDM resistance were located on chromosomes 3 (bin 3.01), 6 (bin 6.01) and 2 (bin 2.02) using composite interval mapping. The locus on chromosome 3 had a major effect and explained up to 12.6% of the phenotypic variation. The other two QTLs on chromosomes 6 and 2 had minor effects with phenotypic variation of 7.1 and 2%. The three QTLs appeared to have additive effects on resistance. The QTLs on chromosomes 3 and 6 were successfully used in the marker-assisted selection programme for introgression of resistance to SDM in eight susceptible maize lines.

Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication.

Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.