Identification of Rhizobia Isolated from Nodules of Mexican Commercial Soybean Varieties

Rhizobia, crucial for nitrogen fixation in leguminous plants, play a vital role in soybean cultivation. This study, conducted in Mexico, a major soybean importer, aimed to identify bacteria from nodules of five soybean varieties in high-production regions. Multilocus sequence analysis (MLSA) was employed for enhanced species resolution. The study identified six Bradyrhizobium species: Bradyrhizobium japonicum USDA 110, Bradyrhizobium japonicum USDA 6, Bradyrhizobium elkanii USDA 76, Bradyrhizobium neotropicale, Bradyrhizobium lablabi, and Bradyrhizobium icense. Bradyrhizobium japonicum USDA 110 predominated in the soils, displaying symbiotic preference for the Huasteca 400 variety. However, phylogenetic analysis didn't reveal a clear association between strains, soil, and soybean variety. This research sheds light on the diversity of rhizobia in Mexican soybean cultivation, contributing to the understanding of symbiotic relationships in soybean production systems.

Differential Expression of Genes Related to Fruit Development and Capsaicinoids Synthesis in Habanero Pepper Plants Grown in Contrasting Soil Types

Habanero pepper(Capsicum chinense Jacq.)is a crop of economic relevance in the Peninsula of Yucatan.Its fruits have a high level of capsaicinoids compared to peppers grown in other regions of the world,which gives them industrial importance.Soil is an important factor that affects pepper development,nutritional quality,and capsaicinoid content.However,the effect of soil type on fruit development and capsaicinoid metabolism has been little understood.This work aimed to compare the effect of soils with contrasting characteristics,black soil(BS)and red soil(RS),on the expression of genes related to the development of fruits,and capsaicinoid synthesis using a transcriptomic analysis of the habanero pepper fruits.Plants growing in RS had bigger fruits and higher expression of genes related to floral development,fruit abscission,and softening which suggests that RS stimulates fruit development from early stages until maturation stages.Fruits from plants growing in BS had enrichment in metabolic pathways related to growth,sugars,and photosynthesis.Besides,these fruits had higher capsaicinoid accumulation at 25 days post-anthesis,and higher expression of genes related to the branched-chain amino acids metabolism(ketol-acid reductisomerase KARI),pentose phosphate pathway and production of NADPH(glucose-6-phosphate-1-dehydrogenase G6PDH),and proteasome and vesicular traffic in cells(26S proteasome regulatory subunit T4 RPT4),which suggest that BS is better in the early stimulation of pathways related to the nutritional quality and capsaicinoid metabolism in the fruits.

Exploring multifaceted factors in chronic kidney disease risk: A comprehensive analysis of biochemistry, lifestyle, and inflammation in elderly Chinese individuals

This letter praises a recent article in the World Journal of Clinical Cases(Roles of biochemistry data,lifestyle,and inflammation in identifying abnormal renal function in old Chinese),examining factors affecting abnormal renal function in elderly Chinese using advanced machine learning.It highlights the importance of uric acid,age,hemoglobin,body mass index,sport hours,and systolic blood pressure.The study's holistic approach,integrating lifestyle and inflammation,offers a nuanced understanding of chronic kidney disease risk factors.The letter suggests exploring mechanistic pathways of hyperuricemia,the link between anemia and renal function,and the connection between body mass index and estimated glomerular filtration rate.It advocates investigating physical activity's impact on renal health and the independent effects of blood pressure.The study significantly contributes to chronic kidney disease understanding,proposing avenues for further exploration and interventions.Commendations are extended to the authors and the journal.

Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.

QTL analysis for ascorbic acid content in strawberry fruit reveals a complex genetic architecture and association with GDP-L-galactose phosphorylase

Strawberry(Fragaria×ananassa)fruits are an excellent source of L-ascorbic acid(AsA),a powerful antioxidant for plants and humans.Identifying the genetic components underlying AsA accumulation is crucial for enhancing strawberry nutritional quality.Here,we unravel the genetic architecture of AsA accumulation using an F1 population derived from parental lines‘Candonga’and‘Senga Sengana’,adapted to distinct Southern and Northern European areas.To account for environmental effects,the F1 and parental lines were grown and phenotyped in five locations across Europe(France,Germany,Italy,Poland and Spain).Fruit AsA content displayed normal distribution typical of quantitative traits and ranged five-fold,with significant differences among genotypes and environments.AsA content in each country and the average in all of them was used in combination with 6,974 markers for quantitative trait locus(QTL)analysis.Environmentally stable QTLs for AsA content were detected in linkage group(LG)3A,LG 5A,LG 5B,LG 6B and LG 7C.Candidate genes were identified within stable QTL intervals and expression analysis in lines with contrasting AsA content suggested that GDP-L-Galactose Phosphorylase FaGGP(3A),and the chloroplast-located AsA transporter gene FaPHT4;4(7C)might be the underlying genetic factors for QTLs on LG 3A and 7C,respectively.We show that recessive alleles of FaGGP(3A)inherited from both parental lines increase fruit AsA content.Furthermore,expression of FaGGP(3A)was two-fold higher in lines with high AsA.Markers here identified represent a useful resource for efficient selection of new strawberry cultivars with increased AsA content.

Calcitriol induces post-thawed bovine sperm capacitation

Background:Capacitation is a set of physiological changes sperms undergo to acquire fertilizing capacity.In vivo,this process is directly associated with high calcium levels in sperm cytoplasm.Calcitriol,the vitamin D hypercalcemic metabolite,is related to human sperm motility,capacitation,and acrosome reaction.This work aimed to study the effect of calcitriol on bull sperm quality parameters and capacitation.Methods:One million freezethawed spermatozoa were obtained from different bulls and treated with 20 nM of calcitriol for 30 min.Untreated cells(negative control)and treated ones with calcitriol or heparin(100μg/mL,positive capacitation control)were evaluated for motility,viability,and functional parameters.Menadione(70μM,30 min)treatment was included as a reactive oxygen species(ROS)positive sperm agent.Results:The results elucidated that sperm exposed to 20 nM calcitriol showed higher viability,vigor,and capacitation than their positive and negative controls.The percentage of sperm with intact plasma and acrosome membranes,mitochondrial membrane potential(ΔΨm),and phosphatidylserine externalization was similar in all the conditions evaluated,while ROS production was higher with heparin and menadione-treated groups than the calcitriol group or negative control.Conclusion:Our results indicate that calcitriol induces the capacitation of thawed bull spermatozoa and maintains acceptable values of progressive motility,viability,and vigor without altering key biological parameters such as redox status,ΔΨm,and cell death.

Litter buffet:On the use of trash bins by birds in six boreal urban settlements

Unintentional food resources in urban areas(street litter,food leftovers,overflowing trash bins)are dietary components of some urban-exploiter bird species.In this study,we report on 13 bird species in six southern Finnish cities using urban trash bins and describe differences in their activity when provided with food resources(i.e.,bait)in different bin types.We used generalized linear models(GLM)and classification and regression trees(CART)to test for associations between environmental variables and bird activity at the binscapes.Bird activity at the binscapes significantly differed among all cities and among types of bins and was significantly higher after placing bait in all cases.Bins with the largest opening had more activity as opposed to those with smaller openings or lids.Corvids and gulls had the highest activity,with corvids usually being present before the bait was placed and gulls increasing their activity thereafter.These differences show that trash bin foraging is highly malleable and thus susceptible to management preventing its occurrence.Suitable waste management measures could aid in reducing the number of species close to bins and their surroundings,benefiting both bird and human health.

In vitro Mutagenesis for the Improvement of Agave Genus

Biotechnological techniques provide a viable alternative to help improve and increase the production of plant species of agricultural and economic importance,which have been affected over the years by climate change,increasing their susceptibility to pests and/or diseases,generating losses in production as well as a decrease in their regenerative and genetic diversity.The application of biotechnological techniques such as in vitro mutagenesis offers a viable option for the generation of crops that are resistant to the different factors caused by abiotic and biotic stress.In vitro mutagenesis has been used in an efficient way to generate genetic changes in different plant species.However,these methods have not been studied thoroughly in crops of agro-industrial interest,such as agave,which represents an economic resource of national importance and are considered as endemic species of Mexico.Therefore,this literary review aimed to focus on the studies that have been used for the genetic improvement of this species via mutagenesis techniques in plants in the agave genus.Therefore,the objective was to set a precedent for future genetic studies that aim to obtain more productive regenerants for various industries,such as food and pharmaceutical.It is also of great interest to compile information from basic research that helps understand and elucidate a model of possible defense mechanisms that are activated in the Agave genus.

Effects of Plant Extracts and Beauveria bassiana on the Activity of Defense-Related Enzymes in Solanum lycopersicum L.during Interaction with Fusarium oxysporum f.sp.lycopersici

The objective to this work was to evaluate the enzymatic activity in the culture of Solanum lycopersicum L.infected with Fusarium oxysporum after the combined application of Beauveria bassiana and plant extracts.Solanum lycopersicum plantlets were transplanted 15 days after the emergency.Five days after transplanting,Beauveria bassiana spores were applied at a concentration of 1×10^(7)spores mL^(−1)onto soil(along with A.indica(N)and P.auritum(H)leaf extracts)where S.lycopersicum plants were planted.Eight days after transplanting,spores of F.oxysporum strain were applied at a concentration of 1×10^(6)spores mL^(−1)to soil where S.lycopersicum plants were growing.The development of S.lycopersicum plants was monitored for 114 days,whereby a randomized complete block treatment design was used,the roots of the plants were crushed with liquid nitrogen,after which UV/VIS spectrophotometry was used to determine protein concentration,as well as the activity ofβ-1,3-glucanases,peroxidases(POX,EC1.11.1.7),catalase and chitinases.The treatments combining B.bassiana and A.indica and P.auritum extracts,had a significant difference in enzymatic activity levels,thus contributing to better defense mechanisms and a greater protection to S.lycopersicum plants in the presence of F.oxysporum.The application of B.bassiana and plant extracts to the ground mitigated damage caused by F.oxysporum on S.lycopersicum plants.

Antifungal Potential of Beauveria bassiana on Solanum lycopersicum L. Infected with Fusarium oxysporum f. sp. lycopersici

The objective of this work was to evaluate the effect of Beauveria bassiana(Bb 1205)on controlling Fusarium oxysporum f.sp.lycopersici(Fol 17108)in tomato plants in greenhouse conditions.Inoculation of Bb 1205 was the most promising among the agronomic variables and expression of the activity of the enzymesβ-1,3-glucanases and chitinases.Inoculation of Bb 1205 occurred at a concentration of 1×108 conidia·mL−1,which was administered onto the leaves,directly into the soil and via injection.Infection with Fol 17108 occurred with 1×106 spores·mL−1,which were added directly to the soil.Spectrophotometry was used for measuring agronomic parameters,namely activity of chitinases andβ-1,3-glucanases in foliage and roots.When Bb 1205 was added to the soil,the chlorophyll index and aerial part length showed significant differences.In addition,it was determined that root length,fresh weight of foliage,flower,and fruit count increased 82 days after inoculation(dai).Chitinase activity induced by Bb 1205 in leaves and roots of tomato plants infected with Fol 17108 was observed when injected into the stem at 32 dai(41.8 and 11.6-fold,respectively).Inoculation on the foliage showed a 10-fold increase ofβ-1,3-glucanases in the roots after 82 dpi.As for leaves,a 3.8-fold increase was found when the stem was inoculated.In the different in vivo applications,Bb 1205 activated its defenses by expressing the chitinase enzymes andβ-1,3-glucanase,thus reducing the damage caused by Fol 17108,demonstrating increase plant growth thereafter.

The best of both worlds:mastering nerve regeneration combining biological and nanotechnological tools

Over the last decade,remarkable developments in nanotechnology have powered medical research,unveiling new approaches for the solution of public health issues such as the treatment of traumatic peripheral neuropathies.

Effect of Water Stress Induced by Polyethylene Glycol on Growth, Proline Accumulation in Agave americana L.

The effect of water deficit was determined on both in vitro and soil seedling as well as in cells in suspension of Agave americana L.In order to do the establishment of cells,the formation of callus was induced;for it two auxins were evaluated:2,4-dichlorophenoxyacetic acid(2,4-D)and 4-mino-3,5,6-trichloropicolinic acid(picloram)at three concentrations(0.25,0.5 and 0.75 mg L−1)in three explants(leaf,root and meristems)cultured in MS semisolid medium.The callogenesis response was related to the type and section of the explant,as well as the regulator used,and a cell suspension was established using 0.5 mg L−1 naphthaleneacetic acid(NAA)+0.5 mg L−1 Benzylaminopurine(BAP).Seedlings were exposed to polyethyleneglycol(15%and 30%w/v)with a water potential of−0.87 and−2.67 MPa,respectively,under soil conditions.Water stress was applied through restricted irrigation.Fresh weight,root system growth,and chlorophyll concentration were some of the parameters that were affected by the effect of water deficit on A.americana L.Chlorophyll concentration values were significantly decreased by 15 at 30%PEG(19.6 SPAD units)compared to the control treatment.In in vitro plants,the highest concentration of proline was found in the roots,being the treatment with 30%polyethylene glycol where the highest concentration of this osmoregulator was obtained(62.5 mg g−1 DW).Under restricted irrigation conditions,an increase in proline concentration was observed both in the aerial part(2.2μg 100 g−1 DW)and in the root system(1.8μg 100 g−1 DW).However,the concentrations found were approximately ten times greater,less than those found under in vitro conditions.Therefore,the accumulation of proline can be considered an indicator of stress in Agave Americana L.growth in vitro.

ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease

AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34.16% vs 41.58% (P = 0.124) for X+of ApoB-100; 4.46% vs 5.94% (P = 0.501) for E2, 85.64% vs 78.22% (P = 0.052) for E3, 9.90% vs 15.84% (P = 0.075) for E4 of ApoE; and 25.74% vs 27.72% (P = 0.653) for C of CYP7A1. Differences in genotypic frequencies between the studied groups were not significant (P < 0.05). CONCLUSION: These results demonstrated that no association exists between the studied polymorphisms and cholelithiasis in this high prevalent population.

Cancer stem cell impact on clinical oncology

Cancer is a widespread worldwide chronic disease. In most cases, the high mortality rate from cancer correlates with a lack of clear symptoms, which results in late diagnosis for patients, and consequently, advanced tumor disease with poor probabilities for cure, since many patients will show chemo-and radio-resistance. Several mechanisms have been studied to explain chemo-and radio-resistance to anti-tumor therapies, including cell signaling pathways, anti-apoptotic mechanisms, stemness, metabolism, and cellular phenotypes. Interestingly, the presence of cancer stem cells(CSCs), which are a subset of cells within the tumors, has been related to therapy resistance. In this review, we focus on evaluating the presence of CSCs in different tumors such as breast cancer, gastric cancer, lung cancer, and hematological neoplasias, highlighting studies where CSCs were identified in patient samples. It is evident that there has been a great drive to identify the cell surface phenotypes of CSCs so that they can be used as a tool for anti-tumor therapy treatment design. We also review the potential effect of nanoparticles, drugs, natural compounds, aldehyde dehydrogenase inhibitors, cell signaling inhibitors, and antibodies to treat CSCs from specific tumors. Taken together, we present an overview of the role of CSCs in tumorigenesis and how research is advancing to target these highly tumorigenic cells to improve oncology patient outcomes.

Insights into the role of major bioactive dietary nutrients in lamb meat quality:a review

Feed supplementation withα-linolenic acid(ALA)and linoleic acid(LA)increases their content in muscle,ALA increases n-3 polyunsaturated fatty acids and decrease n-6/n-3 ratio in muscle,and LA increases rumenic acid.However,high LA supplementation may have negative effects on lambs’lipid oxidative stability of meat.When the sources of ALA and LA are fed as fresh forage,the negative effects are counterbalanced by the presence of other bioactive compounds,as vitamin E(mainlyα-tocopherol)and polyphenols,which delay the lipid oxidation in meat.There is a wide consensus on the capability of vitamin E delaying lipid oxidation on lamb meat,and its feed content should be adjusted to the length of supplementation.A high dietary inclusion of proanthocyanidins,phenolic compounds and terpenes reduce the lipid oxidation in muscle and may improve the shelf life of meat,probably as a result of a combined effect with dietary vitamin E.However,the recommended dietary inclusion levels depend on the polyphenol type and concentration and antioxidant capacity of the feedstuffs,which cannot be compared easily because no routine analytical grading methods are yet available.Unless phenolic compounds content in dietary ingredients/supplements for lambs are reported,no specific association with animal physiology responses may be established.

本地混合菌群微生物氧化难处理含金硫化精矿（英文）

采用含铁氧化菌和硫氧化菌的混合嗜中温菌群浸出阿根廷Andacollo矿的含金硫化浮选精矿。实验在摇瓶中进行,矿浆浓度为10%,采用pH 1.8的含亚铁离子的基础盐溶液作为介质。采用不同的方法对浸出液的pH值、氧化还原电位、亚铁离子和总金属浓度进行测定。结果表明,该种混合菌能够很好地还原浸出该难处理金矿,金的回收率可达91.6%,同时,铜和锌的浸出率也较高。动力学研究表明金属的溶解符合收缩核模型。其中,铜的溶解速率受生成产物层的扩散控制,而锌的溶解没有明显的控制步骤。

Adhesion of <i>Gallibacterium anatis</i>to Chicken Oropharyngeal Epithelial Cells and the Identification of Putative Fimbriae

Microbial infections are typically initiated by the colonization of tissues by a specific mechanism that promotes adherence to host cells or tissues. In this work, we characterized the ability of Gallibacterium anatis F149T to express fimbriae that may be involved in mucosal attachment. Using transmission electron microscopy, the fimbriae-like structures could be observed on the surface of negatively stained G. anatis F149T, and these structures were further visualized after being released by physical shaking. When the fimbriae-like structures were separated by SDS-PAGE, the proteins comprising them were isolated and sized at 13 and 25 kDa. G. anatis F149T was able to adhere to chicken oropharyngeal epithelial cells. Adhesion could be completely inhibited by pretreatment of the bacterial cells with trypsin, whereas 25% inhibition was attained after pretreatment with an antiserum against the 13 kDa protein. We demonstrated by immuno-gold electron microscopy that the antibodies from the antiserum were specifically associated with the fimbria-like structures on G. anatis. These results indicated that G. anatis F149T expresses fimbriae that contribute to its adhesion to chicken oropharyngeal epithelial cells and may be important for colonization of the upper respiratory tract.

Role of platelets and breast cancer stem cells in metastasis

The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells,resistance to chemotherapy and radiotherapy,and tumor regression capacity.In recent years,it has been shown that the presence of breast cancer stem cells is closely associated with the migration and metastatic ability of cancer cells,as well as with their resistance to chemotherapy and radiotherapy.The tumor microenvironment is one of the main molecular factors involved in cancer and metastatic processes development,in this sense it is interesting to study the role of platelets,one of the main communicator cells in the human body which are activated by the signals they receive from the microenvironment and can generate more than one response.Platelets can ingest and release RNA,proteins,cytokines and growth factors.After the platelets interact with the tumor microenvironment,they are called"tumor-educated platelets."Tumor-educated platelets transport material from the tumor microenvironment to sites adjacent to the tumor,thus helping to create microenvironments conducive for the development of primary and metastatic tumors.It has been observed that the clone capable of carrying out the metastatic process is a cancer cell with stem cell characteristics.Cancer stem cells go through a series of processes,including epithelial-mesenchymal transition,intravasation into blood vessels,movement through blood vessels,extravasation at the site of the establishment of a metastatic focus,and site colonization.Tumor-educated platelets support all these processes.

High Light Intensity Increases the CAM Expression in “MD-2” Micro-Propagated Pineapple Plants at the End of the Acclimatization Stage

This work describes the evaluation of morpho-physiological and biochemical changes in “MD-2” micro-propagated pineapple plants (Ananas comosus (L.) Merr.) grown after 30 days under low light intensity (LL, greenhouse light conditions at 250 μmol·m-2·s-1) or high light intensity (HL, field light conditions at 800 μmol·m-2·s-1). Gas exchange, leaf pH, protein content and superoxide dismutase activity (SOD) (EC 1.15.1.1) were measured every 3 h during one day. Chlorophylls content and succulence index (SI) were determined at 9 h. Results showed significant differences in CO2 exchange rates, with a maximum occurring at 6 h (3.00 and 8.25 μmol CO2 m-2·s-1 for leaves under LL and HL conditions respectively). Plants under HL conditions had higher CO2 uptake and lower pH values between 0 h and 6 h respective to LL plants. The maximum pH value was attained 3 h before in HL plants. Leaf SI was increased and chlorophyll content decreased by HL conditions. SOD activity was higher in plants under HL conditions, near doubling those of LL plants at 18 h (2.8 versus 1.5 U·mg-1 Protein respectively). Both groups showed a typical CAM phenotype, but it was stronger in HL conditions, which may confer these plants with a better acclimation to transfer to the field.

HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

AIM:To analyze hepatitis C virus(HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α(IFN-α)plus ribavirin and CIGB-230.METHODS:CIGB-230 was administered in different schedules with respect to IFN-αplus ribavirin therapy.Paired serum and peripheral blood mononuclear cells(PBMC)samples from baseline and end of treatment were analyzed.The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay,neutralizing antibodies were evaluated by cell culture HCV neutralization assays,PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γsecretion was assessed by enzyme-linked immunospot.Data on virological and histological response and their association with immune variables are also provided.RESULTS:From week 12 to week 48,all groups of patients showed a significant reduction in mean leukocyte counts.Statistically significant reductions in antibody titers were frequent,but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response,and the neutralizing antibody response was enhanced only in patients receiving CIGB-230.Cell-mediated immune responses also tended to decline,but significant reductions in IFN-γsecretion and total absence of core-specific lymphoproliferation were exclusive of the control group.Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens.Importantly,it was demonstrated that thequality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy.Specifically,the administration of 6 doses of CIGB-230 as late addon to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γsecretion,both of which were associated with the sustained virological response.CONCLUSION:CIGB-230,combined with IFN-α-based therapy,modifies the immune response in chronic patients.The study provides evidence for the design of more effective therapeutic vaccine interventions against HCV.