Search Results (18,509)

Background and objectives: Sudden cardiac death (SCD) is a natural and unexpected death of cardiac origin that occurs within 1 h from the onset of acute symptoms. The major leading causes of SCD are cardiomyopathies and channelopathies. In this review, we focus on channelopathies, inherited diseases caused by mutations affecting genes encoding membrane ion channels (sodium, potassium or calcium channels) or cellular structures that affect Ca²⁺ availability. The diagnosis of diseases such as long QT, Brugada syndrome, short QT and catecholaminergic polymorphic ventricular tachycardia (CPVT) is still challenging. Currently, genetic testing and next-generation sequencing allow us to identify many rare alterations. However, some non-coding variants, e.g., splice-site variants, are usually difficult to interpret and to classify. Methods: In our review, we searched for splice-site variants of genes involved in channelopathies, focusing on variants of unknown significance (VUSs) registered on ClinVar up to now. Results: The research led to a high number of splice-site VUSs of genes involved in channelopathies, suggesting the performance of deeper studies. Conclusions: In order to interpret the correlation between variants and pathologies, we discuss experimental studies, such as RNA sequencing and functional analysis of proteins. Unfortunately, as these in vitro analyses cannot always be performed, we draw attention to in silico studies as future perspectives in genetics. This review has the aim of discussing the potential methods of detection and interpretation of VUSs, bringing out the need for a future reclassification of variants with currently unknown significance. Full article

Background: The proper development of grana and stroma within chloroplasts is critical for plant vitality and crop yield in rice and other cereals. While the molecular mechanisms underpinning these processes are known, the genetic networks governing them require further exploration. Methods and Results: In this study, we characterize a novel rice mutant termed yellow leaf and dwarf 7 (yld7), which presents with yellow, lesion-like leaves and a dwarf growth habit. The yld7 mutant shows reduced photosynthetic activity, lower chlorophyll content, and abnormal chloroplast structure. Transmission electron microscopy (TEM) analysis revealed defective grana stacking in yld7 chloroplasts. Additionally, yld7 plants accumulate high levels of hydrogen peroxide (H₂O₂) and exhibit an up-regulation of senescence-associated genes, leading to accelerated cell death. Map-based cloning identified a C-to-T mutation in the LOC_Os07g33660 gene, encoding the YLD7 protein, which is a novel ankyrin domain-containing protein localized to the chloroplast. Immunoblot analysis of four LHCI proteins indicated that the YLD7 protein plays an important role in the normal biogenesis of chloroplast stroma and grana, directly affecting leaf senescence and overall plant stature. Conclusions: This study emphasizes the significance of YLD7 in the intricate molecular mechanisms that regulate the structural integrity of chloroplasts and the senescence of leaves, thus providing valuable implications for the enhancement of rice breeding strategies and cultivation. Full article

Development in hemoglobin-based oxygen carriers (HBOCs) that may be used as alternatives to donated blood requires an extensive supply of highly pure hemoglobin (Hb) preparations. Therefore, it is essential to fabricate inexpensive, stable and highly selective absorbents for Hb purification. Molecular imprinting is an attractive technology for preparing such materials for targeted molecular recognition and rapid separations. In this case study, we developed human fetal hemoglobin (HbF)-imprinted polymer beads through the fusion of surface imprinting and Pickering emulsion polymerization. HbF was firstly covalently coupled to silica nanoparticles through its surface-exposed amino groups. The particle-supported HbF molecules were subsequently employed as templates for the synthesis of molecularly imprinted polymers (MIPs) with high selectivity for Hb. After removing the silica support and HbF, the resulting MIPs underwent equilibrium and kinetic binding experiments with both adult Hb (HbA) and HbF. These surface-imprinted MIPs exhibited excellent selectivity for both HbA and HbF, facilitating the one-step isolation of recombinant Hb from crude biological samples. The saturation capacities of HbA and HbF were found to be 15.4 and 17.1 mg/g polymer, respectively. The present study opens new possibilities for designed resins for tailored protein purification, separation and analysis. Full article

Background/Objectives: Supported by a comparative study between conventional, grinding, and microwave techniques, a mild and versatile method based on the [1 + 3] cycloaddition of 2-((3-nitrophenyl)diazenyl)malononitrile to tether pyrazole and pyrimidine derivatives in good yields was used. Methods: The newly synthesized compounds were analyzed with IR, ¹³C NMR, ¹H NMR, mass, and elemental analysis methods. The products show interesting precursors for their antiproliferative anti-breast cancer activity. Results: Pyrimidine-containing scaffold compounds 9 and 10 were the most active, achieving IC₅₀ = 26.07 and 4.72 µM against the breast cancer MCF-7 cell line, and 10.64 and 7.64 µM against breast cancer MDA-MB231-tested cell lines, respectively. Also, compounds 9 and 10 showed a remarkable inhibitory activity against the Hsp90 protein with IC₅₀ values of 2.44 and 7.30 µM, respectively, in comparison to the reference novobiocin (IC₅₀ = 1.14 µM). Moreover, there were possible apoptosis and cell cycle arrest in the G1 phase for both tested compounds (supported by CD1, caspase-3,8, BAX, and Bcl-2 studies). Also, the binding interactions of compound 9 were confirmed through molecular docking, and simulation studies displayed a complete overlay into the Hsp90 protein pocket. Conclusions: Compounds 9 and 10 may have apoptotic antiproliferative action as Hsp90 inhibitors. Full article

Legume crops play a key role in hastening both the agroecological and protein transition and improving the sustainability of cropping systems. Among legumes, chickpea (Cicer arietinum L.) is a valuable source of protein, fibers, and nutraceutical compounds, providing important agri-environmental effects. Nevertheless, few studies have explored the effect of genetic characteristics on production and quality traits in chickpea. Chickpea landraces seem particularly interesting for their positive agronomic and quality characteristics, opening the door for innovation in sustainable food systems. Thus, the present study aimed to characterize two chickpea Tuscan landraces (Rugoso della Maremma and Cappuccio della Valtiberina) in comparison with widely distributed commercial chickpea varieties (Ares, Maragià, Pascià, Principe, Reale, Sultano, and Vittoria). Our findings highlighted positive agronomic traits of landraces in terms of seed yield and yield components, demonstrating performance that is either superior or comparable to commercial varieties. Notably, Cappuccio della Valtiberina showed the highest 1000-seed weight (425.50 g), followed by Maragià (432.92 g), Principe (392.32 g), and Reale (382.79 g), and the highest harvest index (0.55), similar to Reale (0.55). Overall, landraces achieved 18.75% higher yields than commercial varieties. Regarding chickpea quality, landraces exhibited profiles comparable to those of commercial genotypes in terms of protein and oil content, as well as nutraceuticals. Interestingly, the two landraces had the most favorable ω-6/ω-3 ratios (Cappuccio della Valtiberina, 12.45; Rugoso della Maremma, 13.71) among the genotypes except for Maragià (11.78), indicating better nutritional quality compared to commercial varieties (>14.00). These results demonstrated that landraces could offer promising prospects for future chickpea breeding programs, aiding in the selection of genotypes capable of adapting to changing growing conditions and supporting the development of sustainable food systems. Full article

Background/Objectives: Estrogens and HPV are necessary for cervical cancer (CC) development. The levels of the G protein-coupled estrogen receptor (GPER) increase as CC progresses, and HPV oncoproteins promote GPER expression. The role of this receptor is controversial due to its anti- and pro-tumor effects. This study aimed to determine the effect of GPER activation, using its agonist G-1, on the transcriptome, cell migration, and invasion in SiHa cells and non-tumorigenic keratinocytes transduced with the HPV16 E6 or E7 oncogenes. Methods: Transcriptome analysis was performed to identify G-1-enriched pathways in SiHa cells. We evaluated cell migration, invasion, and the expression of associated proteins in SiHa, HaCaT-16E6, and HaCaT-16E7 cells using various assays. Results: Transcriptome analysis revealed pathways associated with proliferation/apoptosis (TNF-α signaling, UV radiation response, mitotic spindle formation, G2/M cell cycle, UPR, and IL-6/JAK/STAT), cellular metabolism (oxidative phosphorylation), and cell migration (angiogenesis, EMT, and TGF-α signaling) in SiHa cells. Key differentially expressed genes included PTGS2 (pro/antitumor), FOSL1, TNFRSF9, IL1B, DIO2, and PHLDA1 (antitumor), along with under-expressed genes with pro-tumor effects that may inhibit proliferation. Additionally, DKK1 overexpression suggested inhibition of cell migration. G-1 increased vimentin expression in SiHa cells and reduced it in HaCaT-16E6 and HaCaT-16E7 cells. However, G-1 did not affect α-SMA expression or cell migration in any of the cell lines but increased invasion in HaCaT-16E7 cells. Conclusions: GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia. Full article

The investigation of the central and external zones of ten industrial and artisanal Maroilles cheeses showed differences in their physicochemical parameters, namely fat, pH, moisture content, ash, and color. This difference significantly impacted the rheological properties of the investigated cheeses, which depended on the protein network englobing lipid and water and its interaction with the other components. Overall, Maroilles cheeses had an elastic-like behavior, with the central zones exhibiting the greatest viscoelastic modules (G′ and G″). The mid-infrared (MIR) spectra highlighted the presence of lipids, proteins, and sugars. A significant difference in α-helix and β-sheet levels in the central zones was noted between artisanal and industrial Maroilles cheeses. It is suggested that the difference between artisanal and industrial Maroilles cheeses observed at the macroscopic level, due to the cheese-making procedure and ripening stage, affects the structure at the molecular level, which can be determined by MIR spectroscopy. This trend was confirmed by the FDA when applied to the MIR spectra, since 96.67% correct classification was noted between artisanal and industrial cheeses. The present study indicates that MIR spectroscopy can be used successfully to study Maroilles cheese samples belonging to different production chains. Full article

Tumor cell-induced platelet aggregation (TCIPA) is a mechanism for the protection of tumor cells in the bloodstream and the promotion of tumor progression and metastases. The platelet C-type lectin-like receptor 2 (CLEC-2) can bind podoplanin (PDPN) on a cancer cell surface to facilitate TCIPA. Selective blockage of PDPN-mediated platelet–tumor cell interaction is a plausible strategy for inhibiting metastases. In this study, we aimed to screen for aptamers, which are the single-stranded DNA oligonucleotides that form a specific three-dimensional structure, bind to specific molecular targets with high affinity and specificity, bind to PDPN, and interfere with PDPN/CLEC-2 interactions. The systematic evolution of ligands by exponential enrichment (SELEX) was employed to enrich aptamers that recognize PDPN. The initial characterization of ssDNA pools enriched by SELEX revealed a PDPN aptamer designated as A1 displaying parallel-type G-quadruplexes and long stem-and-loop structures and binding PDPN with a material with a dissociation constant (K_d) of 1.3 ± 1.2 nM. The A1 aptamer recognized both the native and denatured form of PDPN. Notably, the A1 aptamer was able to quantitatively detect PDPN proteins in Western blot analysis. The A1 aptamer could interfere with the interaction between PDPN and CLEC-2 and inhibit PDPN-induced platelet aggregation in a concentration-dependent manner. These findings indicated that the A1 aptamer is a candidate for the development of biosensors in detecting the levels of PDPN expression. The action by A1 aptamer could result in the prevention of tumor cell metastases, and if so, could become an effective pharmacological agent in treating cancer patients. Full article

Aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) is a rare syndrome affecting dogs. Nutritional management is a pillar of optimal treatment. Currently, there are no specific published data to inform dietary nutrient composition selections for treating affected dogs. Thus, our goal was to establish nutrient targets for the dietary management of ACHES by comparing nutrient profiles of commercial and home-cooked diets fed to dogs after diagnosis and determine if different nutrient inclusions were associated with survival. This retrospective cohort study evaluated nutrient profiles of commercial diets (n = 10) and home-cooked diets (n = 8) fed to dogs with ACHES. Associations between dietary nutrient inclusions and survival duration were determined using Cox proportional hazard analysis. Home-cooked diets were significantly (p < 0.001) higher in dietary protein and several amino acids than commercial diets. Risks of death were significantly (p < 0.05) lower with increasing dietary protein (hazard ratio 0.92 [CI 0.82–1.0]) and sodium (hazard ratio 0.02 [CI < 0.01–0.38]) and higher for dietary fat (hazard ratios 1.15 [CI 1.02–1.37]). An increased risk of death with increasing dietary calcium did not achieve significance (p = 0.067, hazard ratio 9.92 [CI 1.02–201.0]). These results were used to recommend target dietary nutrient ranges, in g/1000 kcal, of 90–130 for protein, 20–40 for fat, 0.7–1.8 for sodium, and 1.0–2.8 for calcium for dietary ACHES management. Full article

Targeting DNA repair pathways is an important strategy in anticancer therapy. However, the unrevealed interactions between different DNA repair systems may interfere with the desired therapeutic effect. Among DNA repair systems, BER and NHEJ protect genome integrity through the entire cell cycle. BER is involved in the repair of DNA base lesions and DNA single-strand breaks (SSBs), while NHEJ is responsible for the repair of DNA double-strand breaks (DSBs). Previously, we showed that BER deficiency leads to downregulation of NHEJ gene expression. Here, we studied BER’s response to NHEJ deficiency induced by knockdown of NHEJ scaffold protein XRCC4 and compared the knockdown effects in normal (TIG-1) and hTERT-modified cells (NBE1). We investigated the expression of the XRCC1, LIG3, and APE1 genes of BER and LIG4; the Ku70/Ku80 genes of NHEJ at the mRNA and protein levels; as well as p53, Sp1 and PARP1. We found that, in both cell lines, XRCC4 knockdown leads to a decrease in the mRNA levels of both BER and NHEJ genes, though the effect on protein level is not uniform. XRCC4 knockdown caused an increase in p53 and Sp1 proteins, but caused G1/S delay only in normal cells. Despite the increased p53 protein, p21 did not significantly increase in NBE1 cells with overexpressed hTERT, and this correlated with the absence of G1/S delay in these cells. The data highlight the regulatory function of the XRCC4 scaffold protein and imply its connection to a transcriptional regulatory network or mRNA metabolism. Full article

The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is a polyphagous insect of various agricultural crops. The methods used for its control have led to the selection of resistant insect populations, which justifies the search for new alternatives for the management of this insect. Accordingly, in the present study, trypsin inhibitors present in the leaf extract of Ricinus communis (Euphorbiaceae) were investigated for their activity against S. frugiperda. Chemometric optimization methods were developed for the extraction, purification, identification, and structural characterization of the inhibitors. In addition, the effect of R. communis extract on S. frugiperda development was evaluated. Inhibitor extraction was chemometrically optimized, yielding an extract with an antitryptic activity of 94,837.14 mUIT g⁻¹. The R. communis extract was purified and found to contain two compounds (adenosine and ricinine) exhibiting trypsin inhibitor activity. However, after purification, only ricinine inhibited S. frugiperda trypsin in vitro (103.21 mUIT mg⁻¹). The extract was added to the diet of S. frugiperda larvae, resulting in reduced digestion, increased protein in the feces (control = 12,571 μg protein/mg feces; 1818.2 g mL⁻¹ = 16,867 μg protein/mg feces), and insect mortality. At the highest concentration, the treatment led to an LT50 of 15.9 days and a cumulative survival rate of 18.5%. Based on the results of this study, it is possible that ricinine binds to the catalytic site of trypsin, causing the mortality of S. frugiperda larvae. Full article

Objectives: This study provides an overview of the composition of the raw root flesh of a panel of 22 sweet potato (Ipomoea batatas L.) cultivars, with a focus on bioactive compounds. The large diversity of the proximate and phytochemical compositions observed between cultivars and within and between different flesh colors pointed out the importance of composition analysis and not only color choice for the design of foods with nutritional benefits. Methods: The nutritional composition (starch, protein, total dietary fibers) and bioactive compound composition of 22 cultivars from Reunion Island, maintained in the Vatel Biological Resource Center, were investigated. Results: Orange and purple cultivars stood out from white and yellow cultivars for their higher nutritional composition. Purple sweet potatoes were notable for their high contents of anthocyanins (55.7 to 143.4 mg/g dry weight (DW)) and phenolic compounds, in particular chlorogenic acid and ferulic acid, contributing to antioxidant activities, as well as their fiber content (14.1 ± 2.1% DW). Orange cultivars were rich in β-carotene (47.2 ± 0.7 mg/100 g DW) and to a lesser extent α-carotene (4.8 ± 1.2 mg/100 g DW). In contrast, certain white cultivars demonstrated suboptimal nutritional properties, rendering them less relevant even for applications where the lack of coloration in food is desired. Conclusions: Those characteristics enable the selection of sweet potato varieties to design food products ensuring optimal nutritional benefits and culinary versatility. Full article

Background: The bHLH genes play a crucial role in plant growth, development, and stress responses. However, there is currently limited research on bHLH genes in the important horticultural plant Rhododendron delavayi Franch. Methods: In this study, we conducted a comprehensive genome-wide identification and in-depth analysis of the bHLH gene family in R. delavayi using bioinformatics approaches. Results: A total of 145 bHLH family members were identified, encoding proteins ranging from 98 to 3300 amino acids in length, with molecular weights ranging from 11.44 to 370.51 kDa and isoelectric points ranging from 4.22 to 10.80. These 145 bHLH genes were unevenly distributed across 13 chromosomes, with three bHLH genes located on contig 52. Chromosome 8 contained the highest number of bHLH family members with 19 genes, while chromosomes 9 and 13 had the lowest, with 7 genes each. Phylogenetic analysis revealed a close evolutionary relationship between bHLH genes in R. delavayi and Arabidopsis thaliana. Subcellular localization analysis indicated that most bHLH genes were located in the nucleus. Promoter analysis of R. delavayi bHLH genes revealed the presence of various cis-regulatory elements associated with light responses, methyl jasmonate responses, low-temperature responses, and coenzyme responses, suggesting that bHLH genes are involved in multiple biological processes in R. delavayi. Through transcriptome analysis, we identified three key functional genes—Rhdel02G0041700, Rhdel03G0013600, and Rhdel03G0341200—that may regulate flower color in R. delavayi. Conclusions: In conclusion, our study comprehensively identified and analyzed the bHLH gene family in R. delavayi and identified three bHLH genes related to flower color, providing a foundation for molecular biology research and breeding in R. delavayi. Full article

During the COVID-19 pandemic, diabetic and obese patients experienced higher rates of hospital admissions, severe illness, and mortality. However, vaccinations failed to provide those vulnerable populations the same level of protection against COVID-19 severity as those without diabetic and obese phenotypes. Our study aimed to investigate how diabetes mellitus (DM) impacts the immune response following vaccination including the artificially designed trimeric SARS-CoV-2 spike (S)-protein. By using two diabetic mouse models, ob/ob mice (obese, hyperglycemic, and insulin-resistant) and STZ-treated mice (insulin-deficient and hyperglycemic), we observed a significant reduction in S-protein-specific IgG antibody titer post-vaccination in both diabetic models compared to wild-type (WT) mice. Both diabetic mouse models exhibited significant abnormalities in spleen tissue, including marked reductions in splenic weight and the size of the white pulp regions. Furthermore, the splenic T-cell and B-cell zones were notably diminished, suggesting an underlying immune dysfunction that could contribute to impaired antibody production. Notably, vaccination with the S-protein, when paired with an optimal adjuvant, did not exacerbate diabetic cardiomyopathy, blood glucose levels, or liver function, providing reassurance about the vaccine′s safety. These findings offer valuable insights into potential mechanisms responsible for the decreased persistence of antibody production in diabetic patients. Full article

An experiment was conducted to investigate the optimal use of high-salt water for alfalfa fodder growth and quality in Aridisol. The experiment included five treatments and was performed using a completely randomized design (CRD) as factorial design with three replications. We used a leaching fraction technique (LF), which is a mitigating technique (MT). The five treatments were T1 = MT1 as normal irrigation (control), T2 = MT2 as a leaching fraction (LF) of 15% with the same quality of water, T3 = MT3 as a LF of 30% with the same quality of water, T4 = MT4 as a LF of 15% with good-quality water (as percentage of total water), in the form of 2–3 irrigations every 3 months, and T5 = MT5 as a LF of 30% with good-quality water (as percentage of total water), in the form of 2–3 irrigations every 3 months. The duration of the experiment was three years and normal soil (non-saline, non-sodic) was used in the current study. Results showed that saline water irrigation negatively affected the growth traits, but the application of the LF technique with same-quality or good-quality water mitigated such negative effects. The fodder quality traits such as crude protein (CP), crude fiber (CF) and ashes were also affected in a negative way with the use of saline irrigation water. This negative impact was more intensified in the third year as the concentration of salts increased in saline water during the three years of the current investigation. A LF with canal water at 15 or 30% reduced the negative effects of salt stress and improved fodder biomass production and quality traits. For examples, using a LF with canal water at 30% increased the biomass production to 33.30 g and 15.87 g when plants were irrigated with W1 and W5, respectively. In addition, it improved quality traits such as crude protein content (5.54% and 3.73%) and crude fiber content (14.55% and 12.75%) when plants were irrigated with W1 and W5, respectively. It was concluded that the LF technique can be recommended for practice in the case of saline water irrigation for the optimized growth and quality of alfalfa fodder. Full article