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Abstract Glypican-3 (GPC-3) is predominantly found in the placenta and fetal liver, with limited expression in adult tissues. Its re-expression in hepatocellular carcinoma (HCC) and secretion into the serum highlights its potential as a diagnostic marker. GPC-3 is involved in important cellular processes such as proliferation, metastasis, apoptosis, and epithelial–mesenchymal transition through various signaling pathways including Wnt, IGF, YAP, and Hedgehog. To review the structure, biosynthesis, and post-translational modifications of GPC-3, and to elucidate its signaling mechanisms and role as a pro-proliferative protein in HCC, emphasizing its diagnostic and therapeutic potential. A comprehensive literature review was conducted, focusing on the expression of GPC-3 in various tumors, with a special emphasis on HCC. The review synthesized findings from experimental studies and clinical trials, analyzing the overexpression of GPC-3 in HCC, its differentiation from other liver diseases, and its potential as a diagnostic and therapeutic target. GPC-3 overexpression in HCC is linked to aggressive tumor behavior and poor prognosis, including shorter overall and disease-free survival. Additionally, GPC-3 has emerged as a promising therapeutic target. Ongoing investigations, including immunotherapies such as monoclonal antibodies and CAR-T cell therapies, demonstrate potential in inhibiting tumor growth and improving clinical outcomes. The review details the multifaceted roles of GPC-3 in tumorigenesis, including its impact on tumor-associated macrophages, glucose metabolism, and epithelial–mesenchymal transition, all contributing to HCC progression. GPC-3’s re-expression in HCC and its involvement in key tumorigenic processes underscore its value as a biomarker for early diagnosis and a target for therapeutic intervention. Further research is warranted to fully exploit GPC-3’s diagnostic and therapeutic potential in HCC management.

BackgroundThe ongoing treatment modalities for breast cancer (BC) primarily rely on the expression status of ER, PR and HER-2 receptors in BC tissues. Our strategy of chemosensitization provides new insights to counter chemoresistance, a major obstacle that limits the benefits of chemotherapy of mammary cancers.MethodsBy utilizing a murine breast cancer model employing NSG mice bearing orthotopic triple-negative breast cancer (TNBC) xenografts, we have evaluated the ability of phytochemical curcumin in chemosensitizing BC to 5-Fluorouracil (5-FU) chemotherapy and the differential modulations of cellular events in response to this strategy, independent of their receptor status.ResultsA significant synergistic antitumor potential was observed in the murine model with a sub-optimal dose treatment of 5-FU plus curcumin, as evaluated by a reduction in the tumor-related parameters. We authenticated the pivotal role of thymidylate synthase (TS) in regulating the 5-FU–curcumin synergism using the TNBC pre-clinical model. Our study also confirmed the pharmacological safety of this chemotherapeutic plus phytoactive combination using acute and chronic toxicity studies in Swiss albino mice. Subsequently, the molecular docking analysis of curcumin binding to TS demonstrated the affinity of curcumin towards the cofactor-binding site of TS, rather than the substrate-binding site, where 5-FU binds. Our concomitant in vivo and in silico evidence substantiates the superior therapeutic index of this combination.ConclusionThis is the first-ever pre-clinical study portraying TS as the critical target of combinatorial therapy for mammary carcinomas and therefore we recommend its clinical validation, especially in TNBC patients, who currently have limited therapeutic options.

Bacterial blight (BB) disease reduces the yield of rice varieties and hybrids considerably in many tropical rice growing countries like India. The present study highlights the development of durable BB resistance into the background of an elite maintainer of rice, DRR17B, by incorporating two major dominant genes, Xa21 and Xa33 through marker-assisted backcross breeding (MABB). Through two sets of backcrosses, the two BB resistance genes were transferred separately to DRR17B. In this process, at each stage of backcrossing, foreground selection was carried out for the target resistance genes and for non-fertility restorer alleles concerning the major fertility restorer genes Rf3 and Rf4, using gene-specific PCR-based markers, while background selection was done using a set of 61 and 64 parental polymorphic SSR markers respectively. Backcross derived lines possessing either Xa21 or Xa33 along with maximum genome recovery of DRR17B were identified at BC3F1 generation and selfed to develop BC3F2s. Plants harboring Xa21 or Xa33 in homozygous condition were identified among BC3F2s and were intercrossed with each other to combine both the genes. The intercross F1 plants (ICF1) were selfed and the intercross F2(ICF2) plants possessing both Xa21 and Xa33 in homozygous condition were identified with the help of markers. They were then advanced further by selfing until ICF4 generation. Selected ICF4 lines were evaluated for their resistance against BB with eight virulent isolates and for key agro-morphological traits. Six promising two-gene pyramiding lines of DRR17B with high level of BB resistance and agro-morphological attributes similar or superior to DRR17B with complete maintenance ability have been identified. These lines with elevated level of durable resistance may be handy tool for BB resistance breeding.

The development of oxygen reduction reaction (ORR) catalyst that are affordable and long-lasting is crucial for the expansion of energy conversion applications. In this study, we synthesized a ZnO–NiO/reduced graphene oxide hybrid electrocatalyst by using the co-precipitation method. X-ray diffraction (XRD), thermogravimetric analysis (TGA), and Brunauer–Emmett–Teller (BET) analysis were used to characterize the synthesized ZnO–NiO/rGO hybrid catalyst. The XRD analysis showed that ZnO had a wurtzite structure, whereas the phase of NiO had a cubic structure. The TGA and BET investigations of the hybrid catalyst revealed its excellent thermal stability and large specific area (395.8 m2 g−1) compared to bare catalysts. Through transmission electron microscopy (TEM) analysis, we observed that ZnO nanorods and NiO nanoparticles are distributed evenly on the rGO surface. The electrochemical analysis showed that the ZnO–NiO/rGO hybrid catalyst had highly efficient catalytic activity for the ORR. It had a high limiting current density (7.1 mA cm−2), a positive onset potential (0.95 V), a low rate of H2O2 formation (less than 15%), and long-term stability. The oxygen reduction process on the ZnO–NiO/rGO hybrid catalyst was demonstrated to occur via a highly efficient 4e− mechanism using rotating ring-disk and rotating disk electrode investigations. The ZnO–NiO/rGO hybrid catalyst demonstrated significant promise as an expensive metal-free catalyst for alkaline fuel cell cathodes. [ABSTRACT FROM AUTHOR]