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Machine learning (ML) holds great promise in advancing risk prediction and stratification for neuroblastoma, a highly heterogeneous pediatric cancer. By utilizing large-scale biological and clinical data, ML models can detect complex patterns that traditional approaches often overlook, enabling more personalized treatments and better patient outcomes. Various ML techniques, such as support vector machines, random forests, and deep learning, have shown superior performance in predicting survival, relapse, and treatment responses in neuroblastoma patients compared to conventional methods. However, challenges like limited data size, model interpretability, data variability, and difficulties in clinical integration hinder broader adoption. Additionally, ethical concerns related to bias and privacy must be addressed. Future work should focus on improving data quality, enhancing model transparency, and conducting thorough clinical validation. With these advancements, ML has the potential to revolutionize neuroblastoma care by refining early diagnosis, risk assessment, and therapeutic decision-making.

Breast cancer (BC) is the most common cancer and the second leading cause of cancer-related deaths in women globally. Despite advancements in treatment strategies, many patients still develop challenging-to-treat metastatic disease. The development and progression of tumors are influenced by genetic/epigenetic changes within tumor cells and alterations in the tumor microenvironment (TME) through a dynamic communication. The TME comprises various elements, including immune, tumor, and stromal cells. Tumor cells at the core of the TME orchestrate complex signals that lead to tumor growth, survival, and resistance to treatment. Human epidermal growth factor receptor 2 (HER2) is overexpressed in a significant proportion of invasive breast cancers, influencing prognosis and prediction. Novel therapeutic approaches target HER2-positive breast cancers by leveraging HER2-targeted therapeuirtcs such as antibody-drug conjugates, monoclonal antibodies, and tyrosine kinase inhibitors. The TME in HER2-positive breast cancers also involves cancer-associated fibroblasts and cancer-associated adipocytes, which play critical roles in tumor progression and therapy resistance. The immune microenvironment also plays a significant role, with studies indicating its impact on outcomes in HER2-positive breast cancer. Trastuzumab, one of the first monoclonal antibodies targeting HER2, has shown promise in enhancing survival rates in HER2-overexpressing breast cancer. Integration of trastuzumab with chemotherapy has demonstrated significant enhancements in disease-free survival as well as overall survival rates during early breast cancer treatment. Trastuzumab functions by inhibiting HER2 signaling pathways, leading to cell cycle arrest and induction of apoptosis. Overall, understanding the complex interplay between HER2, the tumor microenvironment, and therapeutic interventions is essential for improving outcomes in HER2-positive BC.

Neuroblastoma (NBM) is the second leading pediatric cancer that develops from the precursors of the sympathetic nervous system. To date, surgery, chemotherapy, and radiation serve as the first-line treatment against NBM in high-risk patients. However, few of these approaches have severe side effects. Recently, numerous studies have also reported that high chemotherapy doses, along with stem cell rescue, improvise event-free survival in patients. In this review, the authors attempted to discuss the pathogenesis associated with NBM and how stem cell therapy can be employed for the treatment of NBM. Stem cells are a group of multipotent, undifferentiated cells that are capable of producing all cells in a particular tissue, organ, or organism. They have an endogenous self-renewal property. This property is tightly modulated for the normal homeostasis within the body. However, the failure of this process leads to carcinogenesis, including NBM. As these properties are modulated via various intrinsic as well as extrinsic pathways, the arrest of these pathways via various drugs may help in controlling various carcinomas, including NBM. Recently, stem cells were utilized for the diagnosis and treatment of NBM. Nevertheless, most of the studies conducted to date are mainly designed on bulk-cell analysis, which in turn provides little information about the population of cells. Thus, the authors believe that, by employing single-cell RNA sequencing technologies and computational approaches, we can unmask the tumor heterogeneity in NBM in a more comprehensive way. In the near future, this information will be highly useful for the identification of biomarkers and treatment associated with NBM in humans., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hepatocellular carcinoma (HCC) stands third among cancer-related deaths globally. Owing to its high incidence and linked mortality, early diagnosis is alarming for patient survival and the management of patients with developing HCC requires immediate attention. Advances in the knowledge of cancer biology and recognizing unique molecular candidates, including genomic and proteomic profiles, substantiate our understanding about several biological signatures connected with HCC. Precise identification and differential diagnosis of early HCC can remarkably improve patient survival. Currently, detection of HCC in clinical practice is performed by diagnostic imaging and noninvasive methods such as evaluation of serum biomarkers, growth factors, and the like. In this review, we discuss recent developments in targeting biomarkers for HCC.

The recently developed phylogenomic approach provides a unique way to identify disease risk or protective allele in any organism. While risk alleles evolve mostly under purifying selection, protective alleles are evolving either under balancing or positive selection. Owing to insufficient information, authors employed the phylogenomic approach to detect the nature of selection acting on type 2 diabetes (T2D) genes in Drosophila genus using various models of CODEML utility of PAML. The obtained result revealed that T2D gene sequences are evolving under purifying selection. However, only a few sites in membrane proteins encoded via CG8051, ZnT35C, and kar, are significantly evolving under positive selection under specific scenarios, which might be because of positive or adaptive evolution in response to changing niche, diet or other factors. In the near future, this information will be highly useful in the field of evolutionary medicine and the drug discovery process.

Mutation (p.LEU112PRO) in "carotenoid cleavage dioxygenase 8" (CCD8) protein increases tiller formation in rice plants by cross-talking with auxin and cytokinins. However, owing to the nonexistence of a "three-dimension" structure of CCD8, detail information about its structure and function remain elusive until date. Hence, in the present study, computational approaches were adopted to predict "three-dimensional" (3D) structure of CCD8 protein through comparative modeling techniques and to study the effect of mutation (p.LEU112PRO) on its function as well as architecture through "molecular dynamics" simulation studies. The obtained result reveals that wild-type CCD8 protein is made up of 10 α-helix and 25 β-strands while mutant CCD8 is made up of 11 α-helix and 24 β-strands. Further, molecular docking studies reveals that the wild-type has a better binding affinity with auxin and cytokinin in comparison to mutant. Subsequent molecular dynamics simulation of these four complexes, separately, reveals that the movement of both wild-type as well as mutant CCD8 get reduced after binding with auxin, which in turn prevent auxin transport out of the bud and increases tiller number. However, when cytokinin binds with wild-type and mutant CCD8, it inhibits and enhance CCD8 activity, respectively. As cytokinin positively regulates tiller number formation, enhance activity of mutant CCD8 after binding with cytokinin might be the main reason for more tiller number in mutant than wild-type plant. In the near future, mutant CCD8 along with auxin and cytokinin may be utilized for increasing grain yield in rice plants., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Continuous rise in the human population has resulted in an upsurge in food demand, which in turn demand grain yield enhancement of cereal crops, including rice. Rice yield is estimated via the number of tillers, grain number per panicles, and the number of spikes present per panicle. Marker-assisted selection (MAS) serve as one of the best ways to introduce QTLs/gene associated with yield in the rice plant. MAS has also been employed effectively in dissecting several other complex agricultural traits, for instance, drought, cold tolerance, salinity, etc. in rice plants. Thus, in this review, authors attempted to collect information about various genes/QTLs associated with high yield, including grain number, in rice and how different scheme of MAS can be employed to introduce them in rice ( Oryza sativa L.) plant, which in turn will enhance rice yield. Information obtained to date suggest that, numerous QTLs, e.g., Gn1a , Dep1 , associated with grain number and yield-related traits, have been identified either via mapping or cloning approaches. These QTLs have been successfully introduced into rice plants using various schemes of MAS for grain yield enhancement in rice. However, sometimes, MAS does not perform well in breeding, which might be due to lack of resources, skilled labors, reliable markers, and high costs associated with MAS. Thus, by overcoming these problems, we can enhance the application of MAS in plant breeding, which, in turn, may help us in increasing yield, which subsequently may help in bridging the gap between demand and supply of food for the continuously growing population., Competing Interests: Conflict of interestNone., (© Prof. H.S. Srivastava Foundation for Science and Society 2020.)

Background: Coronavirus disease 2019 (COVID-19) is an ongoing, rapidly spreading pandemic caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2). Among all the infected countries around the globe as of now (June 15, 2020), the total confirmed positive cases reported are 7,805,148, with the death of 431,192. At present, no specialized treatments evolved to cure COVID-19. Its treatment is symptomatic. Though huge efforts are being made to produce potential therapies to scuffle COVID-19, no drug has been discovered so far., Objective: Natural products have been playing a significant role in disease control since ancient days. These products serve as templates for designing new anti-microbial agents with a different mechanism of action and also open a door for investigation of effective anti-viral drugs to combat COVID-19. By focusing on this, the authors have narrated the basic structure, infection, and pathogenesis of SARS-CoV2 virus in humans and also reported various natural products or plant-based extracts/bioactive compounds tested against coronaviruses like SARS and MERS, as these viruses are structurally similar to SARS-CoV2 and can be used in designing novel drug against this virus., Conclusion: The natural products having the potential to combat SARS, MERS, and other viruses reviewed in this review article might have anti-viral activities against the SARS-CoV2 virus and can be used directly for further preclinical studies. Therefore, all efforts should be focused on overcoming this serious problem to save many people's lives all over the world., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Since human left Africa about 100 thousand years ago, they experienced numerous environmental as well as social transitions. During these transitions, their genome too experiences various forms of selective pressure and retained favorable advantageous alleles in their genome by either positive selection or balancing selection, while removing deleterious alleles through purifying selection. However, when an individual with certain advantageous genetic diversity is migrated to new contrasting environment or lifestyle, the advantageous genetic diversity becomes disadvantageous and finally causing maladaptation. Thus, understanding the role of evolution in adaptation and also in the regulation of population dynamics, is highly important for identifying naturally occurring advantageous or disease risk allele in contemporary populations. Recent advancements in high-throughput sequence technologies have made it easier for understanding the impact of evolutionary forces on the genetic make-up of human in different environmental and social conditions in a far better way. Statistical tests described in this review will enable reader to identify various signatures of balancing selection in different time scales in a more comprehensive way. Additionally, these tests will also help in identifying naturally occurring advantageous or disease risk alleles with applications in animal breeding, nature conservation and human medicine., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Rice serves as the major food for almost half of the world population. Because of its origin in the tropical and subtropical area, rice is more sensitive towards cold stress. Three homologs of DREB1, namely DREB1A, DREB1B and DREB1C are induced Queryduring cold stress and after binding with GCC-box in the promoter region of the target gene, they enhance cold tolerance in rice plants. Though the majority of DREBs bind GCC-box, the degree of activation varies among DREBs. The protein encoded via these three transcription factors contains a common domain, namely AP2/ERF. In silico method was utilised to predict 3D structure of each AP2/ERF domain. The molecular dynamic analysis suggests, under the normal environmental condition, in each AP2/ERF domain, a positive correlation exists between β-strands and the movement of C-α is constrained. However, during cold stress, when AP2/ERF domain binds with GCC-box present in the promoter region of the target gene, mean pressure of each three AP2/ERF domain gets lowered and final potential energy increases. A positive correlation between β-strands gets disrupted and C-α experiences random movement suggesting enhanced activity of DREB1A, DREB1B and DREB1C during cold stress and enhancement of cold tolerance in plants. Further, MM/PBSA calculations for protein-DNA affinities reveal that, due to lack of α2 in DREB1C, the binding affinity of GCC-box with AP2/ERF domain of DREB1A > DREB1B > DREB1C. Thus, due to a better binding affinity with GCC-box, DREB1A and DREB1B can be utilised in near future for increasing cold tolerance of rice plant and increasing yield.

In silico approach was utilised to identify differentially expressed key hub genes during BPH infestation on Bt rice plant, under laboratory conditions. Re-analysis of GSE74745 data with in-house R scripts and STRING database reveals that only 5 key hub genes, namely Os05g0176100, Os06g0683200, Os07g0208500, Os07g0252400 and Os07g0424400, belonging to cellulose synthase family, are differentially expressed and have confidence score ≥0.9 among themselves. Conserve domain analysis of all proteins encoded via these 5 key hub genes reveals that they have a common cellulose synthase domain, in which "Plant-Conserved Region" (PCR) is highly conserved. After binding with other domains of cellulose synthase proteins or other accessory proteins, like sucrose synthase, PCR serves as a metabolic channel to deliver UDP-Glucose, which is the main substrate for cellulose synthesis, into the active site of cellulose synthase and initiate cellulose synthesis. Simulation study of recently solved topological model of PCR [PDB ID: 5JNP] and molecular docking studies of PCR with UDP-glucose reveals that, during BPH infestation, in nearby phloem tissue where BPH suck sap, there is an increase interaction of UDP-glucose with PCR and other accessory proteins which in turn increases both the stability of PCR and the production of cellulose, finally causing callose deposition at that site and hence causing longer nymphal developmental period and lower fertility of BPH infested on Bt rice. In near future, these differentially identified 5 hub genes could be possible targets for controlling BPH infestation in rice plant under field conditions and increasing rice yield globally., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetes mellitus is clinically characterized by hyperglycemia. Though many studies have been done to understand the mechanism of Type 2 Diabetes (T2D), however, the complete network of diabetes and its associated disorders through polygenic involvement is still under debate. The present study designed to re-analyze publicly available T2D related microarray raw datasets present in GEO database and T2D genes information present in GWAS catalog for screening out differentially expressed genes (DEGs) and identify key hub genes associated with T2D. T2D related microarray data downloaded from Gene Expression Omnibus (GEO) database and re-analysis performed with in house R packages scripts for background correction, normalization and identification of DEGs in T2D. Also retrieved T2D related DEGs information from GWAS catalog. Both DEGs lists were grouped after removal of overlapping genes. These screened DEGs were utilized further for identification and characterization of key hub genes in T2D and its associated diseases using STRING, WebGestalt and Panther databases. Computational analysis reveal that out of 99 identified key hub gene candidates from 348 DEGs, only four genes (CCL2, ELMO1, VEGFA and TCF7L2) along with FOS playing key role in causing T2D and its associated disorders, like nephropathy, neuropathy, rheumatoid arthritis and cancer via p53 or Wnt signaling pathways. MIR-29, and MAZ_Q6 are identified potential target microRNA and TF along with probable drugs alprostadil, collagenase and dinoprostone for the key hub gene candidates. The results suggest that identified key DEGs may play promising roles in prevention of diabetes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human., Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans., Conclusion: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery & radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Extensive epidemiological and clinical studies revealed that Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (T2D) are most likely to appear simultaneously in aged people as T2D is a major risk factor for AD. Therefore, development of potential multifunctional agents for dual therapy of AD and T2D has received much attention. Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis have been used extensively in popular medicine. The present study was aimed at phytochemical profiling and evaluating multifunctional ability of titled plants in the AD and T2D dual therapy., Methods: Methanolic extracts and their derived fractions were evaluated for their inhibitory capacities against acetylcholinesterase (AChE) & butyrylcholinesterase (BuChE), and α- & β-glucosidase besides kinetic analysis of inhibition using methods of Elmann and Shibano, respectively. Antioxidant potency of active fractions was assessed by their DPPH and ABTS radical scavenging activities. Active fractions were tested by the MTT assay to verify cytotoxicity and neuroprotective ability in human nueroblastoma cell lines. Phytochemical screening was done with the aid of spectrophotometric methods., Results: All the methanolic extracts of test plants (BAM, HIM, RMM) showed concentration dependent inhibitory activities against AChE, BuChE, α- and β-glucosidase enzymes. Subsequent fractionation and evaluation revealed that chloroform fractions BAC, HIC and RMC with IC 50 values of 12.29±2.14, 9.94±2.14, 16.65±1.99 and 27.38±1.24; 28.14±0.9, 5.16±0.22, 11.03±0.5 and 87.64±15.41; 41.35±1.6, 15.86±7.3, 26.04±0.37 and 25.33±0.3 were most prominent with regard to inhibition potential against AChE, BuChE, α- and β-glucosidase, respectively. Kinetic analysis of these active fractions proved that they disclosed mixed-type inhibition against AChE, BuChE, α- and β-glucosidase enzymes. In the MTT assay, active fractions BAC, HIC, RMC showed significant cell viability at high concentrations (400 μg). Moreover, in MTT assay, the active fractions displayed excellent neuroprotective effects against oxidative stress induced cell death and significant cell viability in SK N SH cells at all concentrations., Conclusion: The strong anticholinesterase, antiglucosidase, antioxidant and neuroprotective activities of methanolic extracts and their derived chloroform fractions indicate the potential of Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis as multifunctional therapeutic remedies for the dual therapy of T2D and AD.

Hypoxia is a condition of insufficient tissue oxygenation, which is observed during normal development as well as tumorigenesis and its response at the cellular level is primarily mediated through hypoxia inducible factors (HIFs). HIFs have a significant role in the maintenance of stemness in both stem cells as well as in cancer stem cells (CSC) by acting as transcription factors. The CSCs are proposed to be the driving force of colon tumorigenesis and malignancy. These HIFs play a significant role in a wide range of diseases including colon cancer. HIF's signaling functions with stemness, and maintaining Wnt/β-catenin signaling pathways. Due to HIFs functional significance in stemness maintenance in malignancy, targeting HIFs might provide a new approach for development of new therapy for colon cancer. In this review, we will be briefing on the colon and its stem cells, various molecular signaling pathways involved in stemness preservation, and the role hypoxia and its HIFs in the maintenance of stemness in colon stem cells and colon cancer stem cells., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study was to investigate beneficial effect of aqueous extract of Phyllanthus fraternus (AEPF) on bromobenzene (BB) induced changes on cytosolic glutathione S-transferase (GST) isozymes in rat liver. Administration of BB significantly decreased the activity of GST, however, prior administration of AEPF prevented the BB induced decrease in GST activity. Further the cytosolic GSTs were purified from 3 groups of animals (control, BB and AEPF+BB administered) and resolved into three protein bands on SDS-PAGE. Densitometric analysis showed a significant decrease in BB group compared to control. Further, 2D PAGE analysis resolved these proteins into 8 bands which were identified as five isozymes of alpha, two of Mu and one of theta by MALDI-TOF MS and also observed decreased levels of isozymes in BB group. However, on prior administration of AEPF significantly prevented the BB induced decrease in GSTs and restored to normal levels.

A series of fused tricyclic coumarin derivatives bearing iminopyran ring connected to various amido moieties were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. In vitro studies revealed that most of these compounds exhibited high inhibitory activity on acetylcholinesterase (AChE), with IC50 values ranging from 0.003 to 0.357 μM which is 2-220 folds more potent than the positive control, galantamine. Their inhibition selectivity against AChE over butyrylcholinesterase (BuChE) has increased about 194 fold compared with galantamine. The developed compounds also showed potent ABTS radical scavenging activity (IC50 7.98-15.99 μM). Specifically, the most potent AChE inhibitor 6n (IC50 0.003 ± 0.0007 μM) has an excellent antioxidant profile as determined by the ABTS method (IC50 7.98 ± 0.77 μM). Moreover, cell viability studies in SK N SH cells showed that the compounds 6m-q have significant neuroprotective effects against H2O2-induced cell death, and are not neurotoxic at all concentrations except 6n and 6q. The kinetic analysis of compound 6n proved that it is a mixed-type inhibitor for EeAChE (Ki1 0.0103 μM and Ki2 0.0193 μM). Accordingly, the molecular modeling study demonstrated that 6m-q with substituted benzyl amido moiety possessed an optimal docking pose with interactions at catalytic active site (CAS) and peripheral anionic site (PAS) of AChE simultaneously and thereby they might prevent aggregation of Aβ induced by AChE. Furthermore, in silico ADMET prediction studies indicated that these compounds satisfied all the characteristics of CNS acting drugs. Most active inhibitor 6n is permeable to BBB as determined in the in vivo brain AChE activity. To sum up, the multipotent therapuetic profile of these novel tricyclic coumarins makes them promising leads for developing anti-Alzheimer agents., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Cancer stem cells (CSCs) are shown to be responsible for initiation and progression of tumors in a variety of cancers. We previously showed that anthocyanin-containing baked purple-fleshed potato (PP) extracts (PA) suppressed early and advanced human colon cancer cell proliferation and induced apoptosis, but their effect on colon CSCs is not known. Considering the evidence of bioactive compounds, such as anthocyanins, against cancers, there is a critical need to study anticancer activity of PP, a global food crop, against colon CSCs. Thus, isolated colon CSCs (positive for CD44, CD133 and ALDH1b1 markers) with functioning p53 and shRNA-attenuated p53 were treated with PA at 5.0 μg/ml. Effects of baked PP (20% wt/wt) against colon CSCs were also tested in vivo in mice with azoxymethane-induced colon tumorigenesis. Effects of PA/PP were compared to positive control sulindac. In vitro, PA suppressed proliferation and elevated apoptosis in a p53-independent manner in colon CSCs. PA, but not sulindac, suppressed levels of Wnt pathway effector β-catenin (a critical regulator of CSC proliferation) and its downstream proteins (c-Myc and cyclin D1) and elevated Bax and cytochrome c, proteins-mediating mitochondrial apoptosis. In vivo, PP reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis and suppressed tumor incidence similar to that of sulindac. Combined, our data suggest that PP may contribute to reduced colon CSCs number and tumor incidence in vivo via suppression of Wnt/β-catenin signaling and elevation of mitochondria-mediated apoptosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)