Carbon nanotubes in plant dynamics: Unravelling multifaceted roles and phytotoxic implications.

Carbon nanotubes (CNTs) have emerged as a promising frontier in plant science owing to their unique physicochemical properties and versatile applications. CNTs enhance stress tolerance by improving water dynamics and nutrient uptake and activating defence mechanisms against abiotic and biotic stresses. They can be taken up by roots and translocated within the plant, impacting water retention, nutrient assimilation, and photosynthesis. CNTs have shown promise in modulating plant-microbe interactions, influencing symbiotic relationships and mitigating the detrimental effects of phytopathogens. CNTs have demonstrated the ability to modulate gene expression in plants, offering a powerful tool for targeted genetic modifications. The integration of CNTs as sensing elements in plants has opened new avenues for real-time monitoring of environmental conditions and early detection of stress-induced changes. In the realm of agrochemicals, CNTs have been explored for their potential as carriers for targeted delivery of nutrients, pesticides, and other bioactive compounds. CNTs have the potential to demonstrate phytotoxic effects, detrimentally influencing both the growth and developmental processes of plants. Phytotoxicity is characterized by induction of oxidative stress, impairment of cellular integrity, disruption of photosynthetic processes, perturbation of nutrient homeostasis, and alterations in gene expression. This review aims to provide a comprehensive overview of the current state of knowledge regarding the multifaceted roles of CNTs in plant physiology, emphasizing their potential applications and addressing the existing challenges in translating this knowledge into sustainable agricultural practices.

In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches.

Infection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful.

Microbial exopolysaccharides: Unveiling the pharmacological aspects for therapeutic advancements.

Microbial exopolysaccharides (EPSs) have emerged as a fascinating area of research in the field of pharmacology due to their diverse and potent biological activities. This review paper aims to provide a comprehensive overview of the pharmacological properties exhibited by EPSs, shedding light on their potential applications in various therapeutic areas. The review begins by introducing EPSs, exploring their various sources, significance in microbial growth and survival, and their applications across different industries. Subsequently, a thorough examination of the pharmaceutical properties of microbial EPSs unveils their antioxidant, immunomodulatory, antimicrobial, antidepressant, antidiabetic, antiviral, antihyperlipidemic, hepatoprotective, anti-inflammatory, and anticancer activities. Mechanistic insights into how different EPSs exert these therapeutic effects have also been discussed in this review. The review also provides comprehensive information about the monosaccharide composition, backbone, branches, glycosidic bonds, and molecular weight of pharmacologically active EPSs from various microbial sources. Furthermore, the factors that can affect the pharmacological activities of EPSs and approaches to improve the EPSs' pharmacological activity have also been discussed. In conclusion, this review illuminates the immense pharmaceutical promise of microbial EPS as versatile bioactive compounds with wide-ranging therapeutic applications. By elucidating their structural features, biological activities, and potential applications, this review aims to catalyze further research and development efforts in leveraging the pharmaceutical potential of microbial EPS for the advancement of human health and well-being, while also contributing to sustainable and environmentally friendly practices in the pharmaceutical industry.

Algae-Mediated Removal of Prevalent Genotoxic Antibiotics: Molecular Perspective on Algae-Bacteria Consortia and Bioreactor-Based Strategies.

Antibiotic pollution poses a potential risk of genotoxicity, as antibiotics released into the environment can induce DNA damage and mutagenesis in various organisms. This pollution, stemming from pharmaceutical manufacturing, agriculture, and improper disposal, can disrupt aquatic ecosystems and potentially impact human health through the consumption of contaminated water and food. The removal of genotoxic antibiotics using algae-mediated approaches has gained considerable attention due to its potential for mitigating the environmental and health risks associated with these compounds. The paper provides an in-depth examination of the molecular aspects concerning algae and bioreactor-driven methodologies utilized for the elimination of deleterious antibiotics. The molecular analysis encompasses diverse facets, encompassing the discernment and profiling of algae species proficient in antibiotic degradation, the explication of enzymatic degradation pathways, and the refinement of bioreactor configurations to augment removal efficacy. Emphasizing the significance of investigating algal approaches for mitigating antibiotic pollution, this paper underscores their potential as a sustainable solution, safeguarding both the environment and human health.

Unraveling molecular signatures in rare bone tumors and navigating the cancer pathway landscapes for targeted therapeutics.

Rare cancers (RCs), which account for over 20% of cancer cases, face significant research and treatment challenges due to their limited prevalence. This results in suboptimal outcomes compared to more common malignancies. Rare bone tumors (RBTs) constitute 5-10% of rare cancer cases and pose unique diagnostic complexities. The therapeutic potential of anti-cancer drugs for RBTs remains largely unexplored. Identifying molecular alterations in cancer-related genes and their associated pathways is essential for precision medicine in RBTs. Small molecule inhibitors and monoclonal antibodies targeting specific RBT-associated proteins show promise. Ongoing clinical trials aim to define RBT biomarkers, subtypes, and optimal treatment contexts, including combination therapies and immunotherapeutic agents. This review addresses the challenges in diagnosing, treating, and studying RBTs, shedding light on the current state of RBT biomarkers, potential therapeutic targets, and promising inhibitors. Rare cancers demand attention and innovative solutions to improve clinical outcomes.

Alterations in microbiome of COVID-19 patients and its impact on forensic investigations.

The human microbiome is vital for maintaining human health and has garnered substantial attention in recent years, particularly in the context of the coronavirus disease 2019 (COVID-19) outbreak. Studies have underscored significant alterations in the microbiome of COVID-19 patients across various body niches, including the gut, respiratory tract, oral cavity, skin, and vagina. These changes manifest as shifts in microbiota composition, characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. Such microbiome transformations may play a pivotal role in influencing the course and severity of COVID-19, potentially contributing to the inflammatory response. This ongoing relationship between COVID-19 and the human microbiome serves as a compelling subject of research, underscoring the necessity for further investigations into the underlying mechanisms and their implications for patient health. Additionally, these alterations in the microbiome may have significant ramifications for forensic investigations, given the microbiome's potential in establishing individual characteristics. Consequently, changes in the microbiome could introduce a level of complexity into forensic determinations. As research progresses, a more profound understanding of the human microbiome within the context of COVID-19 may offer valuable insights into disease prevention, treatment strategies, and its potential applications in forensic science. Consequently, this paper aims to provide an overarching review of microbiome alterations due to COVID-19 and the associated impact on forensic applications, bridging the gap between the altered microbiome of COVID-19 patients and the challenges forensic investigations may encounter when analyzing this microbiome as a forensic biomarker.

Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy.

Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway has been implicated in the development and progression of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown promising preclinical and clinical activity in various cancers. These agents can inhibit the activation of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy of other anticancer therapies, such as chemotherapy and radiation therapy. The different types of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be effective depending on the specific sarcoma type and stage. The molecular targeting of PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence suggests that these inhibitors may significantly improve patient outcomes. Further research is needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing more selective and effective agents to meet the clinical needs of sarcoma patients.

Metagenomics in the fight against zoonotic viral infections: A focus on SARS-CoV-2 analogues.

Zoonotic viral infections continue to pose significant threats to global public health, as highlighted by the COVID-19 pandemic caused by the SARS-CoV-2 virus. The emergence of SARS-CoV-2 served as a stark reminder of the potential for zoonotic transmission of viruses from animals to humans. Understanding the origins and dynamics of zoonotic viruses is critical for early detection, prevention, and effective management of future outbreaks. Metagenomics has emerged as a powerful tool for investigating the virome of diverse ecosystems, shedding light on the diversity of viral populations, their hosts, and potential zoonotic spillover events. We provide an in-depth examination of metagenomic approaches, including, NGS metagenomics, shotgun metagenomics, viral metagenomics, and single-virus metagenomics, highlighting their strengths and limitations in identifying and characterizing zoonotic viral pathogens. This review underscores the pivotal role of metagenomics in enhancing our ability to detect, monitor, and mitigate zoonotic viral infections, using SARS-CoV-2 analogues as a case study. We emphasize the need for continued interdisciplinary collaboration among virologists, ecologists, and bioinformaticians to harness the full potential of metagenomic approaches in safeguarding public health against emerging zoonotic threats.

Advancing biological investigations using portable sensors for detection of sensitive samples.

Portable biosensors are emerged as powerful diagnostic tools for analyzing intricately complex biological samples. These biosensors offer sensitive detection capabilities by utilizing biomolecules such as proteins, nucleic acids, microbes or microbial products, antibodies, and enzymes. Their speed, accuracy, stability, specificity, and low cost make them indispensable in forensic investigations and criminal cases. Notably, portable biosensors have been developed to rapidly detect toxins, poisons, body fluids, and explosives; they have proven invaluable in forensic examinations of suspected samples, generating efficient results that enable effective and fair trials. One of the key advantages of portable biosensors is their ability to provide sensitive and non-destructive detection of forensic samples without requiring extensive sample preparation, thereby reducing the possibility of false results. This comprehensive review provides an overview of the current advancements in portable biosensors for the detection of sensitive materials, highlighting their significance in advancing investigations and enhancing sensitive sample detection capabilities.

Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence.

Existing therapeutic interventions for controlling cancer are limited and associated with side effects. Furthermore, the recurrence of cancer poses a significant challenge to the cure of cancer. Therefore, avenues are wanted to find novel therapies for cancer treatment and cancer recurrence. In this review, we have highlighted that lactoferrin (LF) and activated protein C (APC) carry enormous potential in cancer treatment. Studies have shown that the decreased level of APC and impaired function of APC are associated with cancer progression and cancer-related mortality. Moreover, APC plays an important role in preventing prothrombotic state-mediated cancer progression and deaths. LF can also inhibit the progression of cancer by controlling the generation of reactive oxygen species, triggering the apoptosis of cancer cells, arresting the cell cycle and hindering the angiogenesis process. Additionally, APC and LF could have the potential to inhibit neutrophil extracellular traps (NETs) formations which are involved in cancer progression and the reawakening of dormant cancer cells. Hence, in this review, the anticancer potential and mechanism of APC and LF along with their potential to mitigate inflammation and NETs-mediated cancer progression and recurrence has been discussed. Additionally, possible future strategies to develop effective and safe anticancer treatment using LF and APC have also been discussed in this review.

Potent antifungal properties of gallic acid in Sarcochlamys pulcherrima against Candida auris.

Candida auris is a major public health concern due to its high transmission and mortality rates, as well as the emergence of pan-resistant strains. This study aimed to identify an antifungal compound from Sarcochlamys pulcherrima , an ethnomedicinal plant, that can inhibit the growth of C. auris. Methanol and ethyl acetate extracts of the plant were obtained, and high-performance thin-layer chromatography (HPTLC) analysis was conducted to identify the major compounds in the extracts. The major compound detected by HPTLC was subjected to in vitro antifungal activity testing, and its antifungal mechanism was determined. The plant extracts inhibited the growth of both C. auris and Candida albicans. HPTLC analysis revealed the presence of gallic acid in the leaf extract. Furthermore, the in vitro antifungal assay showed that gallic acid inhibited the growth of different C. auris strains. In silico studies indicated that gallic acid can bind to the active sites of carbonic anhydrase (CA) proteins in both C. auris and C. albicans, affecting their catalytic activities. Compounds that target virulent proteins such as CA can aid in the reduction of drug-resistant fungi and the development of novel antifungal compounds with unique modes of action. However, additional in vivo and clinical studies are required to conclusively determine gallic acid's antifungal properties. Gallic acid derivatives may be developed in the future to possess more potent antifungal properties and target various pathogenic fungi.

Discovering Deleterious Single Nucleotide Polymorphisms of Human AKT1 Oncogene: An In Silico Study.

BACKGROUND: AKT1 is a serine/threonine kinase necessary for the mediation of apoptosis, angiogenesis, metabolism, and cell proliferation in both normal and cancerous cells. The mutations in the AKT1 gene have been associated with different types of cancer. Further, the AKT1 gene mutations are also reported to be associated with other diseases such as Proteus syndrome and Cowden syndromes. Hence, this study aims to identify the deleterious AKT1 missense SNPs and predict their effect on the function and structure of the AKT1 protein using various computational tools. METHODS: Extensive in silico approaches were applied to identify deleterious SNPs of the human AKT1 gene and assessment of their impact on the function and structure of the AKT1 protein. The association of these highly deleterious missense SNPs with different forms of cancers was also analyzed. The in silico approach can help in reducing the cost and time required to identify SNPs associated with diseases. RESULTS: In this study, 12 highly deleterious SNPs were identified which could affect the structure and function of the AKT1 protein. Out of the 12, four SNPs-namely, G157R, G159V, G336D, and H265Y-were predicted to be located at highly conserved residues. G157R could affect the ligand binding to the AKT1 protein. Another highly deleterious SNP, R273Q, was predicted to be associated with liver cancer. CONCLUSIONS: This study can be useful for pharmacogenomics, molecular diagnosis of diseases, and developing inhibitors of the AKT1 oncogene.

Eco-friendly and safe alternatives for the valorization of shrimp farming waste.

The seafood industry generates waste, including shells, bones, intestines, and wastewater. The discards are nutrient-rich, containing varying concentrations of carotenoids, proteins, chitin, and other minerals. Thus, it is imperative to subject seafood waste, including shrimp waste (SW), to secondary processing and valorization for demineralization and deproteination to retrieve industrially essential compounds. Although several chemical processes are available for SW processing, most of them are inherently ecotoxic. Bioconversion of SW is cost-effective, ecofriendly, and safe. Microbial fermentation and the action of exogenous enzymes are among the significant SW bioconversion processes that transform seafood waste into valuable products. SW is a potential raw material for agrochemicals, microbial culture media, adsorbents, therapeutics, nutraceuticals, and bio-nanomaterials. This review comprehensively elucidates the valorization approaches of SW, addressing the drawbacks of chemically mediated methods for SW treatments. It is a broad overview of the applications associated with nutrient-rich SW, besides highlighting the role of major shrimp-producing countries in exploring SW to achieve safe, ecofriendly, and efficient bio-products.

MERS virus spike protein HTL-epitopes selection and multi-epitope vaccine design using computational biology.

MERS-CoV, a zoonotic virus, poses a serious threat to public health globally. Thus, it is imperative to develop an effective vaccination strategy for protection against MERS-CoV. Immunoinformatics and computational biology tools provide a faster and more cost-effective strategy to design potential vaccine candidates. In this work, the spike proteins from different strains of MERS-CoV were selected to predict HTL-epitopes that show affinity for T-helper MHC-class II HTL allelic determinant (HLA-DRB1:0101). The antigenicity and conservation of these epitopes among the selected spike protein variants in different MERS-CoV strains were analyzed. The analysis identified five epitopes with high antigenicity: QSIFYRLNGVGITQQ, DTIKYYSIIPHSIRS, PEPITSLNTKYVAPQ, INGRLTTLNAFVAQQ and GDMYVYSAGHATGTT. Then, a multi-epitope vaccine candidate was designed using linkers and adjuvant molecules. Finally, the vaccine construct was subjected to molecular docking with TLR5 (Toll-like receptor-5). The proposed vaccine construct had strong binding energy of -32.3 kcal/mol when interacting with TLR5.Molecular dynamics simulation analysis showed that the complex of the vaccine construct and TLR5 is stable. Analysis using in silico immune simulation also showed that the prospective multi-epitope vaccine design had the potential to elicit a response within 70 days, with the immune system producing cytokines and immunoglobulins. Finally, codon adaptation and in silico cloning analysis showed that the candidate vaccine could be expressed in the Escherichia coli K12 strain. Here we also designed support vaccine construct MEV-2 by using B-cell and CD8+ CTL epitopes to generate the complete immunogenic effect. This study opens new avenues for the extension of research on MERS vaccine development.Communicated by Ramaswamy H. Sarma.

Secreted Aspartyl Proteinases Targeted Multi-Epitope Vaccine Design for Candida dubliniensis Using Immunoinformatics.

Candida dubliniensis is an opportunistic pathogen associated with oral and invasive fungal infections in immune-compromised individuals. Furthermore, the emergence of C. dubliniensis antifungal drug resistance could exacerbate its treatment. Hence, in this study a multi-epitope vaccine candidate has been designed using an immunoinformatics approach by targeting C. dubliniensis secreted aspartyl proteinases (SAP) proteins. In silico tools have been utilized to predict epitopes and determine their allergic potential, antigenic potential, toxicity, and potential to elicit interleukin-2 (IL2), interleukin-4 (IL4), and IFN-γ. Using the computational tools, eight epitopes have been predicted that were then linked with adjuvants for final vaccine candidate development. Computational immune simulation has depicted that the immunogen designed emerges as a strong immunogenic candidate for a vaccine. Further, molecular docking and molecular dynamics simulation analyses revealed stable interactions between the vaccine candidate and the human toll-like receptor 5 (TLR5). Finally, immune simulations corroborated the promising candidature of the designed vaccine, thus calling for further in vivo investigation.

Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials.

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network.

Discovering untapped microbial communities through metagenomics for microplastic remediation: recent advances, challenges, and way forward.

Microplastics (MPs) are ubiquitous pollutants persisting almost everywhere in the environment. With the increase in anthropogenic activities, MP accumulation is increasing enormously in aquatic, marine, and terrestrial ecosystems. Owing to the slow degradation of plastics, MPs show an increased biomagnification probability of persistent, bioaccumulative, and toxic substances thereby creating a threat to environmental biota. Thus, remediation of MP-pollutants requires efficient strategies to circumvent the mobilization of contaminants leaching into the water, soil, and ultimately to human beings. Over the years, several microorganisms have been characterized by the potential to degrade different plastic polymers through enzymatic actions. Metagenomics (MGs) is an effective way to discover novel microbial communities and access their functional genetics for the exploration and characterization of plastic-degrading microbial consortia and enzymes. MGs in combination with metatranscriptomics and metabolomics approaches are a powerful tool to identify and select remediation-efficient microbes in situ. Advancement in bioinformatics and sequencing tools allows rapid screening, mining, and prediction of genes that are capable of polymer degradation. This review comprehensively summarizes the growing threat of microplastics around the world and highlights the role of MGs and computational biology in building effective response strategies for MP remediation.

Genome centric engineering using ZFNs, TALENs and CRISPR-Cas9 systems for trait improvement and disease control in Animals.

Livestock is an essential life commodity in modern agriculture involving breeding and maintenance. The farming practices have evolved mainly over the last century for commercial outputs, animal welfare, environment friendliness, and public health. Modifying genetic makeup of livestock has been proposed as an effective tool to create farmed animals with characteristics meeting modern farming system goals. The first technique used to produce transgenic farmed animals resulted in random transgene insertion and a low gene transfection rate. Therefore, genome manipulation technologies have been developed to enable efficient gene targeting with a higher accuracy and gene stability. Genome editing (GE) with engineered nucleases-Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) regulates the targeted genetic alterations to facilitate multiple genomic modifications through protein-DNA binding. The application of genome editors indicates usefulness in reproduction, animal models, transgenic animals, and cell lines. Recently, CRISPR/Cas system, an RNA-dependent genome editing tool (GET), is considered one of the most advanced and precise GE techniques for on-target modifications in the mammalian genome by mediating knock-in (KI) and knock-out (KO) of several genes. Lately, CRISPR/Cas9 tool has become the method of choice for genome alterations in livestock species due to its efficiency and specificity. The aim of this review is to discuss the evolution of engineered nucleases and GETs as a powerful tool for genome manipulation with special emphasis on its applications in improving economic traits and conferring resistance to infectious diseases of animals used for food production, by highlighting the recent trends for maintaining sustainable livestock production.

Fighting Carcinogenesis with Plant Metabolites by Weakening Proliferative Signaling and Disabling Replicative Immortality Networks of Rapidly Dividing and Invading Cancerous Cells.

BACKGROUND: Cancer, an uncontrolled multistage disease causing swift division of cells, is a leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors, resisting cell death, and replicative immortality drive the tumor progression by resisting the therapeutic action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling, enabling replicative immortality through telomere dysfunction. AREA COVERED: The conventional genotoxic drugs have several off-target and collateral side effects associated with them. Thus, the need for the therapies targeting cyclin-dependent kinases or P13K signaling pathway to expose cancer cells to immune destruction, deactivation of invasion and metastasis, and maintaining cellular energetics is imperative. Compounds with anticancer attributes isolated from plants and rich in alkaloids, terpenes, and polyphenols have proven to be less toxic and highly targetspecific, making them biologically significant. This has opened a gateway for the exploration of more novel plant molecules by signifying their role as anticancer agents in synergy and alone, making them more effective than the existing cytotoxic regimens. EXPERT OPINION: In this context, the current review presented recent data on cancer cases around the globe, along with discussing the fundamentals of proliferative signaling and replicative immortality of cancer cells. Recent findings were also highlighted, including antiproliferative and antireplicative action of plant-derived compounds, besides explaining the need for improving drug delivery systems.