Corrigendum: Cytokinins: a genetic target for increasing yield potential in the CRISPR era.

[This corrects the article DOI: 10.3389/fgene.2022.883930.].

Unearthing the inhibitory potential of phytochemicals from Lawsonia inermis L. and some drugs against dengue virus protein NS1: an in silico approach.

Dengue has received the status of an epidemic and endemic disease, with countless number of infections every year. Due to the unreliability of vaccines and non-specificity of drugs, it becomes necessary to find plant-based alternatives, with less harmful side effects. Lawsonia inermis L., is the sole source of dye, Mehendi. The rich repertoire of phytochemicals makes it useful, medicinally. The main objectives of the study are to explore the anti-dengue properties of the phytochemicals from Lawsonia inermis, and to shortlist potential candidates in curing the disease. Phytochemicals from the plant, and a set of drugs were screened and docked against NS1 protein, a less explored drug target, needed for maintenance of virus life cycle. Ligand screening and docking analysis concluded gallic acid, and chlorogenic acid to be good candidates, exhibiting high binding affinity and extensive interactions with the protein. From among the shortlisted drugs, only Vibegron showed effective binding affinity with NS1 protein with zero violations to the Lipinski's Rule of 5. Molecular dynamic simulations, executed for a time period of 100 nanoseconds, reveal the performance of a ligand within a solvated system. Chlorogenic and gallic acid, formed more stable and compact complexes with protein, with stable energy parameters and strong binding affinity. This was further validated with snapshots taken every 50 nanoseconds, showing no change in binding site between the ligand and protein, within the stipulated time frame. It was interesting to see that, a phenol (chlorogenic acid), served as a better drug candidate, against the NS1 protein.Communicated by Ramaswamy H. Sarma.

Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health-promoting activities.

Piper longum (family Piperaceae), commonly known as "long-pepper" or "Pippali" grows as a perennial shrub or as an herbaceous vine. It is native to the Indo-Malaya region and widely distributed in the tropical and subtropical world including the Indian subcontinent, Sri Lanka, Middle-East, and America. The fruits are mostly used as culinary spice and preservatives and are also a potent remedy in various traditional medicinal systems against bronchitis, cough, cold, snakebite, and scorpion-sting and are also used as a contraceptive. Various bioactive-phytochemicals including alkaloids, flavonoids, esters, and steroids were identified from the plant extracts and essential oils from the roots and fruits were reported as antimicrobial, antiparasitic, anthelminthic, mosquito-larvicidal, antiinflammatory, analgesic, antioxidant, anticancer, neuro-pharmacological, antihyperglycaemic, hepato-protective, antihyperlipidaemic, antiangiogenic, immunomodulatory, antiarthritic, antiulcer, antiasthmatic, cardioprotective, and anti-snake-venom agents. Many of its pharmacological properties were attributed to its antioxidative and antiinflammatory effects and its ability to modulate a number of signalling pathways and enzymes. This review comprehensively encompasses information on habit, distribution, ethnobotany, phytochemistry, and pharmacology of P. longum in relation to its medicinal importance and health benefits to validate the traditional claims supported by specific scientific experiments. In addition, it also discusses the safety and toxicity studies, application of green synthesis and nanotechnology as well as clinical trials performed with the plant also elucidating research gaps and future perspectives of its multifaceted uses.

Biotechnological interventions and indole alkaloid production in Rauvolfia serpentina.

Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae), commonly known as Sarpagandha or Indian snakeroot, has long been used in the traditional treatment of snakebites, hypertension, and mental illness. The plant is known to produce an array of indole alkaloids such as reserpine, ajmaline, amalicine, etc. which show immense pharmacological and biomedical significance. However, owing to its poor seed viability, lesser germination rate and overexploitation for several decades for its commercially important bioactive constituents, the plant has become endangered in its natural habitat. The present review comprehensively encompasses the various biotechnological tools employed in this endangered Ayurvedic plant for its in vitro propagation, role of plant growth regulators and additives in direct and indirect regeneration, somatic embryogenesis and synthetic seed production, secondary metabolite production in vitro, and assessment of clonal fidelity using molecular markers and genetic transformation. In addition, elicitation and other methods of optimization of its indole-alkaloids are also described herewith. KEY POINTS: • Latest literature on in vitro propagation of Rauvolfia serpentina • Biotechnological production and optimization of indole alkaloids • Clonal fidelity and transgenic studies in R. serpentina.

Biotechnology for micropropagation and camptothecin production in Ophiorrhiza sp.

Camptothecin (CPT) is a monoterpenoid-alkaloid, an anticancer compound from plant. Ever since its discovery in 1996 from the bark of Camptotheca acuminata, various researches have been conducted for enhancing its production. CPT has also been reported in several other species belonging to the plant families Icacinaceae, Rubiaceae, Apocynaceae, Nyssaceae, Betulaceae, Violaceae, Meliaceae, and Gelseminaceae. Out of these, Ophiorrhiza sp. (Rubiaceae) is the next possible candidate for sustainable CPT production after C. acuminata and Nothapodytes nimoonia. Various biotechnological-studies have been conducted on Ophiorrhiza sp. for searching the elite species and the most optimal strategies for CPT production. The genus Ophiorrhiza has been used as medicines for antiviral, antifungal, antimalarial, and anticancer activities. Phytochemical analysis has revealed the presence of alkaloids, flavonoids, triterpenes, and CPT from the plant. Because of the presence of CPT and its herbaceous habit, Ophiorrhiza sp. has now become a hot topic in research area. Currently, for mass production of the elite spp., tissue culture techniques have been implemented. In the past decades, several researchers have contributed on the diversity assessment, phytochemical analysis, mass production, and in vitro production of CPT in Ophiorrhiza sp. In this paper, we review the on the biotechnological strategies, optimal culture medium, micropropagation of Ophiorrhiza sp., effect of PGR on shoot formation, rhizogenesis, callus formation, and enhanced production of CPT for commercial use. KEY POINTS: • Latest literature on in vitro propagation of Ophiorrhiza sp. • Biotechnological production of camptothecin and related compounds • Optimization, elicitation, and transgenic studies in Ophiorrhiza sp.

Cytokinins: A Genetic Target for Increasing Yield Potential in the CRISPR Era.

Over the last decade, remarkable progress has been made in our understanding the phytohormones, cytokinin's (CKs) biosynthesis, perception, and signalling pathways. Additionally, it became apparent that interfering with any of these steps has a significant effect on all stages of plant growth and development. As a result of their complex regulatory and cross-talk interactions with other hormones and signalling networks, they influence and control a wide range of biological activities, from cellular to organismal levels. In agriculture, CKs are extensively used for yield improvement and management because of their wide-ranging effects on plant growth, development and physiology. One of the primary targets in this regard is cytokinin oxidase/dehydrogenase (CKO/CKX), which is encoded by CKX gene, which catalyses the irreversible degradation of cytokinin. The previous studies on various agronomically important crops indicated that plant breeders have targeted CKX directly. In recent years, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been increasingly used in editing the CKO/CKX gene and phenomenal results have been achieved. This review provides an updated information on the applications of CRISPR-based gene-editing tools in manipulating cytokinin metabolism at the genetic level for yield improvement. Furthermore, we summarized the current developments of RNP-mediated DNA/transgene-free genomic editing of plants which would broaden the application of this technology. The current review will advance our understanding of cytokinins and their role in sustainably increase crop production through CRISPR/Cas genome editing tool.

Multiple roles for basement membrane proteins in cancer progression and EMT.

Metastasis or the progression of malignancy poses a major challenge in cancer therapy and is the principal reason for increased mortality. The epithelial-mesenchymal transition (EMT) of the basement membrane (BM) allows cells of epithelial phenotype to transform into a mesenchymal-like (quasi-mesenchymal) phenotype and metastasize via the lymphovascular system through a metastatic cascade by intravasation and extravasation. This helps in the progression of carcinoma from the primary site to distant organs. Collagen, laminin, and integrin are the prime components of BM and help in tumor cell metastasis, which makes them ideal cancer drug targets. Further, recent studies have shown that collagen, laminin, and integrin can be used as a biomarker for metastatic cells. In this review, we have summarized the current knowledge of such therapeutics, which are either currently in preclinical or clinical stages and could be promising cancer therapeutics. DATA AVAILABILITY: Not applicable.

Enhanced rosmarinic acid production in cultured plants of two species of Mentha.

In the present investigation an attempt has been made to enhance rosmarinic acid level in plants, grown in vitro, of 2 species of Mentha in presence of 2 precursors in the nutrient media during culture. For in vitro culture establishment and shoot bud multiplication, MS basal media were used supplemented with different concentrations and combinations of different growth regulator like NAA (alpha-napthaleneacetic acid), BAP (6-benzylaminopurine). The medium containing NAA (0.25 mg/L) and BAP (2.5 mg/L) gave the highest potentiality of shoot formation (average 58.0 numbers of shoots) per explant for Mentha piperita L. and the medium containing BAP (2.0 mg/L) gave the highest potentiality of shoot (average 19.2 numbers of shoots) formation per explant for Mentha arvensis L. The complete plants were regenerated in above mentioned media after 8 weeks of subculture. For in vitro enhancement of rosmarinic acid production, the 2 precursors tyrosine (Tyr) and phenylalanine (Phe) were added in the nutrient media at different levels (0.5 mg/L to 15.0 mg/L). Tyrosine was found to be very effective for augmenting rosmarinic acid content in Mentha piperita L. It nearly increased the production up to 1.77 times. In case of Mentha arvensis L., phenylalanine significantly affected the production of rosmarinic acid and the production was nearly 2.03 times more than the control. No significant increase in biomass was observed after addition of these precursors indicating that the added amino acids acting as precursors for rosmarinic acid synthesis were readily utilized in producing rosmarinic acid without promoting growth. Total protein profile also revealed the presence of a specific band in polyacrylamide gel electrophoresis.