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The intensification of food production via conventional crop breeding alone is inadequate to cater for global hunger. The development of precise and expeditious high throughput reverse genetics approaches has hugely benefited modern plant breeding programs. Targeting Induced Local Lesions in Genomes (TILLING) is one such reverse genetics approach which employs chemical/physical mutagenesis to create new genetic sources and identifies superior/novel alleles. Owing to technical limitations and sectional applicability of the original TILLING protocol, it has been timely modified. Successions include: EcoTILLING, Double stranded EcoTILLING (DEcoTILLING), Self-EcoTILLING, Individualized TILLING (iTILLING), Deletion-TILLING (De-TILLING), PolyTILLING, and VeggieTILLING. This has widened its application to a variety of crops and needs. They can characterize mutations in coding as well as non-coding regions and can overcome complexities associated with the large genomes. Combining next generation sequencing tools with the existing TILLING protocols has enabled screening of huge germplasm collections and mutant populations for the target genes. In silico TILLING platforms have transformed TILLING into an exciting breeding approach. The present review outlines these multifarious TILLING modifications for precise mutation detection and their application in advance breeding programmes together with relevant case studies. Appropriate use of these protocols will open up new avenues for crop improvement in the twenty first century.

Background: Epidemiological studies have suggested that a regular intake of flavonoids is beneficial for cellular homeostasis and in the prevention of the transformation of normal cells into cancerous cells. Because of their multiple biological targets, flavonoids have been studied and investigated as phytoconstituents with potential anticancer properties. Flavonoids interfere in the development of cancerous cells by inhibition of topoisomerases, protein kinases, angiogenesis, induction of apoptosis, cell cycle arrest, modulation of multidrug resistance, and improvement in anti-oxidative activities. The current review summarizes the anticancer properties of flavonoids along with the key structural features and their mechanisms. The present study provides a detailed analysis of anticancer activities with previously published data on different flavonoids. The review highlighted the structural aspects and mechanism of action of flavonoids with their potential target sites. Flavonoids induce anticancer activity by protein kinases inhibition, P-gp modulation, antiangiogenesis, topoisomerases inhibition, etc. Open ring C, the double bond between C2-C3, the oxo group at C4, and the position of ring B are crucial determinants for their anticancer activity. Flavonoids act by multiple mechanisms but further studies on target selectivity and specificity of flavonoids are necessary to establish them as anticancer therapeutics. The presence of a C2-C3 double bond and oxo group at C4 (also known as an enone moiety) or -OH in the neighbour of a double bond that can transform easily into an enone are common features present in flavonoids. Thus, it can be concluded that enone moiety or its precursor groups are mainly responsible for the anticancer activities of flavonoids via different mechanisms of action., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The exploitation of heterosis through intersubspecific hybridisation between indica and japonica has been a major breeding target in rice, but is marred by the cross incompatibility between the genomes. Wide compatibility (WC) is a triallelic system at the S5 locus on chromosome 6 that ensures the specificity of hybridisation within and between indica and japonica. The S5n allele that favours intercrossing is sparsely distributed in the rice gene pool and therefore warrants identification of diverse WC sources to develop superior intersubspecific hybrids. In this study, we have identified several novel WC sources through the marker-assisted screening of a large set of 950 rice genotypes. Seventeen percent of the genotypes carried S5n , which fell into two subpopulations. The WC genotypes showed wide phenotypic and genotypic variability, including both indica and japonica lines. Based on phenotypic performance, the WC varieties were grouped into three clusters. A subset of 41 WC varieties was used to develop 164 hybrids, of which WC/ japonica hybrids showed relative superiority over WC/ indica hybrids. The multilocation evaluation of hybrids indicated that hybrids derived from WC varieties, such as IRG137, IRG143, OYR128, and IRGC10658, were higher yielding across all the three different locations. Most of the hybrids showed the stability of performance across locations. The identified diverse set of wide compatible varieties (WCVs) can be used in the development of intersubspecific hybrids and also for parental line development in hybrid rice breeding.

Abating the approaching yield plateau in rice requires taking advantage of potential technologies that requires knowledge on genetic diversity. Hybrid breeding, particularly in indica rice, requires the recruitment of large genetic variability from outside because the available genetic diversity of the cultivated pool has already been utilized to a great extent. In this study, we examined an assembly of 200 tropical japonica lines collected worldwide for population genetic structure and variability in yield-associated traits. Tested along with 30 indica and six wild rice lines belonging to India, the tropical japonica lines indicated great phenotypic variability, particularly related to new plant type (NPT) phenology, and formed six clusters. Furthermore, a marker-based characterization using a universal diversity marker panel classified the genotype assembly into four clusters, of which three encompassed tropical japonica lines, while the last cluster included mostly indica lines. The population structure of the panel also revealed a similar pattern, with tropical japonica lines forming three subpopulations. Remarkable variation in the allelic distribution was observed between the subpopulations. Superimposing the geographical sources of the genotypes over the population structure did not reveal any pattern. The genotypes sourced closer to the center of origin of rice showed relatively little diversity compared with the ones obtained from other parts of the world, suggesting migration from a common region of origin. The tropical japonica lines can be a great source of parental diversification for hybrid development after confirming the presence of widely compatible genes.

Background: Neurodegenerative disorders belong to different classes of progressive/ chronic conditions that affect the peripheral/central nervous system. It has been shown through studies that athletes who play sports involving repeated head trauma and sub-concussive impacts are more likely to experience neurological impairments and neurodegenerative disorders in the long run Aims: The aim of the current narrative review article is to provide a summary of various nutraceuticals that offer promise in the prevention or management of sports-related injuries, especially concussions and mild traumatic brain injuries., Methods: This article reviews the various potential nutraceutical agents and their possible mechanisms in providing a beneficial effect in the injury recovery process. A thorough survey of the literature was carried out in the relevant databases to identify studies published in recent years. In the present article, we have also highlighted the major neurological disorders along with the associated nutraceutical(s) therapy in the management of disorders., Results: The exact pathological mechanism behind neurodegenerative conditions is complex as well as idiopathic. However, mitochondrial dysfunction, oxidative stress as well as intracellular calcium overload are some common reasons responsible for the progression of these neurodegenerative disorders. Owing to the multifaceted effects of nutraceuticals (complementary medicine), these supplements have gained importance as neuroprotective. These diet-based approaches inhibit different pathways in a physiological manner without eliciting adverse effects. Food habits and lifestyle of an individual also affect neurodegeneration., Conclusion: Studies have shown nutraceuticals (such as resveratrol, omega-3-fatty acids) to be efficacious in terms of their neuroprotection against several neurodegenerative disorders and to be used as supplements in the management of traumatic brain injuries. Protection prior to injuries is needed since concussions or sub-concussive impacts may trigger several pathophysiological responses or cascades that can lead to long-term complications associated with CNS. Thus, the use of nutraceuticals as prophylactic treatment for neurological interventions has been proposed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The platinum (II) complexes as anticancer agents have been well explored for the development of novel analogs. Yet, none of them achieved clinical importance in oncology. At present, anticancer compounds containing platinum (II) complexes have been employed in the treatment of colorectal, lung, and genitourinary tumors. Among the platinum-based anticancer drugs, Cisplatin (cis-diamine dichloroplatinum (II), cis-[Pt(NH3)2Cl2]) is one of the most potent components of cancer chemotherapy. The nephrotoxicity, neurotoxicity and ototoxicity, and platinum compounds associated resistant cancer are some major disadvantages., Objective: With the rapidly growing interest in platinum (II) complexes in tumor chemotherapy, researchers have synthesized many new platinum analogs as anticancer agents that show better cytotoxicity, and less off-target effects with less cellular resistance. This follows the introduction of oxaliplatin, water-soluble carboplatin, multinuclear platinum and newly synthesized complexes, etc. Methods: This review emphasizes recent advancements in drug design and development, the mechanism of platinum (II) complexes, their stereochemistry, current updates, and biomedical applications of platinum-based anticancer agents., Conclusion: In the last few decades, the popularity of platinum complexes as potent anti-cancer agents has risen as scientists have synthesized many new platinum complexes that exhibit better cytotoxicity coupled with less off-target effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Prostate cancer is considered the second most diagnosed cancer, and one of the most common causes of death from cancer in men. Apalutamide is an effective, safe, and well-tolerated agent used for the treatment of men with non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) and metastatic Hormone-Naive Prostate Cancer (mHNPC). Androgen receptor signaling is a leading factor that drives these prostate tumors. USFDA has approved apalutamide on 14 February 2018 as an agent that targets androgen receptor signaling through inhibition causing significant improvement in metastasis-free survival in patients with prostate cancer., Objective: In this review, various aspects related to apalutamide have been summarized which involve the mechanism of action, chemistry, synthesis, pharmacokinetics, pharmacodynamics, adverse reactions, and safety parameters., Methods: The literature was thoroughly searched in the relevant databases to identify studies published in this field during recent years. Special attention has been given to apalutamide clinical trials phases and its promising future as one of the first-line agents for the treatment of patients with advanced prostate cancer., Results: Ongoing trials are progressing for apalutamide monotherapy and also for its combinations in other disease settings. The expected results of such trials will shape the future scenario of prostate cancer therapy., Conclusion: This review article has highlighted different aspects of Apalutamide like its mechanism of action, adverse effects, pharmacokinetics, pharmacodynamics, clinical trials among others. The contents of this article should make an excellent read for prospective researchers in this field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Epidermal growth factor receptor (EGFR) is a vital intermediate in cell signaling pathway including cell proliferation, angiogenesis, apoptosis, and metastatic spread and also having four divergent members with similar structural features, such as EGFR (HER1/ErbB1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4). Despite this, clinically exploited inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific thus provoking unenviable adverse effects. Some of the paramount obstacles to generate and develop new lead molecules of EGFR inhibitors are drug resistance, mutation, and also selectivity which inspire medicinal chemists to generate novel chemotypes. The discovery of therapeutic agents that inhibit the precise stage in tumorous cells such as EGFR is one of the chief successful targets in many cancer therapies, including lung and breast cancers. This review aims to compile the various recent progressions (2016-2021) in the discovery and development of diverse epidermal growth factor receptor (EGFR) inhibitors belonging to distinct structural classes like pyrazoline, pyrazole, imidazole, pyrimidine, coumarin, benzothiazole, etc. We have summarized preclinical and clinical data, structure-activity relationships (SAR) containing mechanistic and in silico studies to provide proposals for the design and invention of new EGFR inhibitors with therapeutic significance. The detailed progress of the work in the field will provide inexorable scope for the development of novel drug candidates with greater selectivity and efficacy., (Copyright © 2021. Published by Elsevier Inc.)

Climate change has escalated abiotic stresses, leading to adverse effects on plant growth and development, eventually having deleterious consequences on crop productivity. Environmental stresses induce epigenetic changes, namely cytosine DNA methylation and histone post-translational modifications, thus altering chromatin structure and gene expression. Stable epigenetic changes are inheritable across generations and this enables plants to adapt to environmental changes (epipriming). Hence, epigenomes serve as a good source of additional tier of variability for development of climate-smart crops. Epigenetic resources such as epialleles, epigenetic recombinant inbred lines (epiRILs), epigenetic quantitative trait loci (epiQTLs), and epigenetic hybrids (epihybrids) can be utilized in epibreeding for improving stress tolerance of crops. Epigenome engineering is also gaining momentum for developing sustainable epimarks associated with important agronomic traits. Different epigenome editing tools are available for creating, erasing, and reading such epigenetic codes in plant genomes. However, epigenome editing is still understudied in plants due to its complex nature. Epigenetic interventions such as epi-fingerprinting can be exploited in the near future for health and quality assessment of crops under stress conditions. Keeping in view the challenges and opportunities associated with this important technology, the present review intends to enhance understanding of stress-induced epigenetic changes in plants and its prospects for development of climate-ready crops., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The mitogen activated protein kinase (MAPK) belongs to group of kinase that links the extracellular stimuli to intracellular response. The MAPK signalling pathway (RAS-RAF-MEK-ERK) involved in different pathological conditions like cancer, caused due to genetic or any other factor such as physical or environmental. Many studies have been conducted on the pathological view of MAPK cascade and its associated element like RAS, RAF, MEK, ERK or its isoforms, and still the research is going on particularly with respect to its activation, regulation and inhibition. The MAPK signalling pathway has become the area of research to identify new target for the management of cancer. A number of heterocyclics are key to fight with the cancer associated with these enzymes thus give some hope in the management of cancer by inhibiting MAPK cascade. In the present article, we have focussed on MAPK signalling pathway and role of different heterocyclic scaffolds bearing nitrogen, sulphur and oxygen and about their potential to block MAPK signalling pathway. The heterocyclics are gaining importance due to high potency and selectivity with less off-target effects against different targets involved in the MAPK signalling pathway. We have tried to cover recent advancements in the MAPK signalling pathway inhibitors with an aim to get better understanding of the mechanism of action of the compounds. Several compounds in the preclinical and clinical studies have been thoroughly dealt with. In addition to the synthetic compounds, a significant number of natural products containing heterocyclic moieties as MAPK signalling pathway inhibitors have been put together. The structure activity relationship along with docking studies have been discussed to apprehend the mechanistic studies of various compounds that will ultimately help to design and develop more MAPK signalling pathway inhibitors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Electronic witness system (EWS) is one of the recent advancements in the field of in vitro fertilization (IVF) that uses radiofrequency identification (RFID) technology to monitor all critical work carried out in each stage of IVF procedures cycle., Objective: The main objective of the study was validation and integration of electronic witnessing system, assessment of its efficacy on lab performance, and staff satisfaction in a busy tertiary IVF center., Materials and Methods: The study data included analysis of 187 consecutive cycles for installation and validation of EWS. The laboratory outcomes were analyzed for development of good-quality embryos followed up for the pregnancy outcome., Results: A total of 751 RFIG tags were involved with 77 patient-assigned barcodes for the all the analyzed cycles. During validation of EWS, a total of 02 (0.46%) red flags were highlighted by EWS from pre-allocated tags within the frequency range of the reader. The maturation rate (83.1%), fertilization rate (74.3%), cleavage rate (93.5%), day 3 grade-A embryo development rate (64.6%), good grade blastocyst development rate (26.4%) were observed in EWS group that was comparable to other groups with no significant difference ( P > 0.005). Frozen embryo transfer of EWS cases observed a clinical pregnancy rate (50.0%) that was higher than other groups though statistically not significant as sample size was small., Conclusions: Our preliminary study suggests that EWS does not affect the gametes, embryos, and pregnancy rate, however a larger randomized clinical trials should be undertaken to evaluate the safety and efficacy of EWS., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Human Reproductive Sciences.)

One hundred diverse iso-cytoplasmic restorer (ICR) lines carrying WA cytoplasm indicated significant but moderate variability for agro-morphological traits as well as for the microsatellite-based allele patterns. There were two major groups of ICRs based on agro-morphological clustering. Simple sequence repeat (SSR) markers identified allelic variants with an average of 2.48 alleles per locus and the gene diversity (GD) ranged from 0.02 to 0.62 at different loci. ICR lines showed a genetic structure involving two sub-populations, POP1 and POP2. Both the subpopulations had the presence of admixture lines. Nearest ancestry-based grouping of ICRs by neighbour-joining (NJ) method showed near similar grouping as that of sub-population division. The POP2 was the largest group but with fewer admixed lines. POP1 was more distinct than POP2. Since the hybrid parents of the ICRs had limited diversity on maternal lineage, paternal lineage was concluded as the major contributor to the observed divergence and population differentiation. ICRs developed from certain hybrids were more genetically distinct than other hybrids. Even with the moderate variability, ICRs could be considered as a potential source of fertility restoration in hybrid development because of their distinct population structure and the full complement of restorer genes they contained. ICR lines with high per se performance can be utilized in hybrid rice development by estimating their combining ability., Competing Interests: Conflict of interestThe authors declare no conflict of interest.

Iso-cytoplasmic restorers possess the same male sterile cytoplasm as the cytoplasmic male sterile (CMS) lines, thereby minimizing the potential cyto-nuclear conflict in the hybrids. Restoration of fertility of the wild abortive CMS is governed by two major genes namely, Rf3 and Rf4 . Therefore, assessing the allelic status of these restorer genes in the iso-cytoplasmic restorers using molecular markers will not only help in estimating the efficiency of these genes either alone or in combination, in fertility restoration in the hybrids in different environments, but will also be useful in determining the efficacy of these markers. In the present study, the efficiency of molecular markers in identifying genotypes carrying restorer allele of the gene(s) Rf3 and Rf4, restoring male fertility of WA cytoplasm in rice was assessed in a set of 100 iso-cytoplasmic rice restorers using gene linked as well as candidate gene based markers. In order to validate the efficacy of markers in identifying the restorers, a sub-set of selected 25 iso-cytoplasmic rice restorers were crossed with four different cytoplasmic male sterile lines namely, IR 79156A, IR 58025A, Pusa 6A and RTN 12A, and the pollen and spikelet fertility of the F 1 s were evaluated at three different locations. Marker analysis showed that Rf4 was the predominant fertility restorer gene in the iso-cytoplasmic restorers and Rf3 had a synergistic effect on fertility restoration. The efficiency of gene based markers, DRCG-RF4-14 and DRRM-RF3-10 for Rf4 (87%) and Rf3 (84%) genes was higher than respective gene-linked SSR markers RM6100 (80%) and RM3873 (82%). It is concluded that the gene based markers can be effectively used in identifying fertility restorer lines obviating the need for making crosses and evaluating the F 1 s. Though gene based markers are more efficient, there is a need to identify functional polymorphisms which can provide 100% efficiency. Three iso-cytoplasmic restorers namely, PRR 300, PRR 363 and PRR 396 possessing both Rf4 and Rf3 genes and good fertility restoration have been identified which could be used further in hybrid rice breeding.

Background: The influence of ejaculatory abstinence (EA) on semen parameters and subsequent reproductive outcome is still debatable; hence understanding the impact of EA on sperm structural and functional integrity may provide a valuable information on predicting successful clinical outcome., Objective: To understand the influence of EA on sperm chromatin maturity, integrity, longevity and global methylation status., Methods: This experimental prospective study included 76 ejaculates from 19 healthy volunteers who provided ejaculates after observing 1, 3, 5 and 7 days of abstinence. Sperm chromatin maturity, DNA integrity and global methylation status were assessed in the neat ejaculate. Sperm motility, DNA integrity and longevity were assessed in the processed fraction of the fresh and frozen-thawed ejaculates to determine their association with the length of EA., Results: Spermatozoa from 1 day ejaculatory abstinence (EA-1) displayed significantly higher level of sperm chromatin immaturity in comparison to EA-3 (P < 0.05) and EA-5 (P < 0.01) whereas; the number of 5-methyl cytosine immunostained spermatozoa did not vary significantly across groups. On the other hand, in vitro incubation of processed ejaculate from EA-1 resulted in approximately 20 and 40 fold increase in the DNA fragmented spermatozoa at the end of 6 and 24h respectively (P < 0.01-0.001)., Conclusion: Use of short-term EA for therapeutic fertilization would be a clinically valuable strategy to improve the DNA quality. However, use of such spermatozoa after prolonged incubation in vitro should be avoided as it can carry a substantial risk of transmitting DNA fragmentation to the oocytes.

Background: Concerns regarding the safety of ICSI have been intensified recently due to increased risk of birth defects in ICSI born children. Although fertilization rate is significantly higher in ICSI cycles, studies have failed to demonstrate the benefits of ICSI in improving the pregnancy rate. Poor technical skill, and suboptimal in vitro conditions may account for the ICSI results however, there is no report on the effects of oocyte manipulations on the ICSI outcome., Objective: The present study elucidates the influence of mock ICSI on the functional and genetic integrity of the mouse oocytes., Methods: Reactive Oxygen Species (ROS) level, mitochondrial status, and phosphorylation of H2AX were assessed in the in vivo matured and IVM oocytes subjected to mock ICSI., Results: A significant increase in ROS level was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P<0.05-0.001) whereas unique mitochondrial distribution pattern was found only in IVM oocytes (P<0.01-0.001). Importantly, differential H2AX phosphorylation was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P <0.001)., Conclusion: The data from this study suggests that mock ICSI can alter genetic and functional integrity in oocytes and IVM oocytes are more vulnerable to mock ICSI induced changes.

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Ayurveda, the traditional Indian system of medicine has given great emphasis to the promotion of health. Rasayana is one of the eight branches of Ayurveda which refers to rejuvenant therapy. It has been reported that rasayanas have immuno-modulatory, antioxidant and antitumor functions, however, the genotoxic potential and modulation of DNA repair of many rasayanas have not been evaluated., Methods: The present study assessed the role of Brahmarasayana (BR) on Ethyl methanesulfonate (EMS)-and Methyl methanesulfonate (MMS)-induced genotoxicity and DNA repair in in vivo mouse test system. The mice were orally fed with BR (5 g or 8 mg / day) for two months and 24 h later EMS or MMS was given intraperitoneally. The genotoxicity was analyzed by chromosomal aberrations, sperm count, and sperm abnormalities., Results: The results have revealed that BR did not induce significant chromosomal aberrations when compared to that of the control animals (p >0.05). On the other hand, the frequencies of chromosomal aberrations induced by EMS (240 mg / kg body weight) or MMS (125 mg / kg body weight) were significantly higher (p<0.05) to that of the control group. The treatment of BR for 60 days and single dose of EMS or MMS on day 61, resulted in significant (p <0.05) reduction in the frequency of chromosomal aberrations in comparison to EMS or MMS treatment alone, indicating a protective effect of BR. Constitutive base excision repair capacity was also increased in BR treated animals., Conclusion: The effect of BR, as it relates to antioxidant activity was not evident in liver tissue however rasayana treatment was observed to increase constitutive DNA base excision repair and reduce clastogenicity. Whilst, the molecular mechanisms of such repair need further exploration, this is the first report to demonstrate these effects and provides further evidence for the role of brahmarasayana in the possible improvement of quality of life.