Underutilized fruit lasoda (Cordia myxa L.): Review on bioactive compounds, antioxidant potentiality and applications in health bioactivities and food.

Underutilized fruits are thought to be nutrient and antioxidant gold mines. Despite their high nutritive value, therapeutic properties, and ability to grow in adverse soil and climatic conditions, they have received little attention. However, these underutilized fruits are an important component of traditional foods, particularly in arid and semiarid regions of Rajasthan. Lasoda (Cordia myxa) contains numerous phytochemicals that contribute to its antioxidant potential, including tannins, flavonoids, phenolic acids, xanthones, terpenes, and saponins. The primary goal of this review is to emphasize the importance of extracting bioactive compounds from lasoda and evaluating their antioxidant potential. Furthermore, this review emphasizes the major areas for the application of lasoda and its extract as prospective positive health agents that can be used in the preparation of functional foods. The use of lasoda may also improve the value of bakery products and meat quality and prevent postharvest losses. This review is a pilot article that can aid in the nutritional profiling of Cordia fruits and seeds, and it provides information on the effective and efficient use of this underutilized fruit in the food and nutraceutical industries.

CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor.

Among the known nuclear exportins, CRM1 is the most studied prototype. Dysregulation of CRM1 occurs in many cancers, hence, understanding the role of CRM1 in cancer can help in developing synergistic therapeutics. The study investigates how CRM1 affects prostate cancer growth and survival. It examines the role of CRM1 in regulating androgen receptor (AR) and DNA repair in prostate cancer. Our findings reveal that CRM1 influences AR mRNA and protein stability, leading to a loss of AR protein upon CRM1 inhibition. Furthermore, it highlights the involvement of HSP90 alpha, a known AR chaperone, in the CRM1-dependent regulation of AR protein stability. The combination of CRM1 inhibition with an HSP90 inhibitor demonstrates potent effects on decreasing prostate cancer cell growth and survival. The study further explores the influence of CRM1 on DNA repair proteins and proposes a strategy of combining CRM1 inhibitors with DNA repair pathway inhibitors to decrease prostate cancer growth. Overall, the findings suggest that CRM1 plays a crucial role in prostate cancer growth, and a combination of inhibitors targeting CRM1 and DNA repair pathways could be a promising therapeutic strategy.

Potentials of genotypes, morpho-physio-biochemical traits, and growing media on shelf life and future prospects of gene editing in tomatoes.

Background: To study the genetic basis of the impact of genotypes and morpho-physio-biochemical traits under different organic and inorganic fertilizer doses on the shelf life attribute of tomatoes, field experiments were conducted in randomized block designs during the rabi seasons of 2018-2019 and 2019-2020. The experiment comprised three diverse nutrient environments [T1-organic; T2-inorganic; T3-control (without any fertilizers)] and five tomato genotypes with variable growth habits, specifically Angoorlata (Indeterminate), Avinash-3 (semi-determinate), Swaraksha (semi-determinate), Pusa Sheetal (semi-determinate), and Pusa Rohini (determinate). Results: The different tomato genotypes behaved apparently differently from each other in terms of shelf life. All the genotypes had maximum shelf life when grown in organic environments. However, the Pusa Sheetal had a maximum shelf life of 8.35 days when grown in an organic environment and showed an increase of 12% over the control. The genotype Pusa Sheetal, organic environment and biochemical trait Anthocyanin provides a promise as potential contributor to improve the keeping quality of tomatoes. Conclusion: The genotype Pusa Sheetal a novel source for shelf life, organic environment, and anthocyanin have shown promises for extended shelf life in tomatoes. Thus, the identified trait and genotype can be utilized in tomato improvement programs. Furthermore, this identified trait can also be targeted for its quantitative enhancement in order to increase tomato shelf life through a genome editing approach. A generalized genome editing mechanism is consequently suggested.

Disentangling potential genotypes for macro and micro nutrients and polymorphic markers in Chickpea.

The present investigation was conducted to assess the nutritional diverseness and identify novel genetic resources to be utilized in chickpea breeding for macro and micro nutrients. The plants were grown in randomized block design. Nutritional and phytochemical properties of nine chickpea genotypes were estimated. The EST sequences from NCBI database were downloaded in FASTA format, clustered into contigs using CAP3, mined for novel SSRs using TROLL analysis and primer pairs were designed using Primer 3 software. Jaccard's similarity coefficients were used to compare the nutritional and molecular indexes followed by dendrograms construction employing UPGMA approach. The genotypes PUSA-1103, K-850, PUSA-1108, PUSA-1053 and the EST-SSR markers including the 5 newly designed namely ICCeM0012, ICCeM0049, ICCeM0067, ICCeM0070, ICCeM0078, SVP55, SVP95, SVP96, SVP146, and SVP217 were found as potential donor/marker resources for the macro-micro nutrients. The genotypes differed (p < 0.05) for nutritional properties. Amongst newly designed primers, 6 were found polymorphic with median PIC (0.46). The alleles per primer ranged 1 to 8. Cluster analysis based on nutritional and molecular diversities partially matched to each other in principle. The identified novel genetic resources may be used to widen the germplasm base, prepare maintainable catalogue and identify systematic blueprints for future chickpea breeding strategies targeting macro-micro nutrients.

Unclasping potentials of genomics and gene editing in chickpea to fight climate change and global hunger threat.

Genomics and genome editing promise enormous opportunities for crop improvement and elementary research. Precise modification in the specific targeted location of a genome has profited over the unplanned insertional events which are generally accomplished employing unadventurous means of genetic modifications. The advent of new genome editing procedures viz; zinc finger nucleases (ZFNs), homing endonucleases, transcription activator like effector nucleases (TALENs), Base Editors (BEs), and Primer Editors (PEs) enable molecular scientists to modulate gene expressions or create novel genes with high precision and efficiency. However, all these techniques are exorbitant and tedious since their prerequisites are difficult processes that necessitate protein engineering. Contrary to first generation genome modifying methods, CRISPR/Cas9 is simple to construct, and clones can hypothetically target several locations in the genome with different guide RNAs. Following the model of the application in crop with the help of the CRISPR/Cas9 module, various customized Cas9 cassettes have been cast off to advance mark discrimination and diminish random cuts. The present study discusses the progression in genome editing apparatuses, and their applications in chickpea crop development, scientific limitations, and future perspectives for biofortifying cytokinin dehydrogenase, nitrate reductase, superoxide dismutase to induce drought resistance, heat tolerance and higher yield in chickpea to encounter global climate change, hunger and nutritional threats.

Phase I Trial of Intravenous Mistletoe Extract in Advanced Cancer.

Purpose: Mistletoe extract (ME) is widely used for patients with cancer to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration. Materials and Methods: This phase I trial of intravenous mistletoe (Helixor M) aimed to determine the recommended phase II dosing and to evaluate safety. Patients with solid tumor progressing on at least one line of chemotherapy received escalating doses of Helixor M three times a week. Assessments were also made of tumor marker kinetics and QoL. Results: Twenty-one patients were recruited. The median follow-up duration was 15.3 weeks. The MTD was 600 mg. Treatment-related adverse events (AE) occurred in 13 patients (61.9%), with the most common being fatigue (28.6%), nausea (9.5%), and chills (9.5%). Grade 3+ treatment-related AEs were noted in 3 patients (14.8%). Stable disease was observed in 5 patients who had one to six prior therapies. Reductions in baseline target lesions were observed in 3 patients who had two to six prior therapies. Objective responses were not observed. The disease control rate (percentage of complete/partial response and stable disease) was 23.8%. The median stable disease was 15 weeks. Serum cancer antigen-125 or carcinoembryonic antigen showed a slower rate of increase at higher dose levels. The median QoL by Functional Assessment of Cancer Therapy-General increased from 79.7 at week 1 to 93 at week 4. Conclusions: Intravenous mistletoe demonstrated manageable toxicities with disease control and improved QoL in a heavily pretreated solid tumor population. Future phase II trials are warranted. Significance: Although ME is widely used for cancers, its efficacy and safety are uncertain. This first phase I trial of intravenous mistletoe (Helixor M) aimed to determine phase II dosing and to evaluate safety. We recruited 21 patients with relapsed/refractory metastatic solid tumor. Intravenous mistletoe (600 mg, 3/week) demonstrated manageable toxicities (fatigue, nausea, and chills) with disease control and improved QoL. Future research can examine ME's effect on survival and chemotherapy tolerability.

Prospects of microgreens as budding living functional food: Breeding and biofortification through OMICS and other approaches for nutritional security.

Nutrient deficiency has resulted in impaired growth and development of the population globally. Microgreens are considered immature greens (required light for photosynthesis and growing medium) and developed from the seeds of vegetables, legumes, herbs, and cereals. These are considered "living superfood/functional food" due to the presence of chlorophyll, beta carotene, lutein, and minerals like magnesium (Mg), Potassium (K), Phosphorus (P), and Calcium (Ca). Microgreens are rich at the nutritional level and contain several phytoactive compounds (carotenoids, phenols, glucosinolates, polysterols) that are helpful for human health on Earth and in space due to their anti-microbial, anti-inflammatory, antioxidant, and anti-carcinogenic properties. Microgreens can be used as plant-based nutritive vegetarian foods that will be fruitful as a nourishing constituent in the food industryfor garnish purposes, complement flavor, texture, and color to salads, soups, flat-breads, pizzas, and sandwiches (substitute to lettuce in tacos, sandwich, burger). Good handling practices may enhance microgreens'stability, storage, and shelf-life under appropriate conditions, including light, temperature, nutrients, humidity, and substrate. Moreover, the substrate may be a nutritive liquid solution (hydroponic system) or solid medium (coco peat, coconut fiber, coir dust and husks, sand, vermicompost, sugarcane filter cake, etc.) based on a variety of microgreens. However integrated multiomics approaches alongwith nutriomics and foodomics may be explored and utilized to identify and breed most potential microgreen genotypes, biofortify including increasing the nutritional content (macro-elements:K, Ca and Mg; oligo-elements: Fe and Zn and antioxidant activity) and microgreens related other traits viz., fast growth, good nutritional values, high germination percentage, and appropriate shelf-life through the implementation of integrated approaches includes genomics, transcriptomics, sequencing-based approaches, molecular breeding, machine learning, nanoparticles, and seed priming strategiesetc.

Periosteal Ewing Sarcoma: Imaging Features and Clinical Outcomes in 7 Patients.

OBJECTIVE: The aim of this study was to describe imaging features, treatment, and prognosis of patients with periosteal Ewing sarcoma (PES). MATERIALS AND METHODS: Seven patients with PES treated between 2001 and 2020 were studied retrospectively for presenting symptoms, imaging features, treatment, and prognosis. RESULTS: Among the 7 patients (mean age, 27.3 years) with local pain and/or mass of less than 6 months duration, 4 were males and 3 females (1.3:1). These surface tumors involved 3 long bones and 4 pelvic bones. Radiographs showed cortical erosions with 2 and CT with 4 long bone tumors. All 7 surface tumors showed normal marrow on MRI, and 4 tumors demonstrated normal marrow activity on 18FFDG fluorodeoxyglucose PET-CT. The only exception was a PES involving iliac bone with thin cortex and marrow extension, which demonstrated hypermetabolic marrow activity. All patients were treated initially with chemotherapy and optional radiation treatment with complete tumor resolution of a tibial PES in 1 patient. The remaining 2 patients with long bone PES had tumor resection and limb-salvage surgery and the 4 patients with pelvic bone PES had hemipelvectomy after chemotherapy/radiation treatment. Five patients were disease-free with long-term survival. A patient with a long bone PES and solitary lung metastasis at onset had tumor resection and metastasectomy with complete recovery without tumor recurrence. The 2 patients with pubic bone PES had complete recovery without tumor recurrence; however, the remaining 2 patients with iliac bone PES developed distant metastases and died within 2 years of diagnosis. CONCLUSIONS: Periosteal Ewing sarcoma arises in periosteum of bone and spares medullary cavity. As compared with its intramedullary counterpart, the tumor has better prognosis with long-term survival. Rarely, the surface tumor arising at a bone with thin cortex, such as iliac bone or scapula, may have medullary involvement. We have described our experience in diagnosis and clinical management in 7 patients of this rare surface variant of the more common intramedullary Ewing sarcoma.

The testosterone paradox of advanced prostate cancer: mechanistic insights and clinical implications.

The discovery of the benefits of castration for prostate cancer treatment in 1941 led to androgen deprivation therapy, which remains a mainstay of the treatment of men with advanced prostate cancer. However, as early as this original publication, the inevitable development of castration-resistant prostate cancer was recognized. Resistance first manifests as a sustained rise in the androgen-responsive gene, PSA, consistent with reactivation of the androgen receptor axis. Evaluation of clinical specimens demonstrates that castration-resistant prostate cancer cells remain addicted to androgen signalling and adapt to chronic low-testosterone states. Paradoxically, results of several studies have suggested that treatment with supraphysiological levels of testosterone can retard prostate cancer growth. Insights from these studies have been used to investigate administration of supraphysiological testosterone to patients with prostate cancer for clinical benefits, a strategy that is termed bipolar androgen therapy (BAT). BAT involves rapid cycling from supraphysiological back to near-castration testosterone levels over a 4-week cycle. Understanding how BAT works at the molecular and cellular levels might help to rationalize combining BAT with other agents to achieve increased efficacy and tumour responses.

Ewing sarcoma of Hoffa fat pad in the knee: a case report and review of the literature on primary intraarticular sarcomas and Hoffa fat pad masses.

Primary intraarticular sarcomas are rare. We describe a unique case of intraarticular Ewing sarcoma arising in Hoffa fat pad of knee in a woman. The patient was treated successfully with chemotherapy and left knee arthroplasty; however, the tumor recurred after 3 years.We review the literature on primary intraarticular sarcomas and Hoffa fat pad masses in the knee.

Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen therapy through MYC.

Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined. Here, we show that growth inhibition of prostate cancer models by SPA required high androgen receptor (AR) activity and were driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pretreatment AR activity predicted downregulation of MYC, improved clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance was overcome by alternating SPA with the AR inhibitor enzalutamide, which induced adaptive upregulation of AR and resensitized prostate cancer to SPA. This work identifies high AR activity as a predictive biomarker of response to BAT and supports a treatment paradigm for prostate cancer involving alternating between AR inhibition and activation.

Epigenomics as Potential Tools for Enhancing Magnitude of Breeding Approaches for Developing Climate Resilient Chickpea.

Epigenomics has become a significant research interest at a time when rapid environmental changes are occurring. Epigenetic mechanisms mainly result from systems like DNA methylation, histone modification, and RNA interference. Epigenetic mechanisms are gaining importance in classical genetics, developmental biology, molecular biology, cancer biology, epidemiology, and evolution. Epigenetic mechanisms play important role in the action and interaction of plant genes during development, and also have an impact on classical plant breeding programs, inclusive of novel variation, single plant heritability, hybrid vigor, plant-environment interactions, stress tolerance, and performance stability. The epigenetics and epigenomics may be significant for crop adaptability and pliability to ambient alterations, directing to the creation of stout climate-resilient elegant crop cultivars. In this review, we have summarized recent progress made in understanding the epigenetic mechanisms in plant responses to biotic and abiotic stresses and have also tried to provide the ways for the efficient utilization of epigenomic mechanisms in developing climate-resilient crop cultivars, especially in chickpea, and other legume crops.

Exploring Chickpea Germplasm Diversity for Broadening the Genetic Base Utilizing Genomic Resourses.

Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes improve the cropping environment by replenishing the soil nitrogen content. Chickpeas are the second most significant staple legume food crop worldwide behind dry bean which contains 17%-24% protein, 41%-51% carbohydrate, and other important essential minerals, vitamins, dietary fiber, folate, ß-carotene, anti-oxidants, micronutrients (phosphorus, calcium, magnesium, iron, and zinc) as well as linoleic and oleic unsaturated fatty acids. Despite these advantages, legumes are far behind cereals in terms of genetic improvement mainly due to far less effort, the bottlenecks of the narrow genetic base, and several biotic and abiotic factors in the scenario of changing climatic conditions. Measures are now called for beyond conventional breeding practices to strategically broadening of narrow genetic base utilizing chickpea wild relatives and improvement of cultivars through advanced breeding approaches with a focus on high yield productivity, biotic and abiotic stresses including climate resilience, and enhanced nutritional values. Desirable donors having such multiple traits have been identified using core and mini core collections from the cultivated gene pool and wild relatives of Chickpea. Several methods have been developed to address cross-species fertilization obstacles and to aid in inter-specific hybridization and introgression of the target gene sequences from wild Cicer species. Additionally, recent advances in "Omics" sciences along with high-throughput and precise phenotyping tools have made it easier to identify genes that regulate traits of interest. Next-generation sequencing technologies, whole-genome sequencing, transcriptomics, and differential genes expression profiling along with a plethora of novel techniques like single nucleotide polymorphism exploiting high-density genotyping by sequencing assays, simple sequence repeat markers, diversity array technology platform, and whole-genome re-sequencing technique led to the identification and development of QTLs and high-density trait mapping of the global chickpea germplasm. These altogether have helped in broadening the narrow genetic base of chickpeas.

Unraveling Origin, History, Genetics, and Strategies for Accelerated Domestication and Diversification of Food Legumes.

Domestication is a dynamic and ongoing process of transforming wild species into cultivated species by selecting desirable agricultural plant features to meet human needs such as taste, yield, storage, and cultivation practices. Human plant domestication began in the Fertile Crescent around 12,000 years ago and spread throughout the world, including China, Mesoamerica, the Andes and Near Oceania, Sub-Saharan Africa, and eastern North America. Indus valley civilizations have played a great role in the domestication of grain legumes. Crops, such as pigeon pea, black gram, green gram, lablab bean, moth bean, and horse gram, originated in the Indian subcontinent, and Neolithic archaeological records indicate that these crops were first domesticated by early civilizations in the region. The domestication and evolution of wild ancestors into today's elite cultivars are important contributors to global food supply and agricultural crop improvement. In addition, food legumes contribute to food security by protecting human health and minimize climate change impacts. During the domestication process, legume crop species have undergone a severe genetic diversity loss, and only a very narrow range of variability is retained in the cultivars. Further reduction in genetic diversity occurred during seed dispersal and movement across the continents. In general, only a few traits, such as shattering resistance, seed dormancy loss, stem growth behavior, flowering-maturity period, and yield traits, have prominence in the domestication process across the species. Thus, identification and knowledge of domestication responsive loci were often useful in accelerating new species' domestication. The genes and metabolic pathways responsible for the significant alterations that occurred as an outcome of domestication might aid in the quick domestication of novel crops. Further, recent advances in "omics" sciences, gene-editing technologies, and functional analysis will accelerate the domestication and crop improvement of new crop species without losing much genetic diversity. In this review, we have discussed about the origin, center of diversity, and seed movement of major food legumes, which will be useful in the exploration and utilization of genetic diversity in crop improvement. Further, we have discussed about the major genes/QTLs associated with the domestication syndrome in pulse crops and the future strategies to improve the food legume crops.

Chickpea Biofortification for Cytokinin Dehydrogenase via Genome Editing to Enhance Abiotic-Biotic Stress Tolerance and Food Security.

Globally more than two billion people suffer from micronutrient malnutrition (also known as "hidden hunger"). Further, the pregnant women and children in developing nations are mainly affected by micronutrient deficiencies. One of the most important factors is food insecurity which can be mitigated by improving the nutritional values through biofortification using selective breeding and genetic enhancement techniques. Chickpea is the second most important legume with numerous economic and nutraceutical properties. Therefore, chickpea production needs to be increased from the current level. However, various kind of biotic and abiotic stresses hamper global chickpea production. The emerging popular targets for biofortification in agronomic crops include targeting cytokinin dehydrogenase (CKX). The CKXs play essential roles in both physiological and developmental processes and directly impact several agronomic parameters i.e., growth, development, and yield. Manipulation of CKX genes using genome editing tools in several crop plants reveal that CKXs are involved in regulation yield, shoot and root growth, and minerals nutrition. Therefore, CKXs have become popular targets for yield improvement, their overexpression and mutants can be directly correlated with the increased yield and tolerance to various stresses. Here, we provide detailed information on the different roles of CKX genes in chickpea. In the end, we discuss the utilization of genome editing tool clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) to engineer CKX genes that can facilitate trait improvement. Overall, recent advancements in CKX and their role in plant growth, stresses and nutrient accumulation are highlighted, which could be used for chickpea improvement.

Repurposing chia seed oil: A versatile novel functional food.

Chia seed oil (CSO) has been recently gaining tremendous interest as a functional food. The oil is rich in with polyunsaturated fatty acids (PUFAs), especially, alpha linolenic acid (ALA), linoleic acid (LA), tocopherols, phenolic acids, vitamins, and antioxidants. Extracting CSO through green technologies has been highly efficient, cost-effective, and sustainable, which has also shown to improve its nutritional potential and proved to be eco-friendly than any other traditional or conventional processes. Due to the presence of valuable bioactive metabolites, CSO is proving to be a revolutionary source for food, baking, dairy, pharmaceutical, livestock feed, and cosmetic industries. CSO has been reported to possess antidiabetic, anticancer, anti-inflammatory, antiobesity, antioxidant, antihyperlipidemic, insect-repellent, and skin-healing properties. However, studies on toxicological safety and commercial potency of CSO are limited and therefore the need of the hour is to focus on large-scale molecular mechanistic and clinical studies, which may throw light on the possible translational opportunities of CSO to be utilized to its complete potential. In this review, we have deliberated on the untapped therapeutical possibilities and novel findings about this functional food, its biochemical composition, extraction methods, nutritional profiling, oil stability, and nutraceutical and pharmaceutical applications for its health benefits and ability to counter various diseases.

Electrostatic Complementarity in Structure-Based Drug Design.

Optimization of electrostatic complementarity is an important strategy in structure-based drug discovery for improving the affinity of molecules against a specific protein target. In this Miniperspective we identify examples where deliberate optimization of protein-ligand electrostatic complementarity or intramolecular electrostatic interactions gave improvements in target affinity (up to 250-fold), physicochemical properties, in vitro properties, and off-target selectivity. We also look retrospectively at a series of factor Xa inhibitors that show an almost 8000-fold range in potency that can be correlated with the calculated electrostatic potential (ESP) surfaces. Recent developments using a graph-convolutional deep neural network to rapidly generate high quality ESP surfaces have the potential to make this useful tool more accessible for a wider audience within the field of medicinal chemistry.

Palliative radiotherapy: a one-week course in advanced head and neck cancer - quality of life outcomes.

OBJECTIVES: Palliative radiotherapy regimens for advanced head and neck cancers vary in doses and treatment times. Their quality of life (QoL) implications are not clearly established. METHODS: We randomised patients with advanced, non-metastatic, head and neck squamous cell carcinomas (stage IVA-B) with WHO performance score of 2 or higher to receive 30 Gy in 10 fractions over two weeks (arm A) or 20 Gy in 5 fractions over one week (arm B). QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-H&N35 questionnaires at baseline and postradiotherapy. The primary endpoint was the EORTC-defined global health status. Secondary endpoints were functional and symptom scores of QoL, response to radiotherapy and acute toxicities. The primary aim was to evaluate the one-week regimen in terms of QoL to the longer regimen. RESULTS: 110 patients were randomised, the number of patients in the final analysis was 95: 49 in arm A and 46 in arm B. Baseline characteristics were similar. Clinical outcomes post-treatment were comparable. Postradiotherapy, there were improved scores for functional and symptom scales, the differences were non-significant. The duration of treatment was significantly reduced in arm B (p<0.01) with a lower score for financial difficulty (p<0.001). The difference in global health status (primary endpoint) was non-significant (p=0.82). The median overall survival was 7 months, the median progression-free survival was 5 months and these did not vary between the two groups. CONCLUSION: One-week palliative radiotherapy for head and neck cancers achieves similar QoL and clinical outcomes as more protracted radiotherapy schedules with significantly reduced treatment time and financial toxicity.

Genome-wide association mapping identifies an SNF4 ortholog that impacts biomass and sugar yield in sorghum and sugarcane.

Sorghum is a feed/industrial crop in developed countries and a staple food elsewhere in the world. This study evaluated the sorghum mini core collection for days to 50% flowering (DF), biomass, plant height (PH), soluble solid content (SSC), and juice weight (JW), and the sorghum reference set for DF and PH, in 7-12 testing environments. We also performed genome-wide association mapping with 6 094 317 and 265 500 single nucleotide polymorphism markers in the mini core collection and the reference set, respectively. In the mini core panel we identified three quantitative trait loci for DF, two for JW, one for PH, and one for biomass. In the reference set panel we identified another quantitative trait locus for PH on chromosome 6 that was also associated with biomass, DF, JW, and SSC in the mini core panel. Transgenic studies of three genes selected from the locus revealed that Sobic.006G061100 (SbSNF4-2) increased biomass, SSC, JW, and PH when overexpressed in both sorghum and sugarcane, and delayed flowering in transgenic sorghum. SbSNF4-2 encodes a γ subunit of the evolutionarily conserved AMPK/SNF1/SnRK1 heterotrimeric complexes. SbSNF4-2 and its orthologs will be valuable in genetic enhancement of biomass and sugar yield in plants.

Raloxifene-loaded SLNs with enhanced biopharmaceutical potential: QbD-steered development, in vitro evaluation, in vivo pharmacokinetics, and IVIVC.

Raloxifene hydrochloride, a second-generation selective estrogen receptor modulator, has been approved for the management of breast cancer. However, it is known to exhibit poor (~ 2%) and inconsistent oral bioavailability in humans, primarily ascribable to its low aqueous solubility, extensive first-pass metabolism, P-gp efflux, and presystemic glucuronide conjugation. The present research work entails the systematic development and evaluation of SLNs of RLX for its enhanced biopharmaceutical performance against breast cancer. Factor screening studies were conducted using Taguchi design, followed by optimization studies employing Box-Behnken design. Preparation of SLNs was carried out using glyceryl monostearate and Compritol® 888 ATO (i.e., lipid), Phospholipid S-100 (i.e., co-surfactant), and TPGS-1000 (i.e., surfactant) employing solvent diffusion method. The optimized formulation was evaluated for zeta potential, average particle size, field emission scanning electron microscope, transmission electron microscopy, and in vitro release study. Further, MCF-7 cells (cell cytotoxicity assay, apoptosis assay, and reactive oxygen species assay) and Caco-2 cells (cell uptake studies and P-gp efflux assay) were employed to evaluate the in vitro anticancer potential of the developed optimized formulation. In vivo pharmacokinetic studies were conducted in Sprague-Dawley rats to evaluate the therapeutic profile of the developed formulation. The optimized SLN formulations exhibited a mean particle size of 109.7 nm, PDI 0.289 with a zeta potential of - 13.7 mV. In vitro drug dissolution studies showed Fickian release, with release exponent of 0.137. Cell cytotoxicity assay, apoptosis assay, and cellular uptake indicated 6.40-, 5.40-, and 3.18-fold improvement in the efficacy of RLX-SLNs vis-à-vis pure RLX. Besides, the pharmacokinetic studies indicated quite significantly improved biopharmaceutical performance of RLX-SLNs vis-à-vis pure drug, with 4.06-fold improvement in Cmax, 4.40-fold in AUC(0-72 h), 4.56-fold in AUC(0-∞), 1.53-fold in Ka, 2.12-fold in t1/2, and 1.22-fold in Tmax. Further, for RLX-SLNs and pure drug, high degree of level A linear correlation was established between fractions of drug dissolved (in vitro) and of drug absorbed (in vivo) at the corresponding time-points. Stability studies indicated the robustness of RLX-SLNs when stored at for 3 months. Results obtained from the different studies construe promising the anticancer potential of the developed RLX-SLNs, thereby ratifying the lipidic nanocarriers as an efficient drug delivery strategy for improving the biopharmaceutical attributes of RLX.