Pearl millet (
R. Br.) is an important staple and nutritious food crop in the semiarid and arid ecologies of South Asia (SA) and Sub-Saharan Africa (SSA). In view of climate change, depleting water ...resources, and widespread malnutrition, there is a need to accelerate the rate of genetic gains in pearl millet productivity. This review discusses past strategies and future approaches to accelerate genetic gains to meet future demand. Pearl millet breeding in India has historically evolved very comprehensively from open-pollinated varieties development to hybrid breeding. Availability of stable cytoplasmic male sterility system with adequate restorers and strategic use of genetic resources from India and SSA laid the strong foundation of hybrid breeding. Genetic and cytoplasmic diversification of hybrid parental lines, periodic replacement of hybrids, and breeding disease-resistant and stress-tolerant cultivars have been areas of very high priority. As a result, an annual yield increase of 4% has been realized in the last three decades. There is considerable scope to further accelerate the efforts on hybrid breeding for drought-prone areas in SA and SSA. Heterotic grouping of hybrid parental lines is essential to sustain long-term genetic gains. Time is now ripe for mainstreaming of the nutritional traits improvement in pearl millet breeding programs. New opportunities are emerging to improve the efficiency and precision of breeding. Development and application of high-throughput genomic tools, speed breeding, and precision phenotyping protocols need to be intensified to exploit a huge wealth of native genetic variation available in pearl millet to accelerate the genetic gains.
Anemia is the most common hematological abnormality of chemotherapy, which is responsible for poor clinical outcomes. To overcome this complication, the present study was aimed for developing a ...Eudragit/polylactic-co-glycolic acid (PLGA) based nanoparticulate system for a model drug paclitaxel (PTX). The study was planned using a simplex lattice mixture design. PTX nanoparticles (PTXNp) were evaluated in vitro for physicochemical properties, hemolytic effects and cytotoxic effects. Further, the nanoparticles were subjected to in vivo screening using rats for hemocompatibility, pharmacokinetic profile, and biodistribution to the vital organs. The PTXNps were 65.77–214.73 nm in size, showed more than 60% sustained drug release in 360 h and caused less than 8% hemolysis. The parameters like red blood cell count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and C3 complement were similar to the negative control. Cytotoxicity results suggested that all the PTXNp demonstrated drug concentration-dependent cytotoxicity. The in vivo pharmacokinetic study concluded that PTXNp formulations had significantly higher blood AUC (93.194.55–163,071.15 h*ng/mL), longer half-lives (5.80–6.35 h) and extended mean residence times (6.05–8.54 h) in comparison to PTX solution (p < 0.05). Overall, the study provides a nanoparticulate drug delivery system to deliver PTX safely and effectively along with reducing the associated hematological adverse effects.
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•A simplex lattice mixture design of experiment was used to study the influence of formulation polymers (ERSPO, ERLPO and PLGA) and their respective concentrations on particle size, hemolysis and drug release.•Lastly, the three optimized nanoparticles were evaluated in vitro and in vivo specifically for their pharmacokinetic profile, biodistribution studies, and hemocompatibility studies.•The optimized PTX nanoparticles demonstrated significant hemocompatibility as compared to pure drug solution.•The mean AUC and terminal half-life of PTX upon IV administration of PTXNp was significantly higher than from pure PTX solution.
Breast tumors contain tumorigenic cancer cells, termed “tumorinitiating cells” (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer ...cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small molecules that enhance the effect of chemotherapeutic agents on TIC-enriched breast cancer cells. We identified proteins that interact with the lead compound C108, including the stress granule-associated protein, GTPase-activating protein (SH3 domain)-binding protein 2, G3BP2. G3BP2 regulates breast tumor initiation through the stabilization of Squamous cell carcinoma antigen recognized by T cells 3 (SART3) mRNA, which leads to increased expression of the pluripotency transcription factors Octamer-binding protein 4 (Oct-4) and Nanog Homeobox (Nanog). Our findings suggest that G3BP2 is important for the process of breast cancer initiation. Furthermore, these data suggest a possible connection between stress granule formation and tumor initiation in breast cancer cells.
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•Poor aqueous solubility of bortezomib: major drawback in formulation development.•Bortezomib encapsulation in PEGylated PAMAM dendrimers.•Cytotoxicity assay against A549 and MCF-7 ...cancer cells.•In vivo pharmacokinetic studies co-relating the in vitro results.
Poor aqueous solubility of anticancer drug bortezomib (BTZ) still remains a major challenge in the development of a successful formulation. The dendrimeric platform can provide a better opportunity to deliver BTZ with improved solubility. BTZ encapsulated in PEGylated PAMAM dendrimers (BTZ-PEG-PAMAM) was characterized and evaluated comparatively with encapsulated and conjugated dendritic formulations. The particle size of BTZ-PEG-PAMAM was 188.6 ± 4.17 nm, with entrapment efficiency of 78.61 ± 2.91% and drug loading of 39.30 ± 1.98%. The aqueous solubility of BTZ in PAMAM-PEG conjugate was enhanced by 68.11 folds in comparison to pure drug. In vitro drug release profile was found to be sustained up to 72 h. A comparative colorimetric MTT assay against A549 and MCF-7 cancer cells resulted in maximum efficacy from BTZ-PEG-PAMAM with IC50 value 333.14 ± 15.42 and 152.60 ± 24.56 nM, respectively. Significantly higher cellular internalization was observed in FITC tagged BTZ-PEG-PAMAM. In vivo pharmacokinetic study performed on Sprague Dawley rats resulted in 8.63 folds increase in bioavailability for BTZ-PEG-PAMAM than pure drug. Pharmacokinetic parameters of BTZ-PEG-PAMAM were better and improved over BTZ and other dendritic formulations. In conclusion, the prepared formulation of BTZ-PEG-PAMAM has given significant outcome and this strategy may be further explored for better delivery of BTZ in future.
Primary cutaneous blastomycosis is very rare in non-endemic regions like India. Only few cases have been reported from India. Herein, we are reporting a rare case of chronic cutaneous blastomycosis ...in a young immunocompetent male presenting as mycetoma with multiple discharging sinuses in the anterior abdominal wall with no significant travel history.
Glioblastoma multiforme (also known as glioblastoma; GBM) is one of the most malignant types of brain tumors that occurs in the CNS. Treatment strategies for glioblastoma are majorly comprised of ...surgical resection, radiotherapy, and chemotherapy along with combination therapy. Treatment of GBM is itself a tedious task but the involved barriers in GBM are one of the main impediments to move one step closer to the treatment of GBM. Basically, two of the barriers are of utmost importance in this regard, namely blood brain barrier (BBB) and blood brain tumor barrier (BBTB). This review will address different challenges and barriers in the treatment of GBM along with their etiology. The role and recent progress of lipid-based nanocarriers like liposomes, solid lipid nanocarriers (SLNs), nanostructured lipid carriers (NLCs), lipoplexes, and lipid hybrid carriers in the effective management of GBM will be discussed in detail.
Graphical Abstract
Pearl millet is a non-model grain and fodder crop adapted to extremely hot and dry environments globally. In India, a great deal of public and private sectors' investment has focused on developing ...pearl millet single cross hybrids based on the cytoplasmic-genetic male sterility (CMS) system, while in Africa most pearl millet production relies on open pollinated varieties. Pearl millet lines were phenotyped for both the inbred parents and hybrids stage. Many breeding efforts focus on phenotypic selection of inbred parents to generate improved parental lines and hybrids. This study evaluated two genotyping techniques and four genomic selection schemes in pearl millet. Despite the fact that 6× more sequencing data were generated per sample for RAD-seq than for tGBS, tGBS yielded more than 2× as many informative SNPs (defined as those having MAF > 0.05) than RAD-seq. A genomic prediction scheme utilizing only data from hybrids generated prediction accuracies (median) ranging from 0.73-0.74 (1000-grain weight), 0.87-0.89 (days to flowering time), 0.48-0.51 (grain yield) and 0.72-0.73 (plant height). For traits with little to no heterosis, hybrid only and hybrid/inbred prediction schemes performed almost equivalently. For traits with significant mid-parent heterosis, the direct inclusion of phenotypic data from inbred lines significantly (
< 0.05) reduced prediction accuracy when all lines were analyzed together. However, when inbreds and hybrid trait values were both scored relative to the mean trait values for the respective populations, the inclusion of inbred phenotypic datasets moderately improved genomic predictions of the hybrid genomic estimated breeding values. Here we show that modern approaches to genotyping by sequencing can enable genomic selection in pearl millet. While historical pearl millet breeding records include a wealth of phenotypic data from inbred lines, we demonstrate that the naive incorporation of this data into a hybrid breeding program can reduce prediction accuracy, while controlling for the effects of heterosis
allowed inbred genotype and trait data to improve the accuracy of genomic estimated breeding values for pearl millet hybrids.
A large percentage of people are being exposed to mortality due to cardiovascular diseases. Convention approaches have not provided satisfactory outcomes in the management of these diseases. To ...overcome the limitations of conventional approaches, nanomaterials like nanoparticles, nanotubes, micelles, lipid-based nanocarriers, dendrimers, and carbon-based nanoformulations represent the new aspect of diagnosis and treatment of cardiovascular diseases. The unique inherent properties of the nanomaterials are the major reasons for their rapidly growing demand in the field of medicine. Profound knowledge in the field of nanotechnology and biomedicine is needed for the notable translation of nanomaterials into theranostic cardiovascular applications. In this review, the authors have summarized different nanomaterials which are being extensively used to diagnose and treat the diseases, such as coronary heart disease, myocardial infarction, atherosclerosis, stroke and thrombosis.
The traditional criteria for diagnosing preeclampsia include a new onset of hypertension and new-onset proteinuria at 20 weeks gestation. However recent studies suggest preeclampsia and even ...eclampsia may develop in the absence of either proteinuria or hypertension. This paper reports a dual tragedy of maternal and fetal loss after 36 weeks in the third trimester. Autopsy findings revealed an enlarged liver with multiple patchy hemorrhages, and histopathology confirmed submassive hepatic necrosis. Early diagnosis with timely referrals to higher centers is always helpful for the patients in such cases.
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