Less is more: Validating a single method for comprehensive rh-insulin analysis.

The objective of this current study is to establish a single method for potency and related proteins analysis of human insulin formulations using reverse-phase high performance liquid (RP-HPLC) chromatography technique which was validated and verified for the potency analysis in insulin formulations. Chromatographic separation was achieved using an octadecylsilane (C-18) stationary phase and a mobile phase composed of 55% (v/v) buffer (0.2 M sodium sulfate in water, {pH 2.3}) and 45% (v/v) acetonitrile. Detection was performed by UV detector at 214 nm with a flow rate of 1 ml/min and an injection volume of 20 µL, at 40°C. Currently there are separate methods available in Indian Pharmacopoeia for analysis of Potency and Related proteins in human insulin. We have validated a single method where quantitation of potency and related proteins can be performed in the same run. The method validation exhibited linearity over the concentration range of 0.08-4.5 mg/ml (r2=0.999) with limit of detection of 0.094 mg/ml The accuracy of the method was 99-102.8%. Thus, it is proposed that both potency and related proteins in insulin formulations can be precisely evaluated using a single run thus saving the time and cost for quality analysis of insulin preparations both at manufacturing and regulatory laboratories which in turn will increase the market availability of such standard quality insulin preparations for public health use.

Paradigms and Success Stories of Natural Products in Drug Discovery Against Neurodegenerative Disorders (NDDs).

Neurodegenerative disorders (NDDs) are multifaceted complex disorders that have put a great health and economic burden around the globe nowadays. The multi-factorial nature of NDDs has presented a great challenge in drug discovery and continuous efforts are in progress in search of suitable therapeutic candidates. Nature has a great wealth of active principles in its lap that has cured the human population since ancient times. Natural products have revealed several benefits over conventional synthetic medications and scientists have shifted their vision towards exploring the therapeutic potentials of natural products in the past few years. The structural mimicking of natural compounds to endogenous ligands has presented them as a potential therapeutic candidate to prevent the development of NDDs. In the presented review, authors have summarized demographical facts about various NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and various types of sclerosis in the brain. The significant findings of new active principles of natural origin along with their therapeutic potentials on NDDs have been included. Also, a description of clinical trials and patents on natural products has been enlisted in this compilation. Although natural products have shown promising success in drug discovery against NDDs, still their use is associated with several ethical issues which need to be solved in the upcoming time.

Porous SnO2 nanosheets for room temperature ammonia sensing in extreme humidity.

Gas sensors based on tin dioxide (SnO2) for the detection of ammonia (NH3) have become commercially available for environmental monitoring due to their reactive qualities when exposed to different gaseous pollutants. Nevertheless, their implementation in the medical field has been hindered by certain inherent drawbacks, such as needing to operate at high temperatures, lack of selectivity, unreliable operation under high-humidity conditions, and a lower detection limit. To counter these issues, this study created 2D nanosheets of SnO2 through an optimized solvothermal method. It was found that tuning the precursor solution's pH to either neutral or 14 led to aggregated or distributed, uniform-size nanosheets with a higher crystallinity, respectively. Remarkably, the SnO2 nanosheet sensor (SNS-14) displayed a much lower response to water molecules and specific reactivity to ammonia even when subjected to reducing and oxidizing agents at 25 °C due to the micropores and chemisorbed oxygen on the nanosheets. Furthermore, the SNS-14 was seen to have the highest sensitivity to ammonia at 100 ppm, with rapid response (8 s) and recovery times (55 s) even at a high relative humidity of 70%. Its theoretical detection limit was recorded to be 64 ppt, better than any of the earlier SnO2-based chemiresistive sensors. Its exceptional sensing abilities were credited to its optimal crystallinity, specific surface area, defects, chemisorbed oxygen, and porous structure. NH3-TPD measurements and computational simulations were employed to understand the ammonia interaction with atomistic details on the SnO2 nanosheet surface. A real time breath sensing experiment was simulated to test the efficacy of the sensor. Reaching this advancement is an achievement in bypassing past boundaries of SnO2-centered sensors, making it feasible to detect ammonia with enhanced precision, discrimination, dependability, and velocity for probable usages in medical diagnostics and ecological surveillance.

Functionalized Multiwalled Carbon Nanotubes for Highly Stable Room Temperature and Humidity-Tolerant Triethylamine Sensing.

Triethylamine (TEA) poses a significant threat to our health and is extremely difficult to detect at the parts-per-billion (ppb) level at room temperature. Carbon nanotubes (CNTs) are versatile materials used in chemiresistive vapor sensing. However, achieving high sensitivity and selectivity with a low detection limit remains a challenge for pristine CNTs, hindering their widespread commercial application. To address these issues, we propose functionalized multiwalled CNTs (MWCNTs) with carboxylic acid (COOH)-based sensing channels for ultrasensitive TEA detection under ambient conditions. Advanced structural analyses confirmed the necessary modification of MWCNTs after functionalization. The sensor exhibited excellent sensitivity to TEA in air, with a superior noise-free signal (10 ppb), an extremely low limit of detection (LOD ≈ 0.8 ppb), excellent repeatability, and long-term stability under ambient conditions. Moreover, the response values became more stable, demonstrating excellent humidity resistance (40-80% RH). Notably, the functionalized MWCNT sensor exhibited improved response and recovery kinetics (200 and 400 s) to 10 ppm of TEA compared to the pristine MWCNT sensor (400 and 1300 s), and the selectivity coefficient for TEA gas was improved by approximately three times against various interferants, including ammonia, formaldehyde, nitrogen dioxide, and carbon monoxide. The remarkable improvements in TEA detection were mainly associated with the large specific surface area, abundant active sites, adsorbed oxygen, and other defects. The sensing mechanism was thoroughly explained by using Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and gas chromatography-mass spectrometry (GC-MS). This study provides a new platform for CNT-based chemiresistive sensors with high selectivity, low detection limits, and enhanced precision with universal potential for applications in food safety and environmental monitoring.

Microplastics in environment: a comprehension on sources, analytical detection, health concerns, and remediation.

Contamination of ecosystems by microplastics (MPs) has been reported intensively worldwide in the recent decade. A trend of reports indicated their presence in the atmosphere; food items and soil ecosystems are rising continuously. Literature evidenced that MPs are abundant in seawater, beach sand, drinking water, agricultural soils, wastewater treatment plant (WWTP) effluent, and the atmosphere. The greater abundance of MPs in the environment has led to their invasion of seafood, human-consumed food items such as table salts, beverages, takeout food containers, and disposable cups, marine biological lives, and creating serious health hazards in humans. Moreover, the absence of guidelines and specifications for controlling MPs in the environment makes the situation alarming, and the human toxicity data of MPs is scarce. Thereby, the toxicity assessment of MPs in humans is of greater concern. This review compiles the updated information on the potential sources of MPs in different components of the environment (viz. soil, water, and air), their analysis methods, effects on human health, and remediation methods.

The increase in cell death rates in caloric restricted cells of the yeast helicase mutant rrm3 is Sir complex dependent.

Calorie restriction (CR), which is a reduction in calorie intake without malnutrition, usually extends lifespan and improves tissue integrity. This report focuses on the relationship between nuclear genomic instability and dietary-restriction and its effect on cell survival. We demonstrate that the cell survival rates of the genomic instability yeast mutant rrm3 change under metabolic restricted conditions. Rrm3 is a DNA helicase, chromosomal replication slows (and potentially stalls) in its absence with increased rates at over 1400 natural pause sites including sites within ribosomal DNA and tRNA genes. Whereas rrm3 mutant cells have lower cell death rates compared to wild type (WT) in growth medium containing normal glucose levels (i.e., 2%), under CR growth conditions cell death rates increase in the rrm3 mutant to levels, which are higher than WT. The silent-information-regulatory (Sir) protein complex and mitochondrial oxidative stress are required for the increase in cell death rates in the rrm3 mutant when cells are transferred from growth medium containing 2% glucose to CR-medium. The Rad53 checkpoint protein is highly phosphorylated in the rrm3 mutant in response to genomic instability in growth medium containing 2% glucose. Under CR, Rad53 phosphorylation is largely reduced in the rrm3 mutant in a Sir-complex dependent manner. Since CR is an adjuvant treatment during chemotherapy, which may target genomic instability in cancer cells, our studies may gain further insight into how these therapy strategies can be improved.

Genetic analysis of iron, zinc and grain yield in wheat-Aegilops derivatives using multi-locus GWAS.

BACKGROUND: Wheat is a major staple crop and helps to reduce worldwide micronutrient deficiency. Investigating the genetics that control the concentrations of iron (Fe) and zinc (Zn) in wheat is crucial. Hence, we undertook a comprehensive study aimed at elucidating the genomic regions linked to the contents of Fe and Zn in the grain. METHODS AND RESULTS: We performed the multi-locus genome-wide association (ML-GWAS) using a panel of 161 wheat-Aegilops substitution and addition lines to dissect the genomic regions controlling grain iron (GFeC), and grain zinc (GZnC) contents. The wheat panel was genotyped using 10,825 high-quality SNPs and phenotyped in three different environments (E1-E3) during 2017-2019. A total of 111 marker-trait associations (MTAs) (at p-value < 0.001) were detected that belong to all three sub-genomes of wheat. The highest number of MTAs were identified for GFeC (58), followed by GZnC (44) and yield (9). Further, six stable MTAs were identified for these three traits and also two pleiotropic MTAs were identified for GFeC and GZnC. A total of 1291 putative candidate genes (CGs) were also identified for all three traits. These CGs encode a diverse set of proteins, including heavy metal-associated (HMA), bZIP family protein, AP2/ERF, and protein previously associated with GFeC, GZnC, and grain yield. CONCLUSIONS: The significant MTAs and CGs pinpointed in this current study are poised to play a pivotal role in enhancing both the nutritional quality and yield of wheat, utilizing marker-assisted selection (MAS) techniques.

Infection and inflammation stimulate expansion of a CD74+ Paneth cell subset to regulate disease progression.

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.

A Compiled Update on Nutrition, Phytochemicals, Processing Effects, Analytical Testing and Health Effects of Chenopodium album: A Non-Conventional Edible Plant (NCEP).

Bathua (Chenopodium album) is a rich source of extensive-ranging nutrients, including bio-active carbohydrates, flavonoids and phenolics, minerals, and vitamins that translate to countless health benefits such as anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antioxidant activity. Ascaridole, an important phytoconstituent present in aerial parts of the plant, contributes to its anthelmintic property. Even with vast historical use and significant health benefits, its renown has not spread, and utilization has significantly decreased in recent decades. Gradually, the plant has become known under the name of Non-conventional edible plant (NCEP). This compilation is prepared to bring out the plant under the spotlight for further research by foregrounding previous studies on the plant. Scientific research databases, including PubMed, Google Scholar, Scopus, SpringerLink, ScienceDirect, and Wiley Online, were used to fetch data on C. album. This review offers over up-to-date knowledge on nutritious values, phytochemical composition, volatile compounds, as well as health benefits of C. album. The ethnobotanical and ethnomedicinal uses of the plant in India and other parts of the world are deliberately discussed. Scrutinizing the reported literature on C. album reveals its powerful nutrient composition advantageous in the development of food products. The impact of various cooking and processing methods on the nutritional profile and bioavailability are discussed. The future perspectives with regards to the potential for food and nutraceutical products are critically addressed. This review proves the necessity of breakthrough research to investigate the pharmacology and safety of phytochemicals and nutraceutical development studies on the C. album.

Agricultural and Socioeconomic Factors Associated with Farmer Household Dietary Diversity in India: A Comparative Study of Visakhapatnam and Sonipat.

Using primary data from 479 farmer households, this study examined the associations between agricultural and socioeconomic factors and farmer household dietary diversity in Visakhapatnam and Sonipat. Cropping intensity was positively associated with farmers' household dietary diversity score (HDDS), suggesting that higher cropping intensity may expand the gross cropped area and improve food security among subsistence farmers. Distance to food markets was also significantly associated with farmer HDDS, which suggests that market integration with rural households can improve farmer HDDS in Visakhapatnam. In Sonipat, wealth index had a positive association with farmer HDDS, targeting the income pathway by improving farmer HDDS in this region. Considering the relative contribution of these factors, distance to food markets, cropping intensity, and crop diversity were the three most important factors affecting farmer HDDS in Visakhapatnam, whereas wealth index, cropping intensity, and distance to food markets emerged as the top three important factors contributing to farmer HDDS in Sonipat. Our study concludes that the associations between agricultural and socioeconomic factors and farmer HDDS are complex but context- and location-specific; therefore, considering the site- and context-specific circumstances, different connections to HDDS in India can be found to better support policy priorities on the ground.

An Automated Segmentation of Leukocytes Using Modified Watershed Algorithm on Peripheral Blood Smear Images.

Leukemia can be detected by an abnormal rise in the number of immature lymphocytes and by a decrease in the number of other blood cells. To diagnose leukemia, image processing techniques are utilized to examine microscopic peripheral blood smear (PBS) images automatically and swiftly. To the best of our knowledge, the initial step in subsequent processing is a robust segmentation technique for identifying leukocytes from their surroundings. The paper presents the segmentation of leukocytes in which three color spaces are considered in this study for image enhancement. The proposed algorithm uses a marker-based watershed algorithm and peak local maxima. The algorithm was used on three different datasets with various color tones, image resolutions, and magnifications. The average precision for all three-color spaces was the same, i.e. 94% but the Structural Similarity Index Metric (SSIM) and recall of HSV were better than other two. The results of this study will aid experts in narrowing down their options for segmenting leukemia. Based on the comparison, it was concluded that when the colour space correction technique is used, the accuracy of the proposed methodology improves.

Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues.

BCL-2-like protein 1 (BCL2L1) is a key component of cell survival and death mechanisms. Its dysregulation and altered ratio of splicing variants associate with pathologies. However, isoform-specific loss-of-function analysis of BCL2L1 remains unexplored. Here we show the functional impact of genetically inhibiting Bcl-x short-isoform (Bcl-xS) in vivo. Bcl-xS is expressed in most tissues with predominant expression in the spleen and blood cells in mice. Bcl-xS knockout (KO) mice show no overt abnormality until 3 months of age. Thereafter, KO mice develop cardiac hypertrophy with contractile dysfunction and splenomegaly by 6 months. Cardiac fibrosis significantly increases in KO, but the frequency of apoptosis is indistinguishable despite cardiomyopathy. The Akt/mTOR and JNK/cJun signaling are upregulated in male KO heart, and the JNK/cJun is activated with increased Bax expression in KO spleen. These results suggest that Bcl-xS may be dispensable for development but is essential for maintaining the homeostasis of multiple organs.

Cognitive remediation and schizophrenia: Effects on brain complexity.

The objective of this study is to investigate nonlinear neural dynamics of chronic patients with schizophrenia following 3 months of cognitive remediation and to find correlations with neuropsychological measures of cognition. Twenty nine patients were randomized to Cognitive Training (CT) and Treatment as Usual (TAU) group. The system complexity is estimated by Correlation Dimension (D2) and Largest Lyapunov Exponent (LLE) from the reconstructed attractor of the underlying system. Significant increase in dimensional complexity (D2) over time is observed in prefrontal and medial frontal-central regions in eyes open and arithmetic condition; and posterior parietal-occipital region under eyes closed after 3 months. Dynamical complexity (LLE) significantly decreased over time in medial left central region under eyes closed and eyes open condition; prefrontal region in eyes open and lateral right temporal region in arithmetic condition. Interaction is significant for medial left central region with TAU group exhibiting greater decrease in LLE compared to CT group. The CT group showed significant correlation of increased D2 with focused attention. In this study it is found that patients with schizophrenia exhibit higher dimensional and lower dynamical complexity over time indicating improvement in neurodynamics of underlying physiological system.

Diverse strategies adopted by nature for regulating purine biosynthesis via fine-tuning of purine metabolic enzymes.

Purine nucleotides, generated by de novo synthesis and salvage pathways, are essential for metabolism and act as building blocks of genetic material. To avoid an imbalance in the nucleotide pool, nature has devised several strategies to regulate/tune the catalytic performance of key purine metabolic enzymes. Here, we discuss some recent examples, such as stress-regulating alarmones that bind to select pathway enzymes, huge ensembles like dynamic metabolons and self-assembled filaments that highlight the layered fine-control prevalent in the purine metabolic pathway to fulfill requisite purine demands. Examples of enzymes that turn-on only under allosteric control, are regulated via long-distance communication that facilitates transient conduits have additionally been explored.

Ultrasensitive Room-Temperature NO2 Detection Using SnS2/MWCNT Composites and Accelerated Recovery Kinetics by UV Activation.

High performance with lower power consumption is one among the essential features of a sensing device. Minute traces of hazardous gases such as NO2 are difficult to detect. Tin disulfide (SnS2) nanosheets have emerged as a promising NO2 sensor. However, their poor room-temperature conductivity gives rise to inferior sensitivity and sluggish recovery rates, thereby hindering their applications. To mitigate this problem, we present a low-cost ultrasensitive NO2 gas sensor with tin disulfide/multiwalled carbon nanotube (SnS2/MWCNT) nanocomposites, prepared using a single-step hydrothermal method, as sensing elements. Relative to pure SnS2, the conductivity of nanocomposites improved significantly. The sensor displayed a decrease in resistance when exposed to NO2, an oxidizing gas, and exhibited p-type conduction, also confirmed in separate Mott-Schottky measurements. At a temperature of 20 °C, the sensor device has a relative response of about ≈5% (3%) for 25 ppb (1 ppb) of NO2 with complete recovery in air (10 min) and excellent recovery rates with UV activation (0.3 min). A theoretical lower limit of detection (LOD) of 7 ppt implies greater sensitivity than all previously reported SnS2-based gas sensors, to the best of our knowledge. The improved sensing characteristics were attributed to the formation of nano p-n heterojunctions, which enhances the charge transport and gives rise to faster response. The composite sensor also demonstrated good NO2 selectivity against a variety of oxidizing and reducing gases, as well as excellent stability and long-term durability. This work will provide a fresh perspective on SnS2-based composite materials for practical gas sensors.

Single-nucleotide polymorphism and haplotype analysis of macrophage migration inhibitory factor gene and its correlation with serum macrophage migration inhibitory factor levels in North Indian psoriatic patients with moderate disease severity: A cross-sectional study.

BACKGROUND: Psoriasis is associated with significant morbidity and impaired quality of life. Identification of the host genes that influence disease susceptibility and can potentially guide future, targeted therapy is the need of the hour. AIMS: The aim of the study was to investigate the associations of macrophage migration inhibitory factor (MIF) gene polymorphisms, that is, a 5-8-CATT tetra nucleotide repeats at -794 (-794*CATT5-8) and a single-nucleotide polymorphism at -173 (-173*G/C) with the risk of chronic plaque psoriasis and to observe the correlation, if any, of disease determinants with genetic functional variants and circulating MIF levels. METHODS: Five hundred and seventeen individuals (265 psoriasis patients and 252 controls) were genotyped for MIF gene polymorphisms. Data were analyzed with respect to disease susceptibility, serum MIF levels, disease severity, age at onset, disease duration and presence of comorbidities. RESULTS: The presence of co-morbidities was more frequently noted in patients with late onset disease (P = 0.01). No statistically significant differences were observed either in genotype (P = 0.680) or allele frequency (P = 0.69) with respect to distribution of MIF-173*G/C polymorphism between patients and controls. The frequencies of genotypes -794*CATT 5/7 and 7/7 were significantly lower in patients (P = 0.027* and 0.038*, respectively). CATT*5/MIF-173*C haplotype occurred at a higher frequency in patients (odds ratio 3.03, 95% confidence intervals 1.09-8.47, P = 0.02). The mean serum MIF levels were significantly higher in patients as compared to controls (P < 0.001). The presence of either extended MIF -794*CATT repeats or C allele did not reveal any significant association with serum MIF levels or age at onset. Analysis of effect of various disease determinants revealed no significant association with genetic variants and serum MIF levels. LIMITATIONS: The lesional expression of MIF could not be studied. CONCLUSION: Our results showed that CATT*5/MIF-173*C haplotype is associated with increased susceptibility to psoriasis vulgaris.

Compendium of naringenin: potential sources, analytical aspects, chemistry, nutraceutical potentials and pharmacological profile.

Naringenin is flavorless, water insoluble active principle belonging to flavanone subclass. It exhibits a diverse pharmacological profile as well as divine nutraceutical values. Although several researchers have explored this phytoconstituent to evaluate its promising properties, still it has not gained recognition at therapeutic levels and more clinical investigations are still required. Also the neutraceutical potential has limited marketed formulations. This compilation includes the description of reported therapeutic potentials of naringenin in variety of pathological conditions alongwith the underlying mechanisms. Details of various analytical investigations carried on this molecule have been provided along with brief description of chemistry and structural activity relationship. In the end, various patents filed and clinical trial data has been provided. Naringenin has revealed promising pharmacological activities including cardiovascular diseases, neuroprotection, anti-diabetic, anticancer, antimicrobial, antiviral, antioxidant, anti-inflammatory and anti-platelet activity. It has been marketed in the form of nanoformulations, co-crystals, solid dispersions, tablets, capsules and inclusion complexes. It is also available in various herbal formulations as nutraceutical supplement. There are some pharmacokinetic issue with naringenin like poor absorption and low dissolution rate. Although these issues have been sorted out upto certain extent still further research to investigate the bioavailability of naringenin from herbal supplements and its clinical efficacy is essential.

A comprehensive compiled review is presented on source, health benefits, chemistry and analysis, and marketed products of naringenin.Naringenin is a promising phytoconstituent as nutraceutical.Valorization of fruit peels of citrus fruits is a critical step for food and nutraceutical industry.Structure-activity relationship of naringenin derivatives.Nano-formulations incorporating naringenin in themselves can be used for targeted delivery for critical disorders.Naringenin obtained from the peels can be efficiently used in breads, cookies, cakes and other food products.

Preliminary Dissection of Grain Yield and Related Traits at Differential Nitrogen Levels in Diverse Pre-Breeding Wheat Germplasm Through Association Mapping.

Development of nutrient efficient cultivars depends on effective identification and utilization of genetic variation. We characterized a set of 276 pre-breeding lines (PBLs) for several traits at different levels of nitrogen application. These PBLs originate from synthetic wheats and landraces. We witnessed significant variation in various traits among PBLs to different nitrogen doses. There was ~ 4-18% variation range in different agronomic traits in response to nitrogen application, with the highest variation for the biological yield (BY) and the harvest index. Among various agronomic traits measured, plant height, tiller number, and BY showed a positive correlation with nitrogen applications. GWAS analysis detected 182 marker-trait associations (MTAs) (at p-value < 0.001), out of which 8 MTAs on chromosomes 5D, 4A, 6A, 1B, and 5B explained more than 10% phenotypic variance. Out of all, 40 MTAs observed for differential nitrogen application response were contributed by the synthetic derivatives. Moreover, 20 PBLs exhibited significantly higher grain yield than checks and can be selected as potential donors for improved plant nitrogen use efficiency (pNUE).