Regulation of Notch signaling by non-muscle myosin II Zipper in Drosophila.

The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study.

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR's, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1ß) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

MLNAS: Meta-learning based neural architecture search for automated generation of deep neural networks for plant disease detection tasks.

Plant diseases pose a significant threat to agricultural productivity worldwide. Convolutional neural networks (CNNs) have achieved state-of-the-art performances on several plant disease detection tasks. However, the manual development of CNN models using an exhaustive approach is a resource-intensive task. Neural Architecture Search (NAS) has emerged as an innovative paradigm that seeks to automate model generation procedures without human intervention. However, the application of NAS in plant disease detection has received limited attention. In this work, we propose a two-stage meta-learning-based neural architecture search system (ML NAS) to automate the generation of CNN models for unseen plant disease detection tasks. The first stage recommends the most suitable benchmark models for unseen plant disease detection tasks based on the prior evaluations of benchmark models on existing plant disease datasets. In the second stage, the proposed NAS operators are employed to optimize the recommended model for the target task. The experimental results showed that the MLNAS system's model outperformed state-of-the-art models on the fruit disease dataset, achieving an accuracy of 99.61%. Furthermore, the MLNAS-generated model outperformed the Progressive NAS model on the 8-class plant disease dataset, achieving an accuracy of 99.8%. Hence, the proposed MLNAS system facilitates faster model development with reduced computational costs.

Prospecting the Potential of Plant Growth-Promoting Microorganisms for Mitigating Drought Stress in Crop Plants.

Drought is a global phenomenon affecting plant growth and productivity, the severity of which has impacts around the whole world. A number of approaches, such as agronomic, conventional breeding, and genetic engineering, are followed to increase drought resilience; however, they are often time consuming and non-sustainable. Plant growth-promoting microorganisms are used worldwide to mitigate drought stress in crop plants. These microorganisms exhibit multifarious traits, which not only help in improving plant and soil health, but also demonstrate capabilities in ameliorating drought stress. The present review highlights various adaptive strategies shown by these microbes in improving drought resilience, such as modulation of various growth hormones and osmoprotectant levels, modification of root morphology, exopolysaccharide production, and prevention of oxidative damage. Gene expression patterns providing an adaptive edge for further amelioration of drought stress have also been studied in detail. Furthermore, the practical applications of these microorganisms in soil are highlighted, emphasizing their potential to increase crop productivity without compromising long-term soil health. This review provides a comprehensive coverage of plant growth-promoting microorganisms-mediated drought mitigation strategies, insights into gene expression patterns, and practical applications, while also guiding future research directions.

Escin-sorafenib synergy up-regulates LC3-II and p62 to induce apoptosis in hepatocellular carcinoma cells.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common solid cancer and the leading cause of cancer deaths worldwide. Sorafenib is the first drug used to treat HCC but its effectiveness needs to be improved, and it is important to find ways to treat cancer that combine sorafenib with other drugs. Synergistic therapies lower effective drug doses and side effects while enhancing the anticancer effect. PURPOSE: In the present study, the therapeutic potential of sorafenib in combination with escin and its underlying mechanism in targeting liver cancer has been established. STUDY DESIGN/METHODS: The IC50 of sorafenib and escin against HepG2, PLC/PRF5 and Huh7 cell lines were determined using MTT assay. The combination index, dose reduction index, isobologram and concentrations producing synergy were evaluated using the Chou-Talaly algorithm. The sub-effective concentration of sorafenib and escin was selected to analyze cytotoxic synergistic potential. Cellular ROS, mitochondrial membrane potential, annexin V and cell cycle were evaluated using a flow-cytometer, and autophagy biomarkers were determined using western blotting. Moreover, autophagy was knocked down using ATG5 siRNA to confirm its role. A DEN-induced liver cancer rat model was developed to check the synergy of sorafenib and escin. RESULTS: Different concentrations of escin reduced the IC50 of sorafenib in HepG2, PLC/PRF5 and Huh7 cell lines. Chou-Talaly algorithm determined cytotoxic synergistic concentrations of sorafenib and escin in these cell lines. Mechanistically, this combination over-expressed p62 and LC-II, reflecting autophagy block and induced late apoptosis, further reconfirmed by ATG5 knockdown. Sorafenib and escin combination  reduced HCC serum biomarker α-feto protein (α-FP) by 1.5 folds. This combination restricted liver weight, tumor number and size, also, conserved morphological features of liver cells. The combination selectively targeted the G0 /G1 phase of cancer cells. CONCLUSION: Escin and sorafenib combination potentially up-regulates p62 to block autophagy to induce late apoptosis in liver cancer cells.

Improvement in Electrochemical Performance of Waste Sugarcane Bagasse-Derived Carbon via Hybridization with SiO2 Nanospheres.

Sugar industries generate substantial quantities of waste biomass after the extraction of sugar water from sugarcane stems, while biomass-derived porous carbon has currently received huge research attention for its sustainable application in energy storage systems. Hence, we have investigated waste sugarcane bagasse (WSB) as a cheap and potential source of porous carbon for supercapacitors. The electrochemical capacitive performance of WSB-derived carbon was further enhanced through hybridization with silicon dioxide (SiO2) as a cost-effective pseudocapacitance material. Porous WSB-C/SiO2 nanocomposites were prepared via the in situ pyrolysis of tetraethyl orthosilicate (TEOS)-modified WSB biomass. The morphological analysis confirms the pyrolytic growth of SiO2 nanospheres on WSB-C. The electrochemical performance of WSB-C/SiO2 nanocomposites was optimized by varying the SiO2 content, using two different electrolytes. The capacitance of activated WSB-C was remarkably enhanced upon hybridization with SiO2, while the nanocomposite electrode demonstrated superior specific capacitance in 6 M KOH electrolyte compared to neutral Na2SO4 electrolyte. A maximum specific capacitance of 362.3 F/g at 0.25 A/g was achieved for the WSB-C/SiO2 105 nanocomposite. The capacitance retention was slightly lower in nanocomposite electrodes (91.7-86.9%) than in pure WSB-C (97.4%) but still satisfactory. A symmetric WSB-C/SiO2 105//WSB-C/SiO2 105 supercapacitor was fabricated and achieved an energy density of 50.3 Wh kg-1 at a power density of 250 W kg-1, which is substantially higher than the WSB-C//WSB-C supercapacitor (22.1 Wh kg-1).

Clinico-Etiopathogenesis of Vitamin B12, Folic Acid and Iron Deficiency in Severe Acute Malnutrition Children: A Tertiary Care Hospital Experience from Central India.

In severe acute malnutrition, micronutrient deficiency as well as protein energy malnutrition is a major obstacle to growth & development. Iron deficiency dominates the spectrum of nutritional anemia. After taking informed consent, 211 SAM children and 211 age-and sex-matched healthy children with normal nutritional status were enrolled for the study. MUAC was used to diagnose SAM. A 5-part automated hematoanalyzer was used to measure the complete blood count and red cell indices, and the peripheral smear method to determine the red cell morphology. We measured serum ferritin, Vitamin B12, and folic acid using the ELISA method. Compared to controls, children with SAM had significantly lower red cell indices, platelet counts, and white cell counts. The most common clinical symptoms seen in SAM children were diarrhea, pneumonia, acute gastroenteritis, and acute respiratory infection. Children with SAM are more likely to suffer from iron deficiency and B12 deficiency. Severe vitamin B12 deficiency was more frequently associated with severe anemia. The severe anemia in SAM children constantly changes the body's defense mechanism, affecting the haematopoiesis. In this study, haematological indices are recommended for predicting severity of anemia, and hematopoietic changes are described, in order to improve anticipatory care and outcome in children with SAM.

An overview on the types, applications and health implications of fat replacers.

Driven by the demand of consumers for low-fat foods, the field of fat replacers has made a tremendous breakthrough over the past decade. A fat replacer is a substance that replaces whole or part of the fat in food while asserting the same physiological properties. Based on the source, fat replacers can be carbohydrate, protein or lipid-based. They serve two major purposes in food viz. reducing the calorie content and amount of fat used in the preparation of food products as well as impart fat-like properties. Fat replacers exhibit its functionalities by providing texture, acting as stabilizers, emulsifiers, gelling and thickening agents. It is crucial to select the proper kind of fat replacer because fat functionality varies considerably depending on the meal type and the formulation. Evidence suggests that reducing fat intake can help in controlling body weight and the risk of diseases like type-2 diabetes, hypertension and cardiovascular disease. Consumers should not be misled into believing that fat and calorie-reduced foods may be consumed indefinitely. Fat replacers are most beneficial when they aid in calorie control and promote the consumption of meals that provide essential nutrients. This review aims to provide a deep insight into the fact that fat replacers can be utilized in various food commodities in order to meet the dietary guidelines for reducing fat intake with a healthy lifestyle and prudent dietary approach.

Double-stranded RNA mediated knockdown of sucrase gene induced mortality and reduced offspring production in Aphis gossypii.

The importance of gut sucrase in maintaining osmotic equilibrium and utilizing phloem contents as a carbon source has been widely investigated and proven in sap-sucking insects. In the present study, silencing of Aphis gossypii sucrase1 (Agsuc1) was carried out by double-stranded RNA (dsRNA), which would be lethal to it due to disruption of osmotic balance. The dsRNA corresponding to Agsuc1 was synthesized by two methods, i.e., in vitro synthesis using T7/SP6 RNA polymerase and in vivo synthesis by bacterial expression, i.e., Escherichia coli strain HT115 transformed with the L4440 vector system. Oral delivery of double-stranded Agsuc1 synthesized in vitro (dsAgsuc1) and in vivo (HT115Agsuc1) induced around 50% mortality in nymphs of A. gossypii. Moreover, the number of offspring produced by the survived aphids decreased by 39-43%. Parthenogenetic reproduction of the aphids is the critical factor for their fast population build-up, leading to yield losses of economic significance. Thus, the present study demonstrated that the silencing of the Agsuc1 gene reduced the aphid population by killing it and inhibited the population buildup by reducing the number of offspring produced by the survived aphids, likely to result in a significant reduction in crop damage. The production of dsRNA by bacterial expression is a cost-effective method. It has the potential to be used as a biopesticide. The sucrase gene is an excellent putative target gene for RNAi against A. gossypii. It could be used to develop a transgenic plant that produces dsAgsuc1 to keep A. gossypii populations below the economic threshold level.

Simultaneous removal of ternary heavy metal ions by a newly isolated Microbacterium paraoxydans strain VSVM IIT(BHU) from coal washery effluent.

In the present work, the removal of Cr (VI), Cd (II) and Pb (II) at 50 mg/L of each metal ion concentration was investigated by Microbacterium paraoxydans strain VSVM IIT(BHU). The heavy metal binding on the bacterial cell surface was confirmed through X-ray photoelectron spectroscopy and energy dispersive X-ray. X-ray photoelectron spectroscopy analysis also confirmed the reduction of Cr (VI) to Cr (III). Heavy metal removal dynamics was investigated by evaluating dimensionless, and the value of Nk (9.49 × 10-3, 9.92 × 10-3 and 1.23 × 10-2 for Cr (VI), Cd (II) and Pb (II) ions) indicated that the removal of heavy metals by bacterial isolate was mixed diffusion and transfer controlled. It was found that both the experimental and predicted values for isolated bacterial strain coincided with each other with a good R2 value in the L-M Algorithm range of 0.94-0.98 for the ternary metal ion system. The bacterial isolate presented a maximum heavy metal ion removal efficiency of 91.62% Cr (VI), 89.29% Pb (II), and 83.29% Cd (II) at 50 mg/L.

Escin enhanced the efficacy of sorafenib by autophagy-mediated apoptosis in lung cancer cells.

Combining anti-cancer drugs has been exploited as promising treatment strategy to target lung cancer. Synergistic chemotherapies increase anti-cancer effect and reduce effective drug doses and side effects. In this study, therapeutic potential of escin in combination with sorafenib has been explored. 3-(4,5-Dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assay was used to calculate IC50 values. The synergy was evaluated using Chou-Talaly algorithm. Cellular reactive oxygen species, mitochondrial membrane potential, annexin V, and cell-cycle studies were done by flow-cytometer, and autophagy biomarkers expression were determined using western blotting. Moreover, autophagy was knocked down using ATG5 siRNA to confirm its role, diethylnitrosamine-induced lung cancer model was used to check the synergy of sorafenib/escin. Escin significantly reduced the IC50 of sorafenib in A549 and NCIH460 cells. The combination of sorafenib/escin produced a 2.95 and 5.45 dose reduction index for sorafenib in A549 and NCI-H460 cells. The combination of over-expressed p62 and LC3-II reflects autophagy block-mediated late apoptosis. This phenomenon was reconfirmed by ATG5 knockdown. This combination also selectively targeted G0/G1 phase of cancer cells. In in vivo study, the combination reduced tumour load and lower elevated serum biochemical parameters. The combination of sorafenib/escin synergistically inhibits autophagy to induce late apoptosis in lung cancer cells' G0/G1 phase.

Nutritional management and interventions in complications of pregnancy: A systematic review.

Background: Pregnancy, also known as the "gestation period" which lasts for 37-40 weeks, has been marked as the period of "physiological stress" in a woman's life. A wide range of symptoms, from nausea to ectopic pregnancy, are usually aligned with risk factors like abortion, miscarriage, stillbirth, etc. An estimated total of 15% of total pregnant women face serious complications requiring urgent attention for safe pregnancy survival. Over the past decades, several changes in the environment and nutrition habits have increased the possibility of unfavourable changes during the gestation phase. The diagnostic factors, management and nutritional interventions are targeted and more emphasis has been laid on modifying or managing the nutritional factors in this physiologically stressed phase. Aims: This review focuses on dietary modifications and nutritional interventions for the treatment of complications of pregnancy. Nutritional management has been identified to be one of the primary necessities in addition to drug therapy. It is important to set a healthy diet pattern throughout the gestation phase or even before by incorporating key nutrients into the maternal diet. Methods: The published literature from various databases including PubMed, Google Scholar and ScienceDirect were used to establish the fact of management and treatment of complications of pregnancy. Results: The recommendations of dietary supplements have underlined the concept behind the eradication of maternal deficiencies and improving metabolic profiles. Conclusion: Therefore, the present review summarises the dietary recommendations to combat pregnancy-related complications which are necessary in order to prevent and manage the same.

Alterations in certain immunological parameters in the skin mucus of the carp, Cirrhinus mrigala, infected with the bacteria, Edwardsiella tarda.

The bacterial fish pathogen Edwardsiella tarda causes heavy stock mortality, severely hampering fish production, resulting in great economic loss to the farming industry. The first biological barriers that confer immune protection against pathogen entry are the fish mucosal surfaces. The present study was undertaken to investigate the influence of E. tarda on certain enzymatic and non-enzymatic parameters in the skin mucous secretions of the fish Cirrhinus mrigala using spectrophotometry and zymography. Fish were randomly divided into three groups: control, vehicle control, and infected. A sublethal dose of E. tarda (2.2 × 106 CFU/fish) suspended in 50 µL of PBS was injected intra-peritoneally at 0 day (d). Subsequently, mucus samples were collected at 2 d, 4 d, 6 d and 8 d post-infection. The activities of lysozyme (LYZ), protease (PROT), alkaline phosphatase (ALP), acid phosphatase (ACP), catalase (CAT), peroxidase (PER), superoxide dismutase (SOD), and glutathione S-transferase (GST) decreased significantly in the skin mucus of the challenged fish, indicating the suppressed immune system and decreased antioxidant capacity of C. mrigala to E. tarda infection. Lipid peroxidation (LPO) and total nitrate-nitrite were significantly higher at several time points post-infection, suggesting that physiological functions have been impaired following pathogen challenge. The present findings could be relevant for fish aquaculture and underline the importance of skin mucus not only for assessing fish immune status but also for identifying early warning signals of disease caused by pathogens.

Bioactive compounds of corn silk and their role in management of glycaemic response.

Management of glycaemic response is perhaps the most critical part of antidiabetic therapy. Hypoglycaemia is an avoidable complication caused by conventional drugs used in the treatment of diabetes. It triggers commonly during the intensification of anti-hyperglycemic therapy used to render glycemic control in diabetic patients. The commercial oral hypoglycaemic drugs, insulin, herbal medicines and plant extracts are therefore used as a part of the treatment of diabetes. The demand for treating diabetes, through herbal and plant resources is due to their lesser adverse reactions and better phytochemical benefits. Corn silk has been shown to have anti-allergic, anti-inflammatory, and anti-hypertensive effects when extracted in various solvents. Corn silk has medicinal characteristics and has long been used as a traditional medicine in many nations, although the mechanism of action is unknown. The hypoglycaemic effects of corn silk are investigated in this review. The phytochemical components present in corn silk-like flavonoids, phenolics, terpenoids, tannins, sterols, and alkaloids are phytochemical components that have hypoglycemic activity and a mechanism for lowering blood glucose levels. There is a lack of a homogenized database on the hypoglycemic properties of corn silk thus the present review attempts to critically analyse it and provide specific recommendations of its doses.

Nutritional advantages of barnyard millet and opportunities for its processing as value-added foods.

Barnyard millet (Echinochloa species) has received appreciable attention for its susceptibility to biotic and abiotic stresses, multiple harvests in a year and rich in micronutrients, fibers and phytochemicals. It is believed that the consumption of barnyard millet can possess various health benefits against diabetes, cardiovascular diseases, obesity, skin problems, cancer and celiac disease. The flour of barnyard millet is gluten-free and can be incorporated into the diet of celiac and diabetic patients. Considering the nutritional value of millet, various millet-based food products like bread, snack, baby foods, millet wine, porridge, fast foods and millet nutrition powder can be prepared. Future research and developments on barnyard millet and its products may help cope with various diseases known to humans. This paper discusses barnyard millet's nutritional and health benefits as whole grain and its value-added products. The paper also provides insights into the processing of barnyard millet and its effect on the functional properties and, future uses of barnyard millet in the field food industry as ready-to-cook and ready-to-eat products as well as in industrial uses, acting as a potential future crop contributing to food and nutritional security.

Cardiac Late Sodium Channel Current Is a Molecular Target for the Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin.

BACKGROUND: SGLT2 (sodium/glucose cotransporter 2) inhibitors exert robust cardioprotective effects against heart failure in patients with diabetes, and there is intense interest to identify the underlying molecular mechanisms that afford this protection. Because the induction of the late component of the cardiac sodium channel current (late-INa) is involved in the etiology of heart failure, we investigated whether these drugs inhibit late-INa. METHODS: Electrophysiological, in silico molecular docking, molecular, calcium imaging, and whole heart perfusion techniques were used to address this question. RESULTS: The SGLT2 inhibitor empagliflozin reduced late-INa in cardiomyocytes from mice with heart failure and in cardiac Nav1.5 sodium channels containing the long QT syndrome 3 mutations R1623Q or ΔKPQ. Empagliflozin, dapagliflozin, and canagliflozin are all potent and selective inhibitors of H2O2-induced late-INa (half maximal inhibitory concentration = 0.79, 0.58, and 1.26 µM, respectively) with little effect on peak sodium current. In mouse cardiomyocytes, empagliflozin reduced the incidence of spontaneous calcium transients induced by the late-INa activator veratridine in a similar manner to tetrodotoxin, ranolazine, and lidocaine. The putative binding sites for empagliflozin within Nav1.5 were investigated by simulations of empagliflozin docking to a three-dimensional homology model of human Nav1.5 and point mutagenic approaches. Our results indicate that empagliflozin binds to Nav1.5 in the same region as local anesthetics and ranolazine. In an acute model of myocardial injury, perfusion of isolated mouse hearts with empagliflozin or tetrodotoxin prevented activation of the cardiac NLRP3 (nuclear-binding domain-like receptor 3) inflammasome and improved functional recovery after ischemia. CONCLUSIONS: Our results provide evidence that late-INa may be an important molecular target in the heart for the SGLT2 inhibitors, contributing to their unexpected cardioprotective effects.

Prebiotic Catalytic Peptide Ligation Yields Proteinogenic Peptides by Intramolecular Amide Catalyzed Hydrolysis Facilitating Regioselective Lysine Ligation in Neutral Water.

The prebiotic origin of catalyst-controlled peptide synthesis is fundamental to understanding the emergence of life. Building on our recent discovery that thiols catalyze the ligation of amino acids, amides, and peptides with amidonitriles in neutral water, we demonstrate the outcome of ligation depends on pH and that high pKa primary thiols are the ideal catalysts. While the most rapid thiol catalyzed peptide ligation occurs at pH 8.5-9, the most selective peptide ligation, that tolerates all proteinogenic side chains, occurs at pH 7. We have also identified the highly selective mechanism by which the intermediate peptidyl amidines undergo hydrolysis to α-peptides while demonstrating that the hydrolysis of amidines with nonproteinogenic structures, such as ß- and γ-peptides, displays poor selectivity. Notably, this discovery enables the highly α-selective protecting-group-free ligation of lysine peptides at neutral pH while leaving the functional ε-amine side chain intact.

DNA damage induces STING mediated IL-6-STAT3 survival pathway in triple-negative breast cancer cells and decreased survival of breast cancer patients.

Triple-negative breast cancer is aggressive and metastatic breast cancer type and shows immune evasion, drug resistance, relapse and poor survival. Anti-cancer therapy like ionizing radiation and chemotherapeutic drug majorly induces DNA damage hence, alteration in DNA damage repair and downstream pathways may contribute to tumor cell survival. DNA damage during chemotherapy is sensed by cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes (STING), which determines the anti-tumor immune response by modulating the expression of programmed cell death ligand-1 (PD-L1), immune suppressor, in the tumor microenvironment. Triple-negative breast cancer cells are cGAS-STING positive and modulation of this pathway during DNA damage response for survival and immune escape mechanism is not well understood. Here we demonstrate that doxorubicin-mediated DNA damage induces STING mediated NF-κB activation in triple-negative as compared to ER/PR positive breast cancer cells. STING-mediated NF-κB induces the expression of IL-6 in triple-negative breast cancer cells and activates pSTAT3, which enhances cell survival and PD-L1 expression. Doxorubicin and STAT3 inhibitor act synergistically and inhibit cell survival and clonogenicity in triple-negative breast cancer cells. Knockdown of STING in triple-negative breast cancer cells enhances CD8 mediated immune cell death of breast cancer cells. The combinatorial treatment of triple-negative breast cells with doxorubicin and STAT3 inhibitor reduces PD-L1 expression and activates immune cell-mediated cancer cell death. Further STING and IL-6 levels show a positive correlation in breast cancer patients and poor survival outcomes. The study here strongly suggests that STING mediated activation of NF-κB enhances IL-6 mediated STAT3 in triple-negative breast cancer cells which induces cell survival and immune-suppressive mechanism.

3D printed foods-carbs from the lab for better health.

PURPOSE OF REVIEW: The purpose of the review is to describe carbohydrate based 3D food printing technology in light of how it is affected by the use of various ingredients of ink and the properties associated with carbohydrate inks used for printing. Special focus is diverted to evaluate its effect on texture and corresponding health implications associated with carbohydrate based printed foods. RECENT FINDINGS: The focus of 3D food printed products has revolved around texture modulation and carbohydrates are the best possible additives to achieve this modification. Carbohydrate based inks are used to design healthy texturized printed foods to provide various health benefits to consumer in addition to satisfy their aesthetic requirements. Other ingredients such as prebiotics and probiotics are major adjuncts that add value to these carbohydrates based 3D food printed foods and may have synergistic effects. SUMMARY: Although much of the current attention is on texture modulation, health aspects of the foods naturally drive the future course of research associated with the carbohydrate based 3D food printed foods.

Genetic Diversity and Anti-Oxidative Potential of Streptomyces spp. Isolated from Unexplored Niches of Meghalaya, India.

Streptomyces is genetically and functionally diverse genus known to produce a wide array of phenolics and flavonoids with significant biotechnological applications. 52 isolates belonging to 26 species of Streptomyces collected from Meghalaya, India were analyzed for their genetic diversity using BOX-PCR. Significant inter- and intra- generic diversity was observed among the Streptomyces isolates especially those belonging to S. cacaoi, S. lavendulae, S. olivochromogenes, S. aureus, S. flavovirens. During bioactivity screening of the isolates, S. rectiviolaceus MJM72 recorded the highest DPPH activity (77.13 ± 0.91%) whereas S. antimycoticus MSCA162 showed excellent ABTS radical scavenging activity (99.65 ± 0.41%). On the other hand, S. novaecaesareae MJM58 had the highest (756.4 ± 7.38 µg GAE g-1 fresh weight) phenolic content while S. rectiviolaceus MJM72 was recorded with the highest flavonoid content (69.3 ± 0.12 µg QE g-1 fresh weight). As compared to total flavonoid content, total phenolic content had a stronger correlation with antioxidant activities. HPLC analysis of five selected isolates showed presence of gallic acid and pyrocatechol as predominant phenolics. In case of flavonoids, three isolates showed presence of rutin with S. rochei MSCA130 having the highest rutin content (0.95 µg g-1 fresh weight). The results of this study showed high genetic diversity and antioxidant potential among the Streptomyces isolates.