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The genus Aloe (family: Xanthorrhoeaceae) encompasses 490 shrubby-succulent-perennial species which are native to Africa. Among these, Aloe vera has grabbed the limelight in the arena of herbal medicine due to the presence of unique phytochemicals such as Aloin A and B, Homonataloin, Aloe emodin, acemannan etc. in its latex. Moreover, its leaf extract contains 99% water, and 75 active compounds including vitamins (A, B1, B2, B3, B6, B9, B12, C, and E), minerals (Zn, Se, Na, Mn, Mg, K, Cu, Cr, Ca), amino acids, and enzymes (peroxidase, lipase, cellulase, catalase, carboxypeptidase, bradykinase, amylase, alkaline phosphatase). Thus, Aloe vera is revered as a ‘wonder plant’ as it possesses multiple pharmaceutical properties such as anti-oxidant, anti-inflammatory, anti-tumor, anti-fungal, anti-diabetic, anti-ulcer, anti-hypertensive and its juice helps to cure gastrointestinal disorders, and dermal diseases, it also strengthens the immune system. Being a xerophyte, Aloe vera is commercially cultivated in many countries which include South Africa, America, Australia, India etc. The Aloe gel, is meticulously extracted, processed and stabilized before using it in preparation of various health care products. This review focuses on the explicit information on origin, botanical description, phytochemistry, nutritional and medicinal benefits, with special emphasis on value-added products of Aloe vera. The review revealed 46 value-added Aloe-products that are being manufactured by different companies worldwide. Thus, sustainable Aloe-cultivation must be ensured to meet the rising global demands for Aloe vera gel and allied products.

Background: Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution.Methods: We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals.Findings: In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5.Interpretation: Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes.Funding: Bill & Melinda Gates Foundation.

What is the association between VEGF gene sequence variants and its mRNA expression in recurrent pregnancy loss (RPL)? Vascular endothelial growth factor (VEGF) has a prominent role in pregnancy and affects pregnancy outcome. The association of VEGF gene 1154GA, 634GC and 583CT polymorphic variations with cases of RPL and full-term fertile women as controls was investigated.Two hundred women with RPL and 240 women healthy controls were included. The restriction fragment length polymorphism method was used for genotyping and quantitative real-time polymerase chain reaction was used for analysis of mRNA expression.In VEGF 1154GA, significant differences were found in homozygous AA genotype between case and control participants. The variant allele A frequency was significantly more abundant in RPL cases (0.41) than controls (0.19) (P0.0001). Only RPL cases with the multi-generation family history of miscarriages and those without any history showed significant differences of combined genotype GA+AA (P0.0001). In VEGF 634 GC, CC genotype and allele C showed significantly increased frequency in RPL cases compared with healthy controls (P0.0001). The association between VEGF-1154 GA SNP and VEGF-A mRNA expression levels was significant in RPL cases (P = 0.004). Also in VEGF-583 CT, CT genotypes were seen significantly associated with cases (P = 0.003). The heterozygous genotype GA was significantly (P = 0.03) associated with upregulation and downregulation of VEGF mRNA, whereas the homozygous variant genotype AA only leads to low expression levels of VEGF mRNA in patients with RPL.All the variants of VEGF play a vital role in an increased susceptibility to RPL. Also, VEGF-1154, AA genotypes are associated with its altered low mRNA expression in women with RPL and seem to affect pregnancy outcome.

In a combined experimental and theoretical study we assess the role of Co incorporation on the OER activity of LaCox Fe1-x O3 . Phase pure perovskites were synthesized up to x=0.300 in 0.025/0.050 steps. HAADF STEM and EDX analysis points towards FeO2 -terminated (001)-facets in LaFeO3 , in accordance with the stability diagram obtained from density functional theory calculations with a Hubbard U term (DFT+U). Linear sweep voltammetry conducted in a rotating disk electrode setup shows a reduction of the OER overpotential and a nonmonotonic trend with x, with double layer capacitance measurements indicating an intrinsic nature of activity. This is supported by DFT+U results that show reduced overpotentials for both Fe and Co reaction sites with the latter reaching values of 0.32-0.40 V, ∼0.3 V lower than for Fe. This correlates with a stronger reduction of the binding energy difference of the *O and *OH intermediates towards an optimum value of 1.6 eV for x=0.250 , the OH deprotonation being the potential limiting step in most cases. Significant variations of the magnetic moments of both surface and subsurface Co and Fe during OER demonstrate that the beneficial effect is a result of a concerted action involving many surrounding ions, which extends the concept of the active site.

The availability of safe drinking water has become a significant concern for the survival of living organisms. With the advancement and rapid growth in industrialization, a large amount of effluent...

Fine-tuning the exposed active sites of platinum group metal (PGM)-based materials is an efficient way to improve their electrocatalytic performance toward large-scale applications in renewable energy devices such as Zn-air batteries (ZABs). However, traditional synthetic methods trade off durability for the high activity of PGM-based catalysts. Herein, a novel dynamic CO2-bubble template (DCBT) approach was established to electrochemically fine-tuning the exposed Pt active sites in PtFeNi (PFN) porous films (PFs). Particularly, CO2 bubbles were intentionally generated as gas-phase templates by methanol electrooxidation. The generation, adsorption, residing, and desorption of CO2 bubbles on the surface of PFN alloys were explored and controlled by adjusting the frequency of applied triangular-wave voltage. Thereby, the surface morphology and Pt exposure of PFN PFs were controllably regulated by tuning the surface coverage of CO2 bubbles. Consequently, the Pt1.1%Fe8.8%Ni PF with homogeneous nanoporous structure and sufficiently exposed Pt active sites was obtained, showing preeminent activities with a half-wave potential (E1/2) of 0.87 V and onset overpotential (ηonset) of 288 mV at 10 mA cm-2 for oxygen reduction and evolution reactions (ORR and OER), respectively, at an ultralow Pt loading of 0.01 mg cm-2. When tested in ZABs, a high power density of 175.0 mW cm-2 and a narrow voltage gap of 0.64 V were achieved for the long cycling tests over 500 h (750 cycles), indicating that the proposed approach can efficiently improve the activity of PGM catalysts by fine-tuning the microstructure without compromising the durability.

Microorganisms and their hosts communicate through an array of signals. Many physiological processes regulated in quorum sensing (QS) are dependent on auto-inducers, like N-acyl-homoserine lactones (AHLs) as in numerous groups of both gram-positive and gram-negative bacteria. In vitro grown seven-day old chickpea seedlings treated with plant growth promoting bacteria (PGPRs) were used to screen the AHL mimicking and for phytochemical substances like phytohormones and secondary metabolites such as phenolics and flavonoids. Potential anti-quorum sensing (anti-QS) activity surrounding the roots on semi-solid agar lawn of Chromobacterium violaceum (ATCC12742) was observed. Crude protein (4.46–8.30 μg/mL) and methanolic extracts (100 μg/mL) of seedling gave moderate anti-QS activity against CV12742 anti QS bioassay, respectively. Crude protein and methanolic extract of Bacillus amyloliquefaciens (34.00 ± 2.23; 34.00 ± 4.33 mm) and B. subtilis A (27.00 ± 2.10; 3.29 ± 2.16 mm) treated samples showed higher zone of inhibition due to anti-QS activity. Phytohormone analysis using LC–MS for zeatin, auxin and methyl jasmonate (MeJA) indicated that phytohormones were significantly upregulated by 1909.80 ng/g FW, 669.67 ng/g FW and 244.55 ng/g FW, respectively in Pseudomonas brassicacearum treated seedlings compared to control. UHPLC of PGPR treated seedlings showed overly expressed gallic acid, protocatechuic acid, catechin, p-hydroxybenzoic acid, caffeic acid, catechol, vanillin, and ferulic acid in B. amyloliquefaciens treated seedlings compared to others. Enrichment analysis identified significant pathways related to metabolism, biosynthesis of secondary metabolites. The present study indicates that chickpea neutralizes an extensive range of functional responses to AHLs that may play important role in legume host-microbe interactions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01034-x.

Background and aim Although, the anticancer potential of Aqueous Azadirachta indica leaf extract (AAILE) has been robustly established against cutaneous squamous cell carcinoma (SCC) in mice, however, its ability in modulating tumor associated extra cellular matrix (ECM) is largely unknown. Therefore, the present study was conceived to explore changes in ECM during murine skin cancer and its chemoprevention by AAILE. Experimental procedure Skin tumors were induced using a two-stage model of carcinogenesis employing topical application of 7,12-Dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as carcinogen and promoter respectively. AAILE was administered orally to the animals. Male Laca mice were divided into four groups: control, AAILE, DMBA/TPA and AAILE + DMBA/TPA. Results The tumors obtained in DMBA/TPA and AAILE + DMBA/TPA groups were histologically identified as SCC. Tumor induction in these groups was accompanied by raised serum carcinoembryonic antigen (CEA) levels when compared to control counterparts. Assessment of hydroxyproline levels and histochemical staining with sirius red and trichrome stain revealed an increase in collagen in tumors of DMBA/TPA group. An increase in glycosaminoglycans (GAGs) levels was also observed in DMBA/TPA group as made evident by biochemical studies and histochemical staining using mucicarmine and alcian blue-periodic acid schiff’s stain. Administration of AAILE to DMBA/TPA treated animals caused a decrease in collagen and GAG levels along with a decrease in serum CEA levels. Conclusion Skin tumors exhibited altered presence of ECM components which is indicative of a modified ECM. AAILE administration antagonised tumor associated ECM alterations which may be contributing to its chemopreventive activity as reported previously., Graphical abstract Image 1, Highlights • DMBA/TPA induced cutaneous squamous cell carcinoma (SCC) in mice. • SCC formation accompanied by enhanced serum carcinoembryonic antigen (CEA) levels. • Dysregulated extra cellular matrix (ECM) components in tumors of DMBA/TPA group. • Altered histological presence and levels of collagen and glycosaminoglycans in tumors. • Chemoprevention by A.indica reduced CEA levels and antagonised ECM alterations.

Diabetes mellitus (DM)-associated impairments in wound healing include prolonged inflammation, the overexpression of matrix metalloproteases (MMPs), and low levels of growth factors at the wound site. To this end, a layer-by-layer scaffold (SL-B-L) made of cross-linked silk fibroin and hyaluronic acid is developed to deliver chlorhexidine, an antimicrobial agent and an MMP-9 inhibitor, along with the PDGF-BB protein. SL-B-L exhibited highly porous morphology. Diabetic rats treated with SL-B-L demonstrated an early wound closure, a fully reconstructed epithelial layer by 14 days, and reduced levels of IL-6, TNF-α, TGF-β1, and MMP-9. Interestingly, SL-B-L treatment increased angiogenesis, the bioavailability of collagen, DNA content, and VEGF-A levels. Furthermore, enhanced keratinocyte-fibroblast interaction along with ordered collagen deposition was observed in SL-B-L-treated rats. Most interestingly, when compared with a clinically used scaffold SEESKIN+, SL-B-L outperformed in promoting wound healing in a diabetic rat model by regulating the inflammation while delivering growth factor and the MMP-9 inhibitor.

The dried twigs of Piper ribesioides were used to prepare various extracts in different solvents. Each extract was evaluated for their toxicity against 2nd instar larvae of Spodoptera exigua. The highest acute toxicity was observed for ethyl acetate extract with an LD50 of 3.25 and 2.50 μg/larva and LD90 of 9.19 and 8.15 μg/larva after 24 and 48 h post-treatment after topical application. Piperine, methyl piperate, N-cinnamoyl-(2-phenylethyl) amine, pinostrobin, pinocembrin, cinnamic acid, lemairamin, N,N-Diphenylcinnamide, and methyl cinnamate were isolated from this extract that was toxic to S. exigua larvae. Cinnamic acid was the most active compound with a LD50 of 0.17 μg/larva after 48 h of topical treatment. Piperine was significantly similar in activity (LD50 = 0.19 μg/larva), but toxicity decreased with the change in structural configuration as observed with methyl piperate (LD50 = 0.73 μg/larva). Other compounds were 3 to 11-fold less toxic than cinnamic acid and piperine. Growth of survived S. exigua larvae until adult emergence after topical application was recorded and maximum inhibition of about 70% was observed after the application of cinnamic acid. Egg hatch was only 29.11% after cinnamic acid treatment, compared to 97.38% in controls. Neither induction nor inhibition of detoxification enzymes due to treatment of extracts were statistically significant, however, individual compounds like cinnamic acid, methyl cinnamate, piperine, pinostrobin, pinocembrin, and lemairamin did show a moderate impact on these enzymes.

Aim: The present study was carried out to determine the protective potential of Lycopene enriched tomato extract (LycT) against hepatic and renal damage caused in mice by dexamethasone administration. Study Design: Male LACA mice were randomly divided into four treatment groups (n=6-7 animals per group) depending upon the treatment they received. Group I (control) animals served as control and were orally administered with olive oil (vehicle) thrice a week for five weeks. Group II (DEX) animals were intraperitoneallly (i.p.) administered with dexamethasone at a dose of 5 mg/kg b.w. on alternate days for three weeks. Group III (LycT) animals were orally (p.o.) administered with LycT at a dose of 5 mg/kg b.w. on alternate days for five weeks. Group IV (LycT+DEX) animals were co-administered with LycT (p.o.) and dexamethasone (i.p.) according to the above mentioned dose regimen Results: Dexamethasone caused hepatic and renal damage as evident from disturbed histoarchitecture, deranged levels of organ function markers (alkaline phosphatase, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, total and direct bilirubin, urea, creatinine) and enhanced level of cell damage (lactate dehydrogenase) and oxidative stress (lipid peroxidation) markers. Increased blood glucose level, decreased hepatic glycogen level along with inhibited activities of enzymes involved in glycolysis (hexokinase, phosphoglucoisomerase) indicated altered glucose metabolism in DEX group. The mitigation in histoarchitectural alterations, cell damage and oxidative stress markers, improved levels of organ function markers, blood glucose level along with ramped up antioxidant defense system indicated the protective potential of LycT against dexamethasone induced ill effects. Conclusions: These results point towards beneficial effects of LycT against dexamethasone induced damage to hepatic and renal tissues in mice.

Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease without an identifiable cause. It is the most common form of interstitial pneumonias. The prognosis is worst in this disease with median survival of just 2–3 years after diagnosis without a lung transplant. Currently, there are no proven medical therapies to cure IPF. Pharmacological agents such as nintedanib and pirfenidone retard the progression of the disease to an extent but without any survival benefit. The only therapeutic option for IPF is lung transplantation with proven survival benefit. The major concern with lung transplantation is waiting time mortality. Lung allocation score was introduced in 2005 to reduce this mortality. Both single- and double-lung transplantations are used worldwide for IPF. Bilateral lung transplantation has been seen to have better survival rates in some studies, but there are no randomized trials which favor this recent trend. The posttransplant survival is lower than seen in other indications for lung transplantation. Posttransplant follow-up should be vigilant to detect complications as early as possible and treat them accordingly.

The activation of 2'-5'-oligoadenylate synthetase (OAS) enzymes by direct interaction with viral double-stranded RNA (dsRNA) is a key part of the innate immune response to viral infection. A downstream effect of the OAS-dsRNA interaction is to degrade the single-stranded RNA to prevent the spread of the virus. The activation of OAS2, one of the members of the OAS family, depends on dsRNA length. Combining in vitro experiments and mathematical modelling, we test different hypotheses for the OAS2 activation mechanisms by its cofactor dsRNA. After model calibration and selection, the cooperative binding of multiple OAS2 to a single dsRNA is shown to best represent the effect of its cofactor length on enzyme activity.

PI3Kδ inhibitors have been approved for B-cell malignancies like CLL, small lymphocytic lymphoma, and so forth. However, currently available PI3Kδ inhibitors are nonoptimal, showing weakness against at least one of the several important properties: potency, isoform selectivity, and/or pharmacokinetic profile. To come up with a PI3Kδ inhibitor that overcomes all these deficiencies, a pharmacophoric expansion strategy was employed. Herein, we describe a systematic transformation of a "three-blade propeller" shaped lead, 2,3-disubstituted quinolizinone 11, through a 1,2-disubstituted quinolizinone 20 to a novel "four-blade propeller" shaped 1,2,3-trisubstituted quinolizinone 34. Compound 34 has excellent potency, isoform selectivity, metabolic stability across species, and exhibited a favorable pharmacokinetic profile. Compound 34 also demonstrated a differentiated efficacy profile in human germinal center B and activated B cell-DLBCL cell lines and xenograft models. Compound 34 qualifies for further evaluation as a candidate for monotherapy or in combination with other targeted agents in DLBCLs and other forms of iNHL.

Elevated levels of Reactive Oxygen Species (ROS), increased antioxidant ability and the maintenance of redox homeostasis can cumulatively contribute to tumor progression and metastasis. The sources and the role of ROS in a heterogeneous tumor microenvironment can vary at different stages of tumor: initiation, development, and progression, thus making it a complex subject. In this review, we have summarized the sources of ROS generation in cancer cells, its role in the tumor microenvironment, the possible functions of ROS and its important scavenger systems in tumor progression with special emphasis on solid tumors.

Stevia rebaudiana Bertoni is a commercially important zero calorie natural-sweetener herb which produce sweet compounds known as steviol glycosides. Rising demands of steviol glycosides by food and beverage industries has led to an increase in its cultivation in various countries. Unfortunately, stevia cultivation faces 2–25% yield penalty due to weeds which further adds to its cultivation cost. To resolve this major challenge, Agrobacterium-mediated genetic transformation of in vitro derived stevia-nodal explants using herbicide resistance gene (bar) has been optimized, for the production of stable transgenic stevia plants. Several parameters including explant type, pre-incubation duration, acetosyringone (As) concentration, Agrobacterium cell density, Agro-inoculation duration, co-cultivation duration, selection regime and plant growth regulators (PGRs) combination and concentration, have been successfully optimized. Among the two types of explants used, nodal explants showed a higher regeneration response of 82.85%, with an average of 25 shoots/explant. The best PGRs combination and concentration for shoot-induction, shoot-elongation and root-induction was found to be 6-benzyladenine (1.0 mg l−1) + naphthalene acetic acid (0.5 mg l−1), gibberellic acid (1.0 mg l−1), and half-strength MS medium, respectively. The two-step selection (phosphinothricin) regime resulted in an average transformation efficiency of 40.48% with nodal explants. Molecular characterization of putative transformants through PCR, RT-PCR, qRT-PCR and Southern-blot hybridization confirmed the presence, stability, expression as well as copy number of bar gene respectively. Compared to the non-transgenic plants, the T0 transgenic plants successfully tolerated 8 mg l−1 glufosinate ammonium sprays. Thus, the optimized protocol can be useful for the introduction of other genes (inter-kingdom transfer) into stevia genome.

Abstract. The present study revealed the effects of Lycopene enriched tomato extract (LycT) on chemically induced skin cancer in mice. Skin tumors were induced by topical application of 7,12-Dimethylbenz(a)anthracene (DMBA) [500 nmol/100 ul of acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 ul of acetone, twice a week for eighteen weeks] and LycT (5 mg/kg b.w.) was administered orally. Male Balb/c mice were divided into four groups (n = 15 per group): control, DMBA/TPA, LycT and LycT + DMBA/TPA. The chemopreventive response of LycT to skin tumorigenesis was evident by inhibition in tumor incidence, number, size, burden and volume in LycT + DMBA/TPA group when compared to DMBA/TPA group. This was associated with inhibition of cell proliferation in LycT + DMBA/TPA group as observed by the decrease in epidermal morphometric parameters and mRNA and protein expression of proliferating cell nuclear antigen when compared to DMBA/TPA group (p ≤ 0.05). LycT decreased (p ≤ 0.05) the mRNA and protein expression of angiogenic genes (vascular endothelial growth factor, angiopoietin-2, basic fibroblast growth factor) in LycT + DMBA/TPA group, suggesting its anti-angiogenic effects. The increase (p ≤ 0.05) in protein expression of connexin-32 and 43 in LycT + DMBA/TPA group suggests improved inter cellular communication when compared to DMBA/TPA group. Histochemical studies demonstrated that the components of extracellular matrix (fibrous proteins and mucopolysaccharides) were also modulated during skin carcinogenesis and its chemoprevention by LycT. The decrease in cell proliferation parameters and expression of angiogenesis associated genes, modulation of ECM components and increase in expression of connexins suggest that LycT improved multiple dysregulated processes during chemoprevention of skin cancer.

Moringa oleifera Lam., (family: Moringaceae) has begun to gain more popularity as a new ‘superfood’ due to its high nutritive value. It has been used for generations to treat and prevent the diseases such as diabetes, anemia, arthritis, and respiratory, skin, heart, liver and digestive disorders. Apart from these pharmacological activities, it is also a plant growth enhancer. The present work deals with a comparative assessment of the effect of foliar spray of Moringa leaf extracts (MLEs) of different varieties (PKM-1, PKM-2, Jaffna, ODC and Conventional) on the stevioside and mineral contents of Stevia rebaudiana Bertoni, a commercial natural sweetener plant. The decreasing order of stevioside and zeatin content in stevia plants after MLEs foliar spray, as determined by High Performance Liquid Chromatography (HPLC) was: Jaffna (7.73%; 0.0063%) > PKM-1 (6.93%; 0.0056%) > PKM-2 (6.45%; 0.0051%) > ODC (4.14%; 0.0048%) > Conventional (3.86%; 0.0042%) > Control (2.94%; 0.00088%) respectively. While, the decreasing order of mineral contents as determined by flame photometer was: Jaffna > PKM-1> PKM-2 > ODC > Conventional > Control. The comparative study revealed that among all the varieties, Jaffna significantly improved the growth and physiochemical parameters of stevia plants. Thus, this variety can be used as an eco-friendly and cost-effective plant growth enhancer in stevia farming and can be used for other commercially important crops.

The present study investigated the hepatoprotective effects of seabuckthorn (Hippophae rhamnoides) leaf-extract (SLE) supplementation in lead acetate-intoxicated Wistar rats. Adult male Wistar rats...

Respiratory syncytial virus (RSV) is a seasonal virus that infects the lungs and airways of 64 million children and adults every year. It is a major cause of acute lower respiratory tract infection and is associated with significant morbidity and mortality. Despite the large medical and economic burden, treatment options for RSV-associated bronchiolitis and pneumonia are limited and mainly consist of supportive care. This publication covers the medicinal chemistry efforts resulting in the identification of JNJ-53718678, an orally bioavailable RSV inhibitor that was shown to be efficacious in a phase 2a challenge study in healthy adult subjects and that is currently being evaluated in hospitalized infants and adults. Cocrystal structures of several new derivatives helped in rationalizing some of the structure-activity relationship (SAR) trends observed.

Purpose:Exploration of novel strategies to extend the benefit of PARP inhibitors beyond BRCA-mutant cancers is of great interest in personalized medicine. Here, we identified EGFR amplification as a potential biomarker to predict sensitivity to PARP inhibition, providing selection for the glioblastoma (GBM) patient population who will benefit from PARP inhibition therapy.Experimental Design:Selective sensitivity to the PARP inhibitor talazoparib was screened and validated in two sets [test set (n = 14) and validation set (n = 13)] of well-characterized patient-derived glioma sphere-forming cells (GSC). FISH was used to detect EGFR copy number. DNA damage response following talazoparib treatment was evaluated by γH2AX and 53BP1 staining and neutral comet assay. PARP–DNA trapping was analyzed by subcellular fractionation. The selective monotherapy of talazoparib was confirmed using in vivo glioma models.Results:EGFR-amplified GSCs showed remarkable sensitivity to talazoparib treatment. EGFR amplification was associated with increased reactive oxygen species (ROS) and subsequent increased basal expression of DNA-repair pathways to counterelevated oxidative stress, and thus rendered vulnerability to PARP inhibition. Following talazoparib treatment, EGFR-amplified GSCs showed enhanced DNA damage and increased PARP–DNA trapping, which augmented the cytotoxicity. EGFR amplification–associated selective sensitivity was further supported by the in vivo experimental results showing that talazoparib significantly suppressed tumor growth in EGFR-amplified subcutaneous models but not in nonamplified models.Conclusions:EGFR-amplified cells are highly sensitive to talazoparib. Our data provide insight into the potential of using EGFR amplification as a selection biomarker for the development of personalized therapy.

The aqueous and ethanolic leaves and seeds extract of M. oleifera varieties, ‘Jaffna’, ‘PKM-1’ (Periyakulam-1), ‘PKM-2’ (Periyakulam-2), ‘ODC’ and ‘Conventional’ were analyzed for their free radical scavenging effect on DPPH (2, 2-diphenyl-2-picryl hydrazyl) and ABTS (2, 2-azinobis,3-ethyl-benzothiazolin-6-sulfonic acid). The DPPH and ABTS activity (based on IC50 values) trend with leaves extract was: Conventional > ODC > PKM-2 > PKM-1 > Jaffna and Conventional > ODC > PKM-2 > PKM-1 > Jaffna respectively. Similarly, the DPPH and ABTS radical scavenging activities of seeds extract was: Conventional > ODC > PKM-2 > PKM-1 > Jaffna and Conventional > ODC > PKM-2 > PKM-1 > Jaffna respectively. The trend observed with total phenolic content (TPC) and total flavonoid content (TFC) values for both leaves and seeds extracts was: Jaffna > PKM-1 > PKM-2 > ODC > Conventional. The antibacterial activity (disc-diffusion method) of the aqueous and ethanolic leaves and seeds extracts of the five varieties on Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus showed a similar trend: Jaffna > PKM-1 > PKM-2 > ODC > Conventional. A comparative assessment of the plant growth promoting potential of the leaves extracts on Stevia rebaudiana was also performed. The trend observed was: Jaffna > PKM-1 > PKM-2 > ODC > Conventional. Therefore, the comparative study reveals that ethanolic leaf and seed extracts of Jaffna variety possess strong antioxidant and antibacterial properties with a high TPC and TFC, as compared to the other varieties. It also exhibits a promising plant growth promoting activity. Thus, this variety can be explored further as a reliable source of natural bacteriostatic agent, antioxidants and plant growth enhancer.

In this paper, a reliable K-band RF MEMS shunt switch with high isolation is presented. The switch is fabricated on a high-resistivity silicon substrate (ρ = 10,000 Ω cm, er = 11.7, h = 675 µm) using bulk micro-machined techniques. A novel symmetrical tri-layer sandwich (insulator–metal–insulator) concept is implemented in membrane design which results in stress-free membrane and thus results in lower actuation voltage of 15V. The inductive effect created in the CPW ground not only brings down the resonant frequency which eliminates the need to increase the membrane length but also improves the isolation (> 40 dB). This electrostatically actuated switch has measured insertion loss and isolation of 1.51 dB and 46.42 dB at 20.25 GHz, respectively. The switch shows consistent performance in terms of RF as well as mechanical after 8 h of continuous operation without stiction. The switch can have applications in telecommunication, defense and space-based phased array system, etc.

Human 2′–5′ oligoadenylate synthetases (OAS) are a family of interferon-inducible proteins that, upon activation by double-stranded RNA, polymerize ATP into 2′–5′ linked oligoadenylates. In this study, we probed the RNA cofactor specificity of the two smallest isozymes, OAS1 and OAS2. First, we developed a strategy for the expression and purification of recombinant human OAS2 from eukaryotic cells and quantified the activity of the enzyme relative to OAS1 in vitro. We then confirmed that both OAS2 domains, as opposed to only the domain containing the canonical catalytic aspartic acid triad, are required for enzymatic activity. Enzyme kinetics of both OAS1 and OAS2 in the presence of a variety of RNA binding partners enabled characterization of the maximum reaction velocity and apparent RNA-protein affinity of activating RNAs. While in this study OAS1 can be catalytically activated by dsRNA of any length greater than 19 bp, OAS2 showed a marked increase in activity with increasing dsRNA length with a minimum requirement of 35 bp. Interestingly, activation of OAS2 was also more efficient when the dsRNA contained 3′-overhangs, despite no significant impact on binding affinity. Highly structured viral RNAs that are established OAS1 activators were not able to activate OAS2 enzymatic activity based on the lack of extended stretches of dsRNA of greater than 35 bp. Together these results may highlight distinct subsets of biological RNAs to which different human OAS isozymes respond.

The present study demonstrates the epigenetic mechanisms underlying the effect of Bacoside rich extract of Bacopa monniera-a nootropic herb, on scopolamine treated amnesic mice conferred via chromatin modifying enzymes. The focus of the work was to elucidate the modulation of the chromatin modifying enzymes: DNMT1, DNMT3a, DNMT3b, HDAC2, HDAC5 and CPB in scopolamine induced amnesic mice after treatment with bacoside rich extract of Bacopa monniera (BA) and BA encapsulated in lactoferrin conjugated PEG-PLA-PCL-OH based polymersomes (BAN). We observed remarkable difference between the results obtained after the treatment with BA and BAN. Interestingly BAN was found to be more efficient in downregulating DNA methylation and histone chain deacetylation. Scopolamine treatment showed up-regulation of DNMT1 expression in qRT-PCR by 3.14-fold as compared to the control, which was considerably decreased by 1.5-fold after treatment with BA and remarkably decreased 0.11-fold by BAN treatment. Scopolamine treatment up-regulated the expression of DNMT3a by 1.6-fold while for DNMT3b by 3.13-fold. In DNMT3a and DNMT3b the fold change decreased to 0.64 and 0.76 after BA treatment, whereas the BAN treatment further down-regulated to 0.32- and 0.63-fold, respectively. Similarly scopolamine up-regulated HDAC2 and HDAC5 by 3.12 fold and 3.64-fold, respectively. BA treatment reversed the changes by reducing HDAC2 mRNA to 0.89-fold and HDAC5 mRNA 0.83-fold. BAN further reduced expression of HDAC2 further to 0.39-fold and HDAC5 to 0.31-fold. On the other hand scopolamine down-regulated CBP mRNA expression by 0.28-fold and increased by 1.09 after BA treatment. BAN significantly increased the CPB expression by 1.65-fold as compared to BA treatment. These findings were consolidated by DNMT and HDAC enzyme activity assay, methylation in the promoter region of the memory related genes: ARC and BDNF and Dot blot assay for DNA methylation. The percent activity increase of DNMT and HDAC after scopolamine administration was 375.74 and 240.90 respectively. After treatment with BA the downfall in percent activity was observed as 167.99 in DMNT and 130.57 in HDAC. BAN treatment further decreased the percent enzyme activity of DNMT and HDAC significantly by 30.0 and 61.81 respectively. The potency of BAN in reversing the epigenetic changes of scopolamine induced amnesic mouse brain, can be attributed to the brain specific delivery of BA through polymersomes which are able to cross the blood brain barrier (BBB) via receptor mediated endocytosis.

A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs via the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by “HPA-Montmorillonite-KSF” as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions. All the derivatives were subjected to cytotoxicity screening against a panel of four different human cancer cell lines viz. colon (Colo-205), prostate (PC-3), leukemia (THP-1) and lung (A549) to check their effect on percentage growth. MTT [3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide] cytotoxicity assay was employed to check IC50 values. Of the synthesized analogs, 16a showed the best activity with IC50 of 7.1 ± 0.8, 13.1 ± 1.4, 13.8 ± 0.9 and 14.7 ± 1.1 μM against lung (A549), leukemia (THP-1), prostate (PC-3) and colon (Colo-205) cancer lines, respectively. The 16a analog was further checked for its effect on cancer cell properties through clonogenic (colony formation) and scratch motility (wound healing) assays and thereby was found that it reduced both the colony formation and migratory properties of the lung cancer cell line (A549). Further, molecular docking studies were performed with 16a to show its binding mode.

The use of silver nanoparticles (AgNPs) against various pathogens is now being well recognized in the agriculture and health sector. Nanoparticles have been shown to exhibit various novel properties and these properties, on other hand, rely upon the size, shape, and morphology of these particles. Moreover, these physical characteristics enable them to interact with microbes, plants, and animals. Smaller-sized particles have shown more toxicity than larger-sized nanoparticles. AgNPs have shown growth inhibition of many fungi likeAspergillus fumigates,A. niger,A. flavus,Trichophyton rubrum,Candida albicans, andPenicilliumspecies. According to the current hypothesis, AgNPs act by producing reactive oxygen species and free radicals, which cause protein denaturation, nucleic acid and proton pump damage, lipid peroxidation, and cell wall damage. Therefore, they alter the cell membrane permeability, causing cell death. This mini-review summarizes the use of silver nanoparticles against fungal pathogens and fungal biofilm in the agricultural sector.

Moringa oleifera Lam. (Moringaceae) is revered as s ‘miracle tree’ due to its remarkable nutritional, medicinal and industrial uses. In our study, a comparative analysis of the nutritional parameters (antioxidant activity, sugar content—TSS, total soluble proteins—TSP and mineral contents), phytochemicals (HPLC analysis of four anticancer compounds), and cytotoxicity of M. oleifera leaf extracts (MLEs) of five selected varieties (conventional, PKM-1, PKM-2, ODC, and Jaffna), was performed. Jaffna variety possessed the highest antioxidant activity (FRAP) followed by other four varieties. The trend observed was: Jaffna (9.47 µg/mL, 18.48 µg/mL, 29.39 µg/mL, and 35.37 µg/mL) &gt, PKM-1 (4.82 µg/mL, 7.63 µg/mL, 22.33 µg/mL, and 27.71 µg/mL) &gt, PKM-2 (2.10 µg/mL, 7.04 µg/mL, 13.18 µg/mL, and 21.78 µg/mL) &gt, ODC (0.17 µg/mL, 2.10 µg/mL, 4.41 µg/mL and 13.94 µg/mL) &gt, Conventional (0.05 µg/mL, 1.08 µg/mL, 2.86 µg/mL, and 5.40 µg/mL), total soluble proteins (TSP) [0.69 ± 0.01 and 0.94 ± 0.01 µg/mL (young and mature stage, respectively)], sugar content (TSS) [0.39 ± 0.01 and 0.51 ± 0.01 µg/mL (young and mature stage, respectively)], chlorophyll content [1.07 ± 0.01 (plantlet stage), 1.36 ± 0.003 (vegetative-stage), 0.82 ± 0.004 (reproductive stage) mg/g], followed by the other four varieties. The trend observed for cytotoxic activities of ethanolic MLEs on HepG2 cell line, based on the IC50 values, was conventional (1.22 mg/mL) &gt, ODC (0.90 mg/mL) &gt, PKM-2 (0.65 mg/mL) &gt, PKM-1 (0.35 mg/mL) &gt, Jaffna (0.15 mg/mL). The results of HPLC quantification of anticancer compounds [beta-sitosterol (0.244%), quercetin (0.216%), kaempferol (0.013%), and moringin (0.063%)] was also in consonance with that of MTT assay. In summary, the trend observed in all the parameters tested was Jaffna &gt, PKM-1 &gt, PKM-2 &gt, ODC &gt, conventional. Thus, Jaffna variety has a better potential to combat malnutrition and cancer and must be recommended for commercial plantations.

Immunomodulation has long been an adjunct approach in treating critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), and acute pancreatitis (AP). Hyperactive immune response with immunopathogenesis leads to organ dysfunction and alters the clinical outcomes in critically ill. Though the immune response in the critically ill might have been overlooked, it has gathered greater attention during this novel coronavirus disease 2019 (COVID-19) pandemic. Modulating hyperactive immune response, the cytokine storm, especially with steroids, has shown to improve the outcomes in COVID-19 patients. In this review, we find that immune response pathogenesis in critically ill patients with sepsis, ARDS, and AP is nearly similar. The use of immunomodulators such as steroids, broad-spectrum serine protease inhibitors such as ulinastatin, thymosin alpha, intravenous immunoglobulins, and therapies such as CytoSorb and therapeutic plasma exchange may help in improving the clinical outcomes in these conditions. As the experience of the majority of physicians in using such therapeutics may be limited, we provide our expert comments regarding immunomodulation to optimize outcomes in patients with sepsis/septic shock, ARDS, and AP.

Artículo con numerosos autores, sólo se mencionan el primero, los de la UAM y grupo colectivo, A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of, This work was primarily supported by grant OPP1132415 from the Bill & Melinda Gates Foundation awarded to S.I.H.

Current therapies in Pancreatic Cancer (PaCa) are ineffective due to deregulated cell cycle driven by landscape mutations. In this study, we show for the first time that tetrandrine (TET) inhibits proliferation of the PaCa cells and inhibits PaCa tumor growth. TET inhibits cell cycle transition at G1/S boundary. TET increased levels of p21Cip1/Waf1 and p27Kip1, had no effect on the levels of CDK4/6 proteins and decreased the levels of cyclin D1 and pRb proteins. TET resulted in changes in mRNA levels of cyclin D1 and p21Cip1/Waf1 but had no effect on the mRNA of p27Kip1. We show, for the first time in any system, that TET treatment downregulated Skp2, E3 ligase specific for degradation of p27Kip1 during the cell cycle. Taken together our results show, that TET indirectly impairs the activities of CDK4/6 to halt deregulated cell cycle and inhibit PaCa tumor growth. These results suggest that TET may serve as a novel agent for treatment of PaCa, for which there is no effective cure to date.

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells, but not in normal cells; as such, it is a promising therapeutic agent. However, therapeutic resistance limits its clinical use in many malignancies, including prostate cancer. Strategies to sensitize cancer cells to TRAIL are urgently needed. We demonstrate here that small-molecule tetrandrine (TET) potentially sensitizes previously resistant (LNCaP and C4-2B cells) and mildly sensitive (PC3 cells) prostate cancer cells to TRAIL-induced apoptosis, and they do so by upregulating mRNA expression and protein levels of death receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5). Using shRNA knockdown, we show critical requirement of DR4 and DR5 in sensitization of prostate cancer cells to TRAIL. We show that double knockdown of DR4 and DR5 abrogated the apoptotic effects of TET and TRAIL. We also demonstrate that TET-induced DR4 and DR5 expression is independent of p53 status. Given that loss of p53 is associated with progression of prostate cancer to CRPC and NEPC, our results show that TET, by acting as a TRAIL-sensitizing agent in prostate cancer, could serve as a potential therapeutic agent in CRPC and NEPC, for which there is no cure to date. Mol Cancer Ther; 17(6); 1217–28. ©2018 AACR.

Background Thymol is a known natural product with insecticidal activity against several insect species. A recent study on structural modifications of thymol to thymyl esters and their efficacy against Spodoptera litura suggested that such an approach could develop generalized novel insecticides/insect growth inhibitors and requires further studies to establish the efficacy against lepidopterans. Results Thymol and structurally modified eight esters were evaluated against beet armyworm, Spodoptera exigua using the topical application. Thymyl butanoate was the most toxic compound with a median lethal dose (LD50 ) of 2.33 and 1.62 μg/larva after 24 and 48 h posttreatment, respectively. All thymyl esters were potentially better than the parent compound thymol, except thymyl dibromoacetate, in their efficacy against Spodoptera exigua. Essentially, there were three levels of activity vis-a-vis the compounds used, that is, with the LD50 range of 1.5 to 5.0, 7.0 to 15.0, and > 20 μg/larva, respectively. Ovicidal activity and reduction in larval growth were also determined by treating third instars at sub-lethal doses, that is, LD50 doses of second instars. Thymyl butanoate treated larvae inhibited glutathione S-transferase, carboxylesterase, and acetylcholinesterase activities, whereas the other thymyl esters induced these enzymes. Conclusion Thymyl butanoate exhibited higher toxicity against Spodoptera exigua and is the first to report about > 15.5× more toxicity than thymol and > 6.5× than thymyl cinnamate, which suggests that the efficacy was species-specific versus the chemical structural variation of the esters.

BACKGROUND A weak implant-soft tissue interface may lead to bacterial ingression, breakdown of underlying tissues, and eventually implant failure. This study proposes a surface modification technique of titanium alloy (Ti), using a nano-biopolymer scaffold to enhance soft tissue attachment in dental implants. METHODS Gelatin (20% w/v) embedded with 10±2 nm silver nanoparticles (AgNPs) was electrospun to form a Gelatin Electrospun Mat (GEM) scaffold, bonded to Ti alloy surface using chemical surface functionalization. Antimicrobial activity of AgNPs was tested against representative Gram-positive (S. aureus) and Gram-negative bacteria (E. coli) at 4, 24, and 48 hours (h) and after embedding in scaffold at 48 h. Cytotoxicity analysis (MTT assay) was carried out using the 3T3 mouse fibroblast cell line at 24 and 72 h for two groups: Control (unmodified Ti disc) and Experimental (GEM embedded with AgNPs); and further validated by scanning electron microscopy (SEM). RESULTS The AgNPs-embedded GEM showed good antimicrobial activity at 48 h, with the AgNPs showing complete (99.99%) inhibition of bacterial colony counts at 24 h and 48 h. Cell viability and proliferation over the GEM modified Ti discs were seen to be significantly increased (p < 0.05) at 72 h as compared to control. SEM images revealed intimate spreading of fibroblasts, with differentiated cell morphology and pseudopodial processes, indicative of enhanced fibroblastic adhesion, growth, and differentiation over the scaffold. CONCLUSION Results show good antifouling properties and biocompatibility of the fabricated coating, making it a promising strategy to reduce post-operative infections and peri-implant diseases in Ti dental implants. This article is protected by copyright. All rights reserved.

By using the crystalline precursor decomposition approach and direct co-precipitation the composition and mesostructure of cobalt-based spinels can be controlled. A systematic substitution of cobalt with redox-active iron and redox-inactive magnesium and aluminum in a cobalt spinel with anisotropic particle morphology with a preferred 111 surface termination is presented, resulting in a substitution series including Co3 O4 , MgCo2 O4 , Co2 FeO4 , Co2 AlO4 and CoFe2 O4 . The role of redox pairs in the spinels is investigated in chemical water oxidation by using ceric ammonium nitrate (CAN test), electrochemical oxygen evolution reaction (OER) and H2 O2 decomposition. Studying the effect of dominant surface termination, isotropic Co3 O4 and CoFe2 O4 catalysts with more or less spherical particles are compared to their anisotropic analogues. For CAN-test and OER, Co3+ plays the major role for high activity. In H2 O2 decomposition, Co2+ reveals itself to be of major importance. Redox active cations in the structure enhance the catalytic activity in all reactions. A benefit of a predominant 111 surface termination depends on the cobalt oxidation state in the as-prepared catalysts and the investigated reaction.

The discovery of a series of thiophenephenylsulfonamides as positive allosteric modulators (PAM) of α7 nicotinic acetylcholine receptor (α7 nAChR) is described. Optimization of this series led to identification of compound 28, a novel PAM of α7 nicotinic acetylcholine receptor (α7 nAChR). Compound 28 showed good in vitro potency, with pharmacokinetic profile across species with excellent brain penetration and residence time. Compound 28 robustly reversed the cognitive deficits in episodic/working memory in both time-delay and scopolamine-induced amnesia paradigms in the novel object and social recognition tasks, at very low dose levels. Additionally, compound 28 has shown excellent safety profile in phase 1 clinical trials and is being evaluated for efficacy and safety as monotherapy in patients with mild to moderate Alzheimer's disease.

Objective Pyridoxine responsive seizures (PDRs) are characterized by early-onset seizures and epileptic encephalopathy (neonates and infants) which respond to pyridoxine. Any type of seizures can be the first presentation of PDRs in these children. The aim of this 20-year retrospective study was to report the profile of 35 children with PDRs. Materials and Methods Neonatal and infantile seizures responding to pyridoxine were analyzed retrospectively from 1998 to 2018. Depending on the clinical features, laboratory results, and genetic study, they were divided into following four groups: (A) responders with α-aminoadipic semialdehyde dehydrogenase 7A1 (ALDH7A1) mutation, (B) responders with pyridoxal phosphate homeostasis protein (PLPHP) mutation, (C) responders with none of these two known mutations, (D) and responders in combination with antiepileptic medications. Results Sixteen of 35 children had genetic mutation, 4 with ALDH7A1 mutation, and 12 with PLPHP mutation recently described. Nineteen of 35 children had no genetic positivity. Conclusion A large number of children with pyridoxine response do not have known genetic confirmation. Over time, new genes, responsible for pyridoxine dependency, may be identified or an unknown metabolic disorder may be seen in these children.

PI3K-targeting therapy represents one of the most sought-after therapies for glioblastoma (GBM). Several small-molecule inhibitors have been evaluated in clinical trials, however, the emergence of resistance limits treatment potential. Here, we generated a patient-derived glioma sphere–forming cell (GSC) xenograft model resistant to the PI3K-specific inhibitor BKM-120. Integrated RNA sequencing and high-throughput drug screening revealed that the Aurora A kinase (Aurora A)/Polo-like kinase 1 (PLK1)/cyclin-dependent kinase 1 (CDK1) signaling pathway was the main driver of PI3K inhibitor resistance in the resistant xenografts. Aurora kinase was upregulated and pCDK1 was downregulated in resistant tumors from both xenografts and tumor tissues from patients treated with the PI3K inhibitor. Mechanistically, the tyrosine kinase receptor Tie2 physically interacted with FGFR1, promoting STAT3 phosphorylation and binding to the AURKA promoter, which increased Aurora A expression in resistant GSCs. Concurrent inhibition of Aurora A and PI3K signaling overcame PI3K inhibitor–induced resistance. This study offers a proof of concept to target PI3K and the collateral-activated pathway to improve GBM therapy.Significance:These findings provide novel insights into the mechanisms of PI3K inhibitor resistance in glioblastoma.

Bamboo shoots are highly nutritious and a potential rich source of antioxidants and bioactive compounds. Besides nutrients, shoots also contain an anti-nutrient, cyanogenic glucosides accounting for its acrid taste that needs to be removed by adequate processing prior to consumption. However, processing can alter the value of phytochemicals with either desirable or adverse effects on the therapeutic quality of shoots. To evaluate the effects of processing, we investigated the effect of fermented, brine preserved and boiled shoots of Dendrocalamus hamiltonii on antioxidant defense system in mouse liver. Glutathione content increased significantly in the liver tissues of all the groups administered with bamboo shoots extract except the mice that received brine preserved shoots extract, where content decreased by 19%. Glutathione reductase (21%), glutathione peroxidase (20%) and catalase (69%) activity decreased significantly in the group administered with the extract of fresh shoots. The fermentation process was recognized as the most valuable process to improve the activity of hepatic superoxide dismutase (23%), glutathione peroxidase (27%) and catalase (29%).

According to folklore, Bacopa monnieri commonly called as Brahmi is known for its cognitive enhancing properties. The plant is found abundantly in wetlands but the drug content (bacosides) is very low (0.2%), therefore, alternative biotechnological protocols are highly needed to supplement the constant source of this valuable plant material which produces stable amounts of bacosides. The present study was conducted to explore the application of different culture systems for cultivation of shoot biomass and maximization of biologically active bacoside biosynthesis in this medicinally important plant. Shoot cultures of Bacopa were cultivated in two different modified benchtop bioreactors: glass bottle bioreactor and balloon type bubble bioreactor and compared with those grown in traditional Erlenmeyer agitated flask. The shoots cultivated in the balloon type bubble bioreactor system showed excellent growth (growth index 796.47 ± 17.27 fresh weight and 395.55 ± 7.55 dry weight) as compared to glass bottle bioreactor system (growth index 488.17 ± 14.4 fresh weight and 327.79 ± 6.64 dry weight) and agitated flask (growth index 363.43 ± 11 fresh weight and 304.22 ± 6.76 dry weight). Furthermore, bacosides produced by shoot cultures cultivated in the balloon type bubble bioreactor (321.95 ± 17.14 mg/L) and glass bottle bioreactor (180.18 ± 6.25 mg/L) configurations were ∼2.78 fold and ∼1.55 fold higher than that recorded in agitated flask cultures (115.7 ± 3.84 mg/L). The balloon type bubble bioreactor system was found to be advantageous for enhancing B. monnieri shoot biomass and bacoside biosynthesis along with ensuring a successful protocol for continuous supply.

The antimicrobial peptide fragment GF-17 was synthesized in-house and conjugated with DOTA and measured molecular mass of DOTA-GF-17 conjugate was 2489 Da. The peptide conjugate was purified and labeled with [68Ga]. The best radiolabeling efficiency (95.0%) of [68Ga]DOTA-GF-17 was achieved at pH 4 with peptide conjugate amount of 20.0 nmol with 30 min of heating at 95 °C. The product remained stable for up to 3 h. The plasma protein binding and lipophilicity for [68Ga]DOTA-GF-17 were 80.98% and −3.12 respectively. The uptake studies with [68Ga]DOTA- GF-17 in S.aureus and P.aeruginosa bacterial strains demonstrated binding of 69.08% and 43.69% respectively. The animal bio-distribution and PET imaging studies were in agreement showing similar pattern for organs’ tracer distribution and renal excretion. The tracer had rapid blood clearance and uptake in bone marrow and muscles was very low. The highest uptake of [68Ga]DOTA-GF-17 was observed at 45 min and 120 min in S.aureus and P.aeruginosa infections respectively. [68Ga]DOTA-GF-17 could be a promising PET tracer and holds a great scope for taking the product further to perform extensive PET studies in animal infection (using gram negative/positive strains) models to prove the diagnostic utility of this novel PET tracer for futuristic clinical applications.

The present study was premeditated to examine the radioprotective effects of aqueous Aloe vera gel extract against whole-body X-ray irradiation–induced hematological alterations and splenic tissue injury in mice. Healthy male balb/c mice were divided into four groups: group 1, control; group 2, A. vera (50 mg/kg body weight) administered per oral on alternate days for 30 days (15 times); group 3, X-ray exposure of 2 Gy (0.25 Gy twice a day for four consecutive days in the last week of the experimental protocol); and group 4, A. vera + X-ray. X-ray exposure caused alterations in histoarchitecture of spleen along with enhanced clastogenic damage as assessed by micronucleus formation and apoptotic index. Irradiation caused an elevation in proinflammatory cytokines like tumor necrosis factor and interleukin-6, total leucocyte counts, neutrophil counts and decreased platelet counts along with unaltered red blood cell counts and hemoglobin. Irradiation also caused an elevation in reactive oxygen species (ROS), lipid peroxidation (LPO) levels, lactate dehydrogenase activity and alterations in enzymatic and nonenzymatic antioxidant defense mechanism in plasma and spleen. However, administration of A. vera gel extract ameliorated X-ray irradiation–induced elevation in ROS/LPO levels, histopathological and clastogenic damage. It also modulated biochemical indices, inflammatory markers, and hematological parameters. These results collectively indicated that the A. vera gel extract offers protection against whole-body X-ray exposure by virtue of its antioxidant, anti-inflammatory and anti-apoptotic potential.

Chronic Kidney Disease (CKD) is an irreversible and progressive reduction of renal tissue function which affects almost all other systems of the body. It often goes undiagnosed and therefore remains undertreated. For this reason, various biochemical parameters such as: serum creatinine and blood urea nitrogen, urinary protein, urinary albumin, urinary creatinine and Glomerular Filtration Rate (GFR) act as baseline predictors in early detection and management of CKD manifestations. Hence the present study was undertaken to find out the outcome of “Renal diet therapy and Deep breathing exercises” on 21 kidney related biochemical parameters among adult CKD patients who were admitted in SKIMS from 5th March 2012 to 31st July 2013.A total of 200 adult CKD patients being randomly selected were studied in two groups (experimental=100; control=100). The findings of the study revealed that CKD patients in the experimental group who received “Renal diet therapy and Deep breathing exercises” reported a considerable improvement (p≤0.05) in 11 biochemical parameters including: fasting serum glucose, cholesterol, triglycerides, HDL, LDL, calcium, phosphorus, potassium, chloride, hematocrit and platelets as compared to CKD patients in control group who received routine care, had shown a considerable improvement (p≤0.05) in only 5 biochemical parameters such as: fasting serum glucose, cholesterol, triglycerides, calcium and phosphorus. Hence, it can be inferred that “Renal diet therapy and Deep breathing exercises” were effective in regulating various biochemical parameters within normal level in CKD patients. However, the long-term efficacy of these non-pharmacological therapies need to be investigated.

Every plant biological activity is manipulated by more than one hormone, thus the biological phenomenon often reflects the combined interplay of several different hormones. Cinnamic acid, being precursor for the production of various di (lignans), polyphenols (lignins) and also substituted derivatives. In this study a comparative study had been undertaken to ascertain whether, the cinnamate alone or in conjunction with kinetin, indole acetic acid, gibberellin and abscisic acid, can have biochemical effect on the carbohydrate fractions, phytochemical constituents and molecular changes using a photosynthetic tissue. Surface sterilized cucumber seeds were germinated under constant temperature and illumination. The cotyledons scored after 48 h. of germination were subjected to different treatment combinations of cinnamate alone and in conjugation with other plant growth regulators (PGRs) in sterilized petri plates lined with sterile chromatographic grade filter paper discs. Results showed a concomitant increase in the tissue fresh and dry weight contents and also increase in sugar pool with increasing cinnamate dose concentration irrespective of whether these were imposed with any other PGRs. Phytochemical and molecular analysis depicted the same that cinnamate acts independently and also showed both synergistic and antagonistic interference with other PGRs viz., kinetin, auxin, gibberellic acid and abscisic acid.

Background: BacCancer is regarded as second leading cause of death worldwide. Therefore, there is a high demand for the discovery, development and improvement of novel anti-cancer agents which could efficiently prevent proliferative pathways and clonal expansion of cells. Objective: In view of this, a new series of bioactive scaffolds viz triazoles linked 7-hydroxycoumarin (1) were synthesized using click chemistry approach. Method: All the synthesized compounds were screened for cytotoxicity against a panel of seven different human cancer cell lines viz. Colon (Colo-205 and HCT-116), breast (MCF-7), lung (NCI-H322 and A549), prostate (PC-3) and skin (A-431) using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Results: Among all tested analogs, compound 5, displayed better cytotoxic activity as compared to the parent 7- hydroxycoumarin (1) with IC50 of 5.1, 22.7, 14.3 and 10.2 µM against breast (MCF-7), lung (NCI- H322), prostate (PC-3) and skin (A-431) cancer cell lines, respectively; the compound 5 was 8-fold more sensitive against MCF-7 than the parent 7-hydroxycoumarin. Moreover, Compound 5 induced both cytotoxic as well as cytostatic effects via induction of apoptosis and G1 phase arrest, respectively in breast cancer cells (MCF-7). The apoptotic cell population enhanced to 18.8% at 8 µM of 5 from 9.8% in case of negative control, while G1 phase arrest increased to 54.4% at 8 µM compared to negative control of 48.1%. Moreover, Compound 5 also exhibited a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of cancer cells used. Conclusion: The structure-activity relationship study revealed that the derivatives bearing electron-withdrawing substituents were more effective. The present study resulted in identification of the compounds demonstrating broad spectrum cytotoxic activity.