Exploring Steroidal Saponin Composition and Morphometric Characteristics of Rhizomes from Trillium govanianum Wall. ex D. Don: Inference for Medicinal Properties and Genetic Stock Improvement.

Trillium govanianum, a medicinal herb, exhibiting diverse morphometric traits and phytochemicals across developmental stages of plants. The changes in the chemical profile and steroidal saponin levels in the rhizome of T. govanianum across different developmental stages were previously unknown. This study categorizes rhizomes into three types based on scar presence: juvenile (5-10 scars, Type I), young (11-19 scars, Type II), and mature (21-29 scars, Type III). Rhizomes show varying sizes (length 1.2-4.7 cm, girth 0.3-1.6 cm), weight (0.18-5.0 g), and extractive yields (9.7-16.1 % w w-1), with notable differences in saponin content (5.95-21.9 mg g-1). Ultra-high performance liquid chromatography-MS/MS (UHPLC-QTOF-MS/MS)-based chemical profiling identifies 31 phytochemicals, mainly including diverse saponins. Ultra-high performance liquid chromatography coupled with evaporative light scattering detection (UHPLC-ELSD)-based quantitative analysis of seven key saponins reveals stage-specific accumulation patterns, with protodioscin (P) and dioscin (DS) predominant in mature rhizomes. Statistical analysis confirms significant variation (p=0.001) in saponin levels across developmental stages with chemical constituent protodioscin (P=4.03±0.03-15.76±0.14 mg g-1, PAve=9.79±3.03 mg g-1) and dioscin (DS=1.23±0.06-3.93±0.07 mg g-1, DSAve=2.59±0.70 mg g-1), with acceptable power (p=0.738; |δ|>0.5) statistics for effective sample size (n=27 samples used in the study) of T. govanianum. Principal Component Analysis (PCA) and Euclidean clustering further highlighted chemotype distinctions.

Investigating the therapeutic potential of Allium cepa extract in combating pesticide exposure induced ocular damage.

The ocular surface is subject to a range of potentially hazardous environmental factors and substances, owing to its anatomical location, sensitivity, and physiological makeup. Xenobiotic stress exerted by chronic pesticide exposure on the cornea is primarily responsible for ocular irritation, excessive tear production (hyper-lacrimation), corneal abrasions and decreased visual acuity. Traditional medicine hails the humble onion (Allium cepa) for its multi-faceted properties including but not limited to anti-microbial, antioxidant, anti-inflammatory and wound healing. However, there is a lacuna regarding its impact on the ocular surface. Thereby, the current study investigated whether topical application of crude extract of Allium cepa aided in mitigating pesticide-induced damage to the ocular surface. The deleterious effects of pesticide exposure and their mitigation through the topical application of herbal extract of Allium cepa were analysed initially through in vitro evaluation on cell lines and then on the ocular surface via various in-vivo and ex-vivo techniques. Pathophysiological alterations to the ocular surface that impacted vision were explored through detailed neurophysiological screening with special emphasis on visual acuity wherein it was observed that the murine group treated with topical application of Allium cepa extract had comparable visual capacity to the non-pesticide exposed group. Additionally, SOD2 was utilized as an oxidative stress marker along with the expression of cellular apoptotic markers such as Bcl-xL to analyse the impact of pesticide exposure and subsequent herbal intervention on oxidative stress-induced corneal damage. The impact on the corneal epithelial progenitor cell population (ABCG2 and TERT positive cells) was also flowcytometrically analysed. Therefore, from our observations, it can be postulated that the topical application of Allium cepa extract might serve as an effective strategy to alleviate pesticide exposure related ocular damage.

Taxoids-rich extract from Taxus wallichiana alleviates high-fat diet-induced insulin resistance in C57BL/6 mice through inhibition of low-grade inflammation.

The needle powder of Taxus wallichiana is in use for the management of diabetes and inflammation-related complications in the Indian and Chinese Systems of Traditional Medicine but the lack of proper pharmacological intervention has prompted us to investigate the pharmacological mechanism against inflammation-induced insulin resistance in high-fat diet-fed C57BL/6 mice. Hexane (Tw-H), chloroform (Tw-C), and ethyl acetate (Tw-EA) extracts were prepared from a needle of T. wallichiana and its effect on glucose uptake against TNF-α-induced insulin resistance in skeletal muscle cells was studied. Among all, Tw-EA extract has shown promising glucose uptake potential. Tw-EA treatment is also able to decrease the lipid accumulation in adipocytes. Chemical signature of Tw-EA using HPLC showed the presence of taxoids. Efficacy of taxoids-rich extract from T. wallichiana (Tw-EA) was further validated in in vivo system against high-fat diet (HFD)-induced insulin resistance in C57BL/6 mice. Oral treatment of Tw-EA showed significant reduction in blood glucose, pro-inflammatory cytokine production and body weight gain when compared with vehicle-treated HFD-induced insulin resistance in C57BL/6 mice. Histopathology and immunohistochemistry study in skeletal muscle and adipose tissue revealed that oral treatment of Tw-EA is able to reduce the infiltration of inflammatory cells in skeletal muscles, ameliorate the hypertrophy in adipose tissue and upregulate the GLUT4 protein expression. Treatment with Tw-EA significantly up-regulated mRNA expression of insulin signaling pathway (IRS-1, PI3K, AKT, GLUT 4). This study suggested the beneficial effect of taxoids-rich extract from Taxus wallichiana against the inflammation-associated insulin resistance condition.

Pharmacological and Toxicological Study of Coumarinolignoids from Cleome viscosa in Small Animals for the Management of Rheumatoid Arthritis.

This study aims to explore the possible pharmacological potential of Cleome viscosa Linn (Cleomaceae), an annual weed, into therapeutic value-added products. In the present study, we have explored the pharmacological and toxicological profile of coumarinolignoids isolated from Cleome viscose for the management of rheumatoid arthritis and related complications in a small animal model. To avoid the biasness during experiments on animals, we have coded the isolated coumarinolignoids as CLIV-92 to perform the experimental pharmacological study. CLIV-92 was orally administrated (30,100, 300 mg/kg) to animal models of collagen-induced arthritis (CIA), carrageenan-induced acute inflammation, thermal and chemical-induced pain, and Brewer's yeast-induced pyrexia. Oral administration of CLIV-92 significantly decreases the arthritis index, arthritis score, and increases the limb withdrawal threshold in the CIA model in experimental rats. The anti-arthritis studies revealed that the anti-inflammatory effect of CLIV-92 was associated with inhibition of the production of inflammatory mediators like TNF-α, IL-6, IL-17A, MMP-1, MMP-9, Nitric oxide, and C-RP in CIA rat's serum, and also reduced the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue of CIA rats, in a dose-dependent manner. Further individual experiments related to arthritis-related complications in experimental animals demonstrated the analgesic, anti-inflammatory, and antipyretic potential of CLIV-92 in a dose-dependent manner. Further, an in-vivo acute oral toxicity study concluded that CLIV-92 is safe in experimental animals up to 2,000 mg/kg dose. The results of this study suggested that the oral administration of CLIV-92 may be a therapeutic candidate for further investigation in the management of rheumatoid arthritis and related complications.

Process development and preclinical evaluation of a major Plasmodium falciparum blood stage vaccine candidate, Cysteine-Rich Protective Antigen (CyRPA).

Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) is an essential, highly conserved merozoite antigen that forms an important multi-protein complex (RH5/Ripr/CyRPA) necessary for erythrocyte invasion. CyRPA is a promising blood-stage vaccine target that has been shown to elicit potent strain-transcending parasite neutralizing antibodies. Recently, we demonstrated that naturally acquired immune anti-CyRPA antibodies are invasion-inhibitory and therefore a correlate of protection against malaria. Here, we describe a process for the large-scale production of tag-free CyRPA vaccine in E. coli and demonstrate its parasite neutralizing efficacy with commonly used adjuvants. CyRPA was purified from inclusion bodies using a one-step purification method with high purity (>90%). Biochemical and biophysical characterization showed that the purified tag-free CyRPA interacted with RH5, readily detected by a conformation-specific CyRPA monoclonal antibody and recognized by sera from malaria infected individuals thus indicating that the recombinant antigen was correctly folded and retained its native conformation. Tag-free CyRPA formulated with Freund's adjuvant elicited highly potent parasite neutralizing antibodies achieving inhibition of >90% across diverse parasite strains. Importantly, we identified tag-free CyRPA/Alhydrogel formulation as most effective in inducing a highly immunogenic antibody response that exhibited efficacious, cross-strain in vitro parasite neutralization achieving ~80% at 10 mg/ml. Further, CyRPA/Alhydrogel vaccine induced anti-parasite cytokine response in mice. In summary, our study provides a simple, scalable, cost-effective process for the production of tag-free CyRPA that in combination with human-compatible adjuvant induces efficacious humoral and cell-mediated immune response.

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni.

Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. jejuni infection, using intestinal epithelial cells and mouse models focused on the interaction of C. jejuni with the VD signaling pathway and VD treatment to improve C. jejuni-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in C. jejuni-infected epithelial cells and IL-10-/- mice. Furthermore, interference of C. jejuni with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for C. jejuni treatment in humans and animals.

Rootstocks Overexpressing StNPR1 and StDREB1 Improve Osmotic Stress Tolerance of Wild-Type Scion in Transgrafted Tobacco Plants.

In grafted plants, the movement of long-distance signals from rootstocks can modulate the development and function of the scion. To understand the mechanisms by which tolerant rootstocks improve scion responses to osmotic stress (OS) conditions, mRNA transport of osmotic responsive genes (ORGs) was evaluated in a tomato/potato heterograft system. In this system, Solanum tuberosum was used as a rootstock and Solanum lycopersicum as a scion. We detected changes in the gene expression levels of 13 out of the 21 ORGs tested in the osmotically stressed plants; of these, only NPR1 transcripts were transported across the graft union under both normal and OS conditions. Importantly, OS increased the abundance of StNPR1 transcripts in the tomato scion. To examine mRNA mobility in transgrafted plants, StNPR1 and StDREB1 genes representing the mobile and non-mobile transcripts, respectively, were overexpressed in tobacco (Nicotiana tabacum). The evaluation of transgenic tobacco plants indicated that overexpression of these genes enhanced the growth and improved the physiological status of transgenic plants growing under OS conditions induced by NaCl, mannitol and polyethylene glycol (PEG). We also found that transgenic tobacco rootstocks increased the OS tolerance of the WT-scion. Indeed, WT scions on transgenic rootstocks had higher ORGs transcript levels than their counterparts on non-transgenic rootstocks. However, neither StNPR1 nor StDREB1 transcripts were transported from the transgenic rootstock to the wild-type (WT) tobacco scion, suggesting that other long-distance signals downstream these transgenes could have moved across the graft union leading to OS tolerance. Overall, our results signify the importance of StNPR1 and StDREB1 as two anticipated candidates for the development of stress-resilient crops through transgrafting technology.

Strengthening Nutrition Interventions in Antenatal Care Services Affects Dietary Intake, Micronutrient Intake, Gestational Weight Gain, and Breastfeeding in Uttar Pradesh, India: Results of a Cluster-Randomized Program Evaluation.

BACKGROUND: Maternal nutrition interventions are inadequately integrated into antenatal care (ANC). Alive & Thrive aimed to strengthen delivery of micronutrient supplements and intensify interpersonal counseling and community mobilization through government ANC services. OBJECTIVES: We compared nutrition-intensified ANC (I-ANC) with standard ANC (S-ANC) on coverage of nutrition interventions and maternal nutrition practices. METHODS: We used a cluster-randomized design with cross-sectional baseline (2017) and endline (2019) surveys (n ∼660 pregnant and 1800 recently delivered women per survey) and a repeated-measures longitudinal study in 2018-2019 (n = 400). We derived difference-in-difference effect estimates (DIDs) for diet diversity, consumption of micronutrient supplements, weight monitoring, and early breastfeeding practices. RESULTS: Despite substantial secular improvements in service coverage from India's national nutrition program, women in the I-ANC arm received more home visits [DID: 7-14 percentage points (pp)] and counseling on core nutrition messages (DID: 10-23 pp) than in the S-ANC arm. One-third of women got ≥3 home visits and one-fourth received ≥4 ANC check-ups in the I-ANC arm. Improvements were greater in the I-ANC arm than in the S-ANC arm for any receipt and consumption of iron-folic acid (DID: 7.5 pp and 9.5 pp, respectively) and calcium supplements (DID: 14.1 pp and 11.5 pp, respectively). Exclusive breastfeeding improved (DID: 7.5 pp) but early initiation of breastfeeding did not. Maternal food group consumption (∼4 food groups) and probability of adequacy of micronutrients (∼20%) remained low in both arms. Repeated-measures longitudinal analyses showed similar results, with additional impact on consumption of vitamin A-rich foods (10 pp, 11 g/d), other vegetables and fruits (22-29 g/d), and gestational weight gain (0.4 kg). CONCLUSIONS: Intensifying nutrition in government ANC services improved maternal nutrition practices even with strong secular trends in service coverage. Dietary diversity, supplement consumption, and breastfeeding practices remained suboptimal. Achieving greater behavior changes will require strengthening the delivery and use of maternal nutrition services integrated into ANC services in the health system. This trial was registered at clinicaltrials.gov as NCT03378141.

Laxative use in patients with advanced chronic kidney disease transitioning to dialysis.

BACKGROUND: Constipation is highly prevalent in patients with chronic kidney disease (CKD), particularly among those with end-stage renal disease (ESRD), partly due to their dietary restrictions, comorbidities and medications. Laxatives are typically used for constipation management; however, little is known about laxative use and its associated factors in patients with advanced CKD transitioning to ESRD. METHODS: In a retrospective cohort of 102 477 US veterans transitioning to dialysis between October 2007 and March 2015, we examined the proportion of patients who filled a prescription for any type of laxative within each 6-month period over 36 months pre- and post-transition to ESRD. Factors associated with laxative use during the last 1-year pre-ESRD period were identified by multivariable logistic regression. RESULTS: The proportion of patients prescribed laxatives increased as patients progressed to ESRD, peaking at 37.1% in the 6 months immediately following ESRD transition, then remaining fairly stable throughout the post-ESRD transition period. Among laxative users, stool softeners were the most commonly prescribed (∼30%), followed by hyperosmotics (∼20%), stimulants (∼10%), bulk formers (∼3%), chloride channel activator (<1%) and several combinations of these. The use of anticoagulants, oral iron supplements, non-opioid analgesics, antihistamines and opioid analgesics were among the factors independently associated with pre-ESRD laxative use. CONCLUSION: The use of laxatives increased considerably as patients neared transition to ESRD, likely mirroring the increasing burden of drug-induced constipation during the ESRD transition period. Findings may provide novel insight into better management strategies to alleviate constipation symptoms and reduce medication requirements in patients with advanced CKD.

Evaluation of medicinal herbs as a potential therapeutic option against SARS-CoV-2 targeting its main protease.

The COVID-19 disease caused by the SARS-CoV-2 has emerged as a worldwide pandemic and caused huge damage to the lives and economy of more than hundred countries. As on May 10, 2020, more than 4,153,300 people stand infected from the virus due to an unprecedented rate of transmission and 282,700 have lost their lives because of the disease. In this context, medicinal plants may provide a way to treat the disease by targeting specific essential proteins of the virus. We screened about 51 medicinal plants and found that Tea (Camellia sinensis) and Haritaki (Terminalia chebula) has potential against SARS-COV-2 3CLpro , with an IC50 for Green Tea as 8.9 ± 0.5 µg/ml and Haritaki 8.8 ± 0.5 µg/ml. The in-silico studies suggested that Tea component Thearubigins binds to the cysteine 145 of protease active site and could be a pharmacoactive molecule. We predict that the inhibition in protease activity may be able to halt the SARS-CoV-2 replication cycle and therefore, we propose Green Tea, Black Tea, and Haritaki plant extracts as potential therapeutic candidates for SARS-CoV-2 infection. Further investigation on role of bioactive constituents of extracts is needed to establish the molecular basis of inhibition and towards expedited drug discovery.

Combination of Resveratrol and Quercetin Causes Cell Growth Inhibition, DNA Damage, Cell Cycle Arrest, and Apoptosis in Oral Cancer Cells.

Resveratrol and quercetin alone are well reported to have anticancer potential, but their combination studies are very inadequate. We have examined their combination in Cal-33 and SCC-15 oral cancer cells (OCCs) and noncancerous HEK-293 cells. Combination of 10 µM concentration of each resveratrol and quercetin brought additive effect on cellular growth, DNA damage, S-phase cell cycle arrest, and cell death in Cal-33 cells but not in the HEK-293 cells. Augmentation of the cell cycle regulatory protein, Cyclin E, and downregulation of Cyclin A possibly caused S-phase arrest in Cal-33 cancer cells. Comet formation and presence of gamma-H2AX foci confirmed DNA damage, and cleavage of PARP1 and upregulation in Bax level specified apoptosis after combined treatment. Ratio of transcription activation and repression histone marks was found increased after alone as well as combined treatment. Histone deacetylase (HDAC)1, HDAC3, and HDAC8 were downregulated by resveratrol alone and combined treatment. Conclusively, combination of resveratrol and quercetin brings cell growth inhibition, DNA damage, and cell cycle arrest in OCCs but not in normal cells. Additionally, combined treatment causes downregulation of HDACs and apoptosis in cancer cells and it could be an incisive strategy against oral cancer.

Advances in the Characterization of Circulating Tumor Cells in Metastatic Breast Cancer: Single Cell Analyses and Interactions, and Patient-Derived Models for Drug Testing.

Metastasis is the major cause of breast cancer death worldwide. In metastatic breast cancer, circulating tumor cells (CTCs) can be captured from patient blood samples sequentially over time and thereby serve as surrogates to assess the biology of surviving cancer cells that may still persist in solitary or multiple metastatic sites following treatment. CTCs may thus function as potential real-time decision-making guides for selecting appropriate therapies during the course of disease or for the development and testing of new treatments. The heterogeneous nature of CTCs warrants the use of single cell platforms to better inform our understanding of these cancer cells. Current techniques for single cell analyses and techniques for investigating interactions between cancer and immune cells are discussed. In addition, methodologies for growing patient-derived CTCs in vitro or propagating them in vivo to facilitate CTC drug testing are reviewed. We advocate the use of CTCs in appropriate microenvironments to appraise the effectiveness of cancer chemotherapies, immunotherapies, and for the development of new cancer treatments, fundamental to personalizing and improving the clinical management of metastatic breast cancer.

Comparative study on the responses of broiler chicken to hot and humid environment supplemented with different dietary levels and sources of selenium.

Present study was carried out with the objective of investigating the role of green synthesized nano Se (GNS) in growth performance, digestibility of minerals, immunity, stress alleviation, antioxidant status, and body Se content of broiler chicken raised under hot and humid environment with respect to market nano Se (MNS) and inorganic Se. The experimental design was 3 × 3 factorial, in which three levels (0.15, 0.20, and 0.25 ppm) and three sources (inorganic, green nano, and market nano) of Se resulted in nine treatments viz. IS-0.15, GNS-0.15, MNS-0.15, IZ-0.20, GNS-0.20, MNS-0.20, IS-0.25, GNS-0.25, and MNS-0.25 (IS: inorganic Se, GNS: green nano Se, MNS: market nano Se). A total of 432 broiler chicken were divided among nine treatments with six replicates of birds per treatment (8 birds/replicate). Results of present study revealed significantly better growth performance of birds supplemented with 0.25 ppm nano Se. The supplementation of 0.25 ppm nano Se improved the immune response and lymphoid organ development of birds. Significantly higher Se and nitrogen digestibility coefficients, serum antioxidant activity and decline of Heterophil: Lymphocyte ratio and expression of HSP70 gene were observed in birds supplemented with 0.25 ppm Se and nano source of Se compared to inorganic Se. Significantly higher Se concentration in liver and breast muscle and higher serum Se concentration were observed in birds fed 0.25 ppm nano Se. The liver Se concentration was much higher than that of breast muscle. However, the nano Se synthesized by green method in this study did not differ significantly from the chemically synthesized nano Se. It was concluded that 0.25 ppm Se and nano form of Se are superior to lower levels and inorganic form of Se, respectively, in improving the immunity, growth, antioxidant status, and in stress alleviation of broiler chicken. However, GNS is equally efficient as chemically synthesized MNS.

Dietary flaxseed and turmeric is a novel strategy to enrich chicken meat with long chain ω-3 polyunsaturated fatty acids with better oxidative stability and functional properties.

The purpose of the present study was to elucidate the effects of feeding flaxseed meal (FSM) and turmeric rhizome powder (TRP) supplementation on tissue lipid profile, lipid metabolism, health indices, oxidative stability, and physical properties of broiler chicken meat. The 100 g FSM along with 10.0 g TRP supplementation significantly increased the ω-3 PUFA, particularly ALA, EPA, DPA, and DHA of broiler chicken meat due to the corresponding increase ∆9 and Δ5 + Δ6 desaturase activities. The increased activities of the desaturases resulted in significantly better health indices of the broiler chicken meat. The feeding of 100 g FSM along with 10.0 g TRP supplementation reduced the atherogenic and thrombogenic indices of broiler chicken meat. The 100 g FSM feeding reduced the oxidative stability, water holding capacity, extract release volume of broiler chicken meat and increased drip loss, whereas, 10.0 g TRP supplementation reversed these negative effects of FSM.

Feeding value of rice distiller's dried grains with solubles as protein supplement in diet of laying hens.

A feeding trial of 10 weeks duration was undertaken on laying hens (n = 240) to evaluate feeding value of rice distiller's dried grains with soluble (rDDGS) with or without enzyme supplementation (α-amylase, ß-glucanase, xylanase, carboxymethylcellulase, pectinase, proteinase, α-galactosidase, ß-galactosidase, lipase, and phytase), following 4 × 2 factorial design, on egg production, nutrient utilization, and cost economics of egg production. The birds were randomly assigned to eight dietary treatments with 30 birds/treatment. The birds were housed individually in layer cages and each bird was taken as an experimental unit. Eight experimental diets were prepared by incorporating four levels (0, 50, 75, and 100 g/kg) of rDDGS with and without enzyme supplementation. The results revealed a significant (P < 0.01) increase of egg mass, feed intake, egg production, and body weight gain in dietary treatments with up to 75 g rDDGS though the values were statistically similar to the hens fed 100 g rDDGS. Enzyme supplementation resulted in significant (P < 0.01) improvement of egg mass, egg production, feed conversion ratio (FCR) per dozen eggs, FCR per kilogramme egg mass, and net FCR. The significantly (P < 0.01) higher yolk index was observed at 100 g rDDGS level, while shell thickness improved significantly (P < 0.01) up to 75 g rDDGS level. No significant effect of rDDGS inclusion was observed on shape index, albumin index, and Haugh unit. Enzyme supplementation significantly improved the shell thickness and yolk colour of eggs. Nitrogen, calcium, and phosphorus retention and dry matter metabolizability did not show any significant treatment effects. There was significant (P < 0.01) reduction in feed-cost per kilogramme egg mass or per dozen eggs with the increased DDGS levels and dietary enzyme supplementation. It was concluded that rDDGS can be used up to 100 g/kg diet of laying hens along with enzyme supplementation for better productivity of layer hens.

An In Vitro Evaluation of Antibacterial Efficacy of Various Concentration of Eucalyptus globulus Leaf Extract on Periodontal Pathogens.

AIM: The aim of the present study was to evaluate the antibacterial efficacy of various concentrations of Eucalyptus globulus leaf extract on periodontal pathogens. MATERIALS AND METHODS: Matured, healthy and disease-free leaves of Eucalyptus globulus were collected. The leaves were washed under tap water and finally dried in an oven at a temperature of 45°C for 48 hours. The dried plants were ground in an electric blender to make them into a powder. The powder was mixed with 100% ethanol and kept it inside a shaker overnight at 35°C. The mixture was centrifuged for 10 minutes at 2,500 rpm. Three different concentrations (10%, 50%, and 100% v/v) were used as antibacterial agents. Chlorhexidine (0.2%) was considered as positive control and dimethyl formamide was considered as negative control against P. gingivalis and A. actinomycetemcomitans. The disc diffusion method was used to determine the extract's antibacterial activity against the test organisms. A digital Vernier caliper was used to measure the diameter of antibacterial activity showing the zone of inhibition in millimeters. RESULTS: Eucalyptus globulus with 100% concentration showed a maximum zone of inhibition against A. actinomycetemcomitans and P. gingivalis (5.38 ± 0.32 mm, 4.82 ± 0.11 mm) followed by 50% and 10% accordingly. The negative control of dimethyl formamide showed a zone of inhibition of 0.48 ± 0.96 mm and 0.63 ± 0.20 mm against A. actinomycetemcomitans and P. gingivalis. The positive control of 0.2% chlorhexidine showed a zone of inhibition of 8.46 ± 1.02 mm and 7.18 ± 0.54 mm against A. actinomycetemcomitans and P. gingivalis. The ANOVA test showed a highly significant antibacterial efficacy in 0.2% chlorhexidine and 100% concentration Eucalyptus globulus. CONCLUSION: A significant maximum zone of inhibition against A. actinomycetemcomitans and P. gingivalis was showed by 100% concentration of Eucalyptus globulus. CLINICAL SIGNIFICANCE: Other than the systemic diseases treatment, Eucalyptus globulus also serves as an effective promising alternative to antibiotics in the prevention of oral infections because of the natural phytochemicals existing in them.

Fenugreek seed extract ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

Background Natural medicinal plants have been the focus of current research for developing neuroprotective agents to be used in the diabetes-linked cognitive dysfunction. Trigonella foenum-graecum seeds (known as fenugreek, methi in Hindi), is a well-known traditional medicinal herb and possesses anti-diabetic, anti-oxidant, and anti-inflammatory properties. Purpose This study was undertaken to explore the ameliorative effects of T. foenum-graecum seed extract on diabetes-induced cognitive dysfunction. Methods Experimental diabetes was induced by administering a single dose of streptozotocin (60 mg/kg) through intraperitoneal dose. Cognitive function was assessed using a T-maze and the Morris water maze. Lipid peroxidation levels and oxidative stress in the hippocampus was measured. Quantification of hippocampal CA1 and CA3 regions was done using cresyl violet stain. Results Diabetic rats demonstrated learning and memory impairment, which was evident from poor performance in behavioral tasks, i.e. T-maze and Morris water maze tasks. Learning and memory impairment in diabetic animals is associated with increased blood glucose levels, increased oxidative stress in the hippocampus and decreased number of neurons in the CA1 and CA3 regions of the hippocampus. The diabetic rats administered with T. foenum-graecum showed improved performance in behavioral tasks, and these changes were associated with decreased blood glucose levels, decreased oxidative stress in the hippocampus, and decreased neuronal loss from the CA1 and CA3 regions of the hippocampus. Conclusion In conclusion, administration of T. foenum-graecum seed extract ameliorates diabetes-linked cognitive dysfunction in rats by decreasing blood glucose levels, reducing lipid peroxidation and oxidative stress in the hippocampus, and preventing neuronal loss from the hippocampus.

Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host's response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14-15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual's recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4-5, 2019.

Effect of dietary supplementation of hemp (Cannabis sativa) and dill seed (Anethum graveolens) on performance, serum biochemicals and gut health of broiler chickens.

The present study was carried out to study the effect of different doses of hemp seed alone or in combination with dill seed against antibiotic growth promoter on performance, serum biochemicals and gut health of broiler chickens over a period of 42 days. Total 192 broiler chicks were grouped randomly into six treatments and fed with basal diet (BD) along with different levels of seeds, viz., T1 (BD), T2 (BD + 0.2% HS), T3 (BD + 0.2% HS + 0.3 DS), T4 (BD + 0.3% HS) and T5 (BD + 0.3% HS + 0.3 DS) and T6 (BD + 0.025% Bacitracin Methylene Disalicylate-BMD). The performance traits like feed intake, body weight gain and feed conversion ratio (FCR) and carcass traits like cut-up parts, giblet and abdominal fat yield remained unaffected due to dietary treatments for overall trial period; however, the average feed intake in early phase (0-3 weeks) reduced significantly (p < 0.05) in treatment birds than both controls (T1 & T6). Serum protein concentration remained unchanged, whereas significant (p < 0.05) reduction in serum lipids like triglyceride, LDL and total cholesterol concentration was noticed due to dietary inclusion of seeds. Serum enzymes like AST and ALT concentrations depleted significantly (p < 0.05) treated groups, except at higher seed doses (T5); however, alkaline phosphatase levels were unaffected. Coliform count in caecum and jejunum reduced linearly (p < 0.01) due to seed inclusion, whereas dose-dependent proliferation of lactobacilli was evident (p < 0.01) in caecum and jejunum of treated birds. No effect was observed on the villus height and crypt depth of the jejunal mucosa. To conclude, dietary supplementation of hemp and dill seed could not affect the growth performance and carcass traits; however, it positively altered the serum lipid profile of the birds and improved gut health as well, thereby enhanced overall performance of broiler chickens.