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1.
J Food Sci Technol ; 61(8): 1598-1608, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38966794

ABSTRACT

In this present study, a three-factor Box-Behnken, response surface methodology (RSM) design was employed to optimize the skimmed milk powder (SMP)/whey protein concentrate (WPC) ratio (0.25-0.75%w/v) as a source of milk protein, inulin (1-2%w/v), and honey (4-6%w/v) for production of high-quality goat milk yoghurt (GMY). The resulting ANOVA and response surface equations revealed the significant effect (p < 0.05) of these variables on the various attributes such as total solid (%), pH, titratable acidity [(LA) % by weight], syneresis (%), DPPH (% inhibition), viscosity (m.Pa⋅s), whiteness index (WI), and overall acceptability (OA). The coefficient of determination (R2) for all response variables ranged from 0.88 to 0.99. Lack-of-fit tests resulted in non-significant F-values. The optimal conditions were determined as SMP/WPC at 0.36%w/v, inulin at 1.00%w/v, and honey at 6.00%w/v. The optimum values for total solid, pH, titratable acidity, syneresis, DPPH, viscosity, WI, and OA were 22.03, 4.46, 0.77, 6.34, 25.20, 182.30, 76.29 and 8.37, respectively with desirability value of 0.95.

2.
Foods ; 13(14)2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39063340

ABSTRACT

Natural and sustainable plant-based antioxidants and antimicrobials are highly desirable for improving food quality and safety. The present investigation assessed the antimicrobial and antioxidant properties of active components from Alkanna tinctoria L. (herb) roots, also known as Ratanjot root. Two methods were used to extract active components: microwave-assisted hot water (MAHW) and ethanolic extraction. MAHW extract yielded 6.29%, while the ethanol extract yielded 18.27%, suggesting superior Ratanjot root extract powder (RRP) solubility in ethanol over water. The ethanol extract showed significantly higher antioxidant activity than the MAHW extract. Gas Chromatography-Mass Spectrometry analysis revealed three major phenolic compounds: butanoic acid, 3-hydroxy-3-methyl-; arnebin 7, and diisooctyl pthalate. The color attributes (L*, a*, b*, H°ab, C*ab) for the ethanolic and MAHW extracts revealed significant differences (p < 0.05) in all the above parameters for both types of extracts, except for yellowness (b*) and chroma (C*ab) values. The ethanol extract exhibited antimicrobial activity against 14 foodborne bacteria, with a significantly higher inhibitory effect against Gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus) than the Gram-negative bacteria (Salmonella enterica serovar Typhimurium and Escherichia coli). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were both 25 mg/mL for the Gram-negative bacteria, while the MIC and MBC concentrations varied for Gram-positive bacteria (0.049-0.098 mg/mL and 0.098-0.195 mg/mL) and the antimicrobial effect was bactericidal. The antimicrobial activities of RRP extract remained stable under broad temperature (37-100 °C) and pH (2-6) conditions, as well as during refrigerated storage for 30 days. Application of RRP at 1% (10 mg/g) and 2.5% (25 mg/g) levels in a cooked chicken meatball model system prevented lipid oxidation and improved sensory attributes and retarded microbial growth during refrigerated (4 °C) storage for 20 days. Furthermore, the RRP extract was non-toxic when tested with sheep erythrocytes and did not inhibit the growth of probiotics, Lacticaseibacillus casei, and Lactiplantibacillus plantarum. In conclusion, the study suggests that RRP possesses excellent antimicrobial and antioxidant activities, thus making it suitable for food preservation.

3.
Curr Pharm Teach Learn ; 15(7): 699-708, 2023 07.
Article in English | MEDLINE | ID: mdl-37357127

ABSTRACT

BACKGROUND AND PURPOSE: Designed to address the Association of Faculties of Pharmacy of Canada's competency "teach pharmacy team members, the public, and other health care professionals," the PHArmacy Students as Educators (PHASE) program was developed by the institute's entry-to-practice doctor of pharmacy program. The program's objective was to support students in developing the necessary skills to fulfill their role as pharmacist-educators. EDUCATIONAL ACTIVITY AND SETTING: We performed a two-year pilot (2017-2019) of the PHASE program which consists of a large-group didactic session followed by an academic half-day (AHD) session. Evaluation was conducted using Likert-scale and qualitative student survey data collected pre- and post-sessions to determine: (1) how the PHASE program supported students as future educators, and (2) students' perceptions and experiences related to teaching and learning. FINDINGS: All students in the 2020 and 2021 graduating cohorts were included in the study following consent. We determined that while respondents agreed to the statement, "A role of a pharmacist includes being an educator" (93.7% and 98.2% for 2020 and 2021 cohorts) at baseline, the proportion of strongly agree responses increased following the didactic session (P < .005). Of note, average Likert-score for respondents' confidence in educating increased following the AHD session (P < .001). Qualitative analysis identified an increase in students' self-rated ability for determining learners' needs, developing and conducting educational sessions, and confidence related to educating others. SUMMARY: Overall, the PHASE program showed positive impact during the first two years of implementation and lessons learned from the pilot are discussed.


Subject(s)
Pharmacy , Students, Pharmacy , Humans , Curriculum , Educational Measurement , Faculty
4.
Nutrients ; 15(11)2023 May 31.
Article in English | MEDLINE | ID: mdl-37299543

ABSTRACT

Short bowel syndrome (SBS) is a condition that results from a reduction in the length of the intestine or its functional capacity. SBS patients can have significant side effects and complications, the etiology of which remains ill-defined. Thus, facilitating intestinal adaptation in SBS remains a major research focus. Emerging data supports the role of the gut microbiome in modulating disease progression. There has been ongoing debate on defining a "healthy" gut microbiome, which has led to many studies analyzing the bacterial composition and shifts that occur in gastrointestinal disease states such as SBS and the resulting systemic effects. In SBS, it has also been found that microbial shifts are highly variable and dependent on many factors, including the anatomical location of bowel resection, length, and structure of the remnant bowel, as well as associated small intestinal bacterial overgrowth (SIBO). Recent data also notes a bidirectional communication that occurs between enteric and central nervous systems called the gut-brain axis (GBA), which is regulated by the gut microbes. Ultimately, the role of the microbiome in disease states such as SBS have many clinical implications and warrant further investigation. The focus of this review is to characterize the role of the gut microbiota in short bowel syndrome and its impact on the GBA, as well as the therapeutic potential of altering the microbiome.


Subject(s)
Gastrointestinal Microbiome , Short Bowel Syndrome , Humans , Short Bowel Syndrome/complications , Gastrointestinal Microbiome/physiology , Brain-Gut Axis , Intestine, Small/microbiology , Bacteria , Dysbiosis/microbiology
5.
Nutrients ; 16(1)2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38201835

ABSTRACT

Social Determinants of Health (SDOH) impact nearly half of health outcomes, surpassing the influence of human behavior, clinical care, and the physical environment. SDOH has five domains: Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighborhood and Built Environment, and Social and Community Context. Any adversity arising out of these interlinked domains predominantly affects children due to their greater susceptibility, and the adverse outcomes may span generations. Unfavorable SDOH may cause food insecurity, malnutrition, unbalanced gut microbiome, acute and chronic illnesses, inadequate education, unemployment, and lower life expectancy. Systematic screening by health care workers and physicians utilizing currently available tools and questionnaires can identify children susceptible to adverse childhood experiences, but there is a deficiency with respect to streamlined approach and institutional support. Additionally, current ameliorating supplemental food programs fall short of pediatric nutritional requirements. We propose a nutrition-based Surveillance, Screening, Referral, and Reevaluation (SSRR) plan encompassing a holistic approach to SDOH with a core emphasis on food insecurity, coupled with standardizing outcome-based interventions. We also propose more inclusive use of Food Prescription Programs, tailored to individual children's needs, with emphasis on education and access to healthy food.


Subject(s)
Adverse Childhood Experiences , Social Determinants of Health , Humans , Child , Educational Status , Policy , Outcome Assessment, Health Care
6.
J Lab Physicians ; 14(2): 115-118, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35982872

ABSTRACT

Background The burden of hospital-acquired infections (HAIs) is all assumption based, and the true burden remains unknown in most countries, particularly in the developing countries where healthcare facilities are suboptimal and knowledge is limited. Methodology This cross-sectional study was conducted at the trauma center of a tertiary care institute from August to September 2019, to assess the burden of HAI and antibiotic resistance pattern of HAI. The total sample size in our study was 105. Our objective was to estimate the point prevalence of HAI and study the associated factors in a tertiary care hospital. Result In this study, the point prevalence of HAI was five to six times higher when compared with that of developed countries. Gram-negative organisms were the predominant bacteria; with Acinetobacter baumannii the most common among them. Conclusion Point-prevalence survey is an important objective of the antimicrobial stewardship program; it will be helpful in controlling antimicrobial resistance and this tool plays a significant role in hospital settings. Our study is quite pertinent to assess the point prevalence of HAI. It will help in knowing the current prevalence and pattern of the HAI. Therefore, as healthcare administrators, we can further decrease the HAI for better patient outcomes in the future.

7.
J Food Sci ; 87(5): 2083-2095, 2022 May.
Article in English | MEDLINE | ID: mdl-35411572

ABSTRACT

The aim of this study was to find out clove extract's antimicrobial and antioxidant properties, as well as its efficacy as a bioactive ingredient in the development of bio-composite films to increase the storage stability of goat meat balls stored at 4 ± 1°C. The clove extracts (CLEs) were prepared in ethanol, hydroethanol (1:1), and water and evaluated for antioxidant and antimicrobial potential. In vitro assays of CLEs revealed more susceptibility for gram-positive bacteria than gram-negative bacteria. Among the different extracts, the clove ethanol extract (CLEE) had the highest antimicrobial activity against tested microorganisms as well as total phenolics (1.14 mg GAE/g), flavonoids (8.50 µg catechin/g), and DPPH assay (39.59%). Further, the concentration-dependent effect of CLEE (p < 0.05) on thickness and color values and antimicrobial properties of the bio-composite film were observed. The storage qualities of the product T1 (with film; 450 µl CLEE) such as pH (6.45 ± 0.01), TBARS (0.87 ± 0.06 mg malonaldehyde/kg) value, free fatty acid (0.193 ± 0.001% oleic acid), total mesophilic count (4.98 ± 0.05 log10 CFU/g), and sensory attributes (overall acceptability score: 5.67 on 8-point scale) were better (p < 0.05) than T0 (without film; control) on day 20 of storage. Thus, the ethanolic clove extract has a superior antioxidant and antimicrobial potential. Its inclusion in the bio-composite film prolonged the storage stability of goat meat balls by controlling lipid oxidation and microbial growth. Practical Application Today's consumers are more attracted towards meat products added with natural ingredients having preservative effects. Clove extract is a classic example of a natural preservative and has excellent antimicrobial and antioxidant potential. The present study revealed that by wrapping the ethanolic clove extract-based bio-composite film on goat meat balls extended the storage stability of the product due to controlled lipid oxidation and microbial growth. Thus, such bio-composite films can be successfully applied on goat meat balls that function as a antimicrobial packaging for providing optimum organoleptic quality and better shelf life.


Subject(s)
Anti-Infective Agents , Syzygium , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Ethanol , Goats , Lipids , Meat , Syzygium/chemistry
8.
Mol Neurobiol ; 59(3): 1992-2007, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35040038

ABSTRACT

Expansion of CGG trinucleotide repeats in 5' untranslated region of the FMR1 gene is the causative mutation of neurological diseases such as fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and ovarian disorder such as fragile X-associated primary ovarian insufficiency (FXPOI). CGG repeats containing FMR1 transcripts form the toxic ribonuclear aggregates, abrupt pre-mRNA splicing, and cause repeat-associated non-AUG translation, leading to the disease symptoms. Here, we utilized a small molecule library of ~ 250,000 members obtained from the National Cancer Institute (NCI) and implemented a shape-based screening approach to identify the candidate small molecules that mitigate toxic CGG RNA-mediated pathogenesis. The compounds obtained from screening were further assessed for their affinity and selectivity towards toxic CGG repeat RNA by employing fluorescence-binding experiment and isothermal calorimetry titration assay. Three candidate molecules B1, B4, and B11 showed high affinity and selectivity for expanded CGG repeats RNA. Further, NMR spectroscopy, gel mobility shift assay, CD spectroscopy, UV-thermal denaturation assay, and molecular docking affirmed their high affinity and selectivity for toxic CGG RNAs. Next, these lead compounds selectively improved the pre-mRNA alternative splicing defects with no perturbation in global splicing efficacy and simultaneously reduced the FMR1polyG protein aggregate formation without affecting the downstream expression of the gene. Taken together these findings, we addressed compound B1, B4, and B11 as potential lead molecules for developing promising therapeutics against FXTAS. Herein, this study, we have utilized shape similarity approach to screen the NCI library and found out the potential candidate which improves the pre-mRNA splicing defects and reduces FMR1polyG aggregations.


Subject(s)
Fragile X Syndrome , Ataxia/metabolism , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/drug therapy , Fragile X Syndrome/genetics , Fragile X Syndrome/metabolism , Humans , Molecular Docking Simulation , Protein Aggregates , Tremor/metabolism , Trinucleotide Repeat Expansion/genetics
9.
JMIRx Med ; 3(2): e31521, 2022 Apr 29.
Article in English | MEDLINE | ID: mdl-37725547

ABSTRACT

BACKGROUND: University students are at risk of losing their focus on maintaining healthy levels of physical activity because of their engagements with curricular and cocurricular activities. In India, the physical activity levels of the adult population have been reported to be declining in the recent years. However, studies focusing on university students pertaining to their physical activity are lacking in the Indian context. Moreover, a question that has not been properly addressed is the following: "do the curricula in higher education promote physical activity?" OBJECTIVE: Our paper aims at describing the physical activity levels of the students in a large public-funded central university located in northern India. The study also aims at capturing the student perceptions about the emphasis they receive on leading a physically active lifestyle during their routine curricular activities. METHODS: This is a cross-sectional descriptive study and uses International Physical Activity Questionnaire-Long Form to record physical activity among 4586 students. Stratified sampling method was used to enroll the students from each stream (faculty). Out of 30,667 students, about 15% were included from each faculty. The study was conducted between 2016 and 2019. To capture the student perceptions, we used a newly developed 5-item scale. RESULTS: From a total of 4586 participants in the study, 2828 (61.7%) were male and 1758 (38.3%) were female students. The mean age of our sample was 22.34 (SD 3.12) years. Our results indicate that about 14.5% (n=666) of all students in the study fall under the "Inactive" category. Furthermore, the perception about the curricular content pertaining to physical activity varied widely between the students of different streams. CONCLUSIONS: Our sample reported a better physical activity pattern in comparison to the reported overall physical activity levels of the adult population of India. Our results also suggest that health-related topics are inadequately represented in many of the streams of higher education in the university.

10.
Med Teach ; 43(12): 1346-1352, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34499842

ABSTRACT

For this AMEE Guide, we explore the process and application of an evolved tool known as the audio diary. Diaries are a type of qualitative method that has long been advocated for in healthcare education practice and research. However, this tool has been typically underestimated as an approach to capturing how individuals' experiences change over time. In particular, this longitudinal method can nurture a stronger partnership between the researcher and participant, which can empower participants to share their reflections as they make sense of their identities and experiences. There is a wider issue concerning how to use and implement audio diaries in medical education research, this guide outlines a foundational process by which all levels of researchers can use to ensure the purpose, application and use of the audio diary tool is done with quality, rigour and ethics in mind. The processes presented are not a prescriptive approach to utilising audio diaries as a longitudinal method. This AMEE Guide serves as an opportunity for researchers and educators to consult this resource in making decisions to decide whether the audio diary tool is fit for their research and/or educational purpose and how audio diaries can be implemented in health profession education projects. This guide discusses and addresses some of the ethical, operational and contextual considerations that can arise from using audio diaries as a tool for longitudinal data collection, critical reflection, or understanding professionalism.


Subject(s)
Education, Medical , Data Collection , Delivery of Health Care , Humans , Qualitative Research , Research Design
11.
J Food Sci ; 85(9): 2857-2865, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32812228

ABSTRACT

The present study was aimed to develop Manihot esculenta and Carrageenan bio-based composite active film functionalized with anise, caraway, and nutmeg essential oils (EOs) and to assess the shelf life of chicken nuggets wrapped with the developed film at refrigeration storage. Overall, the Minimum Inhibitory Concentration (MIC) values of the three EOs ranged from 0.4 to 0.8% v/v of which nutmeg EO was found most effective. Incorporation of EOs in the film resulted in significant (P ˂ 0.05) decrease in tensile strength and water activity while elongation at break was significantly (P ˂ 0.05) increased. No significant (P ˃ 0.05) changes in thickness and Water Vapor Transmission Rate (WVTR) were observed. Based on physicomechanical and sensory evaluation, films incorporated with 0.5, 1, and 1% concentration of anise, nutmeg, and caraway EO were selected. Chicken nuggets overwrapped with aforementioned films were stored aerobically at refrigeration temperature (4 ± 1 °C) to evaluate antimicrobial, antioxidant, and sensory characteristics. The result indicated that pH, peroxide, free fatty acid (FFA), and thiobarbituric acide (TBA) value of treatments were significantly (P ˂ 0.05) lower than controls however significantly (P < 0.05) higher DPPH activity was observed in all treatments. The total plate count, psychrophilic count and, yeast and mold count were also significantly (P ˂ 0.01) lower in treatment groups and were within the permissible limits. The treated samples were well acceptable during whole storage period of 15 days. The application of composite, active edible bio-based film was found proficient in confining product quality attributes throughout storage. PRACTICAL APPLICATION: The majority of films used for packaging of meat and meat products are derived from synthetic "plastic" materials. The demerits associated with plastics have eventually led to explore natural alternatives such as edible films. The composite-active bio-based films have a huge potential to be molded for specific film properties based on requirements of product-specific packaging conditions.


Subject(s)
Anti-Infective Agents/pharmacology , Antioxidants/analysis , Edible Films , Food Packaging/instrumentation , Meat Products/analysis , Oils, Volatile/analysis , Polymers/chemistry , Animals , Antioxidants/pharmacology , Bacteria/drug effects , Bacteria/growth & development , Carrageenan/chemistry , Chickens , Food Packaging/methods , Food Storage , Fungi/drug effects , Fungi/growth & development , Humans , Manihot/chemistry , Meat Products/microbiology , Microbial Sensitivity Tests , Oils, Volatile/pharmacology , Polymers/chemical synthesis , Refrigeration , Taste
12.
Front Neurosci ; 14: 295, 2020.
Article in English | MEDLINE | ID: mdl-32317919

ABSTRACT

Fragile X-associated tremor ataxia syndrome is an untreatable neurological and neuromuscular disorder caused by unstable expansion of 55-200 CGG nucleotide repeats in 5' UTR of Fragile X intellectual disability 1 (FMR1) gene. The expansion of CGG repeats in the FMR1 mRNA elicits neuronal cell toxicity through two main pathogenic mechanisms. First, mRNA with CGG expanded repeats sequester specific RNA regulatory proteins resulting in splicing alterations and formation of ribonuclear inclusions. Second, repeat-associated non-canonical translation (RANT) of the CGG expansion produces a toxic homopolymeric protein, FMRpolyG. Very few small molecules are known to modulate these pathogenic events, limiting the therapeutic possibilities for FXTAS. Here, we found that a naturally available biologically active small molecule, Curcumin, selectively binds to CGG RNA repeats. Interestingly, Curcumin improves FXTAS associated alternative splicing defects and decreases the production and accumulation of FMRpolyG protein inclusion. Furthermore, Curcumin decreases cell cytotoxicity promptly by expression of CGG RNA in FXTAS cell models. In conclusion, our data suggest that small molecules like Curcumin and its derivatives may be explored as a potential therapeutic strategy against the debilitating repeats associated neurodegenerative disorders.

13.
Mol Neurobiol ; 57(1): 566-584, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31399954

ABSTRACT

In recent years, neurological disorders have globally become a leading cause of disability and death. Neurological disorders are very common in both high- and low-income countries, and the number of patients is predicted to increase in the coming decades. Disorders caused by the expanded trinucleotide repeats (CAG, CGG, CCG, CTG, CUG, GAA, and GCN) in the genome, also described as trinucleotide repeat expansion disorders (TREDs), comprise of the major class of neurological diseases. Various TREDs have different modes of pathogenesis, but the severity and time of onset of disease depends on the trinucleotide repeat numbers. Numerous therapeutic strategies, including symptomatic treatment, blockage of mutant protein synthesis, targeting the toxic protein aggregates and degradation of RNA transcripts have been developed for the treatment of these diseases. However, various limitations to these therapeutic strategies have been reported, and therefore, researchers are exploring different avenues of therapeutics development. One of the recent developments include targeting the expanded repeats with small molecules. Small molecule binds with the secondary/tertiary structure of RNA (like bulges, loops, and hairpins) irrespective of its sequences. Altogether, small molecule-based therapeutics may have the advantage over others to be able to overcome the hurdles of the blood-brain barrier, poor absorption, and allergic reactions. In this review, we have summarized various TREDs and envisage the potential of small molecule-based therapeutics for targeting these hitherto incurable neurological disorders.


Subject(s)
Nervous System Diseases/drug therapy , Small Molecule Libraries/therapeutic use , Trinucleotide Repeat Expansion/genetics , Animals , Humans , Small Molecule Libraries/chemistry
14.
J Food Sci Technol ; 56(11): 5027-5035, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31741527

ABSTRACT

An attempt was made through the present study to prepare gluten free goat meat nuggets by replacing refined wheat flour from product formulation with healthy, dietary fibre rich amaranth (A) and quinoa (Q) flour at different levels. A total of five different treatments viz., AI (1.5% amaranth), AII (3% amaranth), QI (1.5% quinoa) and QII (3% quinoa) were prepared. The physicochemical, colour, texture, sensory and rheological properties of these pseudocereal-added products were evaluated against control (3% refined wheat flour). Emulsion stability of meat batter was significantly affected (P < 0.05) due to addition of amaranth flour (1.5% and 3%) and quinoa (3%). Treatment groups AII and QI had significantly low (P < 0.05) moisture content with respect to control while the amount of fat content showed a reverse trend. Addition of amaranth and quinoa significantly increased (P < 0.05) the dietary fibre in meat products. Rheology of meat batter was affected by types and level of pseudocereal incorporation. Treatment AII had low (P < 0.05) hunter colour lightness value, whereas redness value was low for treatment QI. Effect of added amaranth and quinoa flour was observed on the textural parameters like adhesiveness, cohesiveness, gumminess and chewiness. High scores for almost all the sensory parameters were recorded in pseudocereal-added meat products. Though, all the products were very much acceptable, product with 1.5% quinoa flour was found to have high (P < 0.05) overall acceptability score.

15.
ACS Chem Neurosci ; 10(8): 3778-3788, 2019 08 21.
Article in English | MEDLINE | ID: mdl-31264835

ABSTRACT

An expansion of CGG tandem repeats in the 5' untranslated region (5'-UTR) of fragile X mental retardation 1 (FMR1) gene causes fragile X-associated tremor/ataxia syndrome (FXTAS). The transcripts of these expanded repeats r(CGG)exp either form RNA foci or undergo the repeat-associated non-ATG (RAN) translation that produces toxic homopolymeric proteins in neuronal cells. The discovery of small molecule modulators that possess a strong binding affinity and high selectivity to these toxic expanded repeats RNA could be a promising therapeutic approach to cure the expanded repeat-associated neurological diseases. Therefore, here we sought to test the therapeutic potential of a natural alkaloid, piperine, by assessing its ability to bind and neutralize the toxicity of r(CGG)exp RNA motif. To accomplish this first, we have determined the affinity of piperine to r(CGG)exp RNA using fluorescence-based binding assay and isothermal titration calorimetry assay. These assays showed that piperine forms a thermodynamically favorable interaction with r(CGG)exp RNA with high selectivity to the G-rich RNA motif. Interaction of piperine with r(CGG)exp motif was further validated using several biophysical techniques such as CD, CD melting, NMR spectroscopy, and gel retardation assay. Moreover, piperine was also found to be effective for improving the r(CGG)exp associated splicing defects and RAN translation in a FXTAS cell model system. Our results effectively provided the evidence that piperine strongly interacts with r(CGG)exp RNA and could be used as a suitable candidate for therapeutic development against FXTAS.


Subject(s)
Alkaloids/pharmacology , Ataxia/metabolism , Benzodioxoles/pharmacology , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/metabolism , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , Tremor/metabolism , Trinucleotide Repeat Expansion/drug effects , Humans
16.
Cureus ; 11(2): e4108, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-31058002

ABSTRACT

The use of local radiation to elicit distant tumor response was proposed long back. The abscopal effect is regression of non-irradiated metastatic lesions at the distant site and there is an enormous therapeutic effect of immunomodulation. Radiation causes cancer cells to release antigens which mount an immune response, but this response is short lasting because cancer cells evade recognition by different mechanisms. Programmed Death Ligand-1 (PDL-1) pathway has been extensively studied. Combining immunotherapy and radiotherapy may result in long-term remissions especially for stage 4 cancer. Here we present a case of high grade urothelial carcinoma that progressed after four cycles of chemotherapy and after giving palliative radiation to urinary bladder he was started on nivolumab. First scan done after radiation and six cycles of nivolumab showed complete response. The patient continues to be in remission for the last 17 months from the start of radiation and immunotherapy that was started sequentially. Overall survival till date is 25 months.

17.
ACS Chem Biol ; 13(1): 180-188, 2018 01 19.
Article in English | MEDLINE | ID: mdl-29172480

ABSTRACT

Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to sequestration of muscle blind like-1 splicing factor (MBNL1), and thus both of these elicit the pathogenesis of HD. Targeting the onset as well as progression of HD by small molecules could be a potent therapeutic approach. We have screened a set of small molecules to target this transcript and found Myricetin, a flavonoid, as a lead molecule that interacts with the CAG motif and thus prevents the translation of mutant huntingtin protein as well as sequestration of MBNL1. Here, we report the first solution structure of the complex formed between Myricetin and RNA containing the 5'CAG/3'GAC motif. Myricetin interacts with this RNA via base stacking at the AA mismatch. Moreover, Myricetin was also found reducing the proteo-toxicity generated due to the aggregation of polyglutamine, and further, its supplementation also improves neurobehavioral deficits in the HD mouse model. Our study provides the structural and mechanistic basis of Myricetin as an effective therapeutic candidate for HD and other polyQ related disorders.


Subject(s)
Flavonoids/chemistry , Flavonoids/pharmacology , Huntington Disease/drug therapy , Trinucleotide Repeat Expansion , Animals , COS Cells , Cerebellar Ataxia/genetics , Chlorocebus aethiops , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Female , Humans , Huntingtin Protein/genetics , Huntington Disease/genetics , Magnetic Resonance Spectroscopy , Mutation , Nucleic Acid Conformation , Oxidative Stress/drug effects , Peptides , Rats, Wistar , Small Molecule Libraries
18.
Asian-Australas J Anim Sci ; 29(5): 702-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26954177

ABSTRACT

Aloe vera has been used worldwide for pharmaceutical, food, and cosmetic industries due to its wide biological activities. However, quality improvement of low fat meat products and their acceptability with added Aloe vera gel (AVG) is scanty. The aim of this study was to explore the feasibility of using fresh AVG on physicochemical, textural, sensory and nutritive qualities of goat meat nuggets. The products were prepared with 0%, 2.5%, and 5% fresh AVG replacing goat meat and were analyzed for proximate composition, physicochemical and textural properties, fatty acid profile and sensory parameters. Changes in lipid oxidation and microbial growth of nuggets were also evaluated over 9 days of refrigerated storage. The results showed that AVG significantly (p<0.05) decreased the pH value and protein content of meat emulsion and nuggets. Product yield was affected at 5% level of gel. Addition of AVG in the formulation significantly affected the values of texture profile analysis. The AVG reduced the lipid oxidation and microbial growth in nuggets during storage. Sensory panelists preferred nuggets with 2.5% AVG over nuggets with 5% AVG. Therefore, AVG up to 2.5% level could be used for quality improvement in goat meat nuggets without affecting its sensorial, textural and nutritive values.

19.
J Food Sci Technol ; 52(4): 2288-95, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25829611

ABSTRACT

Effect of salt substitution (Treat I) and added pea hull flour (PHF) at 8 (Treat-II), 10 (Treat-III) and 12 % (Treat-IV) levels on the quality of low fat chicken nuggets (Control) was investigated. Replacement of NaCl significantly affected (P < 0.05) emulsion and product pH, emulsion stability, cooking yield, ash content while PHF had additional effect on moisture and protein. Dietary fibre content in the product significantly (P < 0.05) increased at each level of PHF. The colour parameters remained similar to control due to salt replacement while added PHF decreased their values. Textural properties were lower (P < 0.05) in the treated products. Addition of PHF significantly (P < 0.05) decreased cholesterol and glycolipids contents at 8 % and 12 % levels, respectively. Sensory evaluation exhibited that 40 % NaCl can efficiently be replaced and 8 % PHF can be incorporated as a source of fibre in low fat chicken nuggets without significant effect on various attributes.

20.
Vet World ; 8(1): 97-102, 2015 Jan.
Article in English | MEDLINE | ID: mdl-27047004

ABSTRACT

AIM: The study was conducted to estimate the contribution of edible byproducts of Barbari kids to their live and carcass weight as well as to assess textural and color characteristics and microbiological status of these byproducts. MATERIALS AND METHODS: Percent live weight, Percent carcass weight, Texture, color, and microbiological analysis was done for edible byproducts viz. liver, heart, kidney, spleen, brain and testicle and longissimus dorsi muscle was taken as a reference. RESULTS: The edible byproducts of Barbari kids constitute about 3% of the live weight of an animal of which liver contributed maximum (1.47%) followed by testicles (0.69%) and heart (0.41%). While the same constituted 3.57, 1.70, and 0.99%, respectively on carcass weight. There was significant (p<0.05) difference among all organs regarding textural properties. Liver required the maximum shear force and work of shear (121.48N and 32.19 kg-sec) followed by spleen and heart. All organs revealed characteristics color values (L*, a*, b*, chroma, and hue) which were significantly different (p<0.05) from muscle values. The total viable count, coliform count showed slight differences for all organs studied. The staphylococcus counts were low with little differences among organs. CONCLUSION: Edible byproducts have a significant contribution to carcass weight which could enhance total edible portion of the carcass. Efficient utilization of these by-products returns good source of revenue to the meat industries. Textural and color analysis give information for their incorporation in comminuted meat products, and microbial study tells about the storage study. However, study was in the preliminary and basic step forward toward better utilization of 3% of live animal which could increase the saleable cost of animal by 6.94%.

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