Browsing by Author "Kriti Shrinet"

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Ab initio modeling and ligand docking of quercetin and the MC-LR transporter protein Oatp1b2/OATP1B3
(Elsevier B.V., 2023) Kriti Shrinet; Ritika K. Singh; Riden Saxena; Avinash K. Chaurasia; Arvind Kumar
Trans-membrane proteins (TMPs) play a crucial role in the translocation of organic and inorganic molecules. Unlike other proteins, TMPs are difficult to model structurally because of their location within the amphipathic plasma membrane. In this study, we focused on examining the transport of the cyanotoxin microcystin-LR (MC-LR) through organic ion transporting polypeptides (OATPs) and whether the bioactive phytoconstituent quercetin can function as a barrier to the transportation of MC-LR. To test this hypothesis, we first modeled the transporters OATP1B3 and Oatp1b2 localized in the human and mouse liver, respectively, by ab initio modeling with the Iterative Threading ASSEmbly Refinement server and refined the generated model using the refinement tool of the ModLoop server. Using different tools and servers, the structural quality of the transmembrane helices was validated and found to be an accurate structure of a TMP. Docking analysis was performed with the ligands MC-LR and quercetin with both OATPs using the PatchDock and FireDock online servers. The results, in the form of the global energy of both docked structures, were based on predictions made earlier. The Oatp1b2 global energy for quercetin was −36.4 kcal/mol, compared with the corresponding value at the MC-LR location which was only −5.59 kcal/mol. Similarly, in the case of OATP1B3 with quercetin, the global energy was found to be −39.0 kcal/mol, whereas with MC-LR it was −15.6 kcal/mol. These results clearly show that quercetin competitively inhibits the binding of MC-LR to its respective targets. © 2023 The Authors
Bioactive compounds and their future therapeutic applications
(Elsevier, 2020) Kriti Shrinet; Ritika K. Singh; Avinash K. Chaurasia; Alok Tripathi; Arvind Kumar
Natural bioactive compounds, plant secondary metabolites, are not necessary for the normal survival of the plants but required for inter- or intragenus/species competition, defense, attraction, and signaling in plants. These compounds play a crucial role in the life of animals with having great potential for human well-fare, mostly with pharmacological or toxicological effects, against microbial pathogens and diseases including cancer in humans and animals. Bioactive compounds involve a broad variety of chemical structures and functions that facilitate a better way for the production of nutraceuticals, functional foods, and food additives. Some bioactive compounds found in nature are significantly high in concentration such as polyphenols; examples are phenolic compounds, flavonoids, anthocyanidins, flavans, tannins, and so on, and other concentrations are nonsignificant, but with high commercial values. Bioactive compounds have diverse pharmacological activities and applications for treatment of many diseases. These compounds act as antidiabetic, antipyretic, anticancerous, antidiuretic, antiatherosclerotic, and so on for the human beings. However, the inherent difficulties in screening and manufacturing these compounds have led to the development of advanced technologies. Frequently used methods for their extraction from plants and their parts are the conventional liquid-liquid or solid-liquid extraction, and the advanced methods include pressurized-liquid extraction, subcritical, and supercritical extractions and microwave- and ultrasound-assisted extractions. Extracted compounds are further characterized by MALDI-TOF-MS based on their specific absorption spectra to be used for the formulation of various drugs. © 2021 Elsevier Inc.
CGA mitigates HMGB1 mediated TLR4 activated hepatic cancer in urethane primed mice
(Elsevier B.V., 2024) Alok Tripathi; Kriti Shrinet; Arvind Kumar
Background: Liver cancer is fourth leading cause of cancer deaths worldwide. Urethane presents in herbicides, pesticides and food beverages as preservatives upregulate the expression of inflammatory cytokines in liver tissues for the genesis of cancer. It also naturally formed in fermented food products and distilled beverages. Study design: Balb/c mice of approx same age and body weight were selected and divided into four groups G-I (PBS treated), G-II (urethane of 500 mg/kgb.w.), G-III (CGA of 50 mg/kg b.w.) and G-IV (urethane & CGA). Treatments were given on alternate day upto eight consecutive weeks and 3-12 month of latency period. Blood sample collected was used for counting of inflammatory immune cells by automated cell counter. Total RNA and protein samples isolated from dissected liver of sacrificed mice were used for molecular analysis at transcriptional and translational level. Methods: Gene expression is assessed by RT-PCR at transcriptional level and by western blot at translational level. Immunological effects are evaluated by counting inflammatory immue cells and histopathology is done to examine hepatic tissues injury by carcinogen urethane. Hypothesis and purpose: Inflammatory cytokines create microenvironment for tumor initiation and development which is mediated through TLR-4 pathway activation via HMGB1 upon carcinogen exposure. Here aimed to find out the role of Chlorogenic acid (CGA) a phenolic compound naturally present in plants as anti-cancerous properties to prevent and cure cancer by acting upon HMGB1 & TLR4 pathway. Results: At transcriptional level up-regulated expression of HMGB1, TLR-4 pathway genes, pro-inflammatory cytokines IL-1β, IL-6, TNF-α and IL-18 in urethane treated mice is observed. Western blot results showed up-regulated expression of HMGB1 and NF-κB protein at translational level. CGA treated mice liver showed down-regulated expression of these inflammatory molecules. Increased number of inflammatory immune cells and presence of hepatic tissues injury in histopathological slides is observed in urethane treated mice that is mitigated by CGA. Conclusion: CGA is an important anti-cancerous bioactive compound targets inflammatory cytokines and HMGB1 at molecular level to prevent, cure and mitigate liver cancer. Down regulated expression of HMGB1 and TLR-4 activation pathway in cancerous Balb/c mice liver proved its anti-cancerous properties to become a potential future drug. © 2024
Diagnosis of Genital Tuberculosis in Infertile Women by Using the Composite Reference Standard
(Hindawi Limited, 2022) Riden Saxena; Kriti Shrinet; Sachchida Nand Rai; Kamal Singh; Shivi Jain; Shuchi Jain; Deeksha Singh; Shampa Anupurba; Madhu Jain
Female genital tuberculosis (FGTB) can be asymptomatic or even masquerade as other gynecological conditions. Conventional methods of FGTB diagnosis include various imaging, bacteriological, molecular, and pathological techniques that are only positive in a small percentage of patients, leaving many cases with undiagnosed condition. In the absence of a perfect diagnostic method, composite reference standards (CRSs) have been advocated in this diagnostic study. This study assesses the agreement between traditional diagnostic modalities using CRS and prevalent TB groups among different fallopian tube infertility manifestations. A total of 86 women with primary and secondary infertility were included in the study and subjected to bacteriological, pathological, and radiological examination for the diagnosis of FGTB. Results were evaluated statistically for concordance of the diagnostic tests to the CRS by sensitivity and specificity, while PPV and NPV were calculated for the performance of diagnostic tests of FGTB. We observed that 11.2% of women were found to be true positives by means of CRS. The positive findings by CRS were as follows: ultrasonography (13.9%), laparoscopy (14%), hysteroscopy (12%), GeneXpert (4.8%), culture (4.8%), polymerase chain reaction (4.8%), and histopathology (6.4%). GeneXpert and culture were found to have a perfect agreement with CRS. Hysterosalpingography, laparoscopy, and hysteroscopy have a fair agreement with CRS. Out of 43 women with tubal factor infertility, 6 women were found in the definitive TB group with mixed conditions of tubal manifestations. This study evaluates and demonstrates the reliability of the collective assessment of various diagnostic methods with CRS findings that help in identifying different TB groups of genital tuberculosis patients from all infertile patients by applying the criteria of CRS. © 2022 Riden Saxena et al.
GC-MS Profiling of Phytobioconstituents Present in Andrographis paniculata (Burm.f.) Nees Extract and Pharmacokinetic and Toxicity Properties by ADME/Tox Analysis
(Asian Publication Corporation, 2022) Riden Saxena; Kriti Shrinet; Ritika Saxena; Yatender Singh Panwar; Madhu Jain
Andrographis paniculata, commonly known as the "King of Bitters" has traditionally been used as a medicinal herb. The metabolite composition of A. paniculata is generally determined by its properties, which may be influenced by a range of factors, one of which is the part of the plant extracted. The objective of this research is to identify and characterize the putative metabolite composition in n-hexane extract of stem and leaf using gas chromatography-mass spectrometry. A total of 22 different phytobioconstituents were identified, including flavonoids, terpenoids, fatty acids, phenolic acids, quinones, alkaloids and vitamin. The pharmacokinetic properties of the identified phytobioconstituents, like drug-likeness and toxicity, were also predicted by ADME/Tox analysis. Phytobioconstituents, predicted to be drug-like can be further investigated as ligands by using in silico docking approaches, for disease targets. The study provides empirical evidence for future study that might lead to their therapeutic applications and industrial product development. © 2022 Chemical Publishing Co.. All rights reserved.
HMGB1 protein as a novel target for cancer
(Elsevier Inc., 2019) Alok Tripathi; Kriti Shrinet; Arvind Kumar
Highly conserved nuclear protein High Mobility Group Box1 (HMGB1) present in mammals has functionality as an immuno-modulator in the form of cytokine molecule, as a nuclear factor to regulate these molecules and DNA structural determination. It has proximal homologous DNA binding domains Box-A, Box-B and distal C-terminal domain. Reduced form exists in basic condition has chemotaxis activity, while form with disulphide bond reduced at 106 th cysteine showed cytokine activity. The oxidized form is devoid of both activities. HMGB1 binds and bends dsDNA and also activates genes for secretion of inflammatory cytokines such as IL-1β TNF-α IL-6 and IL-18. It can interact with transcription factors Rel/NF-κB and p53 responsible for up-regulating oncogenes. Oxidative stressed injured tissues actively secrete HMGB1 outside cells to necrotize other nearby tissues passively in cytosol. Acetylation of HMGB1 weakens its binding with DNA, and promotes its migration to different tissues leading to secretion of inflammatory-cytokines. HMGB1 expression has been found very important in the genesis and promotion of different cancer by promoting metastasis. In current article, we emphasized on condition based structural variability of HMGB1, mechanism of release, physiological functions and its functionality as a biomarker for cancer to be targeted to curb cancer genesis and progression. © 2019
Immunotoxicity of cynobacterial toxin Microcystin-LR is mitigated by Quercitin and himalaya tonic Liv52
(Elsevier Ltd, 2023) Kriti Shrinet; Arvind Kumar
Microcystin-LR (MC-LR) has received worldwide concern for its hepatotoxicity with maximum acceptable daily intake of 0.0015 mg/L (1.5 μg/L) [Federal-Provinicial-Territorial-Committee-on-drinking-water-2002]. Comprehensive immunotoxicity data is still deficient with MC-LR. To curb the menace of MC-LR, Quercitin (QE), himalaya made hepatotonic Liv52 were studied. To investigate the immunotoxic properties of MC-LR, QE and Liv52, primary splenocyte cells prepared, cultured, and immunoproliferation assay with mitogens lipopolysaccharide (LPS) or concanavalin A, (Con A) was done for, immunophenotyping, cell cycle and apoptotic studies. In current study, we have divided the splenocytes into 4 groups, i.e., Group I: Normal saline, Group II: MC-LR (0.1 μM), Group III: MC-LR (0.1 μM) + QE (20 μM), and Group IV: MC-LR (0.1 μM) + Liv52 (25 μg/ml) and treated with maximum < CC50 concentration. MC-LR enhanced proliferation of Con A and LPS stirred splenocytes at 24 h, whereas QE and Liv52 both act as antimitogenic. With combined mixture of MC-LR + QE, a significant increase in proliferation compared to mitogen or MC-LR was observed. MC-LR down-regulated expression of CD19+, CD3e+, CD4+, CD8+, (1.05%), (18.9%), (8.9%), and (7.8%) respectively in comparison to Group I. Down-regulation of 10% and 28% is observed in CD19+ and CD4+ populations with MC-LR and QE. The Liv52 addition concealed MC-LR adverse properties in most effective way. MC-LR induced G1-phase significant declined cell cycle arrest at S phase (9.26%) and G2/M phase (26.31%) was observed. QE and Liv52 mask the activity of MC-LR. Further apoptotic study revealed that MC-LR treatment decreases late apoptotic cells compared to control with no significant change in live and early apoptotic cells. Although QE increased live cells and Liv52 significantly increased late apoptotic cells, these results suggest that a