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1.
BMC Plant Biol ; 24(1): 124, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38373874

ABSTRACT

BACKGROUND: Rice (Oryza sativa L.) is one of the globally important staple food crops, and yield-related traits are prerequisites for improved breeding efficiency in rice. Here, we used six different genome-wide association study (GWAS) models for 198 accessions, with 553,229 single nucleotide markers (SNPs) to identify the quantitative trait nucleotides (QTNs) and candidate genes (CGs) governing rice yield. RESULTS: Amongst the 73 different QTNs in total, 24 were co-localized with already reported QTLs or loci in previous mapping studies. We obtained fifteen significant QTNs, pathway analysis revealed 10 potential candidates within 100kb of these QTNs that are predicted to govern plant height, days to flowering, and plot yield in rice. Based on their superior allelic information in 20 elite and 6 inferior genotypes, we found a higher percentage of superior alleles in the elite genotypes in comparison to inferior genotypes. Further, we implemented expression analysis and enrichment analysis enabling the identification of 73 candidate genes and 25 homologues of Arabidopsis, 19 of which might regulate rice yield traits. Of these candidate genes, 40 CGs were found to be enriched in 60 GO terms of the studied traits for instance, positive regulator metabolic process (GO:0010929), intracellular part (GO:0031090), and nucleic acid binding (GO:0090079). Haplotype and phenotypic variation analysis confirmed that LOC_OS09G15770, LOC_OS02G36710 and LOC_OS02G17520 are key candidates associated with rice yield. CONCLUSIONS: Overall, we foresee that the QTNs, putative candidates elucidated in the study could summarize the polygenic regulatory networks controlling rice yield and be useful for breeding high-yielding varieties.


Subject(s)
Genome-Wide Association Study , Oryza , Chromosome Mapping , Oryza/genetics , Plant Breeding , Quantitative Trait Loci/genetics
2.
Plant Biotechnol J ; 22(5): 1051-1066, 2024 May.
Article in English | MEDLINE | ID: mdl-38070179

ABSTRACT

To increase rice yields and feed billions of people, it is essential to enhance genetic gains. However, the development of new varieties is hindered by longer generation times and seasonal constraints. To address these limitations, a speed breeding facility has been established and a robust speed breeding protocol, SpeedFlower is developed that allows growing 4-5 generations of indica and/or japonica rice in a year. Our findings reveal that a high red-to-blue (2R > 1B) spectrum ratio, followed by green, yellow and far-red (FR) light, along with a 24-h long day (LD) photoperiod for the initial 15 days of the vegetative phase, facilitated early flowering. This is further enhanced by 10-h short day (SD) photoperiod in the later stage and day and night temperatures of 32/30 °C, along with 65% humidity facilitated early flowering ranging from 52 to 60 days at high light intensity (800 µmol m-2 s-1). Additionally, the use of prematurely harvested seeds and gibberellic acid treatment reduced the maturity duration by 50%. Further, SpeedFlower was validated on a diverse subset of 198 rice accessions from 3K RGP panel encompassing all 12 distinct groups of Oryza sativa L. classes. Our results confirmed that using SpeedFlower one generation can be achieved within 58-71 days resulting in 5.1-6.3 generations per year across the 12 sub-groups. This breakthrough enables us to enhance genetic gain, which could feed half of the world's population dependent on rice.


Subject(s)
Oryza , Humans , Oryza/genetics , Plant Breeding , Light
3.
J Org Chem ; 89(13): 9313-9321, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38900839

ABSTRACT

ß-l-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil (l-BHDU, 17) is a potent and selective inhibitor of the varicella-zoster virus (VZV). l-BHDU (17) has demonstrated excellent anti-VZV activity and is a preclinical candidate to treat chickenpox, shingles (herpes zoster), and herpes simplex virus 1 (HSV-1) infections. Its monophosphate prodrug (POM-l-BHDU-MP, 24) demonstrated an enhanced pharmacokinetic and antiviral profile. POM-l-BHDU-MP (24), in vivo, effectively reduced the VZV viral load and was effective for the topical treatment of VZV and HSV-1 infections. Therefore, a viable synthetic procedure for developing POM-l-BHDU-MP (24) is needed. In this article, an efficient approach for the synthesis of l-BHDU (17) from a readily available starting material is described in 7 steps. An efficient and practical methodology for both chiral pure l- & d-dioxolane 11 and 13 were developed via diastereomeric chiral amine salt formation. Neutralization of the amine carboxylate salt of l-dioxolane 10 provides enantiomerically pure l-dioxane 11 (ee ≥ 99%). Optically pure 11 was utilized to construct the final nucleoside l-BHDU (17) and its monophosphate ester prodrug (POM-l-BHDU-MP, 24). Notably, the reported process eliminates expensive chiral chromatography for the synthesis of chiral pure l- & d-dioxolane, which offers avenues for the development and structure-activity relationship studies of l- & d-dioxolane-derived nucleosides.


Subject(s)
Antiviral Agents , Dioxolanes , Stereoisomerism , Dioxolanes/chemistry , Dioxolanes/pharmacology , Dioxolanes/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Uracil/analogs & derivatives , Uracil/chemistry , Uracil/chemical synthesis , Uracil/pharmacology , Molecular Structure , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/chemical synthesis
4.
J Infect Chemother ; 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39153544

ABSTRACT

The term "hydatid disease" refers to echinococcosis. Echinococcosis is a zoonotic disease caused by the larval stage of the Echinococcus parasite. The disease is widespread in regions where the parasite is endemic, particularly in developing nations like India. However, there are only a couple of documented case studies of echinococcosis associated with hematological malignancy in the literature. We present an extremely uncommon case of a 36-year-old male who had liver hydatidosis and was diagnosed with acute myeloid leukemia (AML)-M1. The patient received treatment for acute myeloid leukemia (daunomycin, cytarabine, and 5-azacytidine), followed by management of hydatid disease after complete remission of acute leukemia. The patient underwent periodic evaluations for one year and exhibited satisfactory improvement.

5.
Molecules ; 29(10)2024 May 19.
Article in English | MEDLINE | ID: mdl-38792251

ABSTRACT

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.


Subject(s)
Antiviral Agents , Halogenation , Nucleosides , Nucleotides , Humans , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , Fluorine/chemistry , Nucleosides/chemistry , Nucleosides/chemical synthesis , Nucleosides/pharmacology , Nucleotides/chemistry , Nucleotides/pharmacology , Nucleotides/chemical synthesis , Clinical Trials as Topic
6.
Int J Paediatr Dent ; 34(4): 474-484, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38124259

ABSTRACT

BACKGROUND: Paediatric rotary file systems have recently been developed for primary teeth use. AIM: To study the cleaning efficacies of two paediatric rotary endodontic files, the Prime PedoTM, and the Kedo-SG BlueTM against the standard H files. DESIGN: This in vitro study included 54 freshly extracted primary molars, which were randomised into three groups (n = 18 each) and were prepared using either Kedo-SG BlueTM, Prime PedoTM or hand H files after injecting methylene blue dye into the canals. Pre- and post-operative cone beam computerised tomography (CBCT) was performed to assess change in root canal volumes. Methylene blue dye removal from canals was assessed using stereomicroscopy, and canal cleanliness was examined by scanning electron microscopy (SEM). RESULTS: Both Prime PedoTM and Kedo-SG BlueTM files reduced significantly less dentine when compared with conventional hand filing with Prime PedoTM removing the least amount of dentine. No significant difference was found in median SEM scores among the groups in the cervical, middle and apical thirds of the roots. Stereomicroscopic assessment of root canal cleanliness using dye removal technique shows a statistically significant difference existing between Kedo-SG BlueTM and hand H files groups. CONCLUSION: Prime PedoTM removed the least amount of dentine. Kedo-SG BlueTM performed significantly better than conventional hand filing with H files when the root canal cleanliness was assessed.


Subject(s)
Dental Pulp Cavity , Microscopy, Electron, Scanning , Molar , Root Canal Preparation , Tooth, Deciduous , Humans , Root Canal Preparation/instrumentation , Root Canal Preparation/methods , In Vitro Techniques , Dental Instruments , Cone-Beam Computed Tomography , Equipment Design , Methylene Blue
7.
Arch Microbiol ; 205(5): 164, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37012452

ABSTRACT

Cyanometabolites are active compounds derived from cyanobacteria that include small low molecular weight peptides, oligosaccharides, lectins, phenols, fatty acids, and alkaloids. Some of these compounds may pose a threat to human and environment. However, majority of them are known to have various health benefits with antiviral properties against pathogenic viruses including Human immunodeficiency virus (HIV), Ebola virus (EBOV), Herpes simplex virus (HSV), Influenza A virus (IAV) etc. Cyanometabolites classified as lectins include scytovirin (SVN), Oscillatoria agardhii agglutinin (OAAH), cyanovirin-N (CV-N), Microcystis viridis lectin (MVL), and microvirin (MVN) also possess a potent antiviral activity against viral diseases with unique properties to recognize different viral epitopes. Studies showed that a small linear peptide, microginin FR1, isolated from a water bloom of Microcystis species, inhibits angiotensin-converting enzyme (ACE), making it useful for the treatment of coronavirus disease 2019 (COVID-19). Our review provides an overview of the antiviral properties of cyanobacteria from the late 90s till now and emphasizes the significance of their metabolites in combating viral diseases, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has received limited attention in previous publications. The enormous medicinal potential of cyanobacteria is also emphasized in this review, which justifies their use as a dietary supplement to fend off pandemics in future.


Subject(s)
COVID-19 , Cyanobacteria , Humans , Antiviral Agents/metabolism , SARS-CoV-2/metabolism , Lectins , Cyanobacteria/chemistry
8.
Indian J Med Res ; 158(4): 423-431, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-38006345

ABSTRACT

BACKGROUND OBJECTIVES: The World Health Organization (WHO) has endorsed thermal ablation (thermocoagulation) as an efficient and safe modality for treatment of cervical pre-cancer lesions. More evidence is being looked up by WHO through rigorous studies for health delivery models using screen-and-treat strategies incorporating thermal ablation and studies comparing it against the conventional standard modality cryotherapy. The objective of this study was to assess the acceptability of thermal ablation both among the providers and clients and compare the same with cryotherapy. METHODS: A randomized control trial was conducted for one year from September 2019 to October 2020 after obtaining ethics approval. Computer-generated random number table was used for randomization, and eligible candidates were divided into two groups following informed consent. Women with visual inspection with acetic acid (VIA) positive cervical lesions in Group A received cryotherapy and Group B received thermal ablation. After the procedure, the acceptability of the provider and the client were assessed using the International Agency for Research on Cancer-validated questionnaire for both the procedures. Immediate side effects and problems at six weeks and at six months were assessed as well. Efficacy was decided by the absence of VIA positivity at six months. RESULTS: The overall VIA positivity in this study was 11.8 per cent. Thermal ablation (thermocoagulation) had better provision and client acceptability than cryotherapy (significant difference). The efficacy of thermal ablation was 97.6 per cent, while, it was 92 per cent for cryotherapy (not significant). INTERPRETATION CONCLUSIONS: In the context of screen-and-treat programme in settings such as India, thermal ablation appears to be a better method of treatment than cryotherapy for cervical pre-cancerous lesions particularly in terms of better provision and client acceptability.


Subject(s)
Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Acetic Acid , Pilot Projects , Uterine Cervical Dysplasia/surgery , Cryotherapy/methods , Uterine Cervical Neoplasms/surgery , Electrocoagulation
9.
Genomics ; 114(2): 110269, 2022 03.
Article in English | MEDLINE | ID: mdl-35065190

ABSTRACT

The development and utilization of molecular-markers play an important role in genomics-assisted breeding during pyramiding of valuable genes. The aim of present study was to develop and validate a novel core-set of KASP (Kompetitive Allele-Specific PCR) markers associated with traits improving rice grain yield and adaptability under direct-seeded cultivation conditions. The 110 phenotypically validated KASP assays out of 171 designed KASP, include assays for biotic-resistance genes, anaerobic germination, root-traits, grain yield, lodging resistance and early-uniform emergence. The KASP assays were validated for their robustness and reliability at five different levels using diverse germplasm, segregating and advanced population, comparison with SSR markers and on F1s. The present research work will provide (i) breeding material in form of anticipated pre-direct-seeded adapted rice varieties (ii) single improved breeding line with many useful genes and (iii) KASP assay information for the useful QTL/genes providing grain yield and adaptability to rice under direct-seeded cultivation conditions.


Subject(s)
Oryza , Edible Grain/genetics , Oryza/genetics , Phenotype , Plant Breeding , Reproducibility of Results
10.
Int J Mol Sci ; 24(2)2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36674611

ABSTRACT

Plants experience different stresses, i.e., abiotic, or biotic, and to combat them, plants re-program the expression of growth-, metabolism-, and resistance-related genes. These genes differ in their synonymous codon usage frequency and show codon usage bias. Here, we investigated the correlation among codon usage bias, gene expression, and underlying mechanisms in rice under abiotic and biotic stress conditions. The results indicated that genes with higher expression (up- or downregulated) levels had high GC content (≥60%), a low effective number of codon usage (≤40), and exhibited strong biases towards the codons with C/G at the third nucleotide position, irrespective of stress received. TTC, ATC, and CTC were the most preferred codons, while TAC, CAC, AAC, GAC, and TGC were moderately preferred under any stress (abiotic or biotic) condition. Additionally, downregulated genes are under mutational pressure (R2 ≥ 0.5) while upregulated genes are under natural selection pressure (R2 ≤ 0.5). Based on these results, we also identified the possible target codons that can be used to design an optimized set of genes with specific codons to develop climate-resilient varieties. Conclusively, under stress, rice has a bias towards codon usage which is correlated with GC content, gene expression level, and gene length.


Subject(s)
Codon Usage , Oryza , Oryza/genetics , Codon/genetics , Mutation , Acclimatization
11.
Indian J Clin Biochem ; 38(2): 172-181, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36032561

ABSTRACT

Lymphocyte dysregulation in coronavirus disease-19 (COVID-19) is a major contributing factor linked to disease severity and mortality. Apoptosis results in the accumulation of cell-free DNA (cfDNA) in circulation. COVID-19 has a heterogeneous clinical course. The role of cfDNA levels was studied to assess the severity and outcome of COVID-19 patients and correlated with other laboratory parameters. The current case series included 100 patients with mild COVID-19 (MCOV-19) and 106 patients with severe COVID-19 (SCOV-19). Plasma cfDNA levels were quantified using SYBR green quantitative real-time PCR through amplification of the ß-actin gene. CfDNA level was significantly higher in SCOV-19 at 706.7 ng/ml (522.6-1258) as compared to MCOV-19 at 219.8 ng/ml (167.7-299.6). The cfDNA levels were significantly higher in non-survivor than in survivors (p = 0.0001). CfDNA showed a significant correlation with NLR, ferritin, LDH, procalcitonin, and IL-6. The diagnostic sensitivity and specificity of cfDNA in the discrimination of SCOV-19 from MCOV-19 were 90.57% & 80%, respectively. CfDNA showed a sensitivity of 94.74% in the differentiation of non-survivors from survivors. CfDNA levels showed a significant positive correlation with other laboratory and inflammatory markers of COVID-19. CfDNA levels, NLR, and other parameters may be used to stratify and monitor COVID-19 patients and predict mortality. CfDNA may be used to predict COVID-19 severity with higher diagnostic sensitivity.

12.
Dis Colon Rectum ; 65(3): e184-e190, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34856590

ABSTRACT

BACKGROUND: We describe a natural orifice technique for simultaneous endoluminal lateral suspension of apical vaginal wall and rectal prolapse fixation with ultrasound and fluoroscopic assistance. IMPACT OF INNOVATION: The technique is minimally invasive, can be performed under regional anaesthesia, and avoids laparotomy or use of a mesh in addition to preserving the uterus. TECHNOLOGY MATERIALS AND METHODS: This technique involves suprapubic transvaginal ventral suture colposuspension, fixation of the anterior rectal wall to the undersurface of the anterior abdominal wall and tack fixation of the posterior rectal wall to the underlying sacral promontory through a submucosal tunnel performed endoscopically with fluoroscopic and ultrasound assistance. PRELIMINARY RESULTS: Seven patients with a mean age of 63 years were followed between 3 to 11 months. CONCLUSIONS: This is a novel minimally invasive transluminal procedure that repairs concomitant rectal and vaginal prolapse in the same sitting. FUTURE DIRECTIONS: Improvement in the instrument design and incorporation of endoluminal robotic systems will enhance the technical ease. The study needs validation in larger series of patients with longer follow-up.


Subject(s)
Anesthesia, Conduction/methods , Natural Orifice Endoscopic Surgery , Rectal Prolapse , Uterine Prolapse , Feasibility Studies , Female , Fluoroscopy/methods , Humans , Middle Aged , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods , Natural Orifice Endoscopic Surgery/instrumentation , Natural Orifice Endoscopic Surgery/methods , Quality Improvement , Rectal Prolapse/diagnostic imaging , Rectal Prolapse/surgery , Robotic Surgical Procedures/instrumentation , Robotic Surgical Procedures/methods , Surgery, Computer-Assisted/methods , Surgical Fixation Devices , Treatment Outcome , Ultrasonography, Interventional/methods , Uterine Prolapse/diagnostic imaging , Uterine Prolapse/surgery
13.
Plant Biotechnol J ; 18(11): 2173-2186, 2020 11.
Article in English | MEDLINE | ID: mdl-32725933

ABSTRACT

Rice is a staple food for half of the world's population. Changing climatic conditions, water and labour scarcity are the major challenges that shall limit future rice production. Dry direct-seeded rice (DDSR) is emerging as an efficient, resources conserving, mechanized, climate smart and economically viable strategy to be adopted as an alternative to puddled transplanted rice (TPR) with the potential to address the problem of labour-water shortages and ensure sustainable rice cultivation. Despite these benefits, several constraints obstruct the adoption of DDSR. In principle, the plant type for DDSR should be different from one for TPR, which could be achieved by developing rice varieties that combine the traits of upland and lowland varieties. In this context, recent advances in precise phenotyping and NGS-based trait mapping led to identification of promising donors and QTLs/genes for DDSR favourable traits to be employed in genomic breeding. This review discusses the important traits influencing DDSR, research studies to clarify the need for breeding DDSR-specific varieties to achieve enhanced grain yield, climate resilience and nutrition demand. We anticipate that in the coming years, genomic breeding for developing DDSR-specific varieties would be a regular practice and might be further strengthened by combining superior haplotypes regulating important DDSR traits by haplotype-based breeding.


Subject(s)
Oryza , Breeding , Genomics , Oryza/genetics , Quantitative Trait Loci/genetics , Seeds
14.
Plant Biotechnol J ; 17(8): 1612-1622, 2019 08.
Article in English | MEDLINE | ID: mdl-30701663

ABSTRACT

Though several genes governing various major traits have been reported in rice, their superior haplotype combinations for developing ideal variety remains elusive. In this study, haplotype analysis of 120 previously functionally characterized genes, influencing grain yield (87 genes) and grain quality (33 genes) revealed significant variations in the 3K rice genome (RG) panel. For selected genes, meta-expression analysis using already available datasets along with co-expression network provided insights at systems level. Also, we conducted candidate gene based association study for the 120 genes and identified 21 strongly associated genes governing 10-grain yield and quality traits. We report superior haplotypes upon phenotyping the subset of 3K RG panel, SD1-H8 with haplotype frequency (HF) of 30.13% in 3K RG panel, MOC1-H9 (HF: 23.08%), IPA1-H14 (HF: 6.64%), DEP3-H2 (HF: 5.59%), DEP1-H2 (HF: 37.53%), SP1-H3 (HF: 5.05%), LAX1-H5 (HF: 1.56%), LP-H13 (3.64%), OSH1-H4 (5.52%), PHD1-H14 (HF: 15.21%), AGO7-H15 (HF: 3.33%), ROC5-H2 (31.42%), RSR1-H8 (HF: 4.20%) and OsNAS3-H2 (HF: 1.00%). For heading date, Ghd7-H8 (HF: 3.08%), TOB1-H10 (HF: 4.60%) flowered early, Ghd7-H14 (HF: 42.60%), TRX1-H9 (HF: 27.97%), OsVIL3-H14 (HF: 1.72%) for medium duration flowering, while Ghd7-H6 (HF: 1.65%), SNB-H9 (HF: 9.35%) were late flowering. GS5-H4 (HF: 65.84%) attributed slender, GS5-H5 (HF: 29.00%), GW2-H2 (HF: 4.13%) were medium slender and GS5-H9 (HF: 2.15%) for bold grains. Furthermore, haplotype analysis explained possible genetic basis for superiority of selected mega-varieties. Overall, this study suggests the possibility for developing next-generation tailor-made rice with superior haplotype combinations of target genes suiting future food and nutritional demands via haplotype-based breeding.


Subject(s)
Edible Grain/genetics , Genes, Plant , Oryza/genetics , Phenotype , Haplotypes
15.
J Org Chem ; 84(2): 752-759, 2019 01 18.
Article in English | MEDLINE | ID: mdl-30589264

ABSTRACT

2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA, 12) and its phosphoramidate prodrug (FMCAP, 14) have been proven as a potential anti-HBV agent against both adefovir-resistant as well as lamivudine-resistant double (rtL180M/rtM204V) mutants. Furthermore, in vitro, these agents have demonstrated significant activity against lamivudine/entecavir triple mutants (L180M + S202G + M204V). These preliminary results encourage us for further biological evaluation of FMCA and FMCAP to develop as a potential clinical candidate as an anti-HBV agent, which may overcome the problem of drug resistance in HBV therapy. To support the preclinical exploration, a scalable synthesis of this molecule was needed. In this communication, a practical and scalable synthesis of FMCA, and its prodrug, is reported via ketone 1. The selective opening of the isopropylidene group of 2 led to compound 3. Protection of the allylic hydroxyl group of 3, followed by fluorination and deprotection, afforded the key intermediate 10, which was condensed with a Boc-protected adenine, followed by deprotection, furnished the target nucleoside FMCA (12) in high yield. Further coupling of phosphorochloridate of L-alanine isopropyl ester (13) with FMCA gave its phosphoramidate prodrug FMCAP (14) in good yield.


Subject(s)
Adenosine/analogs & derivatives , Amides/chemical synthesis , Antiviral Agents/chemical synthesis , Phosphoric Acids/chemical synthesis , Adenosine/chemical synthesis , Adenosine/chemistry , Adenosine/pharmacology , Amides/chemistry , Amides/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Hepatitis B virus/drug effects , Molecular Conformation , Phosphoric Acids/chemistry , Phosphoric Acids/pharmacology
16.
Women Health ; 59(4): 375-390, 2019 04.
Article in English | MEDLINE | ID: mdl-29920173

ABSTRACT

India has the highest proportion of low birth weight (LBW) babies born in the developing world. Poor maternal nutrition during pregnancy is associated with adverse infant health outcomes. The main objective of this paper was to assess the socioeconomic factors associated with dietary diversity among pregnant women and to investigate the association between maternal dietary diversity and LBW among their babies. The data for these analyses were derived from a survey conducted in November and December, 2014 among 230 women who had newly delivered in hospitals in Uttar Pradesh, the largest Indian state that has the poorest maternal outcomes in the country. The results from multivariate binary logistic regression model indicated that low maternal education and economic status was significantly associated with poor dietary diversity among participants. Also, women with low maternal dietary diversity had a significantly higher proportion of LBW babies compared to those in the medium to high dietary diversity categories. From a policy perspective, these findings suggest that continuous tracking of pregnant women's nutritional needs through existing monitoring systems, e.g., the Nutrition Resource Platform and Health Management Information System, and necessary interventions through Integrated Child Development Services may yield better results, thereby, addressing maternal under-nutrition and LBW.


Subject(s)
Diet , Infant, Low Birth Weight , Nutritional Status , Prenatal Care/methods , Adult , Birth Weight , Female , Health Surveys , Humans , India , Infant, Newborn , Pregnancy , Pregnancy Outcome , Risk Factors , Socioeconomic Factors
17.
Med Res Rev ; 38(3): 977-1002, 2018 05.
Article in English | MEDLINE | ID: mdl-29406612

ABSTRACT

Chronic hepatitis B (CHB) is one of the major causes of morbidity and mortality worldwide. Currently, clinically approved nucleos(t)ide analogs (NAs) are very efficient in reducing the load of hepatitis B virus (HBV) with minimum side effects. However, the long-term administration of antiviral drugs promotes HBV for potential drug resistance. To overcome this problem, combination therapies are administered, but HBV progressively altered mutations remain a threat. Therefore, optimally designed NAs are urgently needed to treat drug-resistant HBV. Herein, 2'-fluoro-6'-methylene carbocyclic adenosine (FMCA) and its phosphoramidate (FMCAP) have been discovered, which may be utilized in combination therapies for curing drug-resistant chronic hepatitis B. In preclinical studies, these carbocyclic NAs demonstrated potential anti-HBV activity against adefovir, as well as lamivudine (LMV/LAM) drug-resistant mutants. In vitro, these molecules have demonstrated significant activity against LMV/entecavir (ETV) triple mutants (L180M + S202G + M204V). Also, preliminary studies of FMCA/FMCAP in chimeric mice and female Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse models having the LMV/ETV triple mutant have shown a high rate of reduction of HBV DNA levels compared to ETV. In this review, we have summarized preclinical studies of FMCA and its phosphoramidate prodrug (FMCAP).


Subject(s)
Adenosine/analogs & derivatives , Amides/pharmacology , Antiviral Agents/pharmacology , Drug Resistance, Viral/genetics , Hepatitis B virus/drug effects , Mutation/genetics , Phosphoric Acids/pharmacology , Prodrugs/pharmacology , Adenosine/chemistry , Adenosine/pharmacology , Amides/chemistry , Animals , Antiviral Agents/chemistry , Drug Resistance, Viral/drug effects , Humans , Phosphoric Acids/chemistry , Prodrugs/chemistry
18.
Mol Ther ; 25(1): 218-231, 2017 01 04.
Article in English | MEDLINE | ID: mdl-28129116

ABSTRACT

The progression of fibrosis in chronic liver disease is dependent upon hepatic stellate cells (HSCs) transdifferentiating to a myofibroblast-like phenotype. This pivotal process is controlled by enzymes that regulate histone methylation and chromatin structure, which may be targets for developing anti-fibrotics. There is limited pre-clinical experimental support for the potential to therapeutically manipulate epigenetic regulators in fibrosis. In order to learn if epigenetic treatment can halt the progression of pre-established liver fibrosis, we treated mice with the histone methyltransferase inhibitor 3-deazaneplanocin A (DZNep) in a naked form or by selectively targeting HSC-derived myofibroblasts via an antibody-liposome-DZNep targeting vehicle. We discovered that DZNep treatment inhibited multiple histone methylation modifications, indicative of a broader specificity than previously reported. This broad epigenetic repression was associated with the suppression of fibrosis progression as assessed both histologically and biochemically. The anti-fibrotic effect of DZNep was reproduced when the drug was selectively targeted to HSC-derived myofibroblasts. Therefore, the in vivo modulation of HSC histone methylation is sufficient to halt progression of fibrosis in the context of continuous liver damage. This discovery and our novel HSC-targeting vehicle, which avoids the unwanted effects of epigenetic drugs on parenchymal liver cells, represents an important proof-of-concept for epigenetic treatment of liver fibrosis.


Subject(s)
Adenosine/analogs & derivatives , Epigenesis, Genetic/drug effects , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Adenosine/administration & dosage , Adenosine/pharmacology , Animals , Biomarkers , Carbon Tetrachloride/adverse effects , Collagen Type I/genetics , Collagen Type I/metabolism , Disease Models, Animal , Disease Progression , Gene Expression Profiling , Gene Expression Regulation/drug effects , Hepatic Stellate Cells/cytology , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Histone Methyltransferases , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Histones/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Male , Mice , Myofibroblasts/cytology , Myofibroblasts/drug effects , Myofibroblasts/metabolism
19.
Indian J Med Res ; 147(3): 263-267, 2018 03.
Article in English | MEDLINE | ID: mdl-29923515

ABSTRACT

Background & objectives: Cancer cervix is one of the most common forms of genital malignancy among Indian women. Recurrence is seen in a significant number of cases. The conventional cervical smear technique has inherent problems and screening and interpretation errors. This study was undertaken to assess the efficacy of liquid-based cytology (LBC) as a method for cytological follow up and detection of recurrence in treated cases of cancer cervix and to compare it with conventional Pap smear technique to find the best screening method for detection of recurrence in these patients. Methods: This cross-sectional study was conducted over a period of one year. Patients attending Gynecology and Radiotherapy outpatient departments for follow up after treatment of cancer cervix were included. Pap smear and LBC were taken in all cases. Colposcopy and biopsy were done for those having epithelial cell abnormality in cytology report. Colposcopy and biopsy were taken as gold standard for diagnosis of cancer cervix recurrence. Results: Ninety four treated patients of carcinoma cervix were studied. The diagnostic accuracy for detection of recurrence of conventional Pap smear was 79.16 per cent, and that of LBC was 97.6 per cent. The difference between the two methods was significant (P<0.001). Interpretation & conclusions: Our findings showed that LBC performed better than the conventional method of cytology to detect recurrence of squamous cell carcinoma. Its sensitivity, specificity as well as accuracy were much higher than conventional method. LBC can be a better method of cytological follow up of post-treated patients of cancer cervix.


Subject(s)
Colposcopy , Papanicolaou Test , Uterine Cervical Neoplasms/diagnosis , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , India , Neoplasm Recurrence, Local , Pregnancy , Sensitivity and Specificity , Uterine Cervical Neoplasms/pathology , Vaginal Smears , Uterine Cervical Dysplasia
20.
Biol Chem ; 398(11): 1259-1265, 2017 10 26.
Article in English | MEDLINE | ID: mdl-28622138

ABSTRACT

Nitric oxide (NO) has a contributory role in hemopoietic cell growth and differentiation. The effects of NO on leukemic cell growth have been predominantly studied in in vitro settings. This study was done to assess the alterations in nitrite level in myeloid leukemias. Thirty-six newly diagnosed cases of myeloid leukemia (16 AML and 20 CML) were enrolled in the study. Neutrophil precursors from the marrow aspirate and peripheral blood were separated into cell bands using the Percoll density gradient method of Borregard and Cowland. The blood plasma and marrow fluid was also collected. Nitrite (stable non-volatile end product of NO) was estimated in the cell bands, blood plasma and marrow fluid using Griess reagent. The mean nitrite level in all cell bands from peripheral blood, bone marrow, blood plasma, and marrow fluid of cases was significantly lower as compared to corresponding value in the controls. No significant difference between AML and CML was seen. On follow-up, analysis of 13 CML patients higher nitrite levels were seen (p>0.05). The significant decrease in nitrite levels in myeloid leukemia suggests a decrease in nitric oxide synthase (NOS) activity. Further work may unfold molecular targets for therapeutic role of NO modulators.


Subject(s)
Leukemia, Myeloid/metabolism , Leukemia, Myeloid/pathology , Nitrites/blood , Nitrites/metabolism , Adult , Female , Humans , Leukemia, Myeloid/blood , Leukemia, Myeloid/enzymology , Male , Nitric Oxide/metabolism
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