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1.
J Microencapsul ; 41(5): 390-401, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945157

ABSTRACT

Green-synthesis of biodegradable polymeric curcumin-nanoparticles using affordable biodegradable polymers to enhance curcumin's solubility and anti-oxidative potential. The curcumin-nanoparticle was prepared based on the ionic-interaction method without using any chemical surfactants, and the particle-size, zeta-potential, surface-morphology, entrapmentefficiency, and in-vitro drug release study were used to optimise the formulation. The antioxidant activity was investigated using H2DCFDA staining in the zebrafish (Danio rerio) model. The mean-diameter of blank nanoparticles was 178.2 nm (±4.69), and that of curcuminnanoparticles was about 227.7 nm (±10.4), with a PDI value of 0.312 (±0.023) and 0.360 (±0.02). The encapsulation-efficacy was found to be 34% (±1.8), with significantly reduced oxidative-stress and toxicity (∼5 times) in the zebrafish model compared to standard curcumin. The results suggested that the current way of encapsulating curcumin using affordable, biodegradable, natural polymers could be a better approach to enhancing curcumin's water solubility and bioactivity, which could further be translated into potential therapeutics.


Subject(s)
Antioxidants , Chitosan , Curcumin , Green Chemistry Technology , Gum Arabic , Nanoparticles , Zebrafish , Animals , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/administration & dosage , Curcumin/pharmacokinetics , Nanoparticles/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/administration & dosage , Chitosan/chemistry , Gum Arabic/chemistry , Drug Carriers/chemistry , Drug Liberation , Solubility , Oxidative Stress/drug effects , Particle Size
2.
Biomed Pharmacother ; 169: 115854, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37951024

ABSTRACT

Garlic (Allium sativum) is an important flavouring component in Indian cuisine. Allicin, a sulphur containing compound, is the most abundant component of garlic and has been widely studied for its antimicrobial and antioxidant properties. It is also known to play a role in the regulation of blood pressure and cholesterol levels. Despite the known health benefits associated with allicin, systematic studies on its anti-cancer properties using animal models are very limited. This study aimed to develop a simple method for the extraction of allicin from fresh garlic, study the stability of the extracted compound at various temperatures, and evaluate the antioxidant, anti-proliferative, pro-apoptotic and anti-angiogenic properties in zebrafish. A five-month stability study indicated that allicin remains significantly stable at temperatures 4 °C and below but shows extensive degradation if stored at room temperature. The in vivo studies in zebrafish using a combination of mutants and transgenic lines demonstrated the antioxidant, anti-proliferative, apoptotic and anti-angiogenic properties of allicin. The study highlights the importance of natural bioactive compounds as potential anti-cancer agents that can be studied further.


Subject(s)
Garlic , Neoplasms , Animals , Zebrafish , Antioxidants/pharmacology
3.
PLoS One ; 18(7): e0289117, 2023.
Article in English | MEDLINE | ID: mdl-37478119

ABSTRACT

The use of herbal products as traditional medicines has been a practice in India for centuries. Due to high ethnic diversity, the pool of herbal medicines is enormous, and they are often preferred over modern medicines in certain parts of the country. Cancer is one of the major non-communicable diseases affecting people worldwide. Despite considerable research, cancer is a disease that is still not understood completely, and there have been constant efforts towards the identification of novel drugs or approaches in cancer management. Parkia javanica, an important medicinal plant and a rich source of flavonoids and terpenoids, is widely studied for its antioxidant and anti-inflammatory activities. Traditionally, the fruit and bark extracts of P. javanica find use as home remedy for dysentery and piles in NE India. Moreover, the fruits are consumed by the people of North-East (NE) India as vegetables, either in steamed or cooked form. In this study, crude extracts of P. javanica fruit and bark were obtained, the sub-lethal dose was determined and were then analyzed for anti-proliferative and anti-angiogenic properties using a battery of assays in zebrafish embryos. The sub-lethal concentration 50 (LC50) was found to be 28.66 mg/L and 346.66 mg/L for bark and fruit extract respectively, indicating a decreased toxicity of the fruit extract compared to that of the bark. The anti-proliferative and anti-angiogenic properties were more pronounced for the fruit extract compared to the bark extract. Although preliminary, the results of the study suggest that P. javanica fruits possess potent anti-angiogenic and anti-proliferative properties, which can be further studied for the isolation of active phytochemicals for use as therapeutic agents.


Subject(s)
Fabaceae , Plants, Medicinal , Animals , Fruit/chemistry , Plant Extracts/chemistry , Zebrafish , Plant Bark/chemistry , Antioxidants/chemistry
4.
Sci Rep ; 13(1): 10026, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37340076

ABSTRACT

Poly (A)-specific ribonuclease (PARN) is the most important 3'-5'exonuclease involved in the process of deadenylation, the removal of poly (A) tails of mRNAs. Although PARN is primarily known for its role in mRNA stability, recent studies suggest several other functions of PARN including a role in telomere biology, non-coding RNA maturation, trimming of miRNAs, ribosome biogenesis and TP53 function. Moreover, PARN expression is de-regulated in many cancers, including solid tumours and hematopoietic malignancies. To better understand the in vivo role of PARN, we used a zebrafish model to study the physiological consequences of Parn loss-of-function. Exon 19 of the gene, which partially codes for the RNA binding domain of the protein, was targeted for CRISPR-Cas9-directed genome editing. Contrary to the expectations, no developmental defects were observed in the zebrafish with a parn nonsense mutation. Intriguingly, the parn null mutants were viable and fertile, but turned out to only develop into males. Histological analysis of the gonads in the mutants and their wild type siblings revealed a defective maturation of gonadal cells in the parn null mutants. The results of this study highlight yet another emerging function of Parn, i.e., its role in oogenesis.


Subject(s)
Neoplasms , Zebrafish , Male , Animals , Zebrafish/genetics , Zebrafish/metabolism , RNA, Messenger/metabolism , Exoribonucleases/metabolism , Telomere/metabolism , Oogenesis/genetics
5.
J Biosci ; 472022.
Article in English | MEDLINE | ID: mdl-36408539

ABSTRACT

The study investigated the gut microbial diversity and the role of gut-associated microorganisms in modulating the immune responses in normal (wild-type) and TP53M214K (cancer-prone) zebrafish. Biochemical tests, genus/species-specific PCR, and 16S rDNA sequencing were performed to characterize the bacteria isolated from the gut of wild-type (WT) and cancer-prone zebrafish. Gut microbiome analysis revealed greater diversity but reduced bacterial load in wild-type zebrafish compared with cancer-prone zebrafish, which had lesser diversity but higher bacterial load. Interestingly, the gut in cancer-prone fish showed selective colonization by opportunistic pathogens. The bacterial isolates showed resistance to antibiotics such as tetracycline, nalidixic acid, and ciprofloxacin. Gnotobiotic zebrafish embryos were established, and mono-colonization with the isolated bacteria was done to examine the expression of anti-inflammatory genes using real-time PCR. Variable expression of IL10 and IL4 was observed in germ-free (GF) wild-type embryos when mono-colonized with Staphylococcus sciuri and Vibrio cholerae. In contrast, germ-free TP53 mutant embryos showed a consistent downregulation of both the anti-inflammatory genes. Thus, a better immune response in WT embryos against S. sciuri or V. cholerae infection than in cancer-prone fish was observed, suggesting that genetic predisposition could contribute to disabling the immune system against infection.


Subject(s)
Gastrointestinal Microbiome , Neoplasms , Animals , Zebrafish/genetics , Gastrointestinal Microbiome/genetics , Bacteria , Anti-Bacterial Agents/pharmacology , Neoplasms/genetics
6.
Mol Biol Rep ; 48(6): 5093-5097, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34181170

ABSTRACT

TP53 functions primarily as a tumor suppressor, controlling a myriad of signalling pathways that prevent a cell from undergoing malignant transformation. This tumor suppressive function requires an activation and stabilization of TP53 in response to cell stressors. However, besides its cancer-preventive functions, TP53 is also known to be involved in diverse cellular processes including metabolism, reproduction, stem cell renewal and development. Indeed, several lines of evidence strongly suggest that TP53 plays crucial role in diabetes. A number of studies have evaluated the association of genetic alterations (single nucleotide variations) in TP53 gene with the development of diabetes. However, the results have not been consistent. The aim of this study was to evaluate whether the C/G polymorphism at codon 72 (Pro72/Arg72), located in exon 4 of TP53, is associated with type 2 diabetes in South Indian population. A total of 74 type 2 diabetic patients and 54 non-diabetic subjects were screened. None of the three genotypes, namely C/C (Pro/Pro), C/G (Pro/Arg), and G/G (Arg/Arg) was found to be significantly associated with type 2 diabetes in our study group. The findings of this study indicate that TP53 codon 72 polymorphism is not associated with increased risk of type 2 diabetes in South Indian population. Further studies with a large cohort size would be necessary to corroborate the observations of this study. Nevertheless, this study represents the first genetic analysis of TP53 variants in South Indian type 2 diabetic patients.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Tumor Suppressor Protein p53/genetics , Adult , Aged , Alleles , Case-Control Studies , Codon/genetics , Cohort Studies , Diabetes Mellitus, Type 2/epidemiology , Exons/genetics , Female , Gene Frequency/genetics , Genes, Tumor Suppressor , Genes, p53/genetics , Genetic Predisposition to Disease , Genotype , Humans , India/epidemiology , Male , Middle Aged , Mutation , Polymorphism, Single Nucleotide/genetics , Risk Factors , Tumor Suppressor Protein p53/metabolism
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