Apoptosis antagonizing transcription factor-mediated liver damage and inflammation to cancer: Therapeutic intervention by curcumin in experimental metabolic dysfunction associated steatohepatitis-hepatocellular carcinoma.

In tandem with the expanding obesity pandemic, the prevalence of metabolic dysfunction associated steatohepatitis (MASH, formerly known as NASH)- driven hepatocellular carcinoma (HCC) is predicted to rise globally, creating a significant need for therapeutic interventions. We previously identified the upregulation of apoptosis antagonizing transcription factor (AATF), which is implicated in facilitating the progression from MASH to HCC. The objective of this study was to examine whether the intervention of curcumin could alleviate AATF-mediated MASH, inhibit tumor growth, and elucidate the underlying mechanism. A preclinical murine model mimicking human MASH-HCC was employed, subjecting mice to either a chow diet normal water (CDNW) or western diet sugar water (WDSW) along with very low dose of carbon tetrachloride (CCl4 - 0.2 µL/g, weekly). Mice receiving curcumin (CUR) alongside WDSW/CCl4 exhibited significant improvements, including reduced liver enzymes, dyslipidemia, steatosis, inflammation, and hepatocellular ballooning. Curcumin treatment also suppressed hepatic expression of inflammatory, fibrogenic, and oncogenic markers. Of note, there was a significant reduction in the expression of AATF upon curcumin treatment in WDSW/CCl4 mice and human HCC cells. In contrast, curcumin upregulated Kruppel-like factor 4 (KLF4) in MASH liver and HCC cells, which is known to downregulate sp1 (specificity protein-1) expression. Thus, curcumin treatment effectively inhibited the progression of MASH to HCC by downregulating the expression of AATF via the KLF4-Sp1 signaling pathway. These preclinical findings establish a novel molecular connection between curcumin and AATF in reducing hepatocarcinogenesis, and provide a strong rationale for the development of curcumin as a viable treatment for MASH-HCC in humans.

Unraveling the Potential Role of Tecomella undulata in Experimental NASH.

The pathophysiology of nonalcoholic steatohepatitis (NASH) is complex, owing to its diverse pathological drivers and, until recently, there were no approved drugs for this disease. Tecomella is a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role of Tecomella undulata in NASH has not yet been scientifically investigated. The administration of Tecomella undulata via oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in western diet sugar water (WDSW) fed mice but had no effect on chow diet normal water (CDNW) fed mice. Tecomella undulata improved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore, Tecomella undulata also alleviated the WDSW-induced Endoplasmic Reticulum stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were comparable to saroglitazar, the approved drug used to treat human NASH and the positive control used in the study. Thus, our findings indicate the potential of Tecomella undulata to ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessing Tecomella undulata for the treatment of NASH.

A concise review on oil extraction methods, nutritional and therapeutic role of coconut products.

The coconut palm belongs to the Arecaceae family, which is distinct from other fruits, known for its versatility. Fresh coconut products are valuable for many food preparations owing to their nutritional and flavour properties. For example, tender coconut yields coconut water, a refreshing nutritious drink that provides good nutrients including electrolytes and other interesting compounds. The mature coconut meat which is rich in fat and protein, aids in coconut milk extraction and is a major component in the wet and dry process of oil extraction. Coconut milk has market potential owing to its increasing applications in food and beverage industries. Coconut is also known for its by-product namely coconut flour, which is rich in protein and dietary fiber, could be used in the preparation of functional foods. The different methods involved in the oil extraction process which helps in more efficient oil recovery were discussed briefly. The nutritional health-promoting functional role of coconut water and virgin coconut oil is highlighted in review paper.

Efficacy of Spirulina 500 mg vs Triamcinolone Acetonide 0.1% for the Treatment of Oral Lichen Planus: A Randomized Clinical Trial.

AIM: The present study aimed at evaluating the efficacy of spirulina 500 mg in reducing the burning sensation and lesion size in oral lichen planus (OLP). MATERIALS AND METHODS: A total of 60 subjects who attended the oral medicine specialty clinic with histopathologically confirmed OLP and having symptoms of burning sensation were recruited for the study. They were randomly divided into two groups: group A (30) subjects were prescribed Spirulina 500 mg twice daily along with only a week application of topical triamcinolone acetonide 0.1% thrice daily; group B subjects were prescribed topical triamcinolone acetonide 0.1% alone thrice daily for 8 weeks. Both the groups were followed up posttreatment monthly for three consecutive months. RESULTS: Data were recorded, and statistical analysis by using ANOVA one-way test, and Chi-square test were performed, which showed statistically significant p-value (<0.005) for the parameters "burning sensation" and "size of the lesion". When compared between groups, group A showed a favorable outcome of the intervention. CONCLUSION: Spirulina 500 mg supplementation twice daily could be effective adjunct therapy with steroids to treat OLP. CLINICAL SIGNIFICANCE: This research allowed us to delve into spirulina as one of the treatment modalities for OLP. Further studies are needed as it is a rich source of proteins and vitamins and demonstrates potent anti-inflammatory, immunomodulatory, and antioxidant actions.

RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata.

Up-regulation of MMP-2 and MMP-9 plays a significant role in promoting cancer progression by degrading the components of the extracellular matrix, thereby enhancing the migration of tumor cells. Although the antiproliferative and apoptotic effect of Annona muricata is well established, its effect on MMP-2 and MMP-9, a major target in several types of cancers, has not been studied. Powdered samples of various parts of A. muricata like fruit, stem, seed, and twig extracted using aqueous methanol showed significant dose-dependent inhibition of MMP-2 and MMP-9 in a highly metastatic fibrosarcoma cell line, HT1080. Additionally, these extracts also up-regulated the expression of several endogenous inhibitors of MMP-2 and MMP-9 like REversion-inducing Cysteine-rich protein with Kazal motifs (RECK) and Tissue Inhibitor of Metalloproteinase- 2 (TIMP-2). Furthermore, primary cells developed from tumor tissues obtained from patients not exposed to chemotherapy, also exhibited similar results. Remarkably, the inhibition of MMP-2 and MMP-9 observed was tumor specific, with the A. muricata fruit extract showing only 2% inhibition in cells obtained from normal tissues, when compared to 60% inhibition observed in cells obtained from tumor samples. The present study elucidates a novel mechanism by which A. muricata extracts selectively exhibit their anti-cancer activity in tumor cells by down-regulating MMP-2 and MMP-9 that are important biomarkers in cancer.

Preclinical models of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) can manifest as non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). NASH is often associated with progressive fibrosis which can lead to cirrhosis and hepatocellular carcinoma (HCC). NASH is increasing as an aetiology for end-stage liver disease as well as HCC. There are currently no approved therapies for NASH. A major barrier to development of therapeutics for NASH is the lack of preclinical models of disease that are appropriately validated to represent the biology and outcomes of human disease. Many in vitro and animal models have been developed. In vitro models do not fully capture the hepatic and extrahepatic milieu of human NASH and large animal models are expensive and logistically difficult to use. Therefore, there is considerable interest in the development and validation of mouse models for NAFLD, including NASH. Several models based on varying genetic or dietary manipulations have been developed. However, the majority do not recreate steatohepatitis, strictly defined as the presence of hepatocellular ballooning with or without Mallory-Denk bodies, accompanied by inflammation in the presence of macrovesicular steatosis. Others lack validation against human disease. Herein, we describe the best practices in development of mouse models of NASH. We further review existing models and the literature supporting their use as a surrogate for human disease. Finally, data on models to evaluate protective genes are discussed. It is hoped that this review will provide guidance for the interpretation of data derived from mouse models and also for the development and validation of newer models.

Vacuolar targeting of r-proteins in sugarcane leads to higher levels of purifiable commercially equivalent recombinant proteins in cane juice.

Sugarcane is an ideal candidate for biofarming applications because of its large biomass, rapid growth rate, efficient carbon fixation pathway and a well-developed storage tissue system. Vacuoles occupy a large proportion of the storage parenchyma cells in the sugarcane stem, and the stored products can be harvested as juice by crushing the cane. Hence, for the production of any high-value protein, it could be targeted to the lytic vacuoles so as to extract and purify the protein of interest from the juice. There is no consensus vacuolar-targeting sequence so far to target any heterologous proteins to sugarcane vacuole. Hence, in this study, we identified an N-terminal 78-bp-long putative vacuolar-targeting sequence from the N-terminal domain of unknown function (DUF) in Triticum aestivum 6-SFT (sucrose: fructan 6-fructosyl transferase). In this study, we have generated sugarcane transgenics with gene coding for the green fluorescent protein (GFP) fused with the vacuolar-targeting determinants at the N-terminal driven by a strong constitutive promoter (Port ubi882) and demonstrated the targeting of GFP to the vacuoles. In addition, we have also generated transgenics with His-tagged ß-glucuronidase (GUS) and aprotinin targeted to the lytic vacuole, and these two proteins were isolated and purified from the transgenic sugarcane and compared with commercially available protein samples. Our studies have demonstrated that the novel vacuolar-targeting determinant could localize recombinant proteins (r-proteins) to the vacuole in high concentrations and such targeted r-proteins can be purified from the juice with a few simple steps.