Giant Retinal Astrocytoma: A Case Report of an Uncommon Presentation of Tuberous Sclerosis in a Young Female.

Tuberous sclerosis (TS) is a rare multisystem autosomal dominant genetic disorder with characteristic pathognomonic genetic mutations involving the TSC (tuberous sclerosis complex) group of genes. Ocular signs are fairly common and include an achromic patch and retinal astrocytic hamartomas, which usually have a maximum size of between 0.5 and 5 mm. The incidence of tuberous sclerosis is estimated to be 1 in 5000-10,000 individuals, with both familial and sporadic cases reported. The diagnostic criteria for tuberous sclerosis include the presence of major and/or minor clinical features as well as genetic mutations. We present the case of a 15-year-old girl, presented with a history of seizures and blurred vision. Physical examination revealed angiofibroma on the face. Further evaluation, including contrast-enhanced MRI of the brain and ophthalmological consultation, led to the diagnosis of tuberous sclerosis. Additional imaging studies confirmed the presence of subependymal giant cell astrocytoma, retinal astrocytoma, lymphangioleiomyomatosis in the lungs, and renal angiomyolipoma. This case highlights the importance of considering tuberous sclerosis in patients presenting with seizures and ocular symptoms. This case sheds light on early diagnosis and appropriate management which are crucial in preventing complications and improving patient outcomes.

An Insight into Synthetic Strategies, SAR Study and Anticancer Mechanism of Chalcone Derivatives: Medicinal Chemistry Perspective.

Chalcone derivatives continue to captivate medicinal chemists due to their modest chemistry, facile synthetic method, and promising biological activities. They have become wellknown in the therapeutic and pharmaceutical industries due to their diverse biological actions. These complexes offer different features and applications in a human biological system due to the flexibility of the reactions, including antimicrobial, antineoplastic, antimalarial, and other uses. As a result, chalcones have sparked much attention in malignancy research. Cancer is characterized by uncontrollably growing and spreading abnormal cells and aberrant cell behavior. These masses destroy surrounding normal tissue and can attack vital organs, leading to widespread disease. Cancer is frequently used as a warning sign for impending patient death. In the age of pharmaceutical chemistry, it is unavoidably a cause for concern and a growing weight on the populace. The pathophysiology of all malignancies is due to faulty genes that regulate the development, division, and death of cells. Various genetic and environmental variables combine to cause mutations in genes encoding essential cell-regulatory proteins, leading to the numerous alterations that characterize the evolution of cancers. Rather than directly targeting DNA synthesis, the new generation of anticancer medications target signals that promote or control the cell cycle, growth factors and their receptors, signal transduction pathways, and pathways impacting DNA repair and death. Drug hunters are focusing their attention on chalcone derivatives with varying chemical structures since they are essential in the search for anticancer drugs. Chalcone's anticancer action may be attributed to molecular changes such as drug efflux protein activities, activation of apoptosis, DNA and mitochondrial damage, inhibition of angiogenesis, tubulin inhibition, and kinase inhibition. Chalcones are used to diagnose cancer as well. The development of chalcone congeners as a prodrug or prime chemical to combat cancer necessitates a thorough investigation. This review gives an update on the different pharmacological activities of natural and synthesized chalcones in recent years. Furthermore, the structure- activity connections and processes are extensively documented, providing essential design and synthesis assistance in the future.

Molecular Insight into the Apoptotic Mechanism of Cancer Cells: An Explicative Review.

Mitosis of somatic cells produces a daughter cell. Apoptosis, a naturally programmed cellular death mechanism, kills abnormal cells produced by mitosis. Cancer can develop when this equilibrium is disrupted, either by an upsurge in cell propagation or a reduction in tissue demise. Cancer therapy aims to cause cancer cells to die while inflicting little harm to healthy cells. This review of apoptotic mechanism processes improves our understanding of how certain malignancies begin and develop. The current cancer treatments can operate either by inducing apoptosis or causing direct cell damage. An insight into the resistance to apoptosis may explicate why malignancy treatments fail in some situations. New therapies grounded on our understanding of apoptotic processes are being developed to induce apoptosis of cancer cells while limiting the simultaneous death of normal cells. Various biological activities require redox equilibrium to function properly. Antineoplastic medications that cause oxidative stress by raising ROS and blocking antioxidant mechanisms have recently attracted much interest. The rapid accumulation of ROS impairs redox balance and damages cancer cells severely. Here, we discuss ROS-instigating malignancy therapy and the antineoplastic mechanism used by prooxidative drugs.

A Comprehensive Review on Targeted Cancer Therapy: New Face of Treatment Approach.

Cancer is one of life's most difficult difficulties and a severe health risk everywhere. Except for haematological malignancies, it is characterized by unchecked cell growth and a lack of cell death, which results in an aberrant tissue mass or tumour. Vascularization promotes tumor growth, which eventually aids metastasis and migration to other parts of the body, ultimately resulting in death. The genetic material of the cells is harmed or mutated by environmental or inherited influences, which results in cancer. Presently, anti-neoplastic medications (chemotherapy, hormone, and biological therapies) are the treatment of choice for metastatic cancers, whilst surgery and radiotherapy are the mainstays for local and non-metastatic tumors. Regrettably, chemotherapy disturbs healthy cells with rapid proliferation, such as those in the gastrointestinal tract and hair follicles, leading to the typical side effects of chemotherapy. Finding new, efficient, targeted therapies based on modifications in the molecular biology of tumor cells is essential because current chemotherapeutic medications are harmful and can cause the development of multidrug resistance. These new targeted therapies, which are gaining popularity as demonstrated by the FDA-approved targeted cancer drugs in recent years, enter molecules directly into tumor cells, diminishing the adverse reactions. A form of cancer treatment known as targeted therapy goes after the proteins that regulate how cancer cells proliferate, divide, and disseminate. Most patients with specific cancers, such as chronic myelogenous leukemia (commonly known as CML), will have a target for a particular medicine, allowing them to be treated with that drug. Nonetheless, the tumor must typically be examined to determine whether it includes drug targets.

Toxicities of CAR T-cell therapy: a review of current literature.

The chimeric antigen receptor (CAR) design, first invented by Zelig Eshhar, paved the way for the use of genetically modified T-cells in targeted therapy against cancer cells. Since then, it has gone through many generations, especially with the integration of co-stimulation in the second and third-generation CARs. However, it also mounts a hyperactive immune response named as cytokine release syndrome with the release of several cytokines eventually resulting in multiple end-organ toxicities. The severity of cytokine release syndrome depends upon certain factors such as the tumor burden, choice of co-stimulation, and degree of lymphodepletion, and can manifest as pulmonary edema, vascular leak, renal dysfunction, cardiac problems, hepatic failure, and coagulopathy. Many grading criteria have been used to define these clinical manifestations but they lack harmonization. Neurotoxicity has also been significantly associated with CAR T-cell therapy but it has not been studied much in previous literature. This review aims to provide a comprehensive account of the clinical manifestations, diagnosis, management, and treatment of CAR T-cell associated neurotoxicity.

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer.

Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability. Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C -80, C-120,C -150, C -200 ns) revealed strong hydrogen bonding in the complexes and showed -12.9, -11.6, and -11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis. Conclusion: Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

Epigenetics of Epstein Barr virus - A review.

Epstein Barr is the first-in-human oncogenic virus, closely related to numerous lymphoproliferative and malignant diseases, including HL, BL, NPC, and GC. EBV establishes life-long persistence infection portraying a biphasic viral life cycle: latent period and lytic replication. B-cells serve as critical regions for EBV latent genes, wherein viral gene expression is suppressed, promoting viral genome maintenance and immune recognition evasion. Upon its lytic reactivation, viral gene expression induces its replication, progeny production, and transmission. Dysregulations of epigenetic regulation in expressions of TSGs lead to carcinogenesis. Several studies reveal that EBV is associated with aberrant viral DNA and host genome methylation patterns, promoting immune monitoring, recognition evasiveness and host cell persistence. Among other epigenetic modifications, DNA methylation suppresses the majority of viral latent gene promoters, sparing a few, and acts as a prerequisite for activating EBV's lytic cycle, giving rise to viral progeny. It affects the host's epigenome via reprogramming cells to oncogenic, long-lasting phenotypes, as evident in several malignancies. At each phase of its life cycle, EBV exploits cellular mechanisms of epigenetic regulation, implying its unique host-pathogen relationship. This review summarized the DNA methylation's regulatory roles on several EBV-related promoter regions, along with the host genome in pathological conditions, highlights viral genes involved in a latent, lytic and latent-lytic phase of EBV infection. Moreover, it provides diagrammatic insights into methylation-based pathways in EBV.

Systematic Analysis of the Therapy Resistance Genes and their Prognostic Relevance in Cervical Cancer.

INTRODUCTION: Critical issues in the therapeutic management of cervical cancer (CC) include therapy resistance and treatment failure. The development of therapy resistance is a multifaceted, progressive process, including genetic and epigenetic abnormalities. The present study aimed to identify genes that may contribute to therapy resistance in CC. MATERIALS AND METHODS: We have created an extensive list of the genes in cancer that are therapy-resistant using a text-mining approach. The list was compared with the TCGA-CESC dataset to identify the differentially expressed therapy resistance genes (DETRGs) in CC. We used online resources (UALCAN, DNMIVD, cBio- Portal, HCMDB, OncoDB, ShinyGO, HPA, KM Plotter, TIMER, and DGIdb) to determine the potential association between methylation and expression of therapy resistance genes with the prognosis and clinical outcomes in CC. RESULTS: The systematic analysis identified 71 out of 91 DETRGs showed aberrant DNA methylation. The overlapping analysis identified 25 genes to show an inverse correlation between methylation and expression. Further, differential expression or methylation could be helpful in CC staging, HPV association, prediction of metastasis and prognosis. The study identified seven driver genes in CC. The PPIN identifies ten hub genes (HGs) associated with CC staging, cancer hallmarks, and prognosis to affect long-term survival. CONCLUSION: Our thorough investigation uncovered several novel genes and pathways that might contribute to therapy resistance in CC. The genes identified in our study may serve as a biomarker, prognostic indicator, and therapeutic target in CC.

Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors.

Dietary rice bran-mediated inhibition of colon carcinogenesis was demonstrated previously for carcinogen-induced rodent models via multiple anti-cancer mechanisms. This study investigated the role of dietary rice bran-mediated changes to fecal microbiota and metabolites over the time course of colon carcinogenesis and compared murine fecal metabolites to human stool metabolic profiles following rice bran consumption by colorectal cancer survivors (NCT01929122). Forty adult male BALB/c mice were subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colon carcinogenesis and randomized to control AIN93M (n = 20) or diets containing 10% w/w heat-stabilized rice bran (n = 20). Feces were serially collected for 16S rRNA amplicon sequencing and non-targeted metabolomics. Fecal microbiota richness and diversity was increased in mice and humans with dietary rice bran treatment. Key drivers of differential bacterial abundances from rice bran intake in mice included Akkermansia, Lactococcus, Lachnospiraceae, and Eubacterium xylanophilum. Murine fecal metabolomics revealed 592 biochemical identities with notable changes to fatty acids, phenolics, and vitamins. Monoacylglycerols, dihydroferulate, 2-hydroxyhippurate (salicylurate), ferulic acid 4-sulfate, and vitamin B6 and E isomers significantly differed between rice bran- and control-fed mice. The kinetics of murine metabolic changes by the host and gut microbiome following rice bran consumption complemented changes observed in humans for apigenin, N-acetylhistamine, and ethylmalonate in feces. Increased enterolactone abundance is a novel diet-driven microbial metabolite fecal biomarker following rice bran consumption in mice and humans from this study. Dietary rice bran bioactivity via gut microbiome metabolism in mice and humans contributes to protection against colorectal cancer. The findings from this study provide compelling support for rice bran in clinical and public health guidelines for colorectal cancer prevention and control.

Quality of Life in People With Unilateral Lower Limb Amputation at a Tertiary Rehabilitation Centre in Northern India: A Cross-Sectional Study.

Background and purpose The patients after amputation undergo a sudden transformation in their quality of life. In India, amputation done at the appropriate time is a rare phenomenon because usually, the patients present themselves at the later stages. The surgeons, however, while performing amputation surgeries, primarily consider saving the life of a patient under adverse conditions when patients report to them very late that the surgeries are carried out urgently. Assessing the quality of life (QOL) and the various sociodemographic factors affecting the QOL paves the way for future rehabilitation programs. Aims and objectives To evaluate the quality of life of subjects with unilateral lower limb amputation among the North Indian population. Materials and methods This cross-sectional study was conducted in the tertiary rehabilitation center. A total of 106 Subjects were recruited. Informed consent was taken. WHOQOL-BREF contains 26 items covering four important aspects of QOL. The WHOQOL-BREF self-administered free questionnaire was used as a data collection tool, and the Hindi version downloaded from the WHO website was also used for those who can't understand English. Results The range of the physical domain, psychological domain, social domain, and environmental domain were 0 and 100. The mean score of different QOL transformed domain scores (on a scale of 100) were 47.91±20.12, 57.37±20.46, 59.36±25.32 and 51.50±21.96, respectively. Trauma was the leading cause of amputation, followed by diabetes mellitus, cancer, peripheral vascular disease, and other causes. Transtibial amputees were more in number compared to transfemoral. The percentage of male and female amputees was 78.30%, and 21.70%, respectively. Conclusion The physical domain was the most affected domain, followed by the psychological, social, and environmental domains. A delay in the prosthesis fitment aggravates the physical burden of amputees. Early prosthesis & psychological counseling will improve the QOL significantly.

Traumatic Bilateral Femoral Fracture And Concurrent Vascular Injury In A 2-Year-Old Child - A Rare Case Report.

Fractures are an ordinary consequence of trauma. Paediatric fractures are rather uncommon because the bony framework is still in its growth phase and therefore compliant to such traumas. The incidence of vascular injuries is also low lying (<1%) in this age group. Nevertheless, management and recovery continue to be a challenge. In this case report, we discuss a 2-year-old child with a traumatic bilateral femoral fracture, a tibial fracture with added vascular injury. Delayed management may give rise to a variety of complications in such a peculiar case. Fortunately, this child is healthy, leading a normal life with no complications.

Emergency groin hernia: outcome after mesh and non-mesh repair.

BACKGROUND: Emergency inguinal and femoral hernia repair can be done by suture or mesh repair, there is still scepticism around using mesh. We aim to evaluate the usage of mesh and the outcome of emergency groin hernia repair after mesh and suture repair. METHODS: Retrospective cohort study of adult patients who underwent emergency inguinal and femoral hernia repair from 1st January 2018 to 31st July 2020. Electronic data and case notes were reviewed and outcome data were collected. RESULTS: Eighty-nine emergency groin hernia repairs were carried out. Sixty-two were males, 60 inguinal hernia and 29 femoral hernia. Median age was 72 years (range 20-95). 74 (83.1%) were primary hernia and 15 (16.9%) recurrent hernias. 67 (75.3%) mesh and 22 (24.7%) suture repairs were carried out. Eleven cases required bowel resection and of those 10 had suture repair. Inguinal hernia was more likely to have mesh repair as compared to femoral (P-value 0.002). Median length of stay was significantly lower in mesh group 2 days (1-5 IQR) versus 7.5 days (5-11 IQR) in suture repair group (P-value <0.0001). Five cases (6.74%) had wound complications (3 wound infections, 2 haematoma). With median 20 months (range 6-36 months) follow-up, 1 recurrence each in both mesh and suture repair groups, no mesh infection and 2 (2.2%) 30-day mortality recorded. Wound infection, recurrence and reoperation were not statistically different in two groups. CONCLUSION: Emergency groin hernia are amenable to mesh repair and in case of bowel resection or gross contamination non- mesh repair is recommended.

Molecular Insights on Selective and Specific Inhibitors of Cyclin Dependent Kinase 9 Enzyme (CDK9) for the Purpose of Cancer Therapy.

Cyclin Dependent Kinase 9 (CDK9), which controls transcriptional elongation, is a promising pharmacological target for a variety of cancerous cells, specifically those characterized by transcriptional dysregulation. CDK9 promotes the pause or release of RNA polymerase II, a rate-limiting stage in normal transcriptional regulation that is often disturbed in cancers. New indications suggest that selective CDK9 antagonism may be beneficial in the treatment of some cancers. CDK9 modulators (inhibitors and degraders) have gained a lot of attention recently, and many molecules are currently in clinical trials. In this review, the CDK9 antagonists under clinical and preclinical trials have been discussed, as well as the structure-activity relationship has been studied, which will help scientists generate more target- specific drug molecules in the future with less toxicity.

AXL kinase inhibitors- A prospective model for medicinal chemistry strategies in anticancer drug discovery.

Deviant expressions of the tyrosine kinase AXL receptor are strongly correlated with a plethora of malignancies. Henceforth, the topic of targeting AXL is beginning to gain prominence due to mounting evidence of the protein's substantial connection to poor prognosis and treatment resistance. This year marked a milestone in clinical testing for AXL as an anti-carcinogenic target, with the start of the first AXL-branded inhibitor study. It is critical to emphasize that AXL is a primary and secondary target in various kinase inhibitors that have been approved or are on the verge of being approved while interpreting the present benefits and future potential effects of AXL suppression in the clinical setting. Several research arenas across the globe resolutely affirm the crucial significance of AXL receptors in the case study of several pathophysiologies including AML, prostate cancer, and breast cancer. This review endeavors to delve deeply into the biological, chemical, and structural features of AXL kinase; primary AXL inhibitors that target the enzyme (either purposefully or unintentionally); and the prospects and barriers for turning AXL inhibitors into a feasible treatment alternative. Furthermore, we analyse the co-crystal structure of AXL, which remains extensively unexplored, as well as the mutations of AXL that may be valuable in the development of novel inhibitors in the upcoming future and take a comprehensive look at the medicinal chemistry of AXL inhibitors of recent years.

Computational modelling strategies in exploring triazolopyridazine PIM1 kinase inhibitors as anticancer agents.

BACKGROUND: PIM (Proviral Integration site for Moloney Murine Leukemia virus) kinases are members of the class of kinase family serine/ threonine kinases, which play a crucial role in cancer development. As there is no drug in the market against PIM-1, kinase has transpired as a budding and captivating target for discovering new anticancer agents targeting PIM-1 kinase. AIM: The current research pondered the development of new PIM-1 kinase inhibitors by applying a ligand-based and structure-based drug discovery approach involving 3D QSAR, molecular docking, and dynamics simulation. METHOD: In this study, association allying the structural properties and biological activity was undertaken using 3D-QSAR analysis. The 3D-QSAR model was generated with the help of 35 compounds from which the best model manifested an appreciated cross-validation coefficient (q2) of 0.8866 and conventional correlation coefficient (r2) of 0.9298, respectively and predicted correlation coefficient (r2 pred) was obtained as 0.7878. RESULT: The molecular docking analysis demonstrated that the analogs under analysis occupied the active site of PIM-1 kinase receptor and interactions with Lys67 in the catalytic region, Asp186 in the DFG motif, and Glu171 were noticed with numerous compounds. DISCUSSION: Furthermore, the molecular dynamics simulation study stated that the ligand portrayed the strong conformational stability within the active site of PIM-1 kinase protein, forming of two hydrogen bonds until 100 ns, respectively. CONCLUSION: Overall outcomes of the study revealed that applications of the ligand-based drug discovery approach and structure-based drug discovery strategy conceivably applied to discovering new PIM-1 kinase inhibitors as anticancer agents.

Gender-based effect of absence of gut microbiota on the protective efficacy of Bifidobacterium longum-fermented rice bran diet against inflammation-associated colon tumorigenesis.

Dietary rice bran (RB) has shown capacity to influence metabolism by modulation of gut microbiota in individuals at risk for colorectal cancer (CRC), which warranted attention for delineating mechanisms for bidirectional influences and cross-feeding between the host and RB-modified gut microbiota to reduce CRC. Accordingly, in the present study, fermented rice bran (FRB, fermented with a RB responsive microbe Bifidobacterium longum), and non-fermented RB were fed as 10% w/w (diet) to gut microbiota-intactspf or germ-free micegf to investigate comparative efficacy against inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC. Results indicated both microbiota-dependent and independent mechanisms for RB meditated protective efficacy against CRC that was associated with reduced neoplastic lesion size and local-mucosal/systemic inflammation, and restoration of colonic epithelial integrity. Enrichment of beneficial commensals (such as, Clostridiales, Blautia, Roseburia), phenolic metabolites (benzoate and catechol metabolism), and dietary components (ferulic acid-4 sulfate, trigonelline, and salicylate) were correlated with anti-CRC efficacy. Germ-free studies revealed gender-specific physiological variables could differentially impact CRC growth and progression. In the germ-free females, the RB dietary treatment showed a ∼72% reduction in the incidence of colonic epithelial erosion when compared to the ∼40% reduction in FRB-fed micegf . Ex vivo fermentation of RB did not parallel the localized-protective benefits of gut microbial metabolism by RB in damaged colonic tissues. Findings from this study suggest potential needs for safety considerations of fermented fiber rich foods as dietary strategies against severe inflammation-associated colon tumorigenesis (particularly with severe damage to the colonic epithelium).

Traversing through half a century research timeline on Ginkgo biloba, in transforming a botanical rarity into an active functional food ingredient.

Neurodegenerative diseases and various other chronic ailments have gradually transformed into public-health issues. Neurodegenerative disorders are a range of progressive neural abnormalities characterized by cellular dysfunctions, neuronal structure, and function loss. Among many chronic disorders, oxidative stress, inflammation, mitochondrial dysregulation, and cellular alterations in the human body are considered the most prevalent diagnostic symptoms. They have a profound impact on patients' health and wellbeing. The disease's poor curability, high healthcare costs, and lethality are the principal reasons for approaching and exploring the conventional treatment's phytotherapeutic alternatives. Ginkgo biloba (Maidenhair tree) is a well-known and widely used herbal plant in the Ginkgoaceae family. Its phytochemical constituents, Flavonoids, and terpenes, have been identified as the primary ingredients of Ginkgo biloba leaf extracts. It has been widely used due to its therapeutic properties, including its neuroprotective, anti-dementia, antioxidant, anti-inflammatory, vasoactive, anti-psychotic, anti-neoplastic, and anti-platelet activity. In recent decades, plenty of Ginkgo-derived substances has been researched and elucidated to have significant therapeutic effects in numerous disease models. This review aims to provide a thorough understanding of the botanical basis for Ginkgo biloba, its usage as herbal medicine, and its pivotal role in functional foods. Additionally, the clinical significance of Ginkgo biloba, as observed in various research works and clinical investigations, is also emphasized, facilitating a better understanding of their molecular basis and application in many chronic diseases.

Transcriptome and metabolome changes induced by bitter melon (Momordica charantia)- intake in a high-fat diet induced obesity model.

Background and aim: Metabolic syndrome (MetS) is a complex disease of physiological imbalances interrelated to abnormal metabolic conditions, such as abdominal obesity, type II diabetes, dyslipidemia and hypertension. In the present pilot study, we investigated the nutraceutical bitter melon (Momordica charantia L) -intake induced transcriptome and metabolome changes and the converging metabolic signaling networks underpinning its inhibitory effects against MetS-associated risk factors. Experimental procedure: Metabolic effects of lyophilized bitter melon juice (BMJ) extract (oral gavage 200 mg/kg/body weight-daily for 40 days) intake were evaluated in diet-induced obese C57BL/6J male mice [fed-high fat diet (HFD), 60 kcal% fat]. Changes in a) serum levels of biochemical parameters, b) gene expression in the hepatic transcriptome (microarray analysis using Affymetrix Mouse Exon 1.0 ST arrays), and c) metabolite abundance levels in lipid-phase plasma [liquid chromatography mass spectrometry (LC-MS)-based metabolomics] after BMJ intervention were assessed. Results and conclusion: BMJ-mediated changes showed a positive trend towards enhanced glucose homeostasis, vitamin D metabolism and suppression of glycerophospholipid metabolism. In the liver, nuclear peroxisome proliferator-activated receptor (PPAR) and circadian rhythm signaling, as well as bile acid biosynthesis and glycogen metabolism targets were modulated by BMJ (p < 0.05). Thus, our in-depth transcriptomics and metabolomics analysis suggests that BMJ-intake lowers susceptibility to the onset of high-fat diet associated MetS risk factors partly through modulation of PPAR signaling and its downstream targets in circadian rhythm processes to prevent excessive lipogenesis, maintain glucose homeostasis and modify immune responses signaling.