Green Seaweed Caulerpa racemosa as a Novel Non-Small Cell Lung Cancer Inhibitor in Overcoming Tyrosine Kinase Inhibitor Resistance: An Analysis Employing Network Pharmacology, Molecular Docking, and In Vitro Research.

The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is Caulerpa racemosa, a type of green algae known as green seaweed, seagrapes, or green caviar. This organism stands out because it has great promise for use in medicine, especially in the study of cancer. Through the utilization of computational modeling (in silico) and cellular laboratory experiments (in vitro), the chemical components included in the green seaweed C. racemosa were effectively analyzed, uncovering its capability to treat non-small cell lung cancer (NSCLC). The study specifically emphasized blocking SRC, STAT3, PIK3CA, MAPK1, EGFR, and JAK1 using molecular docking and in vitro. These proteins play a crucial role in the EGFR Tyrosine Kinase Inhibitor Resistance pathway in NSCLC. The chemical Caulersin (C2) included in C. racemosa extract (CRE) has been identified as a potent and effective agent in fighting against non-small cell lung cancer (NSCLC), both in silico and in vitro. CRE and C2 showed a level of inhibition similar to that of osimertinib (positive control/NSCLC drug).

Novel Functional Food Properties of Forest Onion (Eleutherine bulbosa Merr.) Phytochemicals for Treating Metabolic Syndrome: New Insights from a Combined Computational and In Vitro Approach.

Metabolic syndrome is a global health problem. The use of functional foods as dietary components has been increasing. One food of interest is forest onion extract (FOE). This study aimed to investigate the effect of FOE on lipid and glucose metabolism in silico and in vitro using the 3T3-L1 mouse cell line. This was a comprehensive study that used a multi-modal computational network pharmacology analysis and molecular docking in silico and 3T3-L1 mouse cells in vitro. The phytochemical components of FOE were analyzed using untargeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Next, an in silico analysis was performed to determine FOE's bioactive compounds, and a toxicity analysis, protein target identification, network pharmacology, and molecular docking were carried out. FOE's effect on pancreatic lipase, α-glucosidase, and α-amylase inhibition was determined. Finally, we determined its effect on lipid accumulation and MAPK8, PPARG, HMGCR, CPT-1, and GLP1 expression in the preadipocyte 3T3-L1 mouse cell line. We showed that the potential metabolites targeted glucose and lipid metabolism in silico and that FOE inhibited pancreatic lipase levels, α-glucosidase, and α-amylase in vitro. Furthermore, FOE significantly (p < 0.05) inhibits targeted protein expressions of MAPK8, PPARG, HMGCR, CPT-1, and GLP-1 in vitro in 3T3-L1 mouse cells in a dose-dependent manner. FOE contains several metabolites that reduce pancreatic lipase levels, α-glucosidase, α-amylase, and targeted proteins associated with lipid and glucose metabolism in vitro.

Revealing Novel Source of Breast Cancer Inhibitors from Seagrass Enhalus acoroides: In Silico and In Vitro Studies.

Enhalus arcoides is a highly beneficial type of seagrass. Prior studies have presented proof of the bioactivity of E. acoroides, suggesting its potential to combat cancer. Therefore, this study aims to delve deeper into E. acoroides bioactive molecule profiles and their direct biological anticancer activities potentials through the combination of in-silico and in-vitro studies. This study conducted metabolite profile analysis on E. acoroides utilizing HPLC-ESI-HRMS/MS analysis. Two extraction techniques, ethanol and hexane, were employed for the extraction process. Furthermore, the in-silico study was conducted using molecular docking simulations on the HER2, EGFR tyrosine kinase and HIF-1α protein receptor. Afterward, the antioxidant activity of E. acoroides metabolites was examined to ABTS, and the antiproliferative activity was tested using an MTT assay. An in-silico study revealed its ability to combat breast cancer by inhibiting the HER2/EGFR/HIF-1α pathway through molecular docking. In addition, the MTT assay demonstrated that higher dosages of metabolites from E. acoroides increased the effectiveness of toxicity against cancer cell lines. Additionally, the study demonstrated that the metabolites possess the ability to function as potent antioxidants, effectively inhibiting a series of carcinogenic mechanisms. Ultimately, this study showed a new approach to unveiling the E. acoroides metabolites' anticancer activity through inhibiting HER2/EGFR/HIF-1α receptors, with great cytotoxicity and a potent antioxidant property to prevent a carcinogenic cascade.

Modification of the height of a weight drop traumatic brain injury model that causes the formation of glial scar and cognitive impairment in rats.

OBJECTIVE: Traumatic brain injury (TBI) is a chronic, progressive condition associated with permanent disabilities, particularly cognitive impairments. Glial scar formation following TBI is considered a contributing factor to these persistent disabilities. Currently, limited research exists on pharmacological interventions targeting glial scar prevention that require a standard weight drop TBI model for glial scar formation. Since there is no established standard TBI model for glial scar formation, this study aims to validate and modify the height of the weight drop model to identify glial scar formation and cognitive impairments. METHODS: Fifteen male Sprague Dawley rats were randomly divided into sham, WD1, and WD2 groups. The weight drop model with a 10 g load was applied to the right exposed brain of the rats from a height of 5 cm (WD1) and 10 cm (WD2) using a modified Feeney's weight drop device. Cognitive impairments were confirmed using the novel object recognition (NOR) test with ethovision software on day 15. Subsequently, the rats were decapitated on day 16, and GFAP immunohistochemical staining was performed to confirm the presence of glial scarring. RESULTS: The WD1 and WD2 groups exhibited a significant increase in glial scar formation compared to the sham group, with the WD2 group resulting in even more pronounced glial scar formation. Only the WD2 model caused statistically significant cognitive damage. The negative correlation coefficient indicates that an increase in GFAP + cells will decrease the cognitive function. CONCLUSION: Modification of the height of the weight drop model, by dropping a weight of 10 g from a height of 10 cm (WD2 group) onto the right brain exposed of the rat has been proven to induce the formation of a glial scar and cognitive impairment.

TGF-ß1 Effects on Total Collagen of the New Zealand Rabbit's Urethral Wall (Oryctolagus cuniculus) in Animal Models of Urethral Stricture.

Background: Currently, animal models of urethral stricture are not standardized. Transforming Growth Factor Beta 1 (TGF-ß1) regulates extracellular matrix deposition in homeostatic and pathological responses. Objective: The aim of this study was to present the potential model to be developed as a urethral stricture. Methods: True experimental laboratory research was conducted by using Male New Zealand rabbits (Oryctolagus cuniculus), which were divided into 5 groups; control, placebo, and 3 treatment groups (TGF-ß1 injection of 1 µg, 2 µg, 4 µg). Urethrography, histopathological analysis, and evaluation of total collagen formation of the urethral wall were performed after 6 weeks. Results: An increase in the dose of TGF-ß1 decreased the mean rabbit's urethral lumen diameter (29.3% in the 2µg group and 34% in the 4µg group) compared to controls. Three rabbits decreased as much as ≤ 50% in urethral lumen diameter. Significant increases in total collagen density in the periluminal and peripheral urethral spongiosum were noted by increasing doses of TGF-ß1. The percentage of urethral lumen diameter has a strong negative correlation with periluminal total collagen density (r = -0,798; p = 0,000) and very strong negative correlation with peripheral spongiosa total collagen density (r = -0,748, p = 0,000). Conclusion: TGF-ß1 plays a role in changing total collagen compositions of the rabbit's urethral wall, decreasing the urethral lumen diameter. Further research with increasing doses of TGF-ß1 is needed to determine the effective dose of TGF-ß1 in inducing urethral stricture.

Revealing Edible Bird Nest as Novel Functional Foods in Combating Metabolic Syndrome: Comprehensive In Silico, In Vitro, and In Vivo Studies.

Metabolic dysfunction, which includes intra-abdominal adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hypertension, manifests into metabolic syndrome and related diseases. Therefore, the discovery of new therapies in the fight against metabolic syndrome is very challenging. This study aims to reveal the existence of an edible bird nest (EBN) as a functional food candidate that may be a new alternative in fighting metabolic syndrome. The study included three approaches: in silico molecular docking simulation, in vitro, and in vivo in rats fed on cholesterol- and fat-enriched diets. Four terpenoids of Bakuchiol, Curculigosaponin A, Dehydrolindestrenolide, and 1-methyl-3-(1-methyl-ethyl)-benzene in EBN have been identified through LCMS/MS-QTOF. In molecular docking simulations, Bakuchiol and Dehydrolindestrenolide are considered very potent because they have higher inhibitory power on the four receptors (iNOS, ROS1 kinase, FTO, and lipase) than standard drugs. In vitro tests also provide insight into the antioxidant, antidiabetic, and antiobesity activities of EBN, which is quite feasible due to the smaller EC50 value of EBN compared to standard drugs. Interestingly, in vivo studies also showed significant improvements (p < 0.05) in the lipid profile, blood glucose, enzymatic levels, and inflammatory biomarkers in rats given high-dose dietary supplementation of EBN. More interestingly, high-dose dietary supplementation of EBN upregulates PGC-1α and downregulates HMG-CoA reductase. Comprehensively, it has been revealed that EBN can be novel functional foods for combating metabolic syndrome.

The Evolution of Polyclonal Antibody from Specific Epitope 47kDA for Detection of Bladder Cancer.

OBJECTIVE: This study will identify specific epitopes from the 47kDa protein as the basis for making polyclonal antibodies to increasing sensitivity and specificity of 47kDa protein as bladder cancer biomarkers. METHOD: The 47kDa protein epitope prediction was carried out using the in-silico method. The epitope with the highest and the lowest value was immunized to the mice for four weeks and was harvested at the fifth weeks. The antibody was tested with the patient's urine using western blotting. Total of  186 participants including in this study. For the first stage (antibody confirmation test)  test we have 18 participants, for the second stage (1st antibody diagnosis test) we have 72 participants and for the third stage (2nd antibody diagnosis test) we have 96 participants,  consist of total 64 BC patients 48 of healthy individuals and 74 participants with the other diseases. RESULTS: Some epitopes from the sequenced protein are candidates for immunization, in the chain 108'-136' (with lowest Bepipred score: 0.53) named as peptide1 and chain 42'-56' (with highest bepipred score: 0.58) named as peptide2. In western blotting test, both antibodies showed detection at 47kDa. When examined with western blot using urine from BC patients, urine from other cancer patients (prostate, kidney, ureter, rectal, breast), and healthy persons, both antibodies were found to only express 47kDa in urine from BC patients. The diagnostic tests showed high sensitivity (91.67%) and specificity (94.44%) inAb2 in predicting bladder cancer. CONCLUSSION: The evolution of the polyclonal antibody made from specific epitopes is proven to express specifically on bladder cancer patients and have high sensitivity and specificity to diagnose bladder cancer.

Deciphering the Role of TGF-ß1 in Altering Collagen I and Collagen III in the New Zealand Rabbit's (Oryctolagus cuniculus) Urethral Wall in Urethral Stricture Development.

Background: Presently, there's a lack of standardization in animal models used for studying urethral stricture. Transforming Growth Factor Beta 1 (TGF-ß1) is known to regulate the deposition of extracellular matrix in both normal and pathological conditions. This factor holds promise as a potential model for simulating urethral stricture. Objective: This study aims to investigate the impact of Transforming Growth Factor Beta 1 (TGF-ß1) on Collagen I and Collagen III within the urethral wall of New Zealand Rabbits (Oryctolagus cuniculus) in the context of developing urethral stricture in animal models. Methods: We conducted genuine laboratory experiments using Male New Zealand rabbits (Oryctolagus cuniculus), which were categorized into five groups: control, placebo, and three treatment groups (TGF-ß1 injections of 1 µg, 2 µg, 4 µg). After a duration of 6 weeks, we conducted urethrography, histopathological analysis, and assessed the formation of collagen I and collagen III within the urethral wall. Results: Elevating the dosage of TGF-ß1 led to a reduction in the average urethral lumen diameter of rabbits (29.3% in the 2µg group and 34% in the 4µg group) compared to the control group. In fact, three rabbits experienced a decrease of ≤ 50% in their urethral lumen diameter. As the doses of TGF-ß1 increased, we observed significant increases in the density of collagen I, and collagen III in both the periluminal and peripheral regions of the urethral spongiosum. Additionally, there was a tendency for the collagen I/collagen III ratio to decrease in the periluminal region, with collagen III density surpassing that of collagen I. In the peripheral spongiosa area, notable mean differences were observed between the control group, 1T, and 2T groups, with collagen I density tending to be higher than that of collagen III. Furthermore, the percentage of urethral lumen diameter exhibited a robust negative correlation with periluminal collagen I density (r = -0.672, p = 0.001), peripheral spongiosa collagen I density (r = -0.603, p = 0.005), periluminal collagen III density (r = -0.717, p = 0.001), and an exceptionally strong negative correlation with collagen III density of peripheral spongiosa (r = -0.804, p = 0.000). Conclusion: TGF-ß1 exerts an influence on altering the composition of collagen I and collagen III within the urethral wall of rabbits, leading to a reduction in the diameter of the urethral lumen. Further research is warranted to determine the optimal dose of TGF-ß1 required to induce urethral stricture effectively.

Caulerpa racemosa extract inhibits HeLa cancer cells migration by altering expression of epithelial-mesenchymal transition proteins.

Introduction: Cervical cancer is caused by persistent infections of human papillomavirus types 16 and 18. Also, it is classified as a malignancy since it is able to spread itself to other sites and form a metastasis. Lymph nodes metastasis is an important factor related to cervical cancer survival. The previous study reported that Caulerpa racemosa has an anti-cancer effect by inducing apoptosis by inhibiting p53 protein degradation in HeLa cancer cells. In this study, we conducted a follow-up test to determine the anticancer effect of Caulerpa racemosa as an antimetastatic agent on HeLa cancer cells. Methods: A true experimental study with a post-test-controlled group design was carried out on four groups of HeLa cell cultures by presenting different concentrations of Caulerpa racemosa extract. Moreover, to identify the antimetastatic effect, HeLa cells treated with Caulerpa racemosa extract were subjected to the woud healing scratch test and immunofluorescence staining assays. Data analysis was gained with qualitative and quantitative approaches. Quantitative methods such as One-way analysis of variance, Tukey's multiple comparison test, and Pearson's correlation were conducted. Result: We found that Caulerpa racemosa significantly inhibit HeLa cells wound healing migration. We also demonstrated the effect of Caulerpa racemosa in downregulating Snail and Vimentin protein expression and upregulating E-Cadherin protein expression. Conclusion: Caulerpa racemosa extract inhibits HeLa cancer cells migration by altering important regulator proteins expressions of epithelial-mesenchymal transition pathways.

Bioactive peptides identification and nutritional status ameliorating properties on malnourished rats of combined eel and soy-based tempe flour.

Background and aims: A combined eel and soy-based tempe (CEST) flour is rich in nutrients, especially its high amino acid content in which bioactive peptides (BPs) are expected to be found. Hence, this research aimed to identify the BPs of CEST flour and CEST supplementation's effect on improving nutritional status biomarkers by ameliorating serum protein, hemoglobin, and IGF-1 of malnourished rats. Methods: CEST flour with a ratio of eel and soy-based tempe of 1:3.5 was produced by applying the oven drying method. Amino acid sequences from six BPs were analyzed using a protein sequencer and spectrometer-electrospray ionization (MS-ESI). A total of thirty malnourished male Rattus norvegicus aged 3-4 weeks were given low-protein (LP; 4% w/w protein) diet treatment for 4 weeks. Afterward, rats were divided into 3 groups of 10 rats. Group A and B remained on a low-protein diet for 4 weeks, receiving an LP diet and getting doses of CEST of 100 and 200 mg/kg BW, respectively, via oral. Group C or control was given a Normal-protein (NP) diet (23% w/w of protein) and was allowed to feed ad libitum during the trial period without a dose of CEST. Results: Six bioactive peptides were found, with WMGPY being the most abundant, along with a DPPH radical scavenging activity of 5.0 mg/mL. The results showed that serum protein, hemoglobin, and IGF-1 of group B were significantly higher compared to groups A and C (p = 0.0021). CEST dose of 200 mg/kg BW was more effective to increase serum levels of protein (p = 0.0052), hemoglobin, and IGF-1 (p < 0.0001) compared to a 100 mg/kg BW dose. Conclusion: This indicates that the CEST flour has six bioactive peptides, which may contribute to the improvement of nutritional status biomarkers. To establish its potential impact, a human clinical study is urgently needed.

Anti-cancer properties of Caulerpa racemosa by altering expression of Bcl-2, BAX, cleaved caspase 3 and apoptosis in HeLa cancer cell culture.

The main cause of cervical cancer is infection with Human Papilloma Virus (HPV). Loss of apoptotic control allows cancer cells to survive longer and allows time for mutation accumulation thereby increasing the ability to invade during tumor development. Treatment options for cervical cancer today are surgery, radiotherapy, and chemotherapy. Toxicity to normal cells, adverse side effects, and drug resistance are the main barriers to the use of chemotherapy. Among marine organisms such as bacteria, fungi, actinobacteria, and seaweed have been used for the treatment of cancer. Caulerpa has bioactive metabolites, namely alkaloids, terpenoids, flavonoids, steroids and tannins and its bioactivity has been reported against many diseases including cancer. This study aimed to evaluate the anticancer activity of C. racemosa on HeLa cervical cancer cells. The study used a true experimental post-test only control group design to determine the effect of C. racemosa extract on HeLa cancer cells. C. racemosa extract was given in doses of 50 µg/mL, 100 µg/mL, 200 µg/mL, and 0 µg/mL as controls. Quantitative measurement of apoptosis was measured using flowcytometry and the expression of Bcl-2, BAX, and cleaved-caspase 3 as pro and anti-apoptotic proteins was measured using immunofluorescence. Trypan blue exclusion test was performed to measure cell viability. C. racemosa extract significantly increased the expression of pro-apoptotic proteins BAX and cleaved caspase-3 compared to controls. Annexin V-PI analysis showed the induction of apoptosis in treated cells and decreased HeLa cell viability at 24 hours and 48 hours post-treatment (p-value <0.05). C. racemosa extract has potential as an anti-cancer with pro-apoptotic and anti-proliferative activity on HeLa cancer cells and can be explored further as a cervical cancer therapy.

Amelioration of obesity-related metabolic disorders via supplementation of Caulerpa lentillifera in rats fed with a high-fat and high-cholesterol diet.

Dietary modification, including functional foods, could reduce comorbidities due to obesity. An increase in serum glucose and lipids is often seen in obesity. Furthermore, obesity is also characterized by a decrease in antioxidant capacity (i.e., decrease in superoxide dismutase/SOD) and downregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). It has been well established that PGC-1α is important to regulate mitochondrial biogenesis. Sea grapes (Caulerpa lentillifera) are known as a traditional food in many Asia-Pacific countries. Recent evidence suggests that sea grapes have many beneficial properties as functional foods and may have potential therapeutic functions. We investigated the effect of sea grapes (C. lentillifera) on serum glucose, lipids, PGC-1α, and protein levels of SOD in the liver of Rattus norvegicus, which is induced with a high-fat and high-cholesterol diet. A total of four groups were made, each containing ten male Rattus norvegicus; group A received a standard dry pellet diet as control, group B received cholesterol- and fat-enriched diets (CFED), groups C and D received CFED and 150 and 450 mg/kg body weight (BW) of sea grape extract, respectively, for 4 weeks. Serum glucose and cholesterol were assessed using a blood auto-analyzer. Serum PGC-1α was measured using ELISA. SOD levels were calculated using the superoxide dismutase assay kit by Sigma-Aldrich with blood taken from liver tissue. In this study, sea grape extracts improved total cholesterol levels better than the CFED and normal groups. The efficacy of total cholesterol improvement was similar between the two doses of sea grape extract. Furthermore, sea grape extract increased PCG-1α levels, especially with the dose of 150 mg/kg BW. Blood glucose was also lower in the groups of sea grape extract. Interestingly, the groups treated with sea grapes extract exhibited higher levels of liver SOD compared to the normal and CFED groups. To conclude, sea grapes (C. lentillifera) have promising potential for anti-hyperglycemia and anti-hypercholesterolemia, and for reducing oxidative stress, and providing various health benefits for metabolic disorders.

Modulation of gut microbiota and markers of metabolic syndrome in mice on cholesterol and fat enriched diet by butterfly pea flower kombucha.

Clitoria ternatea, with an alternative name, Butterfly pea, is increasingly being explored for medical purposes and the development of a wide range of processed products. This study aimed to incorporate Butterfly pea into an innovative probiotic drink through a symbiotic culture of bacteria and yeast (SCOBY) fermentation and to evaluate the biological activity. The benefits of the drink, referred to as butterfly pea flower kombucha (KBPF) was determined in vitro and in metabolically disorder mice that receive a diet rich in cholesterol and fat (CFED). Forty white male were categorized into four groups, i.e., A = Control/Normal Diet; B = CFED alone; C = CFED + KBPF 65 mg/kg BW (Body Weight); D = CFED + KBPF 130 mg/kg BW, and then sacrificed after 6 weeks of intervention. Seventy-nine secondary metabolite compounds were successfully identified in KBPF using LC-HRMS. In vitro studies showed the potential activity of KBPF in inhibiting not only ABTS, but also lipid (lipase) and carbohydrate (α-amylase, α-glucosidase) hydrolyzing enzymes to levels similar to acarbose control at 50-250 µg/mL. In the in vivo study, the administration of KBPF (130 mg/kg BW) significantly alleviated metabolic disorders caused by high-fat diet. Specifically, lipid profile (HDL, LDL, TC, TG), blood glucose, markers of oxidative stress (SOD liver), metabolic enzymes (lipase, amylase), and markers of inflammation (PGC-1α, TNF-α, and IL-10) were in most cases restored to normal values. Additionally, the gut microbiota community analysis showed that KBPF has a positive effect (p = 0.01) on both the Bacteroidetes phylum and the Firmicutes phylum. The new KBPF drink is a promising therapeutic functional food for preventing metabolic diseases.

Metabolomic Assay, Computational Screening, and Pharmacological Evaluation of Caulerpa racemosa as an Anti-obesity With Anti-aging by Altering Lipid Profile and Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-α Levels.

Obesity is associated with an accelerated aging process, which prevents healthy aging. Both obesity and aging were manifested in the peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α) level. These studies fulfill the scientific gap in assembled pharmacological activity assay of Caulerpa racemosa done in a previous preclinical trial. Six major compounds from sea grape (C. racemosa) extract were evaluated using an in silico approach against human pancreatic lipase, a-glucosidase, and a-amylase to predict prospective anti-obesity candidates. The lipase inhibitory activity of the extract reached 90.30 ± 0.40%, 1.75% lower than orlistat. The a-amylase inhibitory assay of the extract was 84.07 ± 5.28%, while the inhibitory activity against a-glucosidase was 81.67 ± 1.54%; both were lower than acarbose. We observe the effect of C. racemosa extract as anti-obesity with anti-aging by evaluating the obesity parameters in the human body for a 4-week period. There was a significant decrease in blood glucose, total cholesterol, low-density lipoprotein (LDL), triglycerides (TG), waist circumference, waist-hip ratio, and body weight (p < 0.05); PGC-1α and high-density lipoprotein (HDL) increased significantly (p = 0.000), in Group B when compared with Group A. Our study revealed that sea grape extract is a potent anti-obesity with an anti-aging reagent that does not produce any significant adverse effects.

Anti-aging potential of cookies from sea grapes in mice fed on cholesterol- and fat-enriched diet: in vitro with in vivo study.

This study determines the effect of cookies made from sea grapes (Caulerpa racemosa) on PGC-1α, total cholesterol, and blood glucose levels on mice fed with a Cholesterol- and Fat-Enriched Diet (CFED). The antioxidant activity, tyrosinase inhibition, α-glucosidase, and α-amylase inhibition is also analyzed in order to assess the in vitro anti-aging potential of sea grapes cookies. Forty male Mus muscullus albino mice weighing 20 g-30 g were used and randomly distributed into four groups of ten animals each. Group A served as a normal control (given a standard dry pellet diet), Group B was given CFED only, and mice in Groups C and D were given CFED with 100 mg and 200 mg/20 g body weight of sea grapes cookies, respectively for 4 weeks. In vitro study shows that the percentage of inhibition activity of antioxidant, L-Tyrosine, L-Dopa, α-glucosidase, and α-amylase inhibition were 45.65 ± 1.50, 8.95 ± 0.06, 21.31 ± 0.98, 77.12 ± 4.67 and 70.94 ± 0.98, respectively. This study found that group D had better activity in lowering blood glucose than group C (p < 0.0001). In addition, although there was not found significant difference between groups C and D in blood cholesterol reduction and PGC-1α (p = 0.1482), both groups experienced the same effect in total cholesterol reduction and PGC-1α in mice (significantly, p < 0001). Thus, we conclude that sea grapes cookies are proven to improve PGC-1α, total cholesterol, and blood glucose levels in mice fed with CFED. Hence, sea grapes cookies is a potential anti-aging novel-functional food.

Kombucha drink enriched with sea grapes (Caulerpa racemosa) as potential functional beverage to contrast obesity: An in vivo and in vitro approach.

BACKGROUND AND AIMS: Obesity is currently a global issue and is a major cause of the metabolic disorder, including dyslipidemia. However, currently approved treatments have various limitations including serious side effects, numerous contraindications, and lack of acceptance. Caulerpa racemosa, also referred as Sea grapes, is a seaweed known for its various benefits. C. racemosa extract has the potential to improve lipid profile and role as an anti-obese agent. In order to maximize its health benefits, C. racemosa was made using kombucha drink as a carrier medium. This study aims to assess the effect of Sea grapes kombucha drink on lipase activity in vitro and lipid profile in vivo. METHODS: A lipase inhibition test was carried out by incubating Sea grapes kombucha drink compared with orlistat as the control in porcine pancreatic lipase and p-nitrophenyl butyrate in reaction buffer. A total of four groups were made, each containing 10 male swiss webster albino mice; group A received standard dry pellet diet as control, group B received cholesterol and fat-enriched diets (CFED), group C and D received CFED and 150 and 300 mg/kgBW of kombucha drink from Sea grapes respectively for 4 weeks. RESULTS: Sea grapes kombucha drink improved lipid profiles in the way of reducing total cholesterol, triglyceride, LDL, and increasing HDL levels compared to CFED and normal groups. The effect was more robust following the incrementing dose of the Sea grapes excluding total cholesterol. The lipase inhibitory activity of Sea grapes kombucha drink was similar to orlistat at a dose of 250 µg/mL, otherwise, orlistat was superior in the lower doses. CONCLUSIONS: Sea grapes kombucha drink treatment also induced weight loss and increased level of liver SOD. Kombucha drink from C. racemosa has good potential as a functional beverage with anti-obese and lipid improving activity.

Oncogenic isoform switch of tumor suppressor BCL11B in adult T-cell leukemia/lymphoma.

B-Cell leukemia/lymphoma 11B (BCL11B) is a transcription factor important for T-cell development and acts as a tumor suppressor gene in T-cell acute lymphoblastic leukemia. Here, we identified BCL11B as a candidate leukemia-associated gene in human T-cell leukemia virus type 1 (HTLV-1)-induced adult T-cell leukemia/lymphoma (ATLL). Interestingly, the short form lacking exon 3 (BCL11B/S) protein was more highly expressed than the full-length BCL11B (BCL11B/L) in leukemic cells from most of the ATLL patients, although expression ratios of BCL11B/L to BCL11B/S were almost equal in control CD4+ T cells. BCL11B/S and BCL11B/L exhibited distinct subcellular localization and differential effects on cellular growth; BCL11B/L expression exhibited nuclear localization and inhibited cell growth in ATLL cells, whereas BCL11B/S exhibited nucleocytoplasmic distribution and accelerated cell growth. Furthermore, BCL11B/S expression accelerated the development of T-cell leukemia/lymphomas in transgenic mice carrying HTLV-1/HBZ, a critical viral factor in leukemogenesis, whereas these phenotypes did not occur in the double transgenic mice carrying BCL11B/L and HTLV-1/HBZ. In HTLV-1-infected T-cell lines, BCL11B expression is downregulated by HTLV-1/Tax, a viral factor necessary at the early stage of leukemogenesis. These results suggest that downregulation of BCL11B/L expression and upregulation of BCL11B/S may contribute to the development and progression of ATLL.

Kombucha tea from seagrapes (Caulerpa racemosa) potential as a functional anti-ageing food: in vitro and in vivo study.

This study wants to investigate the effects of kombucha tea based on seagrapes on blood glucose levels, total cholesterol, and PGC-1α in Swiss albino mice that were given cholesterol- and fat-enriched diets (CFED). Anti-glycation, tyrosinase inhibitory, and α-glucosidase inhibitory activity were also determined. Forty male swiss webster albino mice weighing between 20 g-30 g were used for this study. Animals were distributed in random into 4 groups of 10 animals each; group A served as normal control (received standard dry pellet diet), group B were fed on CFED for 4 weeks, and groups C and D were fed on CFED and were administered 150 and 300 mg/kg of kombucha tea from seagrapes (Caulerpa racemosa) (p.o.). In vitro study show that the activity of anti-glycation, L-Tyrosine, L-Dopa, α-glucosidase, and α-amylase inhibition were 62.79 ± 0.78, 9.05 ± 0.16, 27.14 ± 1.62, 90.42 ± 0.77, and 80.44 ± 1.00, respectively. Group C has a better activity in increasing PGC-1-alpha serum in mice than group D (p < 0.05). There were no meaningful differences between group C and D in blood cholesterol and blood glucose reduction (p = 0.222), both groups have the same effect in lowering total cholesterol and blood glucose in mice. In conclusion, kombucha tea from seagrapes has potential as an anti-ageing functional food.