Unraveling diabetes complexity through natural products, miRNAs modulation, and future paradigms in precision medicine and global health.

BACKGROUND AND AIMS: The challenge posed by diabetes necessitates a paradigm shift from conventional diagnostic approaches focusing on glucose and lipid levels to the transformative realm of precision medicine. This approach, leveraging advancements in genomics and proteomics, acknowledges the individualistic genetic variations, dietary preferences, and environmental exposures in diabetes management. The study comprehensively analyzes the evolving diabetes landscape, emphasizing the pivotal role of genomics, proteomics, microRNAs (miRNAs), metabolomics, and bioinformatics. RESULTS: Precision medicine revolutionizes diabetes research and treatment by diverging from traditional diagnostic methods, recognizing the heterogeneous nature of the condition. MiRNAs, crucial post-transcriptional gene regulators, emerge as promising therapeutic targets, influencing key facets such as insulin signaling and glucose homeostasis. Metabolomics, an integral component of omics sciences, contributes significantly to diabetes research, elucidating metabolic disruptions, and offering potential biomarkers for early diagnosis and personalized therapies. Bioinformatics unveils dynamic connections between natural substances, miRNAs, and cellular pathways, aiding in the exploration of the intricate molecular terrain in diabetes. The study underscores the imperative for experimental validation in natural product-based diabetes therapy, emphasizing the need for in vitro and in vivo studies leading to clinical trials for assessing effectiveness, safety, and tolerability in real-world applications. Global cooperation and ethical considerations play a pivotal role in addressing diabetes challenges worldwide, necessitating a multifaceted approach that integrates traditional knowledge, cultural competence, and environmental awareness. CONCLUSIONS: The key components of diabetes treatment, including precision medicine, metabolomics, bioinformatics, and experimental validation, converge in future strategies, embodying a holistic paradigm for diabetes care anchored in cutting-edge research and global healthcare accessibility.

Revealing the mechanism and efficacy of natural products on treating the asthma: Current insights from traditional medicine to modern drug discovery.

Asthma remains a significant global health challenge, demanding innovative approaches to treatment. Traditional medicine has a rich history of using natural products to alleviate asthmatic symptoms. However, transitioning from these traditional remedies to modern drug discovery approaches has provided fresh insights into the mechanisms and effectiveness of these natural products. This study provides our comprehensive review, which examines the current state of knowledge in the treatment of asthma. It delves into the mechanisms through which natural products ameliorate asthma symptoms, and it discusses their potential in the development of novel therapeutic interventions. Our analysis reveals that natural products, traditionally employed for asthma relief, exhibit diverse mechanisms of action. These include anti-inflammatory, bronchodilatory, immunomodulatory effects, and reducing gene expression. In the context of modern drug discovery, these natural compounds serve as valuable candidates for the development of novel asthma therapies. The transition from traditional remedies to modern drug discovery represents a promising avenue for asthma treatment. Our review highlights the substantial efficacy of natural products in managing asthma symptoms, underpinned by well-defined mechanisms of action. By bridging the gap between traditional and contemporary approaches, we contribute to the growing body of knowledge in the field, emphasizing the potential of natural products in shaping the future of asthma therapy.

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.

Unraveling Light-Activated Insulin Action in Regulating Blood Glucose: New Photoactivatable Insight as a Novel Modality in Diabetes Management.

Diabetes, particularly type 2 diabetes (T2D), is the main component of metabolic syndrome. It is highly prevalent and has drastically increased with sedentary lifestyles, notably behaviors linked to ease of access and minimal physical activity. Central to this condition is insulin, which plays a pivotal role in regulating glucose levels in the body by aiding glucose uptake and storage in cells, and what happens to diabetes? In diabetes, there is a disruption and malfunction in insulin regulation. Despite numerous efforts, effectively addressing diabetes remains a challenge. This article explores the potential of photoactivatable drugs in diabetes treatment, with a focus on light-activated insulin. We discuss its advantages and significant implications. This article is expected to enrich the existing literature substantially, offering a comprehensive analysis of potential strategies for improving diabetes management. With its minimal physical intrusion, light-activated insulin promises to improve patient comfort and treatment adherence. It offers precise regulation and localized impact, potentially mitigating the risks associated with conventional diabetes treatments. Additionally, light-activated insulin is capable of explicitly targeting RNA and epigenetic factors. This innovative approach may pave the way for more personalized and effective diabetes treatments, addressing not only the symptoms but also the underlying biological causes of the disease. The advancement of light-activated insulin could revolutionize diabetes management. This study represents a pioneering introduction to this novel modality for diabetes management.

Could Natural Products Help in the Control of Obesity? Current Insights and Future Perspectives.

Obesity is a global issue faced by many individuals worldwide. However, no drug has a pronounced effect with few side effects. Green tea, a well-known natural product, shows preventive effects against obesity by decreasing lipogenesis and increasing fat oxidation and antioxidant capacity. In contrast, other natural products are known to contribute to obesity. Relevant articles published on the therapeutic effect of natural products on obesity were retrieved from PubMed, Web of Science, and Scopus. The search was conducted by entering keywords such as "obesity", "natural product", and "clinical trial". The natural products were classified as single compounds, foods, teas, fruits, herbal medicines-single extract, herbal medicines-decoction, and herbal medicines-external preparation. Then, the mechanisms of these medicines were organized into lipid metabolism, anti-inflammation, antioxidation, appetite loss, and thermogenesis. This review aimed to assess the efficacy and mechanisms of effective natural products in managing obesity. Several clinical studies reported that natural products showed antiobesity effects, including Coffea arabica (coffee), Camellia sinensis (green tea), Caulerpa racemosa (green algae), Allium sativum (garlic), combined Ephedra intermedia Schrenk, Thea sinensis L., and Atractylodes lancea DC extract (known as Gambisan), Ephedra sinica Stapf, Angelica Gigantis Radix, Atractylodis Rhizoma Alba, Coicis semen, Cinnamomi cortex, Paeoniae radix alba, and Glycyrrhiza uralensis (known as Euiiyin-tang formula). Further studies are expected to refine the pharmacological effects of natural products for clinical use.

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.

Sulfated Polysaccharide from Caulerpa racemosa Attenuates the Obesity-Induced Cardiometabolic Syndrome via Regulating the PRMT1-DDAH-ADMA with mTOR-SIRT1-AMPK Pathways and Gut Microbiota Modulation.

Our investigation intended to analyze the effects of sulfated polysaccharides from Caulerpa racemosa (SPCr) in attenuating obesity-induced cardiometabolic syndrome via regulating the protein arginine N-methyltransferase 1-asymmetric dimethylarginine-dimethylarginine dimethylamino-hydrolase (PRMT1-DDAH-ADMA) with the mammalian target of rapamycin-Sirtuin 1-5' AMP-activated protein kinase (mTOR-SIRT1-AMPK) pathways and gut microbiota modulation. This is a follow-up study that used SPs from previous in vitro studies, consisting of 2,3-di-O-methyl-1,4,5-tri-O-acetylarabinitol, 2,3,4,6-tetra-O-methyl-D-mannopyranose, and type B ulvanobiuronicacid 3-sulfate. A total of forty rats were randomly divided into four treatment groups: Group A received a standard diet; Group B was provided with a diet enriched in cholesterol and fat (CFED); and Groups C and D were given the CFED along with ad libitum water, and daily oral supplementation of 65 or 130 mg/kg of body weight (BW) of SPCr, respectively. Group D showed the lowest low-density lipoprotein, triglyceride, total cholesterol, and blood glucose levels, and the highest HDL level compared to the other groups in this study. These results in the group fed high-dose SPCr demonstrated a significant effect compared to the group fed low-dose SPCr (p < 0.0001), as well as in total cholesterol and blood glucose (p < 0.05). Supplementation with SPCr was also observed to have an upregulation effect on peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha, interleukin 10, Sirtuin 1, DDAH-II, superoxide dismutase (SOD) cardio, and AMPK, which was also followed by a downregulation of PRMT-1, TNF-α, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, and mTOR. Interestingly, gut microbiota modulation was also observed; feeding the rats with a cholesterol-enriched diet shifted the gut microbiota composition toward the Firmicutes level, lowered the Bacteroidetes level, and increased the Firmicutes level. A dose of 130 mg/kg BW of SPCr is the recommended dose, and investigation still needs to be continued in clinical trials with humans to see its efficacy at an advanced level.

New Insight on In Vitro Biological Activities of Sulfated Polysaccharides from Ulvophyte Green Algae.

Green algae are natural bioresources that have excellent bioactive potential, partly due to sulfated polysaccharides (SPs) which are still rarely explored for their biological activities. There is currently an urgent need for studies exploring the anticancer biological activity of SPs extracted from two Indonesian ulvophyte green algae: the sulfated polysaccharide of Caulerpa racemosa (SPCr) and the sulfated polysaccharide of Caulerpa lentillifera (SPCl). The method of isolating SPs and their assessment of biological activities in this study were based on previous and similar studies. The highest yield sulfate/total sugar ratio was presented by SPCr than that of SPCl. Overall, SPCr exhibits a strong antioxidant activity, as indicated by smaller EC50 values obtained from a series of antioxidant activity assays compared to the EC50 values of Trolox (control). As an anti-obesity and antidiabetic, the overall EC50 value of both SPs was close to the EC50 of the positive control (orlistat and acarbose). Even more interesting was that SPCl displayed wide-ranging anticancer effects on colorectal, hepatoma, breast cancer cell lines, and leukemia. Finally, this study reveals new insights in that SPs from two Indonesian green algae have the potential to be promising nutraceuticals as novel antioxidative actors, and to be able to fight obesity, diabetes, and even cancer.

Anti-Inflammatory, Antioxidant, Metabolic and Gut Microbiota Modulation Activities of Probiotic in Cardiac Remodeling Condition: Evidence from Systematic Study and Meta-Analysis of Randomized Controlled Trials.

Heart failure (HF) is a global pandemic with increasing prevalence and mortality rates annually. Its main cause is myocardial infarction (MI), followed by rapid cardiac remodeling. Several clinical studies have shown that probiotics can improve the quality of life and reduce cardiovascular risk factors. This systematic review and meta-analysis aimed to investigate the effectiveness of probiotics in preventing HF caused by a MI according to a prospectively registered protocol (PROSPERO: CRD42023388870). Four independent evaluators independently extracted the data using predefined extraction forms and evaluated the eligibility and accuracy of the studies. A total of six studies consisting of 366 participants were included in the systematic review. Probiotics are not significant in intervening left ventricular ejection fraction (LVEF) and high-sensitivity C-reactive protein (hs-CRP) when compared between the intervention group and the control group due to inadequate studies supporting its efficacy. Among sarcopenia indexes, hand grip strength (HGS) showed robust correlations with the Wnt biomarkers (p < 0.05), improved short physical performance battery (SPPB) scores were also strongly correlated with Dickkopf-related protein (Dkk)-3, followed by Dkk-1, and sterol regulatory element-binding protein 1 (SREBP-1) (p < 0.05). The probiotic group showed improvement in total cholesterol (p = 0.01) and uric acid (p = 0.014) compared to the baseline. Finally, probiotic supplements may be an anti-inflammatory, antioxidant, metabolic, and intestinal microbiota modulator in cardiac remodeling conditions. Probiotics have great potential to attenuate cardiac remodeling in HF or post-MI patients while also enhancing the Wnt signaling pathway which can improve sarcopenia under such conditions.

Carotenoids Composition of Green Algae Caulerpa racemosa and Their Antidiabetic, Anti-Obesity, Antioxidant, and Anti-Inflammatory Properties.

Green alga Caulerpa racemosa is an underexploited species of macroalgae, even though it is characterized by a green color that indicates an abundance of bioactive pigments, such as chlorophyll and possibly xanthophyll. Unlike chlorophyll, which has been well explored, the composition of the carotenoids of C. racemosa and its biological activities have not been reported. Therefore, this study aims to look at the carotenoid profile and composition of C. racemose and determine their biological activities, which include antidiabetic, anti-obesity, anti-oxidative, anti-inflammatory, and cytotoxicity in vitro. The detected carotenoids were all xanthophylls, which included fucoxanthin, lutein, astaxanthin, canthaxanthin, zeaxanthin, ß-carotene, and ß-cryptoxanthin based on orbitrap-mass spectrometry (MS) and a rapid ultra-high performance liquid chromatography (UHPLC) diode array detector. Of the seven carotenoids observed, it should be highlighted that ß-carotene and canthaxanthin were the two most dominant carotenoids present in C. racemosa. Interestingly, the carotenoid extract of C. racemosa has good biological activity in inhibiting α-glucosidase, α-amylase, DPPH and ABTS, and the TNF-α and mTOR, as well as upregulating the AMPK, which makes it a drug candidate or functional antidiabetic food, a very promising anti-obesity and anti-inflammatory. More interestingly, the cytotoxicity value of the carotenoid extract of C. racemosa shows a level of safety in normal cells, which makes it a potential for the further development of nutraceuticals and pharmaceuticals.

Antiobesity potential of major metabolites from Clitoria ternatea kombucha: Untargeted metabolomic profiling and molecular docking simulations.

The prevalence of obesity is rapidly increasing and poses serious health risks accompanied by a decrease in life expectancy and quality of life. Therefore, the therapeutic potential of natural-derived nutraceuticals against obesity and its comorbidities needs to be explored. Molecular inhibition of lipase enzymes and fat mass and obesity-associated (FTO) protein has attracted some recent interest in efforts to find antiobesity agents. This study aims to innovate a fermented drink from Clitoria ternatea kombucha (CTK), find out their metabolites profile, and determine the antiobesity potential through a molecular docking study. The CTK formulation refers to previous research while the metabolites profile was determined using HPLC-ESI-HRMS/MS. Major compounds were selected based on best match value > 99.0% of the M/Z cloud database. A total of 79 compounds were identified in CTK, and 13 ideal compounds were selected to be simulated in the molecular docking study against human pancreatic lipase, α-amylase, α-glucosidase, porcine pancreatic lipase, and FTO proteins. The study found that Kaempferol, Quercetin-3ß-D-glucoside, Quercetin, Dibenzylamine, and α-Pyrrolidinopropiophenone showed the best potential as functional antiobesity compounds since their affinity value ranked high in each respective receptor. In conclusion, the major compounds of CTK metabolites have the potential to be promising functional foods against obesity. However, further in vitro and in vivo studies should validate these health benefits.

Dietary Supplementation of Caulerpa racemosa Ameliorates Cardiometabolic Syndrome via Regulation of PRMT-1/DDAH/ADMA Pathway and Gut Microbiome in Mice.

This study evaluated the effects of an aqueous extract of Caulerpa racemosa (AEC) on cardiometabolic syndrome markers, and the modulation of the gut microbiome in mice administered a cholesterol- and fat-enriched diet (CFED). Four groups of mice received different treatments: normal diet, CFED, and CFED added with AEC extract at 65 and 130 mg/kg body weight (BW). The effective concentration (EC50) values of AEC for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and lipase inhibition were lower than those of the controls in vitro. In the mice model, the administration of high-dose AEC showed improved lipid and blood glucose profiles and a reduction in endothelial dysfunction markers (PRMT-1 and ADMA). Furthermore, a correlation between specific gut microbiomes and biomarkers associated with cardiometabolic diseases was also observed. In vitro studies highlighted the antioxidant properties of AEC, while in vivo data demonstrated that AEC plays a role in the management of cardiometabolic syndrome via regulation of oxidative stress, inflammation, endothelial function (PRMT-1/DDAH/ADMA pathway), and gut microbiota.

The correlation between CD4+ T-lymphocyte count and tuberculosis form in TB-HIV coinfected patients in Indonesia.

AIM: to find whether there is a correlation between CD4+ count and TB form in TB-HIV Coinfected patients in Indonesia. METHODS: this is a cross-sectional study of the TB-HIV patients at National HIV Center POKDISUS, Cipto Mangunkusumo Hospital in 2008-2011. We classified TB form as pulmonary TB, extrapulmonary TB, milliary TB, and combination form. The data were analyzed by Spearman and lambda correlation test. We also did partial correlation test to eliminate some counfounding factors, including demography and clinical characteristics, that had been determinated before. RESULTS: there were 122 TB-HIV patients (aged median 31 [18-34], 80% male) included in this study. The most common TB form was pulmonary TB (71.2%), then extrapulmonary TB (7.4%), the combined type (18.9%), and milliary TB (2.5%). Median of CD4+ count was 40 cells/mL (IQR 17.5-100.6). There was a very weak correlation between CD4+ count and TB form in TB-HIV patients in Indonesia (r=0.185; p=0.042). The other factor that also showed a significant correlation to TB form is HIV staging (r=0.289; p=0.001). After adjusting those factors, we found an increase on correlation between CD4+ count and TB form (r=0.353; p=0.000). CONCLUSION: there was a correlation between CD4+ count and TB form in TB-HIV patients in Indonesia, but in a very weak correlation.