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Pharmaceuticals (Basel, Switzerland) May 2024Keloid is characterized as the fibrotic tissue resulting from the increase of fibroblast activity. (Hunter) Roxb. possesses bioactive compounds that have potential as...
Keloid is characterized as the fibrotic tissue resulting from the increase of fibroblast activity. (Hunter) Roxb. possesses bioactive compounds that have potential as antifibrotic agents, while the mechanism of action in keloid has not yet been elucidated. The aim of this study was to investigate the interaction of gambir bioactive compounds with keloid target proteins using an epistatic and molecular simulation approach. The known bioactive compounds of gambir targets and keloid-related protein targets were screened using databases. The network was constructed and analyzed to obtain the core protein targets. The targets were enriched to describe the Gene Ontology (GO) and pathway related to the proteins. Eleven targets were defined as the main targets of gambir bioactive compounds related to keloid disease. Gambiriin C, Isogambirine, and Procyanidin B1 were identified as the most promising compounds with the highest binding energy to transforming growth factor beta 1 (TGFβ1), AKT serine/threonine kinase 1 (AKT1), and matrix metallopeptidase 1 (MMP1) as the target proteins. GO enrichment and pathway analysis found that gambir bioactive compounds may act on keloid-related target proteins to regulate cell proliferation, migration, transcription, and signal transduction activity via profibrotic cytokine and growth factor signaling pathways. This study provides a reference for potential targets, compounds, and pathways to explain the mechanism of gambir against keloid.
PubMed: 38931330
DOI: 10.3390/ph17060662 -
Nutrients Jun 2024Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic... (Review)
Review
Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic regulation via specialized signaling networks. Their association with cardiovascular diseases (CVDs) has become a focal point of scientific debate, with emerging evidence suggesting both beneficial and detrimental roles. This review aims to dissect the multifaceted relationship between BCAAs and cardiovascular health, exploring the molecular mechanisms and clinical implications. Elevated BCAA levels have also been linked to insulin resistance (IR), type 2 diabetes mellitus (T2DM), inflammation, and dyslipidemia, which are well-established risk factors for CVD. Central to these processes are key pathways such as mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-light-chain-enhancer of activate B cells (NF-κB)-mediated inflammation, and oxidative stress. Additionally, the interplay between BCAA metabolism and gut microbiota, particularly the production of metabolites like trimethylamine-N-oxide (TMAO), adds another layer of complexity. Contrarily, some studies propose that BCAAs may have cardioprotective effects under certain conditions, contributing to muscle maintenance and metabolic health. This review critically evaluates the evidence, addressing the biological basis and signal transduction mechanism, and also discusses the potential for BCAAs to act as biomarkers versus active mediators of cardiovascular pathology. By presenting a balanced analysis, this review seeks to clarify the contentious roles of BCAAs in CVD, providing a foundation for future research and therapeutic strategies required because of the rising prevalence, incidence, and total burden of CVDs.
Topics: Humans; Amino Acids, Branched-Chain; Cardiovascular Diseases; Biomarkers; Gastrointestinal Microbiome; Insulin Resistance; Signal Transduction; Diabetes Mellitus, Type 2; Chronic Disease; Inflammation; Oxidative Stress; TOR Serine-Threonine Kinases; Methylamines
PubMed: 38931325
DOI: 10.3390/nu16121972 -
Nutrients Jun 2024Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection,...
Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.
Topics: Humans; Selenomethionine; Apoptosis; Signal Transduction; Reactive Oxygen Species; STAT3 Transcription Factor; Janus Kinases; Antiviral Agents; Membrane Potential, Mitochondrial; A549 Cells
PubMed: 38931321
DOI: 10.3390/nu16121966 -
Nutrients Jun 2024Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived...
Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals.
Topics: Animals; Obesity; Mice; Male; Peptides; Anti-Obesity Agents; Protein Hydrolysates; Liver; Blood Glucose; Hypoglycemic Agents; Lipid Metabolism; AMP-Activated Protein Kinases; Mice, Inbred C57BL; Receptors, Leptin; Adipogenesis; Body Weight
PubMed: 38931268
DOI: 10.3390/nu16121913 -
Nutrients Jun 2024The skin, serving as the body's primary defense against external elements, plays a crucial role in protecting the body from infections and injuries, as well as...
The skin, serving as the body's primary defense against external elements, plays a crucial role in protecting the body from infections and injuries, as well as maintaining overall homeostasis. Skin aging, a common manifestation of the aging process, involves the gradual deterioration of its normal structure and repair mechanisms. Addressing the issue of skin aging is increasingly imperative. Multiple pieces of evidence indicate the potential anti-aging effects of exogenous nucleotides (NTs) through their ability to inhibit oxidative stress and inflammation. This study aims to investigate whether exogenous NTs can slow down skin aging and elucidate the underlying mechanisms. To achieve this objective, senescence-accelerated mouse prone-8 (SAMP8) mice were utilized and randomly allocated into Aging, NTs-low, NTs-middle, and NTs-high groups, while senescence-accelerated mouse resistant 1 (SAMR1) mice were employed as the control group. After 9 months of NT intervention, dorsal skin samples were collected to analyze the pathology and assess the presence and expression of substances related to the aging process. The findings indicated that a high-dose NT treatment led to a significant increase in the thickness of the epithelium and dermal layers, as well as Hyp content ( < 0.05). Additionally, it was observed that low-dose NT intervention resulted in improved aging, as evidenced by a significant decrease in p16 expression ( < 0.05). Importantly, the administration of high doses of NTs could improve, in some ways, mitochondrial function, which is known to reduce oxidative stress and promote ATP and NAD production significantly. These observed effects may be linked to NT-induced autophagy, as evidenced by the decreased expression of p62 and increased expression of LC3BI/II in the intervention groups. Furthermore, NTs were found to upregulate pAMPK and PGC-1α expression while inhibiting the phosphorylation of p38MAPK, JNK, and ERK, suggesting that autophagy may be regulated through the AMPK and MAPK pathways. Therefore, the potential induction of autophagy by NTs may offer benefits in addressing skin aging through the activation of the AMPK pathway and the inhibition of the MAPK pathway.
Topics: Animals; Skin Aging; Autophagy; Mice; AMP-Activated Protein Kinases; Nucleotides; Oxidative Stress; Skin; Male; MAP Kinase Signaling System; Signal Transduction; Mitogen-Activated Protein Kinases
PubMed: 38931262
DOI: 10.3390/nu16121907 -
Nutrients Jun 2024Advanced glycation end products (AGEs) accumulate in the plasma of pregnant women with hyperglycemia, potentially inducing oxidative stress and fetal developmental...
Advanced glycation end products (AGEs) accumulate in the plasma of pregnant women with hyperglycemia, potentially inducing oxidative stress and fetal developmental abnormalities. Although intrauterine hyperglycemia has been implicated in excessive fetal growth, the effects of maternal AGEs on fetal development remain unclear. We evaluated the differentiation regulators and cellular signaling in the skeletal muscles of infants born to control mothers (ICM), diabetic mothers (IDM), and diabetic mothers supplemented with either cis-palmitoleic acid (CPA) or trans-palmitoleic acid (TPA). Cell viability, reactive oxygen species levels, and myotube formation were assessed in AGE-exposed C2C12 cells to explore potential mitigation by CPA and TPA. Elevated receptors for AGE expression and decreased Akt and AMPK phosphorylation were evident in rat skeletal muscles in IDM. Maternal palmitoleic acid supplementation alleviated insulin resistance by downregulating RAGE expression and enhancing Akt phosphorylation. The exposure of the C2C12 cells to AGEs reduced cell viability and myotube formation and elevated reactive oxygen species levels, which were attenuated by CPA or TPA supplementation. This suggests that maternal hyperglycemia and plasma AGEs may contribute to skeletal muscle disorders in offspring, which are mitigated by palmitoleic acid supplementation. Hence, the maternal intake of palmitoleic acid during pregnancy may have implications for fetal health.
Topics: Fatty Acids, Monounsaturated; Glycation End Products, Advanced; Female; Animals; Pregnancy; Receptor for Advanced Glycation End Products; Rats; Muscle, Skeletal; Reactive Oxygen Species; Cell Line; Cell Survival; Mice; Dietary Supplements; Proto-Oncogene Proteins c-akt; Oxidative Stress; Insulin Resistance; Humans; Phosphorylation; Rats, Sprague-Dawley; Pregnancy in Diabetics; Male; Fetal Development
PubMed: 38931253
DOI: 10.3390/nu16121898 -
Nutrients Jun 2024, a polyphenol-rich plant, holds potential for improving inflammation, but its mechanisms are not well understood. Therefore, this study employed network pharmacology...
, a polyphenol-rich plant, holds potential for improving inflammation, but its mechanisms are not well understood. Therefore, this study employed network pharmacology and molecular docking to explore the mechanism by which ameliorates inflammation. In this study, 29 kinds of active ingredients were obtained via data mining. Five main active components were screened out for improving inflammation, which were flemichin D, naringenin, chrysophanol, genistein and orobol. In total, 52 core targets were identified, including AKT serine/threonine kinase 1 (AKT1), tumor necrosis factor (TNF), B-cell lymphoma-2 (BCL2), serum albumin (ALB), and estrogen receptor 1 (ESR1). Gene ontology (GO) enrichment analysis identified 2331 entries related to biological processes, 98 entries associated with cellular components, and 203 entries linked to molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis yielded 149 pathways, including those involved in EGFR tyrosine kinase inhibitor resistance, endocrine resistance, and the PI3K-Akt signaling pathway. Molecular docking results showed strong binding effects between the main active components and the core targets, with binding energies less than -5 kcal/mol. In summary, this study preliminarily elucidated the underlying mechanisms by which , through a multi-component, multi-target, and multi-pathway approach, ameliorates inflammation. This provides a theoretical foundation for the subsequent application of in inflammation amelioration.
Topics: Molecular Docking Simulation; Network Pharmacology; Inflammation; Humans; Signal Transduction; Fabaceae; Anti-Inflammatory Agents; Proto-Oncogene Proteins c-akt; Plant Extracts
PubMed: 38931205
DOI: 10.3390/nu16121850 -
Nutrients Jun 2024Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the...
Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine's suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine's ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine's cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transducti.
Topics: Taurine; Humans; TOR Serine-Threonine Kinases; Female; Ovarian Neoplasms; DNA Damage; Cisplatin; Tumor Suppressor Protein p53; Cell Line, Tumor; Cell Proliferation; Signal Transduction; Glycolysis; Extracellular Signal-Regulated MAP Kinases; Antineoplastic Agents
PubMed: 38931171
DOI: 10.3390/nu16121816 -
Nutrients Jun 2024Nucleotides (NTs) act as pivotal regulatory factors in numerous biological processes, playing indispensable roles in growth, development, and metabolism across...
Nucleotides (NTs) act as pivotal regulatory factors in numerous biological processes, playing indispensable roles in growth, development, and metabolism across organisms. This study delves into the effects of exogenous NTs on hepatic insulin resistance using palmitic-acid-induced HepG2 cells, administering interventions at three distinct dosage levels of exogenous NTs. The findings underscore that exogenous NT intervention augments glucose consumption in HepG2 cells, modulates the expression of glycogen-synthesis-related enzymes (glycogen synthase kinase 3β and glycogen synthase), and influences glycogen content. Additionally, it governs the expression levels of hepatic enzymes (hexokinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase). Moreover, exogenous NT intervention orchestrates insulin signaling pathway (insulin receptor substrate-1, protein kinase B, and forkhead box protein O1) and AMP-activated protein kinase (AMPK) activity in HepG2 cells. Furthermore, exogenous NT intervention fine-tunes the expression levels of oxidative stress-related markers (malondialdehyde, glutathione peroxidase, and NADPH oxidase 4) and the expression of inflammation-related nuclear transcription factor (NF-κB). Lastly, exogenous NT intervention regulates the expression levels of glucose transporter proteins (GLUTs). Consequently, exogenous NTs ameliorate insulin resistance in HepG2 cells by modulating the IRS-1/AKT/FOXO1 pathways and regulate glucose consumption, glycogen content, insulin signaling pathways, AMPK activity, oxidative stress, and inflammatory status.
Topics: Humans; Hep G2 Cells; Insulin Resistance; Palmitic Acid; Insulin Receptor Substrate Proteins; Forkhead Box Protein O1; Proto-Oncogene Proteins c-akt; Signal Transduction; Nucleotides; Glucose; Oxidative Stress; Glycogen; Insulin
PubMed: 38931156
DOI: 10.3390/nu16121801 -
Plants (Basel, Switzerland) Jun 2024As a type of cell-wall-relaxing protein that is widely present in plants, expansins have been shown to actively participate in the regulation of plant growth and...
As a type of cell-wall-relaxing protein that is widely present in plants, expansins have been shown to actively participate in the regulation of plant growth and responses to environmental stress. Wild soybeans have long existed in the wild environment and possess abundant resistance gene resources, which hold significant value for the improvement of cultivated soybean germplasm. In our previous study, we found that the wild soybean expansin gene is specifically transcribed in roots, and its transcription level significantly increases under salt and drought stress. To further identify the function of , in this study, we cloned the CDS sequence of this gene. The transcription pattern of in the roots of wild soybean under salt and drought stress was analyzed by qRT-PCR. Using an -mediated genetic transformation, we obtained soybean hairy roots overexpressing . Under 150 mM NaCl- and 100 mM mannitol-simulated drought stress, the relative growth values of the number, length, and weight of transgenic soybean hairy roots were significantly higher than those of the control group. We obtained the transcriptomes of transgenic and wild-type soybean hairy roots under normal growth conditions and under salt and drought stress through RNA sequencing. A transcriptomic analysis showed that the transcription of genes encoding expansins (EXPB family), peroxidase, H-transporting ATPase, and other genes was significantly upregulated in transgenic hairy roots under salt stress. Under drought stress, the transcription of expansin (EXPB/LB family) genes increased in transgenic hairy roots. In addition, the transcription of genes encoding peroxidases, calcium/calmodulin-dependent protein kinases, and dehydration-responsive proteins increased significantly. The results of qRT-PCR also confirmed that the transcription pattern of the above genes was consistent with the transcriptome. The differences in the transcript levels of the above genes may be the potential reason for the strong tolerance of soybean hairy roots overexpressing the gene under salt and drought stress. In conclusion, the expansin can be used as a valuable candidate gene for the molecular breeding of soybeans.
PubMed: 38931088
DOI: 10.3390/plants13121656