Search Results (1,348)

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine. Full article

Introduction: Here we consider the collision of a genetic factor and an essential instigator in Alzheimer’s neuropathogenesis: (i) the Alzheimer’s gene (APOEε4), which downregulates lysosomal autophagy and induces synthesis of (ii) the instigator, interleukin-1β (IL-1β), which drives synthesis of βAPP for Aβ plaques and of MAPKp38 for phosphorylation of tau for formation of neurofibrillary tangles (NFTs), the two cardinal features of AD. Methods: RT-PCR, immunoblotting and immunohistochemistry techniques were used to assess the levels of IL-1β and its signaling cascade in ADε4,4, ε3,3, and age-matched controls (AMC3,3) in hippocampal regions of the brain. Results: IL-1β and its downstream signaling proteins TLR-2, MyD88, NFκB, COX-1, and COX-2 were greater in tissues from ADε4,4 than ADε3,3 or AMC3,3. Cathepsin B, D, and L levels, which play a pivotal role and are necessary for lysosomal autophagy, were lower in ADε4,4 than in ADε3,3 or AMC ε3,3. IL-1β and its downstream signaling cascade TLR-2, MyD88, NFκB, COX-1, and COX-2 expression levels were high in SH-SY5Y and T98G cells transfected with APOεE4. Conclusions: APOEε4 causes Alzheimer’s by downregulating autophagy, thus inducing IL-1β for Aβ plaque and neurofibrillary tangle formation. Full article

Background/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus seed extract in gastric cancer cells. Antioxidant capacity (DPPH, ABTS) and total phenolic and flavonoid contents were analyzed. Cytotoxicity was assessed using the MTT assay in HGC27, MKN45, and AGS gastric cancer cell lines and CCD-1072Sk fibroblasts. Apoptosis, mitochondrial membrane potential (MMP), and cell cycle changes were evaluated via Annexin V-FITC/PI, Rhodamine 123, and PI staining, respectively. RT-qPCR and gene enrichment analyses were conducted to investigate the molecular mechanisms. Apoptosis-related protein expression was analyzed through enzyme-linked immunosorbent assay (ELISA). Results: The extract exhibited high antioxidant activity and a significant phenolic content. It reduced cell viability in a dose-dependent manner in gastric cancer cells, while exerting low toxicity in fibroblasts. It significantly increased apoptosis, induced G0/G1-phase cell cycle arrest, upregulated pro-apoptotic genes (CASP3, CASP7, TP53, BCL2L11), and downregulated anti-apoptotic genes (XIAP, NOL3). Gene enrichment analysis highlighted pathways like apoptosis, necrosis, and cysteine endopeptidase activity. The extract also disrupted MMP, inhibited migration and spheroid formation, suppressed EMT markers (SNAIL, SLUG, TWIST1, N-CADHERIN), and upregulated E-CADHERIN. The expression of Caspase 3 and Bax proteins increased and Bcl2 protein decreased. Conclusions: These findings suggest that Vitex agnus-castus seed extract exerts strong anticancer effects in gastric cancer cells by promoting apoptosis, reducing proliferation, and inhibiting migration. Further studies are warranted to explore its clinical relevance. Full article

Skeletal muscle development is a critical economic trait in livestock, governed by myogenic satellite cell regulation. Integrins mediate mechanical anchorage to the ECM and enable ECM–intracellular signaling. CIB2, as an EF-hand-domain protein involved in mechanotransduction, shows significant developmental regulation in goat muscle. Although the role of CIB2 in skeletal muscle growth is poorly characterized, we observed pronounced developmental upregulation of IB2 in postnatal goat muscle. CIB2 expression increased >20-fold by postnatal day 90 (P90) compared to P1, sustaining elevation through P180 (p < 0.05). Functional investigations indicated that siRNA-mediated knockdown of CIB2 could inhibit myoblast proliferation by inducing S-phase arrest (p < 0.05) and downregulating the expression of CDK4/Cyclin D/E. Simultaneously, CIB2 interference treatment was found to decrease the proliferative activity of goat myogenic satellite cells, yet it significantly promoted differentiation by upregulating the expression of MyoD/MyoG/MyHC (p < 0.01). Mechanistically, CTCF was identified as a transcriptional repressor binding to an intragenic region of the CIB2 gene locus (ChIP enrichment: 2.3-fold, p < 0.05). Knockdown of CTCF induced upregulation of CIB2 (p < 0.05). RNA-seq analysis established CIB2 as a calcium signaling hub: its interference activated IL-17/TNF and complement cascades, while overexpression suppressed focal adhesion/ECM–receptor interactions and enriched neuroendocrine pathways. Collectively, this study identifies the CTCF-CIB2–integrin α7β1–PI3K/AKT axis as a novel molecular mechanism that regulates the balance of myogenic fate in goats. These findings offer promising targets for genomic selection and precision breeding strategies aimed at enhancing muscle productivity in ruminants. Full article

The premature senescence of red raspberry leaves severely affects plant growth. In this study, the double-season red raspberry cultivar ‘Polka’ was used, with N₁₅₀ (0.10 g N·kg⁻¹) selected as the treatment group (T150) and N₀ (0 g N·kg⁻¹) set as the control (CK). This study systematically investigated the mechanism of premature senescence in red raspberry leaves under different nitrogen application levels by measuring physiological parameters and conducting a combined multi-omics analysis of transcriptomics and metabolomics. Results showed that T150 plants had 8.34 cm greater height and 1.45 cm greater ground diameter than CK. The chlorophyll, carotenoid, soluble protein, and sugar contents in all leaf parts of T150 were significantly higher than those in CK, whereas soluble starch contents were lower. Malondialdehyde (MDA) content and superoxide anion (O₂⁻) generation rate in the lower leaves of T150 were significantly lower than those in CK. Superoxide sismutase (SOD) and peroxidase (POD) activities in the middle and lower functional leaves of T150 were higher than in CK, while catalase (CAT) activity was lower. Transcriptomic analysis identified 4350 significantly differentially expressed genes, including 2062 upregulated and 2288 downregulated genes. Metabolomic analysis identified 135 differential metabolites, out of which 60 were upregulated and 75 were downregulated. Integrated transcriptomic and metabolomic analysis showed enrichment in the phenylpropanoid biosynthesis (ko00940) and flavonoid biosynthesis (ko00941) pathways, with the former acting as an upstream pathway of the latter. A premature senescence pathway was established, and two key metabolites were identified: chlorogenic acid content decreased, and naringenin chalcone content increased in early senescent leaves, suggesting their pivotal roles in the early senescence of red raspberry leaves. Modulating chlorogenic acid and naringenin chalcone levels could delay premature senescence. Optimizing fertilization strategies may thus reduce senescence risk and enhance the productivity, profitability, and sustainability of the red raspberry industry. Full article

Background/Objectives: Blunt cardiac injury (BCI) is a severe medical condition that may arise as a result of various traumas, including motor vehicle accidents and falls. The main objective of this study was to explore the role and underlying mechanisms of the TRPV4 gene in BCI. Elucidating the function of TRPV4 in BCI may reveal potential novel therapeutic targets for the treatment of this condition. Methods: Rats in each group, including the SD control group (SDCON), the SD blunt-trauma group (SDBT), the TRPV4 gene-knockout control group (KOCON), and the TRPV4 gene-knockout blunt-trauma group (KOBT), were all freely dropped from a fixed height with a weight of 200 g and struck in the left chest with a certain energy, causing BCI. After the experiment, the levels of serum IL-6 and IL-1β were detected to evaluate the inflammatory response. The myocardial tissue structure was observed by HE staining. In addition, cardiac transcriptome analysis was conducted to identify differentially expressed genes, and metabolomics studies were carried out using UHPLC-Q-TOF/MS technology to analyze metabolites. The results of transcriptomics and metabolomics were verified by qRT-PCR and Western blot analysis. Results: Compared with the SDCON group, the levels of serum IL-6 and IL-1β in the SDBT group were significantly increased (p < 0.001), while the levels of serum IL-6 and IL-1β in the KOBT group were significantly decreased (p < 0.001), indicating that the deletion of the TRPV4 gene alleviated the inflammation induced by BCI. HE staining showed that myocardial tissue injury was severe in the SDBT group, while myocardial tissue structure abnormalities were mild in the KOBT group. Transcriptome analysis revealed that there were 1045 upregulated genes and 643 downregulated genes in the KOBT group. These genes were enriched in pathways related to inflammation, apoptosis, and tissue repair, such as p53, apoptosis, AMPK, PPAR, and other signaling pathways. Metabolomics studies have found that TRPV4 regulates nucleotide metabolism, amino-acid metabolism, biotin metabolism, arginine and proline metabolism, pentose phosphate pathway, fructose and mannose metabolism, etc., in myocardial tissue. The combined analysis of metabolic and transcriptional data reveals that tryptophan metabolism and the protein digestion and absorption pathway may be the key mechanisms. The qRT-PCR results corroborated the expression of key genes identified in the transcriptome sequencing, while Western blot analysis validated the protein expression levels of pivotal regulators within the p53 and AMPK signaling pathways. Conclusions: Overall, the deletion of the TRPV4 gene effectively alleviates cardiac injury by reducing inflammation and tissue damage. These findings suggest that TRPV4 may become a new therapeutic target for BCI, providing new insights for future therapeutic strategies. Full article

Background: Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii) was widely used in traditional Chinese medicine and also as a health food in China. Gibberellins (GAs) are plant hormones that regulate various aspects of growth and development in A. roxburghii. Ent-kaurene synthase (KS) plays a crucial role in the biosynthesis of GAs in plants. However, there is limited functional analysis of KS in GA biosynthesis and its effect on salt tolerance, especially in A. roxburghii. Methods: The ArKS genes were cloned from A. roxburghii, and its salt tolerance characteristics were verified by prokaryotic expression. Under salt stress, analyze the regulation of KS gene on GA and active ingredient content by qRT-PCR and HPLC-MS/MS, and explore the mechanism of exogenous GAs promoting active ingredient enrichment by regulating the expression level of the KS under salt stress. Results: The ArKS protein was highly homologous to KSs with other plant species; subcellular localization of KS protein was lacking kytic vacuole. The transformants displayed a significant increase in salt tolerance under the stress conditions of 300 mM NaCl. And the expression of ArKS genes and the GAs accumulation was downregulated under the salt stress; among them, the contents of GA3, GA7, GA8, GA24, and GA34 showed a significant decrease. It was further found that there was an increase (1.36 times) in MDA content and a decrease (0.84 times) in relative chlorophyll content under the salt conditions from A. roxburghii. However, the content of active constituents was elevated from A. roxburghii under the NaCl stress, including polysaccharides, total flavonoids, and free amino acids, which increased by 1.14, 1.23, and 1.44 times, respectively. Interestingly, the ArKS gene expression and the chlorophyll content was increased, MDA content showed a decrease from 2.02 μmoL·g⁻¹ to 1.74 μmoL·g⁻¹ after exogenous addition of GAs, and the elevation of active constituents of polysaccharides, total flavonoids, and free amino acids were increased by 1.02, 1.09, and 1.05 times, implying that GAs depletion mitigated the damage caused by adversity to A. roxburghii. Conclusions: The ArKS gene cloned from A. roxburghii improved the salt tolerance of plants under salt stress by regulating GA content. Also, GAs not only alleviate salt tolerance but also play a key role in the synthesis of active components in A. roxburghii. The functions of KS genes and GAs were identified to provide ideas for improving the salt tolerance and quality of ingredients in artificial cultivation from A. roxburghii. Full article

Spurred by the enormous therapeutic success of glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP1-RAs) against diabetes and obesity, glucagon family receptor pharmacology has garnered a tremendous amount of interest. Glucagon family receptors, e.g., the glucagon receptor itself (GCGR), the GLP-1R, and the glucose-dependent insulinotropic peptide receptor (GIPR), belong to the incretin receptor superfamily, i.e., receptors that increase blood glucose-dependent insulin secretion. All incretin receptors are class B1 G protein-coupled receptors (GPCRs), coupling to the G_s type of heterotrimeric G proteins which activates adenylyl cyclase (AC) to produce cyclic adenosine monophosphate (cAMP). Most GPCRs undergo desensitization, i.e., uncouple from G proteins and internalize, thanks to interactions with the βarrestins (arrestin-2 and -3). Since the βarrestins can also mediate their own G protein-independent signaling, any given GPCR can theoretically signal (predominantly) either via G proteins or βarrestins, i.e., be a G protein- or βarrestin-“biased” receptor, depending on the bound ligand. A plethora of experimental evidence suggests that the GLP-1R does not undergo desensitization in physiologically relevant tissues in vivo, but rather, it produces robust and prolonged cAMP signals. A particular property of constant cycling between the cell membrane and caveolae/lipid rafts of the GLP-1R may underlie its lack of desensitization. In contrast, GIPR signaling is extensively mediated by βarrestins and the GIPR undergoes significant desensitization, internalization, and downregulation, which may explain why both agonists and antagonists of the GIPR exert the same physiological effects. Here, we discuss this evidence and make a case for the GLP-1R being a phenotypically or functionally G_s-selective receptor. We also discuss the implications of this for the development of GLP-1R poly-ligands, which are increasingly pursued for the treatment of obesity and other diseases. Full article

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors with different clinical and biological characteristics. Ki-67 staining and mitotic counts are the most commonly used prognostic markers, but these methods are time-consuming and lack reproducibility, highlighting the need for innovative approaches that improve histological evaluation and prognosis. In our previous study, we observed that the microRNA (miRNA) expression profile of GEP-NENs correlates with the three grades of GEP-NENs. This study aimed to characterize a group of miRNAs that discriminate well-differentiated GEP-NENs grading 1 (G1) and grading (G2). Fifty formalin-fixed and paraffin-embedded tissue specimens from well-differentiated GEP-NENs G1 and G2 tissues were used for this study. The expression levels of 21 miRNAs were examined using qRT-PCR, while FGFR2 and FGF1 protein expression were evaluated through immunohistochemistry (IHC). We identified four miRNAs (hsa-miR-133, hsa-miR-150-5p, hsa-miR-143-3p and hsa-miR-378a-3p) that are downregulated in G2 GEP-NENs compared to G1. Bioinformatic analysis revealed that these miRNAs play a key role in modulating the FGF/FGFR signaling pathway. Consistent with this observation, we found that fibroblast growth factor receptor 2 (FGFR2) expression is markedly higher in G2 NENs patients, whereas its expression remains low in G1 NENs. Our findings highlight the potential use of miRNAs to confirm the histological evaluation of GEP-NENs by employing them as biomarkers for improving histological evaluation and tumor classification. Full article

Background. The STING protein is activated by the second messenger cGAMP to promote the innate immune response against infections. Beyond this role, a chronically overactive STING signaling has been described in several disorders. Patients with severe COVID-19 exhibit a hyper-inflammatory response (the cytokine storm) that is in part mediated by the cGAS-STING pathway. Several STING inhibitors may protect from severe COVID-19 by down-regulating several inflammatory cytokines. This pathway has been implicated in the establishment of an optimal antiviral vaccine response. STING agonists as adjuvants improved the IgG titers against the SARS-CoV-2 Spike protein vaccines. Methods. We investigated the association between two common functional STING1/TMEM173 polymorphisms (rs78233829 C>G/p.Gly230Ala and rs1131769C>T/p.His232Arg) and severe COVID-19 requiring hospitalization. A total of 801 non-vaccinated and 105 fully vaccinated (mRNA vaccine) patients, as well as 300 population controls, were genotyped. Frequencies between the groups were statistically compared. Results. There were no differences for the STING1 variant frequencies between non-vaccinated patients and controls. Vaccinated patients showed a significantly higher frequency of rs78233829 C (230Gly) compared to non-vaccinated patients (CC vs. CG + GG; p = 0.003; OR = 2.13; 1.29–3.50). The two STING1 variants were in strong linkage disequilibrium, with the rs78233829 C haplotypes being significantly more common in the vaccinated (p = 0.02; OR = 1.66; 95%CI = 1.01–2.55). We also studied the LTZFL1 rs67959919 G/A polymorphism that was significantly associated with severe COVID-19 (p < 0.001; OR = 1.83; 95%CI = 1.28–2.63). However, there were no differences between the non-vaccinated and vaccinated patients for this polymorphism. Conclusions. We report a significant association between common functional STING1 polymorphisms and the risk of developing severe COVID-19 among fully vaccinated patients. Full article

Estrogens regulate many physiological processes in the human body, including the cardiovascular system. Importantly, Estradiol (E2) exerts its vascular protective actions, in part, by promoting endothelial repair via induction of endothelial cell (EC) proliferation, migration and angiogenesis. Recent evidence that microRNAs (miRNAs) play an important role in vascular health and disease as well as in regulating Estrogen actions in many cell types. We hypothesize that E2 may mediate its vascular protective actions via the regulation of miRNAs. Following initial screening, we found that E2 downregulates the levels of miR-193a-3p in ECs. Moreover, miR-193a-3p downregulation by miR-193a-3p-antimir mimicked the effects as E2 on EC growth, migration, and capillary formation. Restoring miR-193a-3p levels with mimics after E2 treatment abrogated the vasculogenic actions of E2, suggesting a key role of miR-193a-3p in E2-mediated EC-growth-promoting effects. We further investigated the cellular mechanisms involved and found that miR-193a-3p inhibits angiogenesis by blocking phosphoinositide-3-kinase (PI3K)/Akt-vascular endothelial growth factor (VEGF) and Activin receptor-like kinase 1 (ALK1)/SMAD1/5/8 signaling in ECs, both pathways that are important in E2-mediated vascular protection. Additionally, using reverse transcription polymerase chain reaction (RT-PCR), we demonstrate that E2 downregulates miR-193a-3p in ECs via Estrogen Receptor (ER)α, but not ERβ or G protein-coupled estrogen receptor (GPER). Moreover, these actions occur post-transcriptionally, as the expression of pri-miR-193a-3p was not affected. The anti-angiogenic actions of miR-193a-3p were also observed in in vivo Matrigel implant-based capillary formation studies in ovariectomized mice where E2 induced capillary formation, and these effects were abrogated in the presence of miR-193a-3p, but not in the control mimic. Assessment of miR-193a-3p levels in plasma collected from in vitro fertilization (IVF) subjects with low and high E2 levels showed significantly lower miR-193a-3p levels in responders during the high E2 period. Hence, our findings provide the first evidence that miR-193a-3p mimic inhibits angiogenesis whereas its antimir is angiogenic. Importantly, E2 mediates its regenerative actions on ECs/capillary formation by downregulating endogenous miR-193a-3p expression. Both miR-193a-3p mimic or antimir may represent important therapeutic molecules to prevent or to induce endothelial function in treating pathophysiologies associated with capillary growth. Full article

The abnormal growth of smooth muscle cells (SMCs) contributes to the vascular remodeling associated with coronary artery disease, a leading cause of death in women. Estradiol (E2) mediates cardiovascular protective actions, in part, by inhibiting the abnormal growth (proliferation and migration) of SMCs through various mechanism. Since microRNAs (miRNAs) play a major role in regulating cell growth and vascular remodeling, we hypothesize that miRNAs may mediate the protective actions of E2. Following preliminary leads from E2-regulated miRNAs, we found that platelet-derived growth factor (PDGF)-BB-induced miR-193a in SMCs is downregulated by E2 via estrogen receptor (ER)α, but not the ERβ or G-protein-coupled estrogen receptor (GPER). Importantly, miR-193a is actively involved in regulating SMC functions. The ectopic expression of miR-193a induced vascular SMC proliferation and migration, while its suppression with antimir abrogated PDGF-BB-induced growth, effects that were similar to E2. Importantly, the restoration of miR-193a abrogated the anti-mitogenic actions of E2 on PDGF-BB-induced growth, suggesting a key role of miR-193a in mediating the growth inhibitory actions of E2 in vascular SMCs. E2-abrogated PDGF-BB, but not miR-193a, induced SMC growth, suggesting that E2 blocks the PDGF-BB-induced miR-193a formation to mediate its anti-mitogenic actions. Interestingly, the PDGF-BB-induced miR-193a formation in SMCs was also abrogated by 2-methoxyestradiol (2ME), an endogenous E2 metabolite that inhibits SMC growth via an ER-independent mechanism. Furthermore, we found that miR-193a induces SMC growth by activating the phosphatidylinositol 3-kinases (PI3K)/Akt signaling pathway and promoting the G1 to S phase progression of the cell cycle, by inducing Cyclin D1, Cyclin Dependent Kinase 4 (CDK4), Cyclin E, and proliferating-cell-nuclear-antigen (PCNA) expression and Retinoblastoma-protein (RB) phosphorylation. Importantly, in mice, treatment with miR-193a antimir, but not its control, prevented cuff-induced vascular remodeling and significantly reducing the vessel-wall-to-lumen ratio in animal models. Taken together, our findings provide the first evidence that miR-193a promotes SMC proliferation and migration and may play a key role in PDGF-BB-induced vascular remodeling/occlusion. Importantly, E2 prevents PDGF-BB-induced SMC growth by downregulating miR-193a formation in SMCs. Since, miR-193a antimir prevents SMC growth as well as cuff-induced vascular remodeling, it may represent a promising therapeutic molecule against cardiovascular disease. Full article

Curcumin-mediated anti-cancer properties have been correlated with the inhibition of oncogenic molecules such as mutp53 and c-Myc. Their targeting is therapeutically significant, as p53, following point mutations, can acquire oncogenic functions, and c-Myc overexpression, due to translocations, point mutations, protein/protein interactions, or epigenetic modifications, plays a central role in cancer cell proliferation and metabolic reprogramming, particularly in colorectal cancer. In a previous study, we showed that curcumin strongly downregulated mutp53 while activating wtp53 and reduced the expression of methyltransferases such as EZH2, G9a, and MLL-1 in colon cancer cells. Based on this background, here we investigated whether the dysregulation of such methyltransferases could correlate with the effect observed on p53. We also explored whether these epigenetic changes could affect c-Myc expression in these cells. By Western blot analysis and RT-qPCR, we found that the downregulation of EZH2; G9a; and, to a lesser extent, KDM1, which was also reduced by curcumin, correlated with the decrease in mutp53 and that the reduction of EZH2 and KDM1 correlated with the activation of wtp53. Regarding c-Myc, we unveiled the occurrence of a positive feedback loop between it and MLL-1, which was inhibited by curcumin, independently of the p53 status. In conclusion, this study provides new insights into the therapeutic potential of curcumin, which involves its properties to act as an epigenetic modulator and target key molecules in colon cancer cells. Full article

Water temperature significantly affects the physiological balance of aquatic organisms like crustaceans, and heat shock proteins (HSPs) are crucial for stress resistance and pathogen defense. This study conducted a genome-wide analysis to explore the functional characteristics of the Hsp70 gene family in Procambarus clarkii. Fifteen Hsp70 family members were identified, with several genes showing upregulation under non-lethal heat shock (NLHS) and pathogen challenges. RNA-Seq and qPCR analyses confirmed increased expression of certain PcHsp70s during NLHS, indicating NLHS activation of the Hsp70 family to enhance immune regulation. dsRNA-mediated silencing of Hsp70 led to downregulation of TLR pathway genes (e.g., TLR1, TLR6), suggesting Hsp70 regulates the TLR signaling pathway for immune responses. These findings reveal that NLHS-induced Hsp70 upregulation improves pathogen resistance, offering insights for addressing temperature fluctuations and disease outbreaks in aquaculture to optimize management practices. Full article

Background/Objectives: Dendrobium nobile Lindl. (DNL), a traditional dietary supplement, exhibits therapeutic potential for type 2 diabetes mellitus (T2DM), yet its mechanisms remain unclear. Methods: T2DM was induced in db/db mice. DNL (10 g/kg/d) or metformin (65 mg/kg/d) was administered for 4 weeks. This study integrated pharmacodynamic evaluation and multi-omics to elucidate DNL’s anti-diabetic effects in db/db mice. Results: DNL intervention significantly ameliorated T2DM phenotypes, reducing hyperglycemia, insulin resistance, and renal dysfunction. Metabolomics analysis identified 39 differential metabolites (19 upregulated, 20 downregulated) linked to citrate cycle, oxidative phosphorylation, and glycerophospholipid metabolism, while proteomics revealed 113 differentially expressed proteins, with multi-omics integration highlighting DNL’s modulation of three proteins (Ckm, Ache, Selenbp1) and four metabolites (4-guanidinobutanoic acid, phosphorylcholine, homocysteine, succinic acid) across arginine/proline metabolism, glycerophospholipid metabolism, and sulfur metabolism. Pathway analysis demonstrated DNL’s restoration of dysregulated processes, including inflammation suppression via NF-κB and PI3K-Akt pathways, enhanced insulin sensitivity through glycerophospholipid balance, and mitigation of oxidative stress via sulfur metabolism. Key correlations between metabolites and proteins underscored DNL’s multi-target action. Conclusions: These findings systematically decode therapeutic mechanisms of Dendrobium nobile Lindl., emphasizing its role in rectifying metabolic disorders and inflammatory signaling, thereby providing a molecular basis for its clinical application in T2DM management. Full article