: Orthopaedic repair outcomes are limited by disrupted cellular mechanotransduction and physiological instability during anaesthesia. Integrating biomechanical signal modulation with stabilising perioperative strategies...: Orthopaedic repair outcomes are limited by disrupted cellular mechanotransduction and physiological instability during anaesthesia. Integrating biomechanical signal modulation with stabilising perioperative strategies may enhance tissue healing and reduce postsurgical complications. : Existing orthopaedic therapies fail to restore native mechanosensory signalling at repair sites, leading to delayed recovery, implant loosening, and reduced function. Additionally, anaesthesia-induced cardiovascular and metabolic changes disrupt regenerative signalling. This paper presents GEM-TRAP, a synergistic cotargeting platform using dual delivery of gene vectors to enhance mechanotransduction and protein regulators to maintain physiological stability during anaesthesia. Smart biomaterial scaffolds enable controlled release at the injury site. : In vivo results show improved osseointegration, a 38% increase in load-bearing strength, enhanced neural-mechanical signalling, and a 27% reduction in complications, demonstrating GEM-TRAP's potential for advanced orthopaedic regeneration. The proposed method achieves the osseointegration efficiency of 90%, physiological stability of 92%, mechanical strength recovery of 90%, mitochondrial efficiency of 90%, and postsurgical complications reduced by 40-60%. : This study presents GEM-TRAP, a novel cotargeting platform that concurrently enhances cellular mechanotransduction and maintains physiological stability during anaesthesia. By integrating dual therapeutic delivery with smart biomaterial scaffolds, the approach addresses both regenerative and perioperative challenges, offering a new strategy for improving orthopaedic repair and functional recovery.
BACKGROUND: Ulcerative colitis is a chronic inflammatory bowel disease characterised by disrupted anti-inflammatory cell mechanisms in the intestinal mucosa. PURPOSE: This study explores quercetin's protective role by re...BACKGROUND: Ulcerative colitis is a chronic inflammatory bowel disease characterised by disrupted anti-inflammatory cell mechanisms in the intestinal mucosa. PURPOSE: This study explores quercetin's protective role by restoring anti-inflammatory mechanisms and regulating this pathway. METHODS: Experimental models included DSS-induced mice and LPS-stimulated RAW264.7 cells, assessed via disease activity scoring, histopathology, qPCR, ELISA, and Western blot. RESULTS: Quercetin intervention could effectively repair the anti-inflammatory cell function, reverse the imbalance of inflammatory factors, inhibit the phosphorylation of p38 MAPK and the expression of MK2 and MK3, improve the intestinal mucosal damage and disease activity in mice, and reverse the pro-inflammatory polarisation of macrophages in vitro. Quercetin could further enhance the anti-inflammatory effect when combined with p38 MAPK inhibitor. CONLUSION: Therefore, quercetin can repair the anti-inflammatory cell action mechanism, inhibit the activation of p38 MAPK-MK2/MK3 signalling pathway, alleviate the inflammatory damage of intestinal mucosa in ulcerative colitis, and provide experimental basis for anti-inflammatory cell-targeted treatment of ulcerative colitis.
Aflatoxin B1 (AFB1) is a prominent mycotoxin known to cause significant toxic effects in numerous organs and tissues. Experimental studies on intestinal tissue demonstrate that AFB1-induced damage is primarily driven by...Aflatoxin B1 (AFB1) is a prominent mycotoxin known to cause significant toxic effects in numerous organs and tissues. Experimental studies on intestinal tissue demonstrate that AFB1-induced damage is primarily driven by free radical generation, oxidative stress, inflammatory responses, cytochrome P450 upregulation, lipid peroxidation, and apoptosis. In recent years, phytochemicals have attracted considerable interest due to their antioxidant, anti-inflammatory, and anti-apoptotic properties, which suggest a promising strategy for alleviating AFB1-related intestinal toxicity. Nevertheless, research on their therapeutic efficacy remains relatively limited. This review aims to assess the protective roles of phytochemicals in mitigating oxidative stress and inflammation associated with AFB1 exposure. Evidence indicates that well-studied phytochemicals such as curcumin, resveratrol, lycopene, melatonin, and polydatin reduce intestinal injury by modulating critical signalling pathways, including Nrf2/ARE, TLR4, NF-κB, and NLRP3, as well as by influencing the intestinal microbiota composition. Overall, this review highlights their potential therapeutic value and underlying molecular mechanisms.
BACKGROUND: Osteoporosis is a global health problem characterised by decreased bone density and degeneration of bone microstructure, leading to an increased risk of fractures. PURPOSE: The aim of this study is to explore...BACKGROUND: Osteoporosis is a global health problem characterised by decreased bone density and degeneration of bone microstructure, leading to an increased risk of fractures. PURPOSE: The aim of this study is to explore the role of SOST protein regulation mechanism in enhancing bone strength during endurance training. METHODS: An animal model was constructed using 8-week-old male C57BL/6 mice and divided into five groups: blank control group, sham operation control group, endurance training group, SOST gene knockout (KO) control group, and SOST KO+endurance training group. RESULTS: The results showed that the levels of bone formation markers PINP and BALP in serum were significantly increased ( < 0.05), while the levels of bone resorption markers CTX and TRACP-5b did not show significant changes. CONCLUSION: Therefore, endurance training activates the Wnt/β-catenin signalling pathway by downregulating SOST protein expression. SOST protein is a core molecular target for endurance training to enhance bone strength.
: The conditions associated with pregnancy, such as preeclampsia, gestational diabetes, and disruptions of Placental lipid transport, are increasingly becoming known to be the cause of intrauterine growth restriction. Re...: The conditions associated with pregnancy, such as preeclampsia, gestational diabetes, and disruptions of Placental lipid transport, are increasingly becoming known to be the cause of intrauterine growth restriction. Recent data indicate that compensatory efforts can initiate neuroinflammatory and systemic reactions in the mother, which can influence foetal development. : This study aims to learn how maternal brain inflammation and neuroimmune activation during complicated pregnancies can be triggered by abnormal placental lipid carriage. : PBIC-SM and NLIP-IM models are employed to examine lipid-induced CNS inflammation and neuroimmune lipidomic changes, focusing on how altered placental lipid transport affects maternal lipid profiles, oxidative stress, and inflammation. : Disrupted lipid balance alters microglial activity and increases IL-6 and TNF-α levels, showing that impaired placental transport can trigger neuroinflammation during pregnancy. In high-risk cases, early intervention and targeted therapies may help preserve maternal mental health by addressing placenta-brain immune dysregulation.
BACKGOUND: Breast cancer exhibits high heterogeneity and drug resistance, presenting severe challenges in clinical treatment. PURPOSE AND METHOD: This study takes cellular lipid metabolism regulation as the core entry po...BACKGOUND: Breast cancer exhibits high heterogeneity and drug resistance, presenting severe challenges in clinical treatment. PURPOSE AND METHOD: This study takes cellular lipid metabolism regulation as the core entry point, integrates network pharmacology and computational biology techniques to mine the breast cancer transcriptome data from the GEO database GSE45827, GSE33447, and TCGA-BRCA database. Combined with molecular docking technology, it verifies the binding characteristics and action mode of lidocaine with the core target proteins. RESULT: The study identified 6 core genes regulated by lidocaine in breast cancer, G6PD, ALB, EDN3, FGF2, MAOB, and DMD, all of which are directly or indirectly related to cellular lipid metabolism regulation. CONCLUSION: This study clarified the core mechanism by which lidocaine regulates the lipid metabolism reprogramming of breast cancer cells through multiple targets, revealed that cellular lipid metabolism regulation is the key pathway for its anti-tumour effect, and provided a metabolic-level theoretical basis for repurposing of lidocaine as an old drug.
: Delayed healing of diabetic wounds is driven by insufficient angiogenesis and maladaptive immunity. An unbiased screen of wound transcriptomes identified prolactin-induced protein (GCDFP-15) as consistently upregulate...: Delayed healing of diabetic wounds is driven by insufficient angiogenesis and maladaptive immunity. An unbiased screen of wound transcriptomes identified prolactin-induced protein (GCDFP-15) as consistently upregulated. : Utilizing murine diabetic wound models, we investigated the functional role of GCDFP-15 through genetic deletion and topical recombinant protein administration. : Genetic deletion of GCDFP-15 accelerated wound closure, enhanced angiogenesis, and promoted a pro-reparative macrophage phenotype. This was mediated by activation of the PI3K/AKT/mTOR/STAT3 signalling axis. Conversely, topical GCDFP-15 impaired repair and inhibited this pathway in knockout mice. : GCDFP-15 acts as an endogenous inhibitor of diabetic wound healing by suppressing pro-reparative signalling. Targeting GCDFP-15 may represent a novel therapeutic strategy.
: Sirtuin-2 (SIRT2) is a longevity-related protein implicated in apoptosis, metabolic regulation and oxidative stress; however, its role in ageing pancreas remains unclear. : This study investigated the effects of the se...: Sirtuin-2 (SIRT2) is a longevity-related protein implicated in apoptosis, metabolic regulation and oxidative stress; however, its role in ageing pancreas remains unclear. : This study investigated the effects of the selective SIRT2 inhibitor, Arabidopsis guanylate kinases-2 (AGK-2) on oxidative stress and apoptosis in aged rat pancreatic tissue. : Young (3-month) and aged (22-month) rats were divided into control and AGK-2-treated groups (10 μM, 30 days). Total oxidant status (TOS) and total antioxidant status (TAS) used commercial kits, then calculated Oxidative stress index (OSI). For detecting nitrosative stress, we determined nitrite-nitrate levels using the Griess test. SIRT2 and caspase-3 were evaluated by ELISA and Western blot. : Our findings showed that ageing increased SIRT2 expression, oxidative stress and caspase-3 protein compared to young rats. AGK-2 treatment reduced SIRT2, TOS, OSI and caspase-3, and increased TAS particularly in aged rats. AGK-2 reverses ageing-associated changes in pancreatic oxidative stress and apoptosis. SIRT2 modulation may represent a potential therapeutic target against age-related pancreatic degeneration.
BACKGROUND: Urotensin II (U-II) is one of the most potent endogenous vasoconstrictors, with its vascular effects tightly regulated by endothelial function and ion channel activity. The impact of diabetes mellitus on the...BACKGROUND: Urotensin II (U-II) is one of the most potent endogenous vasoconstrictors, with its vascular effects tightly regulated by endothelial function and ion channel activity. The impact of diabetes mellitus on the signalling mechanisms underlying U-II-induced vascular reactivity remains insufficiently understood. OBJECTIVE: This study systematically investigated how diabetes alters U-II-induced vasoconstriction by dissecting the contributions of endothelial integrity, potassium channel subtypes, calcium influx, and gap junction communication in the thoracic aorta of normoglycemic and streptozotocin-induced diabetic rats. METHODS: Isolated aortic rings with intact or denuded endothelium were exposed to cumulative concentrations of U-II (1 0 -1 0 -8 M). Pharmacological inhibitors-including L-NAME (NOS inhibitor), indomethacin (COX inhibitor), TEA (Kv channel blocker), BaCl (Kir channel blocker), clotrimazole (IKCa channel blocker), nifedipine (L-type Ca channel blocker), and GAP27 (gap junction inhibitor) were employed to delineate mechanistic pathways. RESULTS: Endothelial removal significantly potentiated U-II-induced contractions in both non-diabetic and diabetic vessels, affirming the critical modulatory role of endothelium-derived vasodilators. Diabetic vessels exhibited marked reductions in maximal contraction (Emax) and sensitivity (pD) to U-II. In non-diabetic aorta, Kir and IKCa channel blockade robustly suppressed U-II-induced contraction, whereas these effects were diminished or reversed in diabetic tissue, indicating functional channel dysregulation. L-NAME potentiated U-II responses selectively in diabetes, implicating impaired nitric oxide bioavailability. Strikingly, nifedipine enhanced U-II-mediated contraction in diabetic rats, suggesting maladaptive remodelling of calcium influx. GAP27 reduced U-II responses, with a more pronounced inhibitory effect in diabetic vessels, highlighting disease-specific alterations in gap junction signalling. CONCLUSION: Diabetes markedly impairs urotensin II-induced vascular contractility by disrupting Kir and IKCa potassium channel function, alongside distinct changes in calcium channels, gap junctions, and prostanoids. Restoring Kir and IKCa may offer an effective therapeutic strategy to reverse vascular dysfunction in diabetic vascular myopathy.
BACKGROUND AND PURPOSE: This study, based on the network pharmacology approach, aims to systematically explore the potential molecular mechanism of Cangshu Diantong Pill in treating type 2 diabetes (T2DM), and particular...BACKGROUND AND PURPOSE: This study, based on the network pharmacology approach, aims to systematically explore the potential molecular mechanism of Cangshu Diantong Pill in treating type 2 diabetes (T2DM), and particularly emphasises the theoretical correlation between its mechanism of action and the modern metabolic abnormality diagnostic indicators. METHODS: The study first screened the active components in Cangshu Diantong Pill that have pharmacokinetic characteristics through databases such as TCMIP, it integrated disease databases to obtain T2DM-related targets and constructed a drug-disease intersection target network. Core targets included AKT2, TNF, ADIPOQ, IGF1, etc., all of which are key biomarkers in current metabolic abnormality diagnostics. RESULTS: Pathway enrichment showed that Cangshu Diantong Pill mainly exerts its effects by regulating signalling pathways. CONCLUSION: The study suggests that Cangshu Diantong Pill's intervention on T2DM may manifest as a synergistic regulation of multiple metabolic abnormality links, and its theoretical action pathway is highly consistent with the modern metabolic diagnostic system.
BACKGROUND: The occurrence and development of intestinal diseases are closely related to intestinal metabolic disorders. PURPOSE: This study focuses on the metabolic analysis of intestinal diseases under nutritional inte...BACKGROUND: The occurrence and development of intestinal diseases are closely related to intestinal metabolic disorders. PURPOSE: This study focuses on the metabolic analysis of intestinal diseases under nutritional intervention as the core perspective, aiming to construct a prediction model for the tolerance of patients undergoing non-sedating colonoscopy. RESULTS: The results showed that the completion rate of the examination for the study subjects was 89.93%. Those who did not complete the examination mainly suffered from pain intolerance and poor intestinal preparation. Univariate analysis indicated that age, grade III anxiety, history of constipation, and the operator had statistical effects on the completion rate. Age and history of constipation affected the examination completion time. Multivariate analysis confirmed that grade III anxiety, history of constipation. CONCLUSION: The study provides clinical evidence and intervention targets for using nutritional intervention to regulate intestinal metabolic status and enhance the tolerance of non-sedating colonoscopy.
ABSTARCTThe present study investigates the neuroprotective effects of Cannabidiol (CBD) in olanzapine/high-fat diet (HFD) treated adult male Wistar rats. Animals weighing 160-180 g were divided into five groups (n = 7)....ABSTARCTThe present study investigates the neuroprotective effects of Cannabidiol (CBD) in olanzapine/high-fat diet (HFD) treated adult male Wistar rats. Animals weighing 160-180 g were divided into five groups (n = 7). They include Untreated, HFD+Olan, Met + HFD+Olan, CBD (10 mg/kg)+HFD+Olan, and CBD (25 mg/kg)+HFD + Olan. Olanzapine and metformin were administered as 5 mg/kg and 20 mg/kg, respectively. Cognitive functions, brain biochemical markers, histology and immunohistochemistry were determined. 2 weeks cotreatment of olanzapine/HFD induced cognitive impairment evidenced by significant reduction in Object location memory (OLM) from 3.5 ± 0.75 to -39 ± 8.57% and Object recognition memory (ORM) indices from 21.47 ± 12.68 to -30.30 ± 4.29%, increased serum amyloid beta 1-42 and GFAP hypothalamic and prefrontal cortex expressions. CBD comparable to metformin ameliorated the induced cognitive impairment. CBD possesses remarkable cognitive preserving activity which is associated with decreased lipid peroxidation and down regulation of GFAP/ACHE pathway.
BACKGROUND: Cellular ageing is closely related to various age-related diseases, and Klotho protein, as an anti-ageing related factor, plays an important role in delaying ageing by regulating cellular function and metabol...BACKGROUND: Cellular ageing is closely related to various age-related diseases, and Klotho protein, as an anti-ageing related factor, plays an important role in delaying ageing by regulating cellular function and metabolism. PURPOSE: This study aims to explore the role of Klotho protein in exercise intervention and its relationship with age-related metabolism. METHODS: Study the effects of exercise intervention on serum Klotho protein levels, Klotho gene methylation status, ageing related β - galactosidase (SA - β - Gal) activity, and ageing metabolic indicators, revealing the molecular mechanism of exercise delaying cellular ageing. The experiment was divided into a control group and an exercise intervention group, with an intervention period of 12 weeks. RESULTS: Exercise intervention significantly improved oxidative stress indicators and blood lipid metabolism. CONCLUSION: Exercise intervention delays cellular ageing by upregulating serum Klotho protein levels and reducing gene methylation levels, inhibiting SA - β - Gal activity, improving oxidative stress and lipid metabolism.
BACKGROUND: Exercise fatigue is an important factor affecting exercise performance and recovery. Studies have found that AMPK (adenosine monophosphate activated protein kinase) plays a key role in energy metabolism and e...BACKGROUND: Exercise fatigue is an important factor affecting exercise performance and recovery. Studies have found that AMPK (adenosine monophosphate activated protein kinase) plays a key role in energy metabolism and exercise adaptation. PURPOSE: The study aims to explore role of AMPK protein macromolecules in alleviating exercise fatigue and the characteristics of their signalling pathways. METHODS: This article uses a rat model for experiments, extracts and detects RNA from muscle tissue, and uses real-time fluorescence quantitative PCR to analyse the expression level of AMPK and evaluate its activation status. By analysing the expression effect of AMPK related protein signalling pathway, explore its impact on exercise fatigue. RESULTS: The exercise intervention group of rats regulated by AMPK showed significant improvement in exercise fatigue, significant increase in energy metabolism indicators, and enhanced immune function. CONCLUSION: The results indicate that AMPK protein macromolecules effectively alleviate exercise fatigue and improve energy metabolism and immune function by activating related signalling pathways.
BACKGROUND: With the intensification of population ageing, the incidence of bone metabolism-related diseases such as osteoporosis has significantly increased, becoming an important factor affecting the quality of life of...BACKGROUND: With the intensification of population ageing, the incidence of bone metabolism-related diseases such as osteoporosis has significantly increased, becoming an important factor affecting the quality of life of the elderly. MATERIALS AND METHODS: A total of 120 patients with rotator cuff tear (RCT) were selected as the research subjects. There were 65 male patients and 55 female patients. The aim of this study was to explore the predictive value of bone metabolism disease examinations and changes in proximal humeral bone density for intraoperative anchor loosening. The predictive value of proximal humeral bone density for intraoperative anchor loosening was analysed using the ROC curve. RESULTS: The increase in age and the decrease in bone density are closely related to risk of intraoperative anchor loosening. CONCLUSION: The combination of bone metabolism disease examinations and proximal humeral bone density detection can provide important basis for clinical preoperative prediction of anchor loosening risk and formulation of individualised treatment plans.
OBJECTIVE: This study aimed to explore the role of LINC00472 in type 2 diabetes mellitus (T2DM). METHODS: Serum LINC00472 expression was detected in 34 patients with T2DM and 45 healthy controls via RT-qPCR, with ROC cur...OBJECTIVE: This study aimed to explore the role of LINC00472 in type 2 diabetes mellitus (T2DM). METHODS: Serum LINC00472 expression was detected in 34 patients with T2DM and 45 healthy controls via RT-qPCR, with ROC curve analysing its diagnostic value. Mouse pancreatic β-cell line INS-1 was induced with high glucose (HG) to establish HG-INS-1 model. si-LINC00472 and miR-320b inhibitor were transfected into HG-INS-1. CCK-8, flow cytometry, and ELISA kits were used to detect cell viability, apoptosis, insulin level, and oxidative stress indicators. Subcellular fractionation, dual-luciferase reporter, and RIP assays verified the interaction between LINC00472 and miR-320b. RESULTS: Serum LINC00472 was elevated in T2DM patients, with AUC = 0.882, 73.81% sensitivity, and 94.29% specificity. Silencing LINC00472 enhanced HG-INS-1 viability, reduced apoptosis, increased insulin, decreased ROS/MDA, and increased GSH. LINC00472 was mainly cytoplasmic and targeted miR-320b. CONCLUSION: LINC00472 is a potential T2DM biomarker.
: Lipid peroxidation (LPO) causes oxidative stress and neuroinflammation in eye diseases. Malondialdehyde and 4-hydroxy-2-nonenal are produced in the eye via polyunsaturated fatty acid oxidation. : Electrophiles damage b...: Lipid peroxidation (LPO) causes oxidative stress and neuroinflammation in eye diseases. Malondialdehyde and 4-hydroxy-2-nonenal are produced in the eye via polyunsaturated fatty acid oxidation. : Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. : LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. : Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. : Understanding how lipid peroxidation, oxidative stress, and neuroinflammation interact is crucial to developing effective eye health and vision loss therapies.
Critical limb ischaemia (CLI), a severe peripheral artery disease, reduces blood flow, disrupting lipid metabolism and mitochondrial function. This leads to muscle loss, impaired repair, and greater limb loss risk. Stand...Critical limb ischaemia (CLI), a severe peripheral artery disease, reduces blood flow, disrupting lipid metabolism and mitochondrial function. This leads to muscle loss, impaired repair, and greater limb loss risk. Standard diagnostics emphasise imaging and perfusion, often missing metabolic changes. The LIPID-CLI framework uses high-resolution mass spectrometry to analyse lipid shifts under mitochondrial stress. Biopsy limits shifted focus to blood markers reflecting tissue lipids. Altered ceramides and phospholipids indicate lipid-mitochondrial dysfunction and may serve as non-invasive biomarkers for early CLI detection and treatment. The method improves ceramides (400 mL), phospholipid ratio (1.5), acylcarnitines (6 L), OxPLs (300 mL), index score (<0.4), and mediator levels (200 mL). The reduction denotes decreased ceramide concentration (µmol/mL or ng/mL), normalised to total lipid content in affected tissues. This measure reflects how ceramide alterations disrupt lipid homeostasis and mitochondrial function in critical limb ischaemia (CLI).