Explore the vast range of titles available.

Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.

The role of trimethylamine oxide (TMAO) in patients with cognitive impairment remains controversial. This study aimed to assess the association between TMAO and its precursors and the prevalence of cognitive impairment. PubMed, Embase, and Web of Science databases were searched for studies that met the inclusion criteria from their inception to 14 September 2024, and references were manually searched to identify any additions. Odds ratio (OR) was assessed by random-effects modeling, subgroup analyses to identify potential sources of heterogeneity, and the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) Inventory for qualitative evaluation. Nine studies involving 82,246 participants were included in the analysis. Meta-analyses suggested that elevated TMAO levels were strongly associated with an increased risk of cognitive impairment (OR: 1.39, 95% confidence interval [95%CI]: 1.09-1.77,  < 0.05, I :60%), and consistent results were obtained across all subgroups examined and sensitivity analyses. However, in the TMAO dose-response meta-analysis and TMAO precursor meta-analyses, the results were not significantly different (dietary choline: OR: 0.93, 95%CI: 0.78-1.10, = 0.385, I :68%, plasma choline: OR: 0.65, 95%CI: 0.41-1.02,  = 0.063, I :76%, plasma betaine: OR: 0.74, 95%CI: 0.52-1.05,  = 0.094, I :61%). We found that high TMAO concentrations were positively associated with the risk of cognitive impairment. TMAO is expected to be a potential risk predictor and therapeutic target for cognitive impairment. However, more high-quality studies are needed to further investigate the dose relationship between circulating TMAO concentrations and cognitive impairment. PROSPERO, identifier: CRD42023464543.

Patients with type 2 diabetes mellitus (T2DM) often exhibit dysregulated lipid metabolism, which contributes to the development and progression of complications, such as cardiomyopathy and nephropathy. Lipid droplet (LD) dynamics involve several processes, such as synthesis, lipolysis, and lipophagy. They also interact with organelles, such as the endoplasmic reticulum, mitochondria, and Golgi apparatus. These dynamic behaviors are essential for the maintenance of cellular energy homeostasis. Under physiological conditions, LDs in pancreatic β-cells are involved in lipid metabolism that regulates insulin secretion, while also isolating harmful lipids to protect β-cells from damage due to nutrient excess. In the adipose tissue, LDs respond to nutrient fluctuations by modulating lipolysis and releasing free fatty acids (FFAs) and glycerol. Glycerol can enter the liver for gluconeogenesis and changes in FFA levels affect systemic insulin sensitivity, thereby influencing glucose uptake by skeletal muscles and contributing to whole-body glucose homeostasis. Under pathological conditions, abnormal LD accumulation can lead to ectopic lipid deposition and lipotoxicity, exacerbating T2DM and its complications in target organs, such as the heart, kidneys, retina, and brain. Lifestyle interventions, such as diet and exercise, influence LD homeostasis in tissues affected by T2DM. Pharmacological agents, including certain antidiabetic and lipid-lowering drugs as well as bioactive natural products, have demonstrated tissue-specific regulatory effects on LD dynamics. Emerging therapeutic strategies targeting LDs, such as photodynamic therapy, gene editing, and gut microbiota modulation, are also being investigated. In summary, a deeper understanding of the physiological and pathological roles of LDs in different organs may offer targeted and integrated treatment options for T2DM and its associated complications.

Objective: This study aimed to assess the efficacy and safety of traditional Chinese medicine decoction as an adjunctive treatment for diabetic nephropathy in systematic evaluations. Methods: A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering the period from January 2013 to July 2023. The search was restricted to randomized controlled trials (RCTs) conducted within the past decade that investigated the use of TCM decoction as an adjunctive treatment for diabetic nephropathy. The control group received western medicine treatment, while the intervention group received TCM decoction in addition to the conventional treatment. Endnote and Excel were employed for literature management and data organization, and Revman 5.3 and Stata 16 software were used for the analyses. Results: 66 RCTs involving 6,951 participants were included in this study. The clinical efficacy of TCM decoction as an adjunctive treatment for diabetic nephropathy was found to be significantly higher than that of the control group (OR = 3.12, 95% CI [2.70, 3.60], I 2 = 0%, p < 0.00001). The incidence of adverse events did not differ significantly between the intervention group and the control group (OR = 0.94, 95% CI [0.60, 1.48], I 2 = 0%, p = 0.94). According to the secondary outcomes of renal function and blood glucose indicators, the intervention group showed better therapeutic efficacy compared to the control group. The most frequently used TCM categories were tonifying medicine, blood-activating medicine, astringent medicine, diuretic medicine, heat-clearing medicine, and laxative medicine. Among them, the top five frequently used Chinese medicine were Astragalus mongholicus Bunge [Fabaceae; Astragali mongholici radix](58 times), Salvia miltiorrhiza Bunge [Lamiaceae; Radix et rhizoma salviae miltiorrhizae] (42 times), Dioscorea oppositifolia L. [Dioscoreaceae; Dioscoreae rhizoma] (38 times), Poria cocos (Schw.) Wolf [Polyporaceae; Poria] (38 times), and Cornus officinalis Siebold & Zucc. [Cornaceae; Corni fructus] (35 times). Conclusion: The combined use of TCM decoction with western medicine in the treatment of diabetic nephropathy can enhance clinical effectiveness and 2 This is a provisional file, not the final typeset article achieve superior therapeutic effects in comparison to western medicine alone, without significant risks. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails , identifier [ CRD42022529144 ].

[This corrects the article DOI: 10.3389/fnagi.2024.1465457.].

Background: Diabetic kidney disease (DKD) is an important public health problem worldwide that increases the mortality of patients and incurs high medical costs. Traditional Chinese Medicine injections (TCMIs) are widely used in clinical practice. However, their efficacy is unknown owing to a lack of definitive evidence. This study conducted a network meta-analysis (NMA) to evaluate the efficacy and safety of traditional Chinese medicine injections in the treatment of DKD to provide a reference for clinical treatment. Methods: Total 7 databases had been searched, which included PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese scientific journal database (VIP), WanFang, and SinoMed. Only randomised controlled trials (RCT) had been included for analysis. The retrieval time limit was from the establishment of the database until 20 July 2022. Cochrane Risk of Bias 2.0 tool was used to evaluate the quality of the studies. Network meta-analyses, and Trial Sequential Analyses (TSA) were used to analysis the effectiveness of the included RCTs for DKD. The Stata 15.1 and R 4.0.4 were used to perform the network meta-analysis. Sensitivity analysis was used to assess the robustness of the findings. The effect of the intervention evidence are summarized on the basis of the minimum background framework. Results: NMA showed that the total effective rate of SMI, DCI, DHI, HQI, and SKI combined with alprostadil injection (PGE1) was better than PGE1 single used. Based on the surface under the cumulative ranking curve values, PGE1+DHI was the most effective for urinary albumin excretion rate and 24 h urinary albumin, PGE1+HQI was the most effective for the total response rate and β2-MG, and PGE1+SKI was the most effective for serum creatinine and blood urea nitrogen. Cluster analysis found that PGE1+HQI and PGE1+SKI could be the best treatments in terms of primary outcome measures. PGE1+SKI was found to be most effective on glomerular filtration function. PGE1+DHI was most effective for urinary protein-related indices. Conclusion: The efficacy of TCMI combined with PGE1 was higher than PGE1 single used. PGE1+HQI and PGE1+SKI were the most effective treatments. The safety of TCMI treatment should be investigated further. This study needs to be validated using large-sample, double-blind, multicentre RCTs. Systematic Review Registration : [ https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=348333 ], identifier [CRD42022348333].

Unique fucosylated chondroitin sulfate (FCS) extracted from the sea cucumber Stichopus horrens was subjected to deacetylation and deaminative depolymerization to generate oligosaccharide fragments containing anTal-diol, which were further purified to obtain the trisaccharide ShFCS-3. Subsequently, the coupling of ShFCS-3 and 4-azidoaniline was achieved by reductive amination. After purification, the main product ShFCS-A1 and by-product ShFCS-A2 were obtained, which were identified as (N-(L-Fuc2S4S-α1,3-D-GlcA-β1,3-D-anTalA4S6S-1-)-4-azidoaniline) and (4S)-[2-(3-L-Fuc2S4S-α1)-D-GlcA-β1]-2,4,5-trihydroxy-5-sulfated-pent-2-enoic-acid) by 1D/2D NMR spectroscopy, respectively. ELISA experiments revealed that ShFCS-A1 exhibited P-selectin inhibition rates of 19.73% ± 9.60% at 1 μM, 96.28% ± 2.37% at 10 μM, and near-complete inhibition (99.92% ± 0.84%) at 100 μM. ShFCS-A2 demonstrated inhibition rates of 8.29% ± 3.00% at 1 μM, 74.02% ± 8.80% at 10 μM, and maximal inhibition approaching 100% at 100 μM. Cellular-level experiments revealed that ShFCS-A1 and ShFCS-A2 inhibited P-selectin binding to HL-60 cells by 92.72% ± 0.85% and 96.97% ± 1.16% at 100 μM, respectively. Molecular docking analysis indicated binding energies of −5.954 kcal/mol for ShFCS-A1 and −6.140 kcal/mol for ShFCS-A2 with P-selectin, confirming their potent inhibitory effects. These findings highlight the therapeutic potential of FCS oligosaccharides as pharmacophores and provide an important foundation for developing novel small-molecule P-selectin inhibitors.

ObjectiveTo alleviate the economic burden of innovative drugs on patients in China, the government has been negotiating drug prices since 2016 to enhance their accessibility. This systematic review aimed to discuss the impact of the National Medication Price Negotiation Policy (NMPNP) on the accessibility of drugs in China in the years 2016–2024.DesignSystematically reviewed the studies’ findings and evaluated their quality using the Newcastle-Ottawa Scale (NOS) collaborative tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 were used to facilitate transparent and complete reporting of our systematic review.Data sourcesPubMed, Web of Science, CNKI and Wanfang were searched from 1 January 2016 to 1 October 2024.Eligibility criteria for selecting studiesThe inclusion criteria of this study is a quantitative study to evaluate the accessibility of negotiated drugs after the implementation of the NMPNP.Data extraction and synthesisTwo researchers independently searched the literature, extracted the data and cross-checked them. Any disagreements were resolved by discussion or consultation with a third party. The quality of systematic reviews was assessed using the NOS.ResultsA total of 32 studies were included in this review, 8 of the studies were assessed to be high quality based on the NOS, 17 as moderate quality and the remaining 7 as low quality. Most of them showed that after the implementation of the NMPNP, the availability, affordability, defined daily doses, hospital purchase volume and expenditure of negotiated drugs increased, and the price and defined daily dose cost of negotiated drugs decreased. However, a few studies found that some drugs are difficult to be admitted to hospitals and consumption dropped after the implementation of the NMPNP due to low clinical demand and weak competitiveness.ConclusionsThe implementation of NMPNP improved drug accessibility for patients and most regions had good implementation effects which can provide some insights for other countries. However, the high utilisation of successfully negotiated drugs has increased health insurance expenditures, potentially affecting the fund’s stability. This necessitates government regulation of both the use of these drugs and health insurance funds. Moreover, different regions and medical institutions had different development levels and resource allocations, resulting in uneven effects of the NMPNP which need to be improved in the future.

Microliquid-dispensing technology is widely used in the life sciences and other fields. In this paper, a syringe-pump-actuated microliquid-dispensing system is designed, and its bond-graph model is constructed. Combining a syringe pump and pipeline, the system controls the piston movement inside the syringe pump to dispense microliquid. The bond-graph model is derived from integrating the electromechanical model with the fluid model. The lumped parameter method is utilized to divide the fluid model into several blocks for higher accuracy. Model correctness is verified by simulations and experiments, and further simulation studies on the pipeline pressure and flow rate based on the bond-graph model are carried out. Results are used to guide the design and control work on the proposed system.

Articular cartilage repair in osteoarthritis (OA) remains a major clinical challenge. Although approaches using mesenchymal stem cells (MSCs) have demonstrated partial efficacy in OA, the regenerated tissue is often unable to form stable hyaline-like cartilage phenotype. Here, we introduce immunity-and-matrix-regulatory cells (IMRCs), derived from human embryonic stem cells (ESCs), as an alternative cell source for OA therapy. Using a multiple-level platform including 2D chondrocytes, 3D OA cartilage organoids (OCOs), rabbit cartilage explants, and a rat OA model, we demonstrate that IMRCs significantly enhance hyaline-like matrix formation while suppressing inflammation, angiogenesis, and fibrotic remodeling. Mechanistically, IMRC-mediated cartilage repair is partially associated with MMP1-dependent matrix remodeling. This study establishes a translational evaluation strategy for IMRCs and points to their potential as an alternative cell source for inducing cartilage repair in OA. Notably, the OCOs established in this study provide a pathologically relevant in vitro platform for evaluating cartilage regeneration in OA. [Display omitted] •ESC-derived IMRCs promote hyaline-like cartilage regeneration and exhibit superior anti-fibrotic effects compared with UC-MSCs.•IMRC-driven hyaline-like cartilage repair is partially associated with MMP1-dependent matrix remodeling.•OA cartilage organoids (OCOs) provide a promising platform for evaluating the efficacy of cell-based therapies.