Improving Clinical Outcomes: Hightibialosteotomy Plate Placement Combined with Arthroscopic Surgery.

Objective: Our study aimed to investigate the clinical efficacy of hightibialosteotomy (HTO) posterior plate placement combined with arthroscopic surgery for degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower extremity, improve joint function or relieve pain. Methods: The case data of 98 patients with osteoarthritis of the knee admitted to the Department of Orthopedics in our hospital from January 2019 to January 2023 were selected for retrospective analysis. The patients were divided into 54 patients, each in the study group and the comparison group according to the different treatment regimens. The study group received hightibialosteotomy plate placement combined with arthroscopic surgery, while the comparison group underwent hightibialosteotomy plate placement alone. The differences in knee scores, knee Lysholm scores, Lysholm scores, Healthcare Security and Safety (HSS) scores, Tegner scores, Visual Analog Scale (VAS), lower extremity force lines, femorotibial angles, and tibial plateau were counted and compared between the two groups. Results: HSS knee function scores, Lysholm scores, and VAS scores of the study group were statistically significant compared with those of the comparison group at the final follow-up of patients, and the postoperative clinical outcomes improved significantly (P < .05). The differences in Hip-Knee-Ankle(HKA) angle andMedial-Pateral Tibial Angle (MPTA) of patients in the study group were statistically significant compared with the comparison group, and the increase in HKA (12.31±2.13)°, MPTA (11.84±2.32)° and lower limb force line was significantly improved (P < .05). Preoperatively, there was no statistically significant comparison between the visual analog scores of the knee joint in the study group and the comparison group. After surgery, the difference between the two groups was statistically significant (P < .05). The relative position of the mechanical axis of the lower limb through the tibial plateau, the femorotibial angle, and the posterior tibial plateau angle increased in patients after surgery, and the differences were statistically significant when compared with the preoperative period (P < .05). Both the tibial posterior displacement distance and the lateral knee gap opening were reduced compared with the preoperative period, and the differences were statistically significant (P < .05). Conclusion: Hightibialosteotomy after plate placement combined with arthroscopic surgery has better clinical efficacy in the early stage and can effectively treat the degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower limb, improve the joint function, and relieve the symptoms of patients.

Renoprotective Effect of Isoorientin in Diabetic Nephropathy via Activating Autophagy and Inhibiting the PI3K-AKT-TSC2-mTOR Pathway.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the most common cause of death. The autophagy of podocytes plays an important role in the pathogenesis of DN. Here, through screening the constituent compounds of practical and useful Chinese herbal formulas, we identified that isoorientin (ISO) strongly promoted the autophagy of podocytes and could effectively protect podocytes from high glucose (HG)-induced injury. ISO significantly improved autophagic clearance of damaged mitochondria under HG conditions. Through a proteomics-based approach, we identified that ISO could reverse the excessive phosphorylation of TSC2 S939 under HG conditions and stimulate autophagy through inhibition of the PI3K-AKT-TSC2-mTOR pathway. Furthermore, ISO was predicted to bind to the SH2 domain of PI3Kp85[Formula: see text], which is crucial for the recruitment and activation of PI3K. The protective effect of ISO and its effects on autophagy and particularly on mitophagy were further proved using a DN mice model. To summarize, our study identified the protective effects of ISO against DN and demonstrated that ISO was a strong activator of autophagy, which could provide a basis for drug development.

Mechanism of Yiqi Huoxue Huatan recipe in the treatment of coronary atherosclerotic disease through network pharmacology and experiments.

In recent years, with population aging and economic development, morbidity and mortality of atherosclerotic cardiovascular disease associated with atherosclerosis (AS) have gradually increased. In this study, a combination of network pharmacology and experimental verification was used to systematically explore the action mechanism of Yiqi Huoxue Huatan Recipe (YHHR) in the treatment of coronary atherosclerotic heart disease (CAD). We searched and screened the active ingredients of Coptis chinensis, Astragalus membranaceus, Salvia miltiorrhiza, and Hirudo. We also searched multiple databases for related target genes corresponding to the compounds and CAD. STRING was used to construct the protein-protein interaction (PPI) network of genes. Metascape was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common targets to analyze the main pathways, and finally, the molecular docking and main possible pathways were verified by experimental studies. Firstly, a total of 1480 predicted target points were obtained through the Swiss Target Prediction database. After screening, merging, and deleting duplicate values, a total of 768 targets were obtained. Secondly, "Coronary atherosclerotic heart disease" was searched in databases such as the OMIM, GeneCards, and TTD. 1844 disease-related targets were obtained. Among PPI network diagram of YHHR-CAD, SRC had the highest degree value, followed by AKT1, TP53, hsp90aa1 and mapk3. The KEGG pathway bubble diagram was drawn using Chiplot, the Signal pathways such as NF kappa B signaling pathway, Lipid and AS, and Apelin signaling pathway are closely related to the occurrence of CAD. The PCR and Western blot methods were used to detect the expression of NF-κB p65. When compared with that in the model group, the expression of NF-κB p65mRNA decreased in the low-concentration YHHR group, with P < .05, while the expression of NF-κB p65mRNA decreased significantly in the high-concentration YHHR group, with P < .01. On the other hand, when compared with that in the model group, the expression of NF-κB p65 decreased in the low-concentration YHHR group, but was not statistically significant, while the expression of NF-κB p65 was significant in the high-concentration YHHR group, and has statistical significance with P < .05. YHHR has been shown to resist inflammation and AS through the SRC/NF-κB signaling pathway.

Construction and validation of prognostic scoring models to risk stratify patients with acquired immune deficiency syndrome-related diffuse large B cell lymphoma.

Acquired immune deficiency syndrome (AIDS)-related diffuse large B cell lymphoma (AR-DLBCL) is a rare disease with a high risk of mortality. There is no specific prognostic model for patients with AR-DLBCL. A total of 100 patients diagnosed with AR-DLBCL were enrolled in our study. Clinical features and prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by univariate and multivariate analyses. Central nervous system (CNS) involvement, opportunistic infection (OI) at lymphoma diagnosis, and elevated lactate dehydrogenase (LDH) were selected to construct the OS model; CNS involvement, OI at lymphoma diagnosis, elevated LDH, and over four chemotherapy cycles were selected to construct the PFS model. The area under the curve and C-index of GZMU OS and PFS models were 0.786/0.712; 0.829/0.733, respectively. The models we constructed showed better risk stratification than International Prognostic Index (IPI), age-adjusted IPI, and National Comprehensive Cancer Network-IPI. Furthermore, in combined cohort, the Hosmer-Lemeshow test showed that the models were good fits (OS: p = 0.8244; PFS: p = 0.9968) and the decision curve analysis demonstrated a significantly better net benefit. The prognostic efficacy of the proposed models was validated independently and outperformed the currently available prognostic tools. These novel prognostic models will help to tackle a clinically relevant unmet need.

Resveratrol reverses TGF-ß1-mediated invasion and metastasis of breast cancer cells via the SIRT3/AMPK/autophagy signal axis.

Resveratrol (Resv) has antitumorigenic and antimetastatic activities; however, the molecular mechanisms underlying the inhibitory effects of Resv on the invasion and metastasis of breast cancer cells are still a subject of debate. In our study, we demonstrated that Resv inhibited tumor cell proliferation and tumor growth. It also suppressed invasion and pulmonary metastasis of breast cancer by reversing the transforming growth factor beta 1 (TGF-ß1)-mediated EMT process. Meanwhile, the anticarcinogenic effects of Resv were abolished by the autophagy blocker 3-methyladenine (3-MA) or Beclin 1 small interfering RNA. Moreover, Resv upregulated autophagy-related genes and protein levels and induced the formation of autophagosomes in 4T1 breast cancer cells and xenograft mice, suggesting that autophagy was involved in the anticarcinogenic activities of Resv in both models. In addition, Resv-induced autophagy by increasing the expression of SIRT3 and phosphorylated AMPK. SIRT3 knockdown reduced AMPK phosphorylation and autophagy-related proteins levels, and suppressed the anticancer effects of Resv, demonstrating that the inhibitory effects of Resv on tumor progression were mediated via the SIRT3/AMPK/autophagy pathway. Taken together, our study provided novel insight into the anticancer effects of Resv and revealed that targeting the SIRT3/AMPK/autophagy pathway can serve as a new therapeutic target against breast cancer.

Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia.

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology. METHODS: HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology. RESULTS: The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP. CONCLUSIONS: In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

Kaempferol impairs aerobic glycolysis against melanoma metastasis via inhibiting the mitochondrial binding of HK2 and VDAC1.

Metastasis is the leading cause of death in melanoma patients. Aerobic glycolysis is a common metabolic feature in tumor and is closely related to cell growth and metastasis. Kaempferol (KAM) is one of the active ingredients in the total flavonoids of Chinese traditional medicine Sparganii Rhizoma. Studies have shown that it interferes with the cell cycle, apoptosis, angiogenesis and metastasis of tumor cells, but whether it can affect the aerobic glycolysis of melanoma is still unclear. Here, we explored the effects and mechanisms of KAM on melanoma metastasis and aerobic glycolysis. KAM inhibited the migration and invasion of A375 and B16F10 cells, and reduced the lung metastasis of melanoma cells. Extracellular acidification rates (ECAR) and glucose consumption were obviously suppressed by KAM, as well as the production of ATP, pyruvate and lactate. Mechanistically, the activity of hexokinase (HK), the first key kinase of aerobic glycolysis, was significantly inhibited by KAM. Although the total protein expression of HK2 was not significantly changed, the binding of HK2 and voltage-dependent anion channel 1 (VDAC1) on mitochondria was inhibited by KAM through AKT/GSK-3ß signal pathway. In conclusion, KAM inhibits melanoma metastasis via blocking aerobic glycolysis of melanoma cells, in which the binding of HK2 and VDAC1 on mitochondria was broken.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

[Chemical constituents of cyclic peptides from fibrous roots of Pseudostellaria heterophylla].

Four cyclic peptides were isolated from the 75% ethanol extract of the fibrous roots of Pseudostellaria heterophylla by silica gel, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Through mass spectrometry, NMR and other methods, they were identified as pseudostellarin L(1), heterophyllin B(2), pseudostellarin B(3), and pseudostellarin C(4). Among them, compound 1 was a new cyclic peptide, and compounds 2-4 were isolated from the fibrous roots of P. heterophylla for the first time. None of these compounds displayed cytotoxic activities against MCF-7, A549, HCT-116, and SGC-7901 cells.

Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases causing infertility in women of childbearing age. It is characterized by hyperandrogenemia (HA), chronic anovulation, and polycystic ovary morphology (PCOM). Most women with PCOS have metabolic abnormalities. Sex hormone-binding globulin (SHBG), a transport carrier that binds estrogen and androgens and regulates their biological activity, is usually used as an indicator of hyperandrogenism in women with PCOS. Low serum SHBG levels are considered a biomarker of metabolic abnormalities and are associated with insulin resistance (IR), HA, and abnormal glucose and lipid metabolism in PCOS patients. SHBG is also related to the long-term prognosis of PCOS, whereas SHBG gene polymorphism is associated with PCOS risk. In addition, the administration of metformin (MET), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), thiazolidinediones (TZDs), compound oral contraceptives (COCs), as well as nutrient supplements such as inositol (MI), vitamin D, and synbiotics can regulate SHBG levels to ameliorate PCOS complications and improve prognosis. This review focuses on the interaction between SHBG and various PCOS complications as well as the regulation of SHBG by various drugs and nutrients and its therapeutic effects on PCOS.

A new cyclic peptide from the fibrous root of Pseudostellaria heterophylla.

A new cyclic peptide, Pseudostellarin K (1), together with thirteen known compounds, including two cyclic peptides (2 and 3), one ß-carboline alkaloid (4), two amides (5 and 6), three phenylpropanoids (7-9) and other compounds (10-14), were isolated from the fibrous root of Pseudostellaria heterophylla. Their structures were elucidated by extensive spectroscopic analysis. Compounds 1, 4-6, 10 were isolated from the genus pseudostellaria for the first time. All compounds were evaluated for cytotoxic activities against MCF-7, A549, HCT-116 and SGC-7901 cell lines by MTT assay. Unfortunately, all these compounds displayed weak cytotoxic activities.

[An optimization method of weighted network module partition based on TCM theory of "monarch, minister, assistant and guide"].

The disease-gene-drug multi-level network constructed by network pharmacology can predict drug targets and has been widely used in the study of material basis and mechanism of action of Chinese medicinal prescriptions. However, most of the current studies have normalized the efficacies of Chinese herbal medicines in the compounds during the construction of the network. There is also a lack of in-depth exploration of the mechanism of synergy among multiple components. This study proposed a network module partition method based on group collaboration and the pharmacological network was weighed according to the traditional Chinese medicine(TCM) theory of "monarch, minister, assistant and guide". Taking the Tanyu Tongzhi Prescription as an example, we constructed its pharmacological network for the treatment of myocardial ischemia-reperfusion injury. The group collaboration module in the network was identified and the network changes before and after the weighting were compared based on the network topology analysis to explore a new method to find the core nodes of the network as well as the core drugs that affected the efficacy of the compounds. The results showed that the module partition method based on group collaboration could be used to identify and partition group collaboration mo-dules in pharmacological networks of compounds. The proposed weighted network based on the TCM theory of "monarch, minister, assistant, and guide" could identify and partition the modules based on the characteristics of the pharmacological network. The identification and partition results of modules of Tanyu Tongzhi Prescription in the weighted network were superior to those in the unweighted network. The weighted closeness centrality(WCC) evaluation method was conducive to finding key nodes and relations in the network as compared with traditional methods, thereby providing a basis for analyzing the core components of drugs and extracting more accurate drug components and targets.

A network pharmacology approach to uncover the key ingredients in Ginkgo Folium and their anti-Alzheimer's disease mechanisms.

This study aimed to identify potential anti-Alzheimer's disease (AD) targets and action mechanisms of Ginkgo Folium (GF) through a network pharmacology approach. Eighty-four potential targets of 10 active anti-AD ingredients of GF were identified, among which genkwanin (GK) had the greatest number of AD-related targets. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathway of GF against AD was Alzheimer disease (hsa05010). More importantly, 29 of the 84 targets were significantly correlated with tau, Aß or both Aß and tau pathology. In addition, GO analysis suggested that the main biological processes of GF in AD treatment were the regulation of chemical synaptic transmission (GO:0007268), neuron death (GO:0070997), amyloid-beta metabolic process (GO:0050435), etc. We further investigated the anti-AD effects of GK using N2A-APP cells (a classical cellular model of AD). Treatment N2A-APP cells with 100 µM GK for 48 h affected core targets related to tau pathology (such as CDK5 and GSK3ß). In conclusion, these findings indicate that GF exerts its therapeutic effects on AD by acting directly on multiple pathological processes of AD.

The effectiveness of coenzyme Q10, vitamin E, inositols, and vitamin D in improving the endocrine and metabolic profiles in women with polycystic ovary syndrome: a network Meta-analysis.

OBJECTIVE: This research evaluated the efficacy of oral nutritional agents including CoQ10, vitamin E, inositols and vitamin D on androgen-associated hormones, glycolipid metabolism and body weight in women with PCOS. METHOD: A multi-database search was performed from inception to December 2020. Using multi-variate random effects method, a NMA was conducted by synthesizing data pooled from RCTs. It was registered with PROSPERO (registration number CRD42021230292). RESULTS: Twenty-three RCTs and 1291 participants were included. Based on NMA, CoQ10, vitamin E, CoQ10 combined with vitamin E, and inositols were successful in decreasing TT as compared with PA; vitamin E was superior to other agents. Vitamin E and inositols were successful in increasing SHBG levels; inositols were stronger than vitamin E. CoQ10 alone or combined with vitamin E, and inositols were successful in decreasing HOMA-IR. Inositols had the best results among included nutraceuticals to ameliorate HOMA-IR, FBG, FINS, TG, TC, and LDL-C and correlated to improvements in BMI. There was no significant difference between the CoQ10 or vitamin E group and the PA group in ameliorating lipid metabolism, and vitamin D had no positive effects in ameliorating hyperandrogenism, BMI, glycolipid metabolism profiles compared with PA. CONCLUSION: For women with PCOS, inositols supplementation have some certain advantages in increasing SHBG and improving glycolipid metabolism when compared with nutraceuticals like CoQ10, vitamin E, vitamin D. Besides, vitamin E may be a better option in reducing TT and increasing SHBG. CoQ10 alone or combined with vitamin E can be helpful in decreasing HOMA-IR as well.

The effect of drug dose and duration of adjuvant Amoxicillin-plus-Metronidazole to full-mouth scaling and root planing in periodontitis: a systematic review and meta-analysis.

OBJECTIVES: The aim is to explore the optimal drug dose and duration of adjunctive Amoxicillin-plus-Metronidazole (AMX/MET) to full-mouth scaling and planing (FMSRP) in periodontitis. METHODS: An electronic search in four databases and manual search in four journals were conducted for randomised clinical trials comparing AMX/MET adjunct to FMSRP with FMSRP alone for at least 3 months. RESULTS: Eleven studies were eligible and included. The primary outcome was clinical attachment level (CAL) gain, the secondary outcomes were periodontal pocket depth (PPD) reduction and adverse events. Our results showed a beneficial effect of adjunctive AMX/MET with higher drug dose to FMSRP for CAL gain and PPD reduction at 3 months, and the benefit remained stable at 6 months. However, minimal difference among three-seven-and ten-day drug duration was observed. In addition, the risk difference of adverse events was minimal between two groups. CONCLUSION: FMSRP adjunct to a high drug dose of 500/500 mg of AMX/MET showed a significant and stable improvement on 6-month follow-up period. No decision for drug duration could be made due to limited evidence. CLINICAL RELEVANCE: On 6-month follow-up, higher dose of AMX/MET adjunct to FMSRP could provide a stable clinical effect. No recommendation for drug duration could be made.

The effect of low-level laser therapy as an adjunct to periodontal surgery in the management of postoperative pain and wound healing: a systematic review and meta-analysis.

The meta-analysis and systematic review aimed to evaluate the effect of low-level laser therapy (LLLT) as an adjunct to periodontal surgery in the management of postoperative pain and wound healing. An electronic search in 4 databases (PubMed, Embase, Cochrane, and OpenGrey) was conducted for randomized clinical trials reporting the effectiveness of LLLT used as an adjunct to periodontal surgery to alleviate pain and accelerate wound healing compared with surgery alone. Finally, 13 studies were eligible and included. The results showed a significant difference of pain relief between groups at day 3 post-surgery, whereas no difference was found at day 7. Moreover, a significant reduction was observed in the mean analgesic intake during the first week in the LLLT group. On day 14, the adjunctive use of LLLT showed significantly faster re-epithelialization and better wound healing in palatal donor sites following free gingival graft procedures. Based on the results, LLLT used as an adjunct to periodontal surgery positively influenced postsurgical pain control. Low power (≤ 500 mW) combined with energy density ≥ 5 J/cm2 might be more appropriate for postoperative pain relief. Moreover, adjunctive LLLT to free gingival grafts could significantly accelerate wound healing of palate sites at early healing phase. Multicenter studies using different LLL parameters without postsurgical analgesics are needed to determine optimal laser settings.

Resolvin D1 suppresses pannus formation via decreasing connective tissue growth factor caused by upregulation of miRNA-146a-5p in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, and the damage of cartilage as well as bone. Resolvin D1 (RvD1) can promote inflammation resolution in acute inflammatory diseases, and recently, effects of RvD1 on chronic inflammatory diseases also attracted attention. This study aimed to examine the effect of RvD1 on pannus formation in RA and the underlying mechanism. METHODS: Serum levels of RvD1 and CTGF were determined in RA patients and healthy persons by UPLC-MS/MS and ELISA respectively. The levels of CTGF and inflammatory factors were assessed by qRT-PCR and ELISA. MicroRNA expression profile was determined by miRNA microarray. The effects of CTGF, RvD1, and miR-146a-5p on angiogenesis were evaluated with tube formation and chick chorioallantoic membrane (CAM) assays. Collagen-induced arthritis (CIA) mice were constructed to detect the effects of RvD1 and miR146a-5p on RA. STAT3 activation was determined by Western blotting. RESULTS: RvD1 levels decreased while CTGF levels increased in RA patients' serum, and an inverse correlation of the concentrations of RvD1 and CTGF in the serum of RA patients was synchronously observed. In CIA mice, RvD1 suppressed angiopoiesis and decreased the expression of CTGF. Simultaneously, RvD1 significantly decreased CTGF and pro-inflammation cytokines levels in RA FLS. Furthermore, CTGF suppressed angiopoiesis and RvD1 inhibited the proliferation and migration of RA FLS and angiopoiesis. MiRNA microarray and qRT-PCR results showed that RvD1 upregulated miRNA-146a-5p. The transfection experiments demonstrated that miRNA-146a-5p could decrease inflammatory factors and CTGF levels. Moreover, miRNA-146a-5p decreased the proliferation of FLS and angiogenesis in vivo. MiRNA-146a-5p also suppressed angiogenesis and downregulated the expression of CTGF in CIA mice. Finally, Western blot results revealed that miRNA-146a-5p inhibited the activation of STAT3. CONCLUSION: RvD1 is prone to alleviate RA progression through the upregulation of miRNA-146a-5p to suppress the expression of CTGF and inflammatory mediators, thereby decreasing pannus formation and cartilage damage.

Exonuclease III-assisted signal amplification strategy for sensitive fluorescence detection of polynucleotide kinase based on poly(thymine)-templated copper nanoparticles.

A sensitive and label-free fluorometric method has been developed for the determination of polynucleotide kinase (PNK) activity, by employing exonuclease III (Exo III)-assisted cyclic signal amplification and poly(thymine)-templated copper nanoparticles (polyT-CuNPs). In the presence of PNK, cDNA with 5'-hydroxyl termini was phosphorylated and then hybridized with tDNA to form the cDNA/tDNA duplex, which subsequently triggered the λ exonuclease cleavage reaction, eventually resulting in the release of tDNA. The released tDNA could unfold the hairpin structure of HP DNA to generate partially complementary duplex (tDNA/HP DNA), wherein the HP DNA possessed T-rich sequences (T30) and tDNA recognition sequence. With the help of Exo III digestion, the tDNA was able to initiate the cycle for the generation of T-rich sequences, the template for the formation of fluorescent CuNPs. Conversely, the cDNA could not be cleaved by λ exonuclease without PNK and individual HP DNA could not be hydrolyzed by Exo III. The T-rich sequence was caged in HP DNA, resulting in a weak fluorescence signal. Under optimized conditions, the fluorescence intensity was linearly correlated to a concentration range of 0.001 to 1 U mL-1 with a low detection limit of 2 × 10-4 U mL-1. Considering the intriguing analytical performance, this approach could be explored to screen T4 PNK inhibitors and hold promising applications in drug discovery and disease therapy.

Marine n-3 PUFA protects hearts from I/R injury via restoration of mitochondrial function.

OBJECTIVES: Overwhelming evidence shows that dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) elicits protective effects on patients with cardiovascular disease. However, the detailed mechanisms underlying n-3 PUFA-mediated cardioprotection are unknown, and examined in the present study. METHODS: We evaluated heart performances with Langendorff perfusion apparatus. Meanwhile, whole mitochondria were purified from non-perfused hearts for functional assessment, and lipid peroxidation level was measured as well. RESULTS: Compared with control groups, hearts from n-3 PUFA-supplemented rats showed improved functional recovery and reduced tissue injury following ischemia/reperfusion (I/R). Furthermore, the mitochondrial function of PUFA-treated hearts was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity. In addition, thiobarbituric acid-reactive substance or TBARS assay revealed that lipid peroxidation product, malondialdehyde or MDA, in the mitochondria was significantly reduced by PUFA treatment. CONCLUSION: Taken together, our data indicate that marine n-3 PUFA could improve cardiac performance after I/R injury by restoring mitochondrial respiratory activities and attenuating lipid peroxidation.

PPARγ-dependent pathway in the growth-inhibitory effects of K562 cells by carotenoids in combination with rosiglitazone.

BACKGROUND: Carotenoids have been found to play roles in the prevention and therapy of some cancers which PPARγ was also discovered to be involved in. The present studies were directed to determine the inhibitory effects of carotenoids in combination with rosiglitazone, a synthetic PPARγ agonist, on K562 cell proliferation and elucidate the contribution of PPARγ-dependent pathway to cell proliferation suppression. METHODS: The effects of carotenoid and rosiglitazone combination on K562 cell proliferation were evaluated by trypan blue dye exclusion assay and MTT assay. When PPARγ has been inhibited by GW9662 and siRNA, cycle-related regulator expression in K562 cells treated with carotenoid and rosiglitazone combination was analyzed by Western blotting. RESULTS: Rosiglitazone inhibited K562 cell proliferation and augmented the inhibitory effects of carotenoids on the cell proliferation greatly. Specific PPARγ inhibition attenuated the cell growth suppression induced by carotenoid and rosiglitazone combination. GW9662 pre-treatment attenuated the enhanced up-regulation of PPARγ expression caused by the combination treatment. Moreover, GW9662 and PPARγ siRNA also significantly attenuated the up-regulation of p21 and down-regulation of cyclin D1 caused by carotenoids and rosiglitazone. CONCLUSIONS: PPARγ signaling pathway, via stimulating p21 and inhibiting cyclin D1, may play an important role in the anti-proliferative effects of carotenoid and rosiglitazone combination on K562 cells. GENERAL SIGNIFICANCE: Carotenoids in combination with rosiglitazone are hopeful to provide attractive dietary or supplementation-based and pharmaceutical strategies to treat cancer diseases.