Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen.

This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment.

Laboratory features of effects of peloidotherapy and aromatherapy in patients with rheumatoid arthritis.

Peloidotherapy and aromatherapy have been used for years in the treatment of numerous inflammatory conditions, including rheumatoid arthritis (RA). The exact mechanism of their action in RA is unclear. The goal of our research is to determine the effect of peloidotherapy and aromatherapy on inflammation parameters in RA patients. Our study included 20 patients of both sexes, with confirmed diagnosis of RA, older than 18 years. Patients were treated during 28 days with combination of peloidotherapy and aromatherapy. Serum samples for detection of levels of inflammation parameters were taken at two intervals: before the start of therapy and at the end of treatment. The results of our study show that there were no significant changes in the parameters of the complete blood count. Nevertheless, a statistically significant decrease in the serum concentration of two markers of inflammation-interleukin-6 (IL-6) and nitrogen-oxide (NO)-was detected. Correlation analyses results say that there is a synchronized drop in the serum concentrations of CRP and the sedimentation rate, and the serum concentrations of fibrinogen and IL-6 are in the same relationship as well as serum levels of IL-6 and NO. Bearing in mind the importance of IL-6 and NO in the pathogenesis of inflammation in RA, we conclude that the application of our therapeutic protocol can be a significant add-on treatment to classic immunomodulators. Due to the small number of study participants, the lack of a control group, and the short follow-up time of patients, additional research is needed.

Anti-Citrullinated Protein Antibodies With Multiple Specificities Ameliorate Collagen Antibody-Induced Arthritis in a Time-Dependent Manner.

OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and have long been regarded as pathogenic. Despite substantial in vitro evidence supporting this claim, reports investigating the proinflammatory effects of ACPAs in animal models of arthritis are rare and include mixed results. Here, we sequenced the plasmablast antibody repertoire of a patient with RA and functionally characterized the encoded ACPAs. METHODS: We expressed ACPAs from the antibody repertoire of a patient with RA and characterized their autoantigen specificities on antigen arrays and enzyme-linked immunosorbent assays. Binding affinities were estimated by bio-layer interferometry. Select ACPAs (n = 9) were tested in the collagen antibody-induced arthritis (CAIA) mouse model to evaluate their effects on joint inflammation. RESULTS: Recombinant ACPAs bound preferentially and with high affinity (nanomolar range) to citrullinated (cit) autoantigens (primarily histones and fibrinogen) and to auto-cit peptidylarginine deiminase 4 (PAD4). ACPAs were grouped for in vivo testing based on their predominant cit-antigen specificities. Unexpectedly, injections of recombinant ACPAs significantly reduced paw thickness and arthritis severity in CAIA mice as compared with isotype-matched control antibodies (P ≤ 0.001). Bone erosion, synovitis, and cartilage damage were also significantly reduced (P ≤ 0.01). This amelioration of CAIA was observed for all the ACPAs tested and was independent of cit-PAD4 and cit-fibrinogen specificities. Furthermore, disease amelioration was more prominent when ACPAs were injected at earlier stages of CAIA than at later phases of the model. CONCLUSION: Recombinant patient-derived ACPAs ameliorated CAIA. Their antiinflammatory effects were more preventive than therapeutic. This study highlights a potential protective role for ACPAs in arthritis.

Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3).

The aims of this study are to characterize the antiplatelet activity of StSBTc-3, a potato serine protease with fibrino (geno) lytic activity, and to provide information on its mechanism of action. The results obtained show that StSBTc-3 inhibits clot retraction and prevents platelet aggregation induced by thrombin, convulxin, and A23187. Platelet aggregation inhibition occurs in a dose-dependent manner and is not affected by inactivation of StSBTc-3 with the inhibitor of serine proteases phenylmethylsulfonyl fluoride (PMSF). In addition, StSBTc-3 reduces fibrinogen binding onto platelets. In-silico calculations show a high binding affinity between StSBTc-3 and human α2bß3 integrin suggesting that the antiplatelet activity of StSBTc-3 could be associated with the fibronectin type III domain present in its amino acid sequence. Binding experiments show that StSBTc-3 binds to α2bß3 preventing the interaction between α2bß3 and fibrinogen and, consequently, inhibiting platelet aggregation. StSBTc-3 represents a promising compound to be considered as an alternative to commercially available drugs used in cardiovascular therapies.

Blood and liver telomere length, mitochondrial DNA copy number, and hepatic gene expression of mitochondrial dynamics in mid-lactation cows supplemented with l-carnitine under systemic inflammation.

The current study was conducted to examine the effect of l-carnitine (LC) supplementation on telomere length and mitochondrial DNA copy number (mtDNAcn) per cell in mid-lactation cows challenged by lipopolysaccharide (LPS) in blood and liver. The mRNA abundance of 31 genes related to inflammation, oxidative stress, and the corresponding stress response mechanisms, the mitochondrial quality control and the protein import system, as well as the phosphatidylinositol 3-kinase/protein kinase B pathway, were assessed using microfluidics integrated fluidic circuit chips (96.96 dynamic arrays). In addition to comparing the responses in cows with or without LC, our objectives were to characterize the oxidative and inflammatory status by assessing the circulating concentration of lactoferrin (Lf), haptoglobin (Hp), fibrinogen, derivates of reactive oxygen metabolites (dROM), and arylesterase activity (AEA), and to extend the measurement of Lf and Hp to milk. Pluriparous Holstein cows were assigned to either a control group (CON, n = 26) or an LC-supplemented group (CAR; 25 g LC/cow per day; d 42 ante partum to d 126 postpartum (PP), n = 27). On d 111 PP, each cow was injected intravenously with LPS (Escherichia coli O111:B4, 0.5 µg/kg). The mRNA abundance was examined in liver biopsies of d -11 and +1 relative to LPS administration. Plasma and milk samples were frequently collected before and after the challenge. After LPS administration, circulating plasma fibrinogen and serum dROM concentrations increased, whereas AEA decreased. Moreover, serum P4 initially increased by 3 h after LPS administration and declined thereafter irrespective of grouping. The Lf concentrations increased in both groups after LPS administration, with the CAR group showing greater concentrations in serum and milk than the CON group. After LPS administration, telomere length in blood increased, whereas mtDNAcn per cell decreased; however, both remained unaffected in liver. For mitochondrial protein import genes, the hepatic mRNA abundance of the translocase of the mitochondrial inner membrane (TIM)-17B was increased in CAR cows. Moreover, TIM23 increased in both groups after LPS administration. Regarding the mRNA abundance of genes related to stress response mechanisms, 7 out of 14 genes showed group × time interactions, indicating a (local) protective effect due to the dietary LC supplementation against oxidative stress in mid-lactating dairy cows. For mtDNAcn and telomere length, the effects of the LPS-induced inflammation were more pronounced than the dietary supplementation of LC. Dietary LC supplementation affected the response to LPS primarily by altering mitochondrial dynamics. Regarding mRNA abundance of genes related to the mitochondrial protein import system, the inner mitochondrial membrane translocase (TIM complex) seemed to be more sensitive to dietary LC than the outer mitochondrial membrane translocase (TOM complex).

Anti-inflammatory and antioxidant actions of extracts from Rheum rhaponticum and Rheum rhabarbarum in human blood plasma and cells in vitro.

Rheum rhaponticum L. (rhapontic rhubarb) and Rheum rhabarbarum L. (garden rhubarb) are edible and medicinal rhubarb species used for many centuries in traditional medicine. This work is focused on the biological activity of extracts from petioles and roots of R. rhaponticum and R. rhabarbarum as well as rhapontigenin and rhaponticin, typical stilbenes present in these rhubarbs, in a context of their effects on blood physiology and cardiovascular health. Anti-inflammatory properties of the examined substances were evaluated in human peripheral blood mononuclear cells (PBMCs) and THP1-ASC-GFP inflammasome reporter cells. Due to the coexistence of inflammation and oxidative stress in cardiovascular diseases, the study design included also antioxidant assays. This part of the work involved the assessment of the protective efficiency of the examined substances against the peroxynitrite-triggered damage to human blood plasma components, including fibrinogen, a protein of critical importance for blood clotting and maintaining the haemostatic balance. Pre-incubation of PBMCs with the examined substances (1-50 µg/mL) considerably decreased the synthesis of prostaglandin E2 as well as the release of pro-inflammatory cytokines (IL-2 and TNF-α) and metalloproteinase-9. A reduced level of secreted apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks in the THP-1-ASC-GFP cells was also observed. The examined substances significantly diminished the extent of ONOO‾induced oxidative modifications of blood plasma proteins and lipids and normalized, or even strengthened blood plasma antioxidant capacity. Furthermore, a reduction of oxidative damage to fibrinogen, including modifications of tyrosine and tryptophan residues along with the formation of protein aggregates was found.

Effect of acupuncture on hematologic, muscular biomarkers, fibrinogen and serum lactate parameters in training rodeo bulls.

The study aimed to evaluated the effects of acupuncture in rodeo bulls in training, by determining hematological variables, creatine kinase (CK), aspartate aminotransferase (AST), fibrinogen, and plasma lactate. Thirty adult healthy bulls, crossbred, were included in the study and randomly allocated into two groups of 15 animals, according to the use of acupuncture treatment for six months (GA) or not (GB). The variables were measured 30 min before (TP0) and 10 min (TP10min), 12 (TP12h), 24 (TP24h), 48 (TP48h), and 72 h (TP72h) after a single episode of jumping emulating rodeo exercise. The GB group showed variations in hemoglobin between TP0 and TP10min (p = 0.002) and TP0 and TP12h (p = 0.004), and the GA presented an increase in eosinophil values between TP0 and TP12h (p = 0.013) and TP0 and TP24h (p = 0.034). Leukopenia was observed in GB between TP10min and TP72h ((p = 0.008). The CK values were high (↑ 300 UI/l) after exercise until the TP24h, and decreased in TP48h, in both groups. The plasma lactate elevation was lower in the GA at TP10min (p = 0.011), TP12h (p = 0.008), TP72h (p < 0.001). The rodeo bulls submitted to acupuncture treatment showed smaller variations in hemogram, elevated eosinophils levels, and lower plasma lactate levels after exercise.

Systematic mapping of the conformational landscape and dynamism of soluble fibrinogen.

BACKGROUND: Fibrinogen is a soluble, multisubunit, and multidomain dimeric protein, which, upon its proteolytic cleavage by thrombin, is converted to insoluble fibrin, initiating polymerization that substantially contributes to clot growth. Fibrinogen contains numerous, transiently accessible "cryptic" epitopes for hemostatic and immunologic proteins, suggesting that fibrinogen exhibits conformational flexibility, which may play functional roles in its temporal and spatial interactions. Hitherto, there have been limited integrative approaches characterizing the solution structure and internal flexibility of fibrinogen. METHODS: Here, utilizing a multipronged, biophysical approach involving 2 solution-based techniques, temperature-dependent hydrogen-deuterium exchange mass spectrometry and small angle X-ray scattering, corroborated by negative stain electron microscopy, we present a holistic, conformationally dynamic model of human fibrinogen in solution. RESULTS: Our data reveal 4 major and distinct conformations of fibrinogen accommodated by a high degree of internal protein flexibility along its central scaffold. We propose that the fibrinogen structure in the solution consists of a complex, conformational landscape with multiple local minima. This is further supported by the location of numerous point mutations that are linked to dysfibrinogenemia and posttranslational modifications, residing near the identified fibrinogen flexions. CONCLUSION: This work provides a molecular basis for the structural "dynamism" of fibrinogen that is expected to influence the broad swath of its functionally diverse macromolecular interactions and fine-tune the structural and mechanical properties of blood clots.

Alternative blood products in trauma.

PURPOSE OF REVIEW: Hemorrhage and trauma-induced coagulopathy cause significant morbidity and mortality in trauma patients. Although blood products are the cornerstone of resuscitation, these resources are scarce, necessitating alternatives. This review examines the use of alternative blood products in trauma as well as the literature supporting their use. RECENT FINDINGS: There is no single true blood product alternative. In recent years, there has been great progress in understanding trauma-induced pathophysiology and blood component alternatives. Products such as tranexamic acid and prothrombin complex concentrate have become well established and are frequently utilized in trauma centers, and many more alternatives are still undergoing further research and development. SUMMARY: Stabilization of hemorrhage and resuscitation is priority in trauma-induced coagulopathy treatment. Alternative products such as tranexamic acid, recombinant factors, prothrombic complex concentrate, fibrinogen concentrates, and desmopressin may also be considered based on the clinical context. Viscoelastic hemostatic assays such as rotational thromboelastometry and thromboelastography can help guide these efforts. Following initial stabilization, additional interventions such as iron supplementation, erythropoietin stimulating agents, and vitamin D may help with chronic sequela.

Liver protection and hemostatic effects of medicinal plant Arnebia euchroma (Royle) I.M.Johnst extract in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Arnebia euchroma (Royle) I.M.Johnst. (AE) is a Chinese medicinal herb that is traditionally used to treat various circulatory diseases. It exhibits certain effects, such as the promotion of blood circulation and cooling, rash clearance, and detoxification. AIM OF THE STUDY: This study was designed to explore the hepatoprotective and hemostatic effects of the ethyl acetate extract of AE in rats with carbon tetrachloride (CCl4)-induced liver injury. MATERIALS AND METHODS: Wistar rats were treated via oral gavage with different doses of the ethyl acetate extract of AE (3.5, 7, or 14 g kg-1·day-1) for 14 consecutive days, following which hemostatic and liver function tests were conducted. For the hemostatic tests, the platelet count, blood platelet aggregation, blood platelet adhesion to fibrinogen, platelet factor 4 (PF-4) secretion from blood platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen levels were measured at the end of the treatment period. For the liver function tests, 0.25 mL/200 g (1.25 mL kg-1·day-1) of olive oil was injected into the abdominal cavity of the control rats, whereas 15% CCl4 plus olive oil (prescription: 7.5 mL CCl4 + 42.5 olive oil) was injected into that of the treated rats at 1 h after extract administration on day 6, 13, and 20. Additionally, food and water were withheld from all the animals. On the following day, the rats were anesthetized and their albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), reactive oxygen species (ROS), methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. Glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx) levels among the groups were determined using a one-way analysis of variance. RESULTS: The platelet count and blood platelet aggregation, blood platelet adhesion to fibrinogen and PF-4 secretion levels were significantly increased in the (3.5 g kg-1 day-1) AE group as compared to those in the control group (all p < 0.001; for the 7 and 14 g kg-1 day-1 AE groups, all p > 0.05, respectively). Although the PT and aPTT were not affected by the AE extract (all p > 0.05), the TT was reduced and the FIB levels were significantly increased in all AE groups (p < 0.05). Liver function tests showed that CCl4 caused significant liver damage, thereby decreasing the albumin, SOD, CAT, GSH, GST, GR, and GPx levels, while increasing the AST, ALT, ALP, SGOT, SGPT, GGT, LDH, ROS, and MDA levels (all p < 0.001). By contrast, treatment with the different doses of AE extract reversed the CCl4 effects on all these parameters. Compared with the levels in the CCl4 group, the GSH and GR levels in the three AE groups (3.5, 7, and 14 g kg-1·day-1) were significantly higher (p < 0.05, p < 0.01, and p < 0.001, respectively), whereas the differences in the other parameters for these three groups were all at the significance levels of p < 0.05, p < 0.05, and p < 0.01, respectively. CONCLUSIONS: AE extracts administered orally exhibited hepatoprotective activity by affecting platelet production and blood coagulation and ameliorating liver function-damaging modifications. Specifically, a dosage of 3.5 g kg-1·day-1 resulted in the most optimal effects.

Exploring the mechanism of the antithrombotic effects of Pueraria lobata and Pueraria lobata var. thomsonii based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi and Pueraria lobata var. thomsonii (Benth.) Maesen are nutritious medicine food homology plants that are widely used in the food and health products industry and are excellent natural materials for the development of new health foods, with great potential for domestic and foreign markets. Clinically, P. lobata and P. thomsonii are used to treat coronary heart disease, atherosclerosis, cerebral infarction and other cardiovascular diseases, and antithrombotic actions may be their core effect in the treatment of thrombotic diseases. However, the underlying mechanisms of the antithrombotic properties of P. lobata and P. thomsonii have not been clarified. METHODS: First, P. lobata and P. thomsonii were identified by high-performance liquid chromatography (HPLC). An arteriovenous bypass thrombosis rat model was established. Thrombus dry‒wet weight, platelet accumulation rate and the four coagulation indices, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB), were detected in plasma to manifest the P. lobata and P. thomsonii antithrombotic function. Network pharmacology and molecular docking methods were used to obtain key targets and verify reliability. David 6.8 was used for GO and KEGG analyses to explore pathways and potential targets for P. lobata and P. thomsonii antithrombotic functions. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2), cyclooxygenase 2 (COX-2), myeloperoxidase (MPO) and endothelial nitric oxide synthase (eNOS) were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicated that P. lobata and P. thomsonii can reduce thrombus dry‒wet weight and platelet accumulation in rats and inhibit TT, APTT, FIB, and PT. A comprehensive network pharmacology approach successfully identified 9 active ingredients in P. lobata and P. thomsonii. The main active ingredients include polyphenols, amino acids and flavonoids. A total of 15 antithrombotic function targets were obtained, including 3 key targets (PTGS2, NOS3, MPO). Pathway analysis showed 10 significant related pathways and 29 biological processes. P. lobata and P. thomsonii inhibited platelet aggregation by upregulating PGI2 and downregulating TXA2, inhibited PTGS2 to reduce inflammation, and increased the level of eNOS to promote vasodilation. In addition, P. lobata and P. thomsonii alleviated oxidative stress by increasing SOD levels and significantly decreasing MDA contents. CONCLUSION: The results of the study further clarify the antithrombotic mechanism of action of P. lobata and P. thomsonii, which provides a scientific basis for the development of new drugs for thrombogenic diseases and lays the foundation for the development of P. lobata and P. thomsonii herbal resources and P. lobata and P. thomsonii health products.

In vivo near-infrared fluorescent fibrin highlights growth of nerve during regeneration across a nerve gap.

Significance: Exogenous extracellular matrix (ECM) proteins, such as fibrinogen and the thrombin-polymerized scaffold fibrin, are used in surgical repair of severe nerve injuries to supplement ECM produced via the injury response. Monitoring the dynamic changes of fibrin during nerve regeneration may shed light on the frequent failure of grafts in the repair of long nerve gaps. Aim: We explored whether monitoring of fibrin dynamics can be carried out using nerve guidance conduits (NGCs) containing fibrin tagged with covalently bound fluorophores. Approach: Fibrinogen was conjugated to a near-infrared (NIR) fluorescent dye. NGCs consisting of silicone tubes filled with the fluorescent fibrin were used to repair a 5-mm gap injury in rat sciatic nerve ( n = 6 ). Results: Axonal regeneration in fluorescent fibrin-filled NGCs was confirmed at 14 days after implantation. Intraoperative fluorescence imaging after implantation showed that the exogenous fibrin was embedded in the early stage regenerative tissue. The fluorescent signal temporarily highlighted a cable-like structure within the conduit and gradually degraded over two weeks. Conclusions: This study, for the first time, visualized in vivo intraneural fibrin degradation, potentially a useful prospective indicator of regeneration success, and showed that fluorescent ECM, in this case fibrin, can facilitate imaging of regeneration in peripheral nerve conduits without significantly affecting the regeneration process.

A low-dose therapy of fibrinogen supplement during perioperative period of total knee arthroplasty in an asymptomatic man with congenital dysfibrinogenemia: A case report.

RATIONALE: Congenital dysfibrinogenemia (CD) is a rare coagulation system disease that is often treated without unified management. Individualized treatment thereof presents clinicians with great challenges. PATIENT CONCERNS: A patient who was about to undergo total knee arthroplasty was found to have CD. DIAGNOSES: Coagulation screening revealed low fibrinogen, prolonged thrombin time, minor prolonged prothrombin time, and normal activated partial thromboplastin time were detected during admission, but no abnormal personal and family history findings were observed. Therefore, CD and hypofibrinogenemia were suspected. The gene sequencing confirmed the diagnosis of CD. INTERVENTIONS: The patient received plenty and low level of fibrinogen concentrate during 2 perioperative periods, respectively. OUTCOMES: Successful clinical outcomes were obtained using different treatment strategies. LESSONS: In contrast to prior case reports, this case illustrates the feasibility of low dosing of fibrinogen supplements within an asymptomatic patient in a selective operation. Changes in the level of fibrinogen and fibrin degradation product are of great importance for individualized treatment after supplementation.

Efficacy of Ginkgo biloba Extract Combined with Hormones in the Treatment of Sudden Deafness and Its Effect on the Reactivity of Peripheral Blood T Cell Subsets.

This work was aimed at exploring the efficacy of Ginkgo biloba extract combined with hormones in the treatment of sudden deafness and the influence on the reactivity of peripheral blood T cell subsets (PBTCSs). In this work, 64 patients with sudden deafness who were treated in The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2019 to August 2022 were selected as the research objects. The patients were randomly divided into a hormone group (treatment with prednisone acetate, n = 34) and a combination group (treatment with Ginkgo-Damole combined with prednisone acetate, n = 30). After the two groups of patients were treated in different ways, their efficacy, symptom improvement, changes in blood rheology, and PBTCSs were compared. The total effective rates (TERs) of the hormone group and the combination group were 76.32% and 95.73%, respectively (P < 0.05). The fibrinogen contents of the patients in the combination group were obviously lower than those in the hormone group after 5 d, 7 d, and 10 d of treatment (P < 0.05). The high blood viscosity (HBV) values of patients in the combination group at 5 d, 7 d, and 10 d after treatment were greatly lower than those in the hormone group (P < 0.05). The low blood viscosity (LBV) values after 3 d, 7 d, and 10 d of treatment in the combined group were much lower in contrast to those in the hormone group (P < 0.05). The CD3+, CD4+, and CD4+/CD8+ in peripheral blood in the combination group were sharply higher while the CD8+ in the combined group was lower in contrast to the hormone group (P < 0.05). There was no visible difference in the incidence of adverse reactions between the two groups of patients after treatment (P > 0.05). In conclusion, the combined application of Ginkgo biloba extract and hormones could effectively improve the abnormal hemorheological indexes of patients with sudden deafness and effectively relieve the imbalance of PBTCSs, which was safe.

Efficacy of traditional Chinese medicine combined with rivaroxaban in the treatment of lower extremity deep vein thrombosis: A meta-analysis.

BACKGROUND: Despite the usefulness of traditional Chinese medicine (TCM) in the treatment of lower deep vein thrombosis (DVT), there is no consensus on safety and efficacy. We aim to systematically evaluate the safety and efficacy of TCM combined with Rivaroxaban in the treatment of lower limb DVT. METHODS: An online search of databases such as Cochrane Library, Embase, Pubmed, and Web of science, as well as CBM, China Science and Technology Journal Database, China Knowledge Network (CNKI) and Wanfang Data (from inception to July, 2021) was performed. All published clinical randomized controlled trials (RCTs) were screened manually, evaluated for quality and considered for meta-analysis using RevMan 5.3. RESULTS: Nine RCTs with a total of 730 cases were included, 368 cases in the trial group were treated with TCM combined with Rivaroxaban, and 362 cases in the control group were treated with Rivaroxaban alone after surgery. Clinical efficiency was significantly higher in the test group [OR = 3.33, 95% CI (2.01, 5.53), P < .00001], the circumference of the affected limb was significantly lower in the thigh and calf, respectively [MD = -1.48, 95% CI (-1.88, -1.09), P < .00001], [MD = -0.54, 95% CI (-0.62, -0.46), P < .00001], pain scores were significantly lower [MD = -0.97, 95% CI (-1.58, -0.36), P = .002], coagulation index plasma fibrinogen (FIB) was significantly lower [MD = -0.85, 95% CI (-1.18, -0.52), P < .00001], coagulation function index D-2 aggregates were significantly reduced [MD = -0.69, 95% CI (-1.13, -0.24), P = .002], serum hypersensitive C-reactive protein (hs-CRP) measurements were significantly reduced [MD = -5.37, 95% CI (-9.20, -1.55), P = .006], complications measurement was significantly lower [OR = 0.60, 95% CI (0.27, 1.30), P = .20], activated partial thrombin time (ATPP) measurement was significantly lower [MD = 5.70, 95% CI (4.28, 7.12), P < .00001] and prothrombin time (PT) measurement was significantly lower [MD = 1.64, 95% CI (0.70, 2.57), P = .0006]. CONCLUSION: Based on the available evidence, TCM combined with Rivaroxaban for treating lower extremity DVT have better clinical efficacy and safety profile, reducing the risk of bleeding complications and adverse effects. Further improved studies are needed to support this inference.

Abietic acid ameliorates nephropathy progression via mitigating renal oxidative stress, inflammation, fibrosis and apoptosis in high fat diet and low dose streptozotocin-induced diabetic rats.

BACKGROUND: Abietic acid (AA) has been reported to exhibit anti-inflammatory activity, however its protective effect against inflammation and its trigger factor i.e., oxidative stress and the related sequelae i.e., apoptosis and fibrosis in the kidney in diabetes mellitus (DM) is unknown. PURPOSE: To identify the ability of AA to mitigate the inflammatory and inflammation-related insults to the kidney in DM. METHODS & STUDY DESIGN: Adult male rats were induced type-2 DM by feeding with a high-fat diet for twelve weeks followed by injection with a single dose of streptozotocin (STZ) (30 mg/kg/bw) intraperitoneally at twelve weeks. Following DM confirmation, AA (10 and 20 mg/kg/day) was given orally for another four weeks. Then the fasting blood glucose (FBG) and renal profile were determined and oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) tests were performed. A day after the last treatment, rats were sacrificed and kidneys were harvested and subjected for histopathological and molecular biological analysis. RESULTS: AA treatment was found to reduce the FBG, serum urea and creatinine levels (p < 0.05) while improving the OGTT and ITT (p < 0.05) in diabetic rats. Besides, AA treatment also mitigated kidney histopathological changes, reduces kidney oxidative stress as reflected by reduced levels of RAGE and Keap1 but increased levels of kidney antioxidants Nrf2, SOD, CAT, GPX, HO-1 & NQO-1 (p < 0.05). Additionally, AA treatment also decreases kidney inflammation (NF-kB p65, IL-1ß, IL-6, TNF-α and iNOS) and fibrosis (TGF-ß1 and GSK-3ß) (p < 0/05). Kidney apoptosis decreased as reflected by decreased levels of Bax, caspase-3 and caspase-9 while its anti-apoptosis Bcl-2 protein levels increased (p < 0.05). CONCLUSION: AA helps to mitigate nephropathy development in DM via counteracting oxidative stress, inflammation and apoptosis.

Dual immunological and proliferative regulation of immune checkpoint FGL1 in lung adenocarcinoma: The pivotal role of the YY1-FGL1-MYH9 axis.

Rational: Lung cancer is the most common tumor worldwide, with the highest mortality rate and second highest incidence. Immunotherapy is one of the most important treatments for lung adenocarcinoma (LUAD); however, it has relatively low response rate and high incidence of adverse events. Herein, we explored the therapeutic potential of fibrinogen-like protein 1 (FGL1) for LUAD. Methods: Data from GEPIA and ACLBI databases were assessed to explore gene-gene correlations and tumor immune infiltration patterns. A total of 200 patients with LUAD were recruited. FGL1 levels in the serum and cellular supernatant were determined by enzyme-linked immunosorbent assay. In vitro and in vivo experiments were performed to assess the effect FGL1 on the proliferation of LUAD cells. Cocultures were performed to explore the effect of FGL1 knockdown in lung cancer cells on T cells, concerning cytokine secretion and viability. PROMO and hTFtarget databases were used for transcription factor prediction. Quantitative polymerase chain reaction (qPCR), chromatin immunoprecipitation, and dual luciferase reporter assays were performed to validate the identified transcription factor of FGL1. Immunoprecipitation, mass spectrometry and gene ontology analysis were performed to explore the downstream partners of FGL1. Results: FGL1 expression in LUAD was positively associated with PDL1, but not for PD1 expression. Moreover, FGL1 was positively associated with the CD3D expression and negatively associated with FOXP3, S100A9, and TPSB2 within the tumor site. FGL1 promotes the secretion of interleukin-2 by T cells in vitro, simultaneously inducing their apoptosis. Indeed, YY1 is the upstream molecule of FGL1 was found to be transcriptionally regulated by YY1 and to directly by to MYH9 to promote the proliferation of LUAD cells in vitro and in vivo. Conclusions: FGL1 is involved in the immunological and proliferative regulation of LUAD cells by controlling the secretion of important immune-related cytokines via the YY1-FGL1-MYH9 axis. Hence, targeting FGL1 in LUAD may pave the way for the development of new immunotherapies for tackling this malignancy.

20S-ginsenoside Rg3 inhibits the biofilm formation and haemolytic activity of Staphylococcus aureus by inhibiting the SaeR/SaeS two-component system.

Introduction. Staphylococcus aureus is a major cause of chronic diseases and biofilm formation is a contributing factor. 20S-ginsenoside Rg3 (Rg3) is a natural product extracted from the traditional Chinese medicine red ginseng.Gap statement. The effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial mechanism against S. aureus have not been reported.Aim. This study aimed to investigate the effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial action against clinical S. aureus isolates.Methodology. The effect of Rg3 on biofilm formation of clinical S. aureus isolates was studied by crystal violet staining. Haemolytic activity analysis was carried out. Furthermore, the influence of Rg3 on the proteome profile of S. aureus was studied by quantitative proteomics to clarify the mechanism underlying its antibacterial action and further verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR).Results. Rg3 significantly inhibited biofilm formation and haemolytic activity in clinical S. aureus isolates. A total of 63 with >1.5-fold changes in expression were identified, including 34 upregulated proteins and 29 downregulated proteins. Based on bioinformatics analysis, the expression of several virulence factors and biofilm-related proteins, containing CopZ, CspA, SasG, SaeR/SaeS two-component system and SaeR/SaeS-regulated proteins, including leukocidin-like protein 2, immunoglobulin-binding protein G (Sbi) and fibrinogen-binding protein, in the S. aureus of the Rg3-treated group was downregulated. RT-qPCR confirmed that Rg3 inhibited the regulation of SaeR/SaeS and decreased the transcriptional levels of the biofilm-related genes CopZ, CspA and SasG.Conclusions. Rg3 reduces the formation of biofilm by reducing cell adhesion and aggregation. Further, Rg3 can inhibit the SaeR/SaeS two-component system, which acts as a crucial signal transduction system for the anti-virulence activity of Rg3 against clinical S. aureus isolates.