Improvement of antibacterial activity of polysaccharides via chemical modification: A review.

Antibiotic residue and bacterial resistance induced by antibiotic abuse have seriously threatened food safety and human healthiness. Thus, the development and application of safe, high-efficiency, and environmentally friendly antibiotic alternatives are urgently necessary. Apart from antitumor, antivirus, anti-inflammatory, gut microbiota regulation, immunity improvement, and growth promotion activities, polysaccharides also have antibacterial activity, but such activity is relatively low, which cannot satisfy the requirements of food preservation, clinical sterilization, livestock feeding, and agricultural cultivation. Chemical modification not only provides polysaccharides with better antibacterial activity, but also promotes easy operation and large-scale production. Herein, the enhancement of the antibacterial activity of polysaccharides via acetylation, sulfation, phosphorylation, carboxymethylation, selenation, amination, acid graft, and other chemical modifications is reviewed. Meanwhile, a new trend on the application of loading chemically modified polysaccharides into nanostructures is discussed. Furthermore, possible limitations and future recommendations for the development and application of chemically modified polysaccharides with better antibacterial activity are suggested.

Diagnostic value of high-frequency ultrasound combined with fine needle aspiration cytology and BRAF gene for papillary thyroid microcarcinoma.

We attempted to evaluate clinical application value of high-frequency ultrasound (HFUS), fine needle aspiration cytology (FNAC), BRAF gene, and combination of HFUS, FNAC, and BRAF gene in diagnosing papillary thyroid microcarcinoma (PTMC). The 150 patients with thyroid minimal lesions who underwent HFUS, FNAC and BRAF gene testing before surgery in our hospital from June 2020 to December 2021 were selected as research subjects. Patients were divided into two groups based on postoperative pathological results. The consistency of diagnostic results of HFUS, FNAC, and BRAF gene and their combination with those of pathological examination, diagnostic efficacy of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis, and diagnostic value of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis received analysis and comparison. The consistency of diagnostic results of combined detection with pathological examination exhibited elevation relative to that of HFUS, FNAC and BRAF gene detection alone (P < 0.05). The negative predictive value, sensitivity and accuracy of combined detection exhibited elevation relative to individual detection (P < 0.05). The AUC of combined detection in diagnosing PTMC lymph node metastasis exhibited elevation relative to that of HFUS and BRAF gene alone (P < 0.05). HFUS combined with FNAC and BRAF genes possesses high diagnostic value, with high diagnostic sensitivity, specificity, and accuracy. Thus, combined detection for PTMC before surgery can accurately determine whether lymph node metastasis occurs, reduce occurrence of missed diagnosis and misdiagnosis, and thus improve diagnostic precision.

Frequent injections of high-dose human umbilical cord mesenchymal stem cells slightly aggravate arthritis and skeletal muscle cachexia in collagen-induced arthritic mice.

A single injection of low-dose human umbilical cord-derived mesenchymal stem cells (UC-MSCs) has been previously demonstrated to relieve synovitis and bone erosion in animal models of arthritis, but whether frequent injections of high-dose UC-MSCs relieve arthritis and inhibit loss of muscle mass has remained elusive. In the present study, DBA/1 mice were randomly divided into three groups: Normal (wild-type mice; n=11), collagen-induced arthritis (CIA; n=12) and CIA treated with UC-MSCs (n=11; 5x106 UC-MSCs per week for 3 weeks). Arthritis and skeletal muscle cachexia were evaluated until the end of the experiment on day 84. It was indicated that both the CIA and UC-MSC groups had lower body weights compared with the normal mice. Clinical arthritis scores, hind ankle diameters, synovitis and bone erosion progressively increased and were similar between the CIA and UC-MSC groups. Although there was no difference in food intake among the three groups, the normalized food intake of normal group was significantly higher than CIA group and UC-MSC group from day 42 onwards; there was no significance on day 77 but this could be neglected. Furthermore, gastrocnemius muscle weight in the UC-MSC group was significantly reduced compared with that in the CIA and normal groups. The UC-MSC group had higher levels of proinflammatory cytokines, such as TNF-α, IL-6 and IL-1ß than those in the CIA group. However, the other cytokines assessed and the fibrosis indices in the CIA and UC-MSC groups were not different from those in the control group and there was no inflammatory cell infiltration. Thus, frequent injections of high-dose UC-MSCs slightly aggravated synovitis and muscle cachexia in the murine CIA model and should therefore be avoided in the treatment of arthritis.

Inflammation-Targeted Celastrol Nanodrug Attenuates Collagen-Induced Arthritis through NF-κB and Notch1 Pathways.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder which can cause bone and cartilage damage leading to disability, yet the treatment remains unsatisfactory nowadays. Celastrol (Cel) has shown antirheumatic activity against RA. However, the frequent parenteral delivery and poor water solubility of Cel restrict its further therapeutic applications. Here, aiming at effectively overcoming the poor water solubility and short half-life of Cel to boost its beneficial effects for treating RA, we developed a polymeric micelle for Cel delivery based on a reactive oxygen species (ROS) sensitive polymer. Our results demonstrated that Cel may inhibit the repolarization of macrophages toward the pro-inflammatory M1 pheno-type via regulating the NF-κB and Notch1 pathways, which resulted in significantly decreased secretion of multiple pro-inflammatory cytokines to suppress the RA progression. Consequently, the Cel-loaded micelle effectively alleviated the major RA-associated symptoms including articular scores, ankle thickness, synovial inflammation, bone erosion, and cartilage degradation.

Usefulness of complement activation products in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To evaluate the roles of complement activation products C3d and C4d binding to lymphocytes in the diagnosis of systemic lupus erythematosus (SLE) in a Chinese cohort of patients. METHODS: 96 patients with SLE, 44 patients with other autoimmune disease and 40 healthy control individuals were enrolled in this study. The levels of C3d and C4d binding to peripheral CD4+ T and CD19+ B lymphocyts (designated as T-C3d, T-C4d, B-C3d, B-C4d ) was assessed by flow cytometry. The diagnostic values of these biomarkers were determined by receiver-operator characteristic analysis. RESULTS: The levels of T-C3d, T-C4d, B-C3d, B-C4d were significantly higher in SLE patients than patients with other disease and healthy controls (p<0.01). As diagnostic tools, T-C4d and B-C4d were 61.1% sensitive/94.3% specific and 63.9% sensitive/94.3% specific in differentiating SLE patients from patients with other disease and healthy controls, respectively. T-C4d and B-C4d were significantly associated with SLE disease activity as measured by the SLE disease activity index (SLEDAI) (p<0.001), low serum C3 (p<0.001), low serum C4 (p=0.006), anti-dsDNA (IIF) (p=0.001), and anti-dsDNA (ELISA) (p=0.001). CONCLUSIONS: Complement activation products C3d and C4d binding to lymphocytes can reflect the disease activity of SLE and can be used as biomarkers for SLE.

[Clinical features and prognostic analysis of retroperitoneal fibrosis in 32 patients].

OBJECTIVE: To analyze the clinical features and imaging manifestations of retroperitoneal fibrosis (RPF) for improving clinical diagnosis and treatment. METHODS: The medical records of 32 cases from Jul. 2009 to Dec. 2011 with definite diagnosis of RPF were reviewed retrospectively, and the fibro-inflammatory tissue in CT/MRI imagings were classified and measured. The clinical symptoms, the acute phase reactants, kidney function, and radiological imaging,with or without double-J ureteral stenting were observed and compared between prior and post medications and their correlations were also analysed. RESULTS: The average age at onset was 60 years, ranging from 30-78, with male-to-female ratio of 1.91:1. Among these 32 cases, the most common presenting manifestations included abdominal pain, abdominal distension, lumbago, loss of body weight, and pitting edema of lower extremities. Hydronephrosis was found by colour doppler untrasonography in 26 (81.25%) patients. RPF was confirmed by typical CT/MRI imagings in all the patients. All of the patients in our study were treated with corticosteroids and in combination with tamoxifen or immunosuppressive agents in most of the patients, of whom 18 patients were followed up for an average of 14 months. After drug therapy, the patients' symptoms were relieved, ESR and CRP droped, renal function improved, and the size of RPF reflected in CT/MRI imagings became smaller significantly. The average time of removal double-J ureteral stenting was 13.1 months and the extubated rate was 80%. The correlation coefficients between changes of ESR or CRP and transverse diameter in CT/MRI imagings were 0.50 or 0.66 (P<0.05) respectively. CONCLUSION: The presenting manifestations of RPF were nonspecific. However, it is extremely important to recognize RPF, because early drug therapy could alleviate symptoms and reduce the acute phase reactants, improve renal function and improve imaging and extubated rate. When compared with the changes between prior and post medications, changes of ESR and CRP had good correlations with CT/MRI imaging changes respectively.