Comparing musculoskeletal and connective tissue disorder risks of teriparatide and abaloparatide in osteoporosis: an analysis based on FDA adverse event reporting system (FAERS).

BACKGROUND: Osteoporosis (OP), characterized by low bone mass and increased fracture risk, is a prevalent skeletal disorder. Teriparatide (TP) and abaloparatide (ABL) are anabolic agents that may reduce fracture incidence, but their impact on musculoskeletal and connective tissue disorders (MCTD) risk is uncertain. RESEARCH DESIGN AND METHODS: A retrospective, observational disproportionality analysis was conducted utilizing FAERS data from Q1 2004 to Q3 2023, where TP or ABL was identified as the primary suspect drug. Multiple data mining algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to detect MCTD safety signals. RESULTS: A total of 366,747 TP-related and 422,377 ABL-related cases were identified, predominantly among female patients aged ≥45 years. The top specific AEs involved musculoskeletal, connective tissue, and administration site disorders. Comparative analysis revealed a higher frequency of AEs related to the nervous, cardiovascular, and gastrointestinal systems for ABL compared to TP. Both drugs exhibited strong signals for arthralgia, limb pain, back pain, muscle spasms, bone pain, muscle pain, and muscle weakness. CONCLUSION: The analysis suggests a potential MCTD risk with TP and ABL treatment in OP patients, highlighting the need for AE monitoring and management in clinical practice. This contributes to a better understanding of the safety profiles of these anabolic medications.

The second member of the bacterial UDP-N-acetyl-d-glucosamine:heparosan alpha-1, 4-N-acetyl-d-glucosaminyltransferase superfamily: GaKfiA from Gallibacterium anatis.

Bacterial UDP-N-acetyl-d-glucosamine:heparosan alpha-1, 4-N-acetyl-d-glucosaminyltransferases (KfiAs) are in high demand for the development of animal-free heparin (HP) production. Until now, EcKfiA from Escherichia coli O10:K5:H4 was the sole identified member of this family. The lack of known members has limited research into molecular structure and catalytic mechanism of the KfiA superfamily, and restricted its application in enzymatic glycan synthesis. Herein, we report the identification and characterization of Gallibacterium anatis GaKfiA, doubling the number of known members of the KfiA family. GaKfiA is a monofunctional enzyme that transfers N-acetyl-d-glucosamine (GlcNAc) residues from their nucleotide forms to the nonreducing ends of saccharide chains structurally equivalent to the backbone of HP. The catalytic efficiency of GaKfiA is lower than that of EcKfiA. However, a single mutation of GaKfiA, N56D, resulted in a drastic increase in kcat/Km compared with wild-type GaKfiA. These data once again indicate the key role of a complete DXD motif for the catalytic efficiency of glycosyltransferases. This study deepens understanding of the mechanism of KfiA, and will assist in research into animal-free HP production.

Effect of Co-overexpression of Nisin Key Genes on Nisin Production Improvement in Lactococcus lactis LS01.

Nisin is a small antimicrobial peptide produced by several subset strains of Lactococcus lactis. To improve nisin yield in the producer L. lactis LS01, we proposed a successive fusion of nisA with nisRK and nisFEG into a single shuttle expression vector pMG36e under the control of the native strong constitutive promoter p32. Subsequently, the recombinant vectors were transplanted into the producer cell through electroporation. Nisin productivity was determined through sodium dodecyl sulfate-polyacrylamide gel electrophoresis and bioactivity assays. Expression of nisin peptide was detected by agar diffusion bioassay, and the transcriptional levels of the target genes involved in nisin biosynthesis were investigated via semi-quantitative reverse transcription PCR expression analysis using 16S ribosomal RNA (rRNA) as an internal control. Results suggested that the introduction of empty plasmid did not affect nisin production of L. lactis LS01, whereas by our rational construction and screening, the engineered strain co-overexpressing nisA, nisRK, and nisFEG achieved a maximum increment in bioactive nisin production with a yield of 2470 IU/ml in shake flasks and 4857 IU/ml in 1.0-l fermenters, which increased by approximately 66.3 and 52.6% (P < 0.05), respectively, compared with that of the original strain under the given fermentation conditions. Meanwhile, the transcriptional analysis revealed that the expression of most of these multicopy genes except nisE at transcriptional level were upregulated in the two recombinant strains (LS01/pAR and LS01/pARF), possibly contributing to the improved nisin production. Therefore, this study would provide a potential strategy to improve the economic benefits of nisin manufacture for large-scale industrial production.

Analysis of the essential oil from Gaillardia pulchella Foug. and its antioxidant activity.

The essential oil from Gaillardia pulchella Foug. flowers was obtained by hydrodistillation and its chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). Twenty-eight compounds representing 92.63% of the essential oil were identified, of which the most prominent were n-Hexadecanoic acid (26.90%), Phytol (7.58%) and Cyclopropaneoctanoic acid, 2-[[2-[(2-ethylcyclopropyl) methyl] cyclopropyl] methyl]-, methyl ester (6.73%). Meanwhile, antioxidant activity of the essential oil was tested. The essential oil showed certain antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) with an EC50 of 70.95 µg/ml. This is the first report on the essential oil of this particular species. Its bioactivities warrant further studies.

[Comparison study on knee osteoarthritis in rabbits induced by different concentrations of papain].

OBJECTIVE: To compare the knee osteoarthritis (OA) models in rabbits by different concentrations of papain and provide data for exploring pathogenesis and treatments of this disease. METHODS: Sixty New Zealand white rabbits were randomly divided into four groups of 15 each and given injections into the right knee on days 1, 3 and 5 including intra-articular injections of 2%, 5% or 10% (w/v) papain and 0.03 mol/L L-cysteine at the dose of 0.1 ml/kg (experimental groups). The 0.9% NaCl (w/v) with a dose of 0.1 ml/kg were injected intra-articularly into the right knees of rabbits in the control group. The rabbits were sacrificed at 2, 4, 6 weeks respectively after the initiation of papain injection and these OA models were evaluated through recording the width of knee joint, performing the morphological observation and histological evaluation of articular cartilage and synovium. RESULTS: The degenerative changes were demonstrated in knee joints of rabbit in all experimental groups, such as thinner articular cartilage, fibrillation and destroyed cartilage matrix, and inflammation, proliferation, and degeneration of the synovial tissue. All these changes were much worse with increased concentration and prolonged observation time. CONCLUSION: Different severity of OA are established through intra-articular injections of 2%, 5% or 10% papain and 0.03 mol/L L-cysteine at the dose of 0.1 ml/kg. These models are of the characters of short period and a good reproducibility.

Therapeutic effect of an injectable sustained-release sinomenine hydrochloride and sodium hyaluronate compound in a rabbit model of osteoarthritis.

BACKGROUND: While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection. METHODS: An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package. RESULTS: In the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P < 0.05). In further paired comparisons of the CSSSI group vs. modeling control/sodium hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P < 0.05), whereas sodium hyaluronate vs. sinomenine hydrochloride comparison failed to reach significance (P > 0.05). CONCLUSIONS: CSSSI has a sustained-release effect on sinomenine hydrochloride. Intra-articular injection of CSSSI was significantly better than the sole sodium hyaluronate or sinomenine hydrochloride for the treatment of osteoarthritis in a rabbit model.

Effects of chitosan and heparin on early extension of burns.

Chitosan, a naturally occurring high-molecular glycosaminoglycan (GAG), has been widely used in wound healing, including burns. Heparin is also a highly used glycosaminoglycan in burns. To evaluate the effects of chitosan and heparin alone and the mixture of chitosan and heparin on early extension of burn wound, deep partial-thickness burns were performed on the dorsum of rats. Then chitosan and heparin powder and the mixture of chitosan and heparin were applied, respectively, on the burn wounds. After 72 h, histological examination of the burn wounds was performed. Outcome showed that the burn degree of chitosan group was less severe than control group and chitosan greatly prevented the extension of burns in early phase. However, heparin had no protective effect on the early extension of burns. Use of chitosan and heparin together attenuated chitosan's protective effect.

[Preparation and characterization of chitosan coated puerarin liposomes].

OBJECTIVE: To prepare chitosan coated puerarin liposomes and investigate their physicochemical properties. METHODS: Puerarin liposomes were prepared by reverse phase evaporation technique and then coated with chitosan. Using encapsulation efficiency as index of examination and designing an orthogonal experiment, the optimal formulation of liposomes was determined. The physicochemical properties of uncoatd and chitosan coated puerarin liposomes were investigated, respectively. RESULTS: Uncoated and chitosan coated puerarin liposomes were spherelike and smooth. The mean particles size of uncoated and coated liposomes were 217. 3nm and 632. 6nm, respectively. The Zeta potential were -14.44 mV and +35.61 mV, respectively. The encapsulating efficency was 50. 6% and 51.1%, respectively. CONCLUSION: Puerarin liposomes can be prepared by reverse phase evaporation technique successfully. The chitosan coated purarin liposomes ware spherelike and smooth.

Oral absorption of hyaluronic acid and phospholipids complexes in rats.

AIM: To prepare a complex of hyaluronic acid (HA) and phospholipids (PL), and study the improvement effect of PL on the oral absorption of HA. METHODS: The complex of HA-PL (named Haplex) was prepared by film dispersion and sonication method, its physico-chemical properties were identified by infrared spectra and differential scanning calorimetry (DSC). The oral absorption of Haplex was studied. Thirty-two healthy rats were divided into 4 groups randomly: (1) a normal saline (NS) control group; (2) an HA group; (3) a mixture group and (4) a Haplex group. After intragastric administration, the concentration of HA in serum was determined. RESULTS: The physico-chemical properties of Haplex were different from HA or PL or their mixture. After Haplex was administered to rats orally, the serum concentration of HA was increased when compared with the mixture or HA control groups from 4 h to 10 h (P<0.05). The DeltaAUC0-12 h of Haplex was also greater than that of the other three groups (P<0.05). CONCLUSION: The method of film dispersion and sonication can prepare HA and PL complex, and PL can enhance the oral absorption of exogenous HA.

[The application of sodium hyaluronate in joint diseases].

OBJECTIVE: To review the physiological function of sodium hyaluronate in joints and its clinical applications. METHODS: Many literatures were reviewed and analysed on therapeutic mechanism and the application foreground of sodium hyaluronate. RESULTS: Extrinsic sodium hyaluronate plays an important role in improving synovial fluid and protecting cartilages as well as suppressing inflammation, so it is used in the treatment of joint diseases such as knee osteoarthritis, rheumatoid arthritis or temporomandibular osteoarthritis. CONCLUSION: Sodium hyaluronate possesses a good applied prospect in joint diseases.