Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency.

BACKGROUND: The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. METHODS: Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. RESULTS: The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05). CONCLUSIONS: T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.

Epidemiological Characteristics of COVID-19 Outbreak in Yangzhou, China, 2021.

Objective: Epidemiological characteristics of COVID-19 outbreak in Yangzhou city caused by the highly contagious Delta variant strain of SARS-CoV-2 virus were investigated in this retrospective descriptive study to provide prevention and control guidelines for outbreaks in the future. Methods: All the epidemiological data used in this study were collected manually from the official website of the Yangzhou Municipal Health Committee from 28 July to 26 August 2021, and then were analyzed systematically and statistically in this study. Results: A total of 570 COVID-19 cases were reported during the short-term outbreak in Yangzhou City. The ages of infected individuals ranged from 1 to 90 years with the average age at 49.47 ± 22.69 years. As for gender distributions, the ratio of male- to-female patients was 1:1.36 (242:328). Geographic analysis showed that 377 patients (66.1%) were in Hanjiang District while 188 patients (33.0%) were in Guangling District. Clinical diagnosis showed that 175 people (30.7%) had mild symptoms, 385 people were in moderate conditions (67.5%), and 10 people were in severe situations (1.8%). Significant age differences were found among the three groups (P < 0.001). However, no significant difference was identified in terms of gender ratio (P > 0.05). Based on the transmission chain formed by 6 generations of infected persons with a clear transmission relationship, the age showed a gradually decreasing trend, while the median time of diagnosis in 2 adjacent generations was 3 days. In addition, the estimated basic reproduction number R 0 of the Delta variant was 3.3651 by the classical Susceptible, Infectious, and/or Recovered (SIR) model. Conclusion: The Delta variant of SARS-CoV-2 was highly infectious and has obvious clustering characteristics during the Yangzhou outbreak in China.

Preparation of polyethersulfone-organophilic montmorillonite hybrid particles for the removal of bisphenol A.

Polyethersulfone (PES)-organophilic montmorillonite (OMMT) hybrid particles, with various proportions of OMMT, were prepared by using a liquid-liquid phase separation technique, and then were used for the removal of bisphenol A (BPA) from aqueous solution. The adsorbed BPA amounts increased significantly when the OMMT were embedded into the particles. The structure of the particle was characterized by using scanning electron microscopy (SEM); and these particles hardly release small molecules below 250 degrees C which was testified by using thermogravimetric analysis (TGA). The experimental data of BPA adsorption were adequately fitted with Langmuir equations. Three simplified kinetics model including the pseudo-first-order (Lagergren equation), the pseudo-second-order, and the intraparticle diffusion model were used to describe the adsorption process. Kinetic studies showed that the adsorbed BPA amount reached an equilibrium value after 300 min, and the experimental data could be expressed by the intraparticular mass transfer diffusion model. Furthermore, the adsorbed BPA could be effectively removed by ethanol, which indicated that the hybrid particles could be reused. These results showed that the PES-OMMT hybrid particles have the potential to be used in the environmental application.

Peripheral pain is enhanced by insulin-like growth factor 1 and its receptors in a mouse model of type 2 diabetes mellitus.

BACKGROUND: Insulin-like growth factor 1 (IGF1) is a neurotrophic factor with many actions, including a possible hyperalgesic effect. This study investigated the effects of IGF1 on the overall behavior of diabetic mice and explored the possible mechanisms underlying IGF1-induced pain. METHODS: Mice were divided into five groups (db/m, db/db, vehicle-treated db/db, IGF1-treated db/db, and IGF1 + JB1-treated db/db mice). Behavioral studies were conducted using the hot plate and Von Frey tests after intraplantar injection of recombinant (r) IGF1 (50 µg/kg) and the IGF1 receptor (IGF1R) antagonist JB1 (6 µg/mouse). Morphological changes in dorsal root ganglia (DRG) were evaluated using electron microscopy. Immunofluorescence was used to detect IGF1R expression and colocalisation with pain mediators in the DRG. Changes in the expression of IGF1R, extracellular signal-regulated kinase (ERK), and ras-associated factor-1 (c-raf) in the DRG were evaluated using western blotting. RESULTS: Intraplantar injection of rIGF1 resulted in a hyperalgesic effect after 2 hours. This IGF1-induced hypersensitivity was attenuated by prior intraplantar injection of the IGF1R antagonist. There was no significant change in neuronal structure in the db/m group, whereas neuronal structure was impaired in the other four groups. Moreover, IGF1R was colocalised with pain mediators in the DRG of mice. Intraplantar injection of rIGF1 resulted in increased IGF1R, phosphorylated (p-) ERK, and c-raf expression in the DRG; prior intraplantar injection of the IGF1R antagonist attenuated rIGF1-induced increases in p-ERK and c-raf. CONCLUSIONS: The results indicate that IGF1-induced acute hyperalgesia may be associated with the IGF1R/c-raf/ERK pathway. The IGF1-induced hypersensitivity was attenuated by an IGF1R antagonist.

Chitosan gel beads immobilized Cu (II) for selective adsorption of amino acids.

Chitosan (CS) gel beads were prepared by using phase inversion and precipitation technique. The gel beads could bind copper (II), by which Cu (II) ion-immobilized chitosan gel beads (CS-Cu2+ gel beads) were prepared, and the amount of the immobilized Cu (II) was about 35 mg/g when the CS gel beads were incubated in 150 ppm cupric sulfate solution. The CS-Cu2+ gel beads could selectively adsorb histidine (His) from the mixed solution containing His and tryptophan (Trp); and the selective coefficient which was defined as the adsorbed amount ratio of His to Trp was about 8.0 at the pH value of 7.4. The effect of the pH value on the amino acid adsorption was also studied. In order to investigate the relationship of the amino acid adsorption and protein adsorption, the adsorbed amounts for IgG and albumin were determined; and the results indicated that the CS-Cu2+ gel beads could adsorb a larger amount of IgG than albumin due to the larger amount of the exposed residual His. The study provided a sorbent and a method to selectively remove His and IgG.

Protection of insulin­like growth factor 1 on experimental peripheral neuropathy in diabetic mice.

The present study investigated whether insulin­like growth factor­1 (IGF­1) exerts a protective effect against neuropathy in diabetic mice and its potential underlying mechanisms. Mice were divided into four groups: Db/m (control), db/db (diabetes), IGF­1­treated db/db and IGF­1­picropodophyllin (PPP)­treated db/db. Behavioral studies were conducted using the hot plate and von Frey methods at 6 weeks of age prior to treatment. The motor nerve conduction velocity (NCV) of the sciatic nerve was measured using a neurophysiological method at 8 weeks of age. The alterations in the expression levels of IGF­1 receptor (IGF­1R), c­Jun N­terminal kinase (JNK), extracellular signal­regulated kinase (ERK), p38 and effect of IGF­1 on the sciatic nerve morphology were observed by western blotting and electron microscopy. Compared with the control group, the diabetes group developed hypoalgesia after 12 weeks, and neurological lesions improved following an intraperitoneal injection of recombinant (r)IGF­1. The sciatic NCV in the diabetes group was significantly lower compared with the control group. The sciatic NCV improved following rIGF­1 intervention; however, was impaired following administration of the IGF­1 receptor antagonist, PPP. The myelin sheath in the sciatic nerve of the diabetes group was significantly more impaired compared with the control group. The myelin sheath in the sciatic nerves of the rIGF­1­treated group was significantly improved compared with the diabetes group; whereas, they were significantly impaired following administration of the IGF­1R inhibitor. In addition, the expression of IGF­1R, phosphorylated (p)­JNK and p­ERK of sciatic nerves in the db/db mice was significantly increased following treatment with IGF­1. The expression levels of these proteins were significantly lower in the IGF­1­PPP group compared with the IGF­1 group; however, no significant difference was observed in the expression levels of p­p38 following treatment with IGF­1. The results of the present study demonstrated that IGF­1 may improve neuropathy in diabetic mice. This IGF­1­induced neurotrophic effect may be associated with the increased phosphorylation levels of JNK and ERK, not p38; however, it was attenuated by administration of an IGF­1R antagonist.