Exosomes derived from MSC as drug system in osteoarthritis therapy.

Osteoarthritis (OA) is the most common degenerative disease of the joint with irreversible cartilage damage as the main pathological feature. With the development of regenerative medicine, mesenchymal stem cells (MSCs) have been found to have strong therapeutic potential. However, intraarticular MSCs injection therapy is limited by economic costs and ethics. Exosomes derived from MSC (MSC-Exos), as the important intercellular communication mode of MSCs, contain nucleic acid, proteins, lipids, microRNAs, and other biologically active substances. With excellent editability and specificity, MSC-Exos function as a targeted delivery system for OA treatment, modulating immunity, inhibiting apoptosis, and promoting regeneration. This article reviews the mechanism of action of MSC-Exos in the treatment of osteoarthritis, the current research status of the preparation of MSC-Exos and its application of drug delivery in OA therapy.

Comparative analysis of pathogen distribution in patients with fracture-related infection and periprosthetic joint infection: a retrospective study.

BACKGROUND: The purpose of this study is to investigate the microbial patterns of periprosthetic joint infection (PJI) and fracture-related infection (FRI), and guide for the formulation of more accurate empirical antimicrobial regimens based on the differences in pathogen distribution. METHODS: A comparative analysis of pathogen distribution was conducted between 153 patients (76 with PJI and 77 with FRI). Predicted analyses against isolated pathogens from two cohorts were conducted to evaluate the best expected efficacy of empirical antimicrobial regimens (imipenem + vancomycin, ciprofloxacin + vancomycin, and piperacillin/tazobactam + vancomycin). RESULTS: Our study found significant differences in pathogen distribution between the PJI and FRI cohorts. Staphylococci (61.3% vs. 31.9%, p = 0.001) and Gram-negative bacilli (GNB, 26.7% vs. 56.4%, p < 0.001) were responsible for the majority of infections both in the PJI and FRI cohorts, and their distribution in the two cohorts showed a significant difference (p < 0.001). Multi-drug resistant organisms (MDRO) were more frequently detected in the FRI cohort (29.3% vs. 44.7%, p = 0.041), while methicillin-resistant coagulase-negative Staphylococci (MRCoNS, 26.7% vs. 8.5%, p = 0.002) and Canidia albicans (8.0% vs. 1.1%, p = 0.045) were more frequently detected in the PJI cohort. Enterobacter spp. and Acinetobacter baumannii were detected only in the FRI cohort (11.7% and 8.5%, respectively). CONCLUSIONS: Staphylococci and GNB were responsible for the majority of infections in both PJI and FRI. Empirical antimicrobial therapy should focus on the coverage of Staphylococci in PJI and GNB in FRI, and infections caused by MDROs should be more vigilant in FRI, while the high incidence of MRCoNS in PJI should be noted, which could guide for the formulation of more accurate empirical antimicrobial regimens. Targeted therapy for FRI caused by A. baumannii and PJI caused by C. albicans needs to be further investigated. Our study reports significant differences in pathogen distribution between the two infections and provides clinical evidence for studies on the mechanism of implant-associated infection.

The continuous physiological changes of zebrafish (Danio rerio) based on metabolism under controlled thallium stress.

In this research, the continuous physiological changes of zebrafish (Danio rerio) in 0.1 µg/L thallium (Tl) in 15 days were investigated. The results showed that Tl(I) stress had a significant positive linear correlation with zebrafish ammonia nitrogen excretion (ANE) (p < 0.001), and the mean value of ANE in Tl(I) treatment (435 ±â€¯227 mg/kg/h) was approximately 2 times higher than in the control group (239 ±â€¯168 mg/kg/h), which suggested that ANE was suitable for Tl(I) stress assessment. A substantial difference based on oxygen consumption rate (OCR) between the control group (587 ±â€¯112 mg/kg/h) and Tl(I) treatment (260 ±â€¯88 mg/kg/h) with a high significance p < 0.001 could be observed, and the results indicated that Tl(I) played a negative role in OCR of zebrafish. The characteristics of both ANE and OCR changes under slight Tl(I) stress could be reflected by the ammonia quotient (AQ). It was noteworthy that AQ increased rapidly in first 6 h from 0.66 to 4.50, which was 3 times higher than 1.2, indicating rapid increase in both anaerobic energy utilization and protein metabolism in 0.1 µg/L Tl(I) exposure. It is concluded that the physiological changes of zebrafish based on metabolism can be regarded as a sensitive biological indicator of Tl(I) pollution, which could work as a substitute of potassium that disrupts the normal biological metabolism in the process of transport.

The online monitoring and assessment of thallium stress using oxygen consumption rate and carbon dioxide excretion rate of zebrafish (Danio rerio).

An online monitoring and assessment system of metabolism to measure oxygen consumption rate (OC) and carbon dioxide (CO2) excretion rate (CR) of zebrafish (Danio rerio) was used to illustrate changes in stressful states in 15 days' (360 h) 0.1 µg/L Tl exposure. Tl had a significant inhibition on zebrafish OC and CR (p < 0.01). OC was more suitable for Tl stress assessment than CR, considering that the OC response was more stable and discernible from the control comparing with CR. However, CR is a suitable alternative to characterize toxic effects on different metabolic substrates. Both OC and CR were integrated to present the respiratory quotient (RQ) analysis. RQ was efficient in differentiating between CO2 produced by respiration in the control group (RQ less than 0.7) and CO2 used for urination or stored in tissues after Tl exposure (some RQs larger than 1.0). Circadian rhythm was observed in RC and CR in the controls and persisted in 0.1 µg/L Tl treatments. The rhythm was relatively more disordered in CR. OC and CR would be suitable for indicating physiological stress in the online system as sensitive physiological indices.

Discovery of benzotriazole-azo-phenol/aniline derivatives as antifungal agents.

A series of benzotriazole-azo-phenol/aniline derivatives were prepared and evaluated for their antifungal activities against six phytopathogenic fungi such as Fusarium graminearum, Fusarium solani, Alternaria alternate, Valsa mali, Botrytis cinerea, and Curvularia lunata. Among them, compounds IIf, IIn, and IIr showed a broad-spectrum of potent antifungal activities. Especially some compounds displayed 3.5-10.8 folds more potent activities than carbendazim against A. alternata and C. lunata. Notably, compounds IIc, IIm, and IIr exhibited good protective and therapeutic effects against B. cinerea at 200 µg/mL. Their structure-activity relationships were also discussed.

Cadmium stress assessment based on the electrocardiogram characteristics of zebra fish (Danio rerio): QRS complex could play an important role.

The electrocardiogram (ECG) of zebra fish (Danio rerio) expresses cardiac features that are similar to humans. Here we use sharp microelectrode measurements to obtain ECG characteristics in adult zebra fish and analyze the effects of cadmium chloride (CdCl2) on the heart. We observe the overall changes of ECG parameters in different treatments (0.1 TU, 0.5 TU and 1.0 TU CdCl2), including P wave, Q wave, R wave, S wave, T wave, PR interval (atrial contraction), QRS complex (ventricular depolarization), ST segment, and QT interval (ventricular repolarization). The trends of the ECG parameters showed some responses to the concentration and exposure time of CdCl2, but it was difficult to obtain more information about the useful indicators in water quality assessment depending on tendency analysis alone. A self-organizing map (SOM) showed that P values, R values, and T values were similar; R wave and T wave amplitude were similar; and most important, QRS value was similar to the CdCl2 stress according to the classified data patterns including CdCl2 stress (E) and ECG components based on the Ward linkage. It suggested that the duration of QRS complex was related to environmental stress E directly. The specification and evaluation of ECG parameters in Cd2+ pollution suggested that there is a markedly significant correlation between QRS complex and CdCl2 stress with the highest r (0.729) and the smallest p (0.002) among all ECG characteristics. In this case, it is concluded that QRS complex can be used as an indicator in the CdCl2 stress assessment due to the lowest AIC data abased on the linear regression model between the CdCl2 stress and ECG parameters.

The physiological characteristics of zebra fish (Danio rerio) based on metabolism and behavior: A new method for the online assessment of cadmium stress.

In order to illustrate heavy metal ecotoxicology associated with interactions between chemicals and biological systems, we investigated physiological changes (metabolism and behavior response) of zebra fish (Danio rerio) under 48 h Cadmium chloride (CdCl2) exposure using online monitoring technique. The concentrations of CdCl2 were designed as 4.26, 42.6 and 85.2 mg/L, which were 0.1, 1.0, and 2.0 based on toxic unit (TU), respectively. The metabolism was assessed using the oxygen consumption (OC), and the behavior response was analyzed in behavior strength (BS). Significant inhibition of both OC and BS could be observed: OC was 617.39 ± 30.48 mg/kg/h in the control, and it decreased rapidly to 229.07 ± 28.66 mg/kg/h in 2.0 TU treatment. BS changed from 0.76 ± 0.07 (control) to 0.39 ± 0.04 (2.0 TU) with the increase of exposure concentrations. Further results suggested that both factors were related to diurnal variation during 48 h exposure, which could be regarded as circadian rhythms: the average values of OC and BS during photo-phase were significantly higher than both during scoto-phase in CdCl2 treatments (p < 0.05). After integrated analysis, the original values of both OC and BS with wide fluctuation showed a negative linear relationship with CdCl2 concentration. The levels of both OC and BS were positively correlated with CdCl2 (r = 0.93 and p < 0.01). It is suggested that both OC and BS provide an objective ground for CdCl2 stress assessment, and that also could be applied to test the changes of organisms quantitatively in toxic physiology.

Does time difference of the acetylcholinesterase (AChE) inhibition in different tissues exist? A case study of zebra fish (Danio rerio) exposed to cadmium chloride and deltamethrin.

In order to illustrate time difference in toxic effects of cadmium chloride (CdCl2) and deltamethrin (DM), AChE activities were measured in different tissues, liver, muscle, brain, and gill, of Zebra fish (Danio rerio) across different concentrations in this research. The average AChE activity decreased comparing to 0.0 TU with DM (82.81% in 0.1 TU, 56.14% in 1.0 TU and 44.68% in 2.0 TU) and with CdCl2 (74.68% in 0.1 TU, 52.05% in 1.0 TU and 50.14% in 2.0 TU) showed an overall decrease with the increase of exposure concentrations. According to Self-Organizing Map (SOM), the AChE activities were characterized in relation with experimental conditions, showing an inverse relationship with exposure time. As the exposure time was longer, the AChE activities were correspondingly lower. The AChE inhibition showed time delay in sublethal treatments (0.1 TU) in different tissues: the AChE was first inhibited in brain by chemicals followed by gill, muscle and liver (brain > gill > muscle > liver). The AChE activity was almost inhibited synchronously in higher environmental stress (1.0 TU and 2.0 TU). As the AChE inhibition can induce abnormal of behavior movement, these results will be helpful to the mechanism of stepwise behavior responses according to the time difference in different tissues rather than the whole body AChE activity.

Semisynthesis of Esters of Fraxinellone C4/10-Oxime and Their Pesticidal Activities.

A total of 20 esters of fraxinellone C4/10-oxime were synthesized and determined by melting points, optical rotation, infrared spectra, proton nuclear magnetic resonance spectra, and high-resolution mass spectrometry spectra. Two steric configurations of compounds 7i and 8i were unambiguously confirmed by X-ray crystallography. Additionally, their pesticidal activities were assessed on two typical lepidopteran pests, Mythimna separata Walker and Plutella xylostella Linnaeus. Generally, all compounds exhibited less potent oral toxicity than toosendanin against third-instar larvae of P. xylostella. However, all compounds showed the growth inhibitory property against early third-instar larvae of M. separata. Notably, compounds 7m, 8b, 8k, 9, and 11 displayed more potent pesticidal activity than toosendanin. This demonstrated that introducing the C-4 carbonyl or oxime group on fraxinellone resulted in more promising derivatives than those bearing a C-10 carbonyl or oxime substituent.