Effects of Muscone on Cartilage Morphology and Matrix Metalloproteinases-3 (MMP-3h) and Matrix Metalloproteinases-9 (MMP-9) Expression in Rheumatoid Arthritis Rat Models

Aim: To discuss Muscone treatment in Rheumatoid Arthritis Rat Models and relative mechanisms. Materials and methods: Dividing 36 rats as 4 groups as Normal, Model, DMSO and Muscone groups (n = 9). Rats of Model, DMSO and Muscone groups were made Rheumatoid Arthritis model. Muscone group were treated with 2 mg/kg Muscone after modeling. HE staining and Masson staining were used to observe the morphological changes of cartilage tissue, measuring MMP-3 and MMP-9 expression by RT-PCR, Western Blotting (WB) and Immunohistochemistry (IHC). Results: Compared with Model group, the pathological changes of Muscone group was significantly improved and average optical density of collagen fibers was significantly depressed (P < 0.001, respectively) via MMP-3 and MMP-9 proteins significantly depressing (P < 0.001, respectively). Conclusion: Muscone improved Rheumatoid Arthritis by depressing MMP-3 and MMP-9 proteins in vivo study.

Anti-Gout Effects of the Medicinal Fungus Phellinus igniarius in Hyperuricaemia and Acute Gouty Arthritis Rat Models

Background:Phellinus igniarius (P. igniarius) is an important medicinal and edible fungus in China and other Southeast Asian countries and has diverse biological activities. This study was performed to comparatively investigate the therapeutic effects of wild and cultivated P. igniarius on hyperuricaemia and gouty arthritis in rat models.Methods: UPLC-ESI-qTOF-MS was used to identify the chemical constituents of polyphenols from wild P. igniarius (WPP) and cultivated P. igniarius (CPP). Furthermore, WPP and CPP were evaluated in an improved hyperuricaemia rat model induced by yeast extract, adenine and potassium oxonate, which was used to examine xanthine oxidase (XO) activity inhibition and anti-hyperuricemia activity. WPP and CPP therapies for acute gouty arthritis were also investigated in a monosodium urate (MSU)-induced ankle swelling model. UHPLC-QE-MS was used to explore the underlying metabolic mechanisms of P. igniarius in the treatment of gout.Results: The main active components of WPP and CPP included protocatechuic aldehyde, hispidin, davallialactone, phelligridimer A, hypholomine B and inoscavin A as identified by UPLC-ESI-qTOF-MS. Wild P. igniarius and cultivated P. igniarius showed similar activities in reducing uric acid levels through inhibiting XO activity and down-regulating the levels of UA, Cr and UN, and they had anti-inflammatory activities through down-regulating the secretions of ICAM-1, IL-1β and IL-6 in the hyperuricaemia rat model. The pathological progression of kidney damage was also reversed. The polyphenols from wild and cultivated P. igniarius also showed significant anti-inflammatory activity by suppressing the expression of ICAM-1, IL-1β and IL-6 and by reducing the ankle joint swelling degree in an MSU-induced acute gouty arthritis rat model. The results of metabolic pathway enrichment indicated that the anti-hyperuricemia effect of WPP was mainly related to the metabolic pathways of valine, leucine and isoleucine biosynthesis and histidine metabolism. Additionally, the anti-hyperuricemia effect of CPP was mainly related to nicotinate and nicotinamide metabolism and beta-alanine metabolism.Conclusions: Wild P. igniarius and cultivated P. igniarius both significantly affected the treatment of hyperuricaemia and acute gouty arthritis models in vivo and therefore may be used as potential active agents for the treatment of hyperuricaemia and acute gouty arthritis.

Positron Emission Tomography in Animal Models of Tauopathies

The microtubule-associated protein tau (MAPT) plays an important role in Alzheimer’s disease and primary tauopathy diseases. The abnormal accumulation of tau contributes to the development of neurotoxicity, inflammation, neurodegeneration, and cognitive deficits in tauopathy diseases. Tau synergically interacts with amyloid-beta in Alzheimer’s disease leading to detrimental consequence. Thus, tau has been an important target for therapeutics development for Alzheimer’s disease and primary tauopathy diseases. Tauopathy animal models recapitulating the tauopathy such as transgenic, knock-in mouse and rat models have been developed and greatly facilitated the understanding of disease mechanisms. The advance in PET and imaging tracers have enabled non-invasive detection of the accumulation and spread of tau, the associated microglia activation, metabolic, and neurotransmitter receptor alterations in disease animal models. In vivo microPET studies on mouse or rat models of tauopathy have provided significant insights into the phenotypes and time course of pathophysiology of these models and allowed the monitoring of treatment targeting at tau. In this study, we discuss the utilities of PET and recently developed tracers for evaluating the pathophysiology in tauopathy animal models. We point out the outstanding challenges and propose future outlook in visualizing tau-related pathophysiological changes in brain of tauopathy disease animal models.

Different sites of actions make different responses to thiazolidinediones between mouse and rat models of fatty liver

Therapeutic approach for NAFLD is limited and there are no approved drugs. Pioglitazone (PGZ), a thiazolidinedione (TZD) that acts via peroxisome proliferator activated receptor gamma (PPARγ) is the only agent that has shown consistent benefit and efficacy in clinical trials. However, the mechanism of its therapeutic effect on NAFLD remains unclear. The poor understanding may be due to problems with mouse, a species most used for animal experiments. TZDs exacerbate fatty liver in mouse models while they improve it in rat models like in human patients. Therefore, we compared the effects of TZDs including PGZ and rosiglitazone (RGZ) in ob/ob mice and Lepmkyo/Lepmkyo rats, models of leptin-deficient obesity, and A-ZIP/F-1 mice and seipin knockout (SKO) rats, models of generalized lipodystrophy. Pparg mRNA expression was markedly upregulated in fatty livers of mouse models while it was unchanged in rat models. TZDs exacerbated fatty liver in ob/ob and A-ZIP/F-1 mice, improved it in Lepmkyo/Lepmkyo rats and showed no effect in SKO rats. Gene expression analyses of Pparg and its target gene, Fsp27 revealed that PPARγ in the adipose tissue is the exclusive therapeutic target of TZDs in rats but PPARγ in the liver in addition to the adipose tissue is also a major site of actions for TZDs in mice. Although the response to TZDs in mice is the complete opposite of that in human patients, no report has pointed out the problem with TZD studies using mouse models so far. The present study might provide useful suggestions in research on TZDs.

Protectin DX Attenuates Lumbar Radicular Pain of Non-compressive Disc Herniation by Autophagy Flux Stimulation via Adenosine Monophosphate-Activated Protein Kinase Signaling

Background: Neuroinflammation plays a crucial role in initiating and sustaining lumbar radicular pain (LRP). Protectin DX (PDX) has been experimentally verified to possess pro-resolving properties and anti-inflammatory effects. This study aimed to observe the analgesic effects of PDX and its potential mechanisms in LRP rats with non-compressive lumbar disc herniation (NCLDH).Method: Only male rats were selected to avoid gender-related interferences. Rat models of NCLDH were established, and rats were randomly divided into four groups: the sham group, the vehicle group, the PDX (10 ng PDX) group, and the PDX (100 ng PDX) group. Changes in the mechanical withdrawal threshold and thermal withdrawal latency were observed for 7 days. The mRNAs of pro-inflammatory and anti-inflammatory mediators were evaluated via real-time polymerase chain reaction, whereas western blot and immunohistochemistry were separately conducted to assess the expression levels of autophagy-related proteins and adenosine monophosphate-activated protein kinase (AMPK) signaling.Results: Intrathecal delivery of PDX reduced interleukin (IL)-6 and IL-1β mRNA levels and facilitated mRNA transcription of transforming growth factor-β1, with attenuation of mechanical and thermal hyperalgesia in LRP rat models. With the application of nucleus pulposus to the dorsal root ganglion, autophagy flux and AMPK signaling were severely disrupted in the spinal dorsal horns, and intrathecal treatment with PDX could dose-dependently restore the dysfunction of autophagy flux and AMPK signaling.Conclusion: These data suggest that PDX possesses pro-resolving properties and exerts potent analgesic effects in LRP by affecting autophagy flux via AMPK signaling.

Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature

<b><i>Introduction:</i></b> Up to 30% of patients with post-traumatic stress disorder (PTSD), especially combat veterans, remain refractory to conventional treatment. For them, deep brain stimulation (DBS) has been suggested. Here, we review the literature on animal models of PTSD in which DBS has been used to treat PTSD-type behavior, and we review and discuss patient reports of DBS for PTSD. <b><i>Methods:</i></b> A broad search was performed to find experimental animal articles and clinical reports on PubMed, Ovid MEDLINE, Cochrane Library, and PsycINFO, using combinations and variations of search words pertinent to DBS and PTSD. <b><i>Results:</i></b> The search yielded 30 articles, 24 on DBS in rat models of PTSD, and 6 publications between 2016 and 2020 reporting on a total of 3 patients. DBS in rat models targeted 4 brain areas: medial prefrontal cortex (mPFC), ventral striatum, amygdala, and hippocampus. Clinical publications reported on 2 male combat veterans who received DBS in basolateral amygdala, and 1 female with PTSD due to domestic abuse, who received DBS of mPFC. All 3 patients benefitted to various extents from DBS, at follow-ups of 4 years, 6 months, and 7 months, respectively. <b><i>Conclusions:</i></b> PTSD is the only potential clinical indication for DBS that shows extensive animal research <i>prior</i> to human applications. Nevertheless, DBS for PTSD remains highly investigational. Despite several years of government funding of DBS research in view of treating severe PTSD in combat veterans, ethical dilemmas, recruitment difficulties, and issues related to use of DBS in such a complex and heterogenous disorder remain prevalent.

Comparison of urine proteome among rat models by intraperitoneal injection with single bacteria and co-injection with two bacteria

Purpose To explore and compare urine proteome changes among rat models by intraperitoneal injection with single bacteria and co-injection with two bacteria. Method Escherichia coli and Staphylococcus aureus are two common human pathogens. Three rat models were established: (i) the intraperitoneal co-injection of E. coli and S. aureus model (ES model), (ii) intraperitoneal injection of E. coli model (E model), and (iii) intraperitoneal injection of S. aureus model (S model). Urinary proteomes on days 0, 1 and 2 of the three models were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Results A total of 111, 34 and 94 differential proteins were identified in the ES model, E model and S model, respectively. Among them, some differential proteins were reported to be associated with bacterial infection. Approximately 47% differential proteins in the E model overlapped with ES model, and 37% differential proteins in the S model overlapped with ES model. Compared with the E model and S model, a total of 71 unique differential proteins were identified in the ES model. Conclusion Our results indicated that (1) the urine proteome could distinguish different bacterial intraperitoneal injections models and (2) the effects of co-injection with two bacteria on the urine proteome were not simple superposition of single injection.