Animal models of human pain conditions allow for detailed interrogation of known and hypothesized mechanisms of pain physiology in awake, behaving organisms. The importance of the glycinergic system for pain modulation is well known; however, manipulation of this system to treat and alleviate pain has not yet reached the sophistication required for the clinic. Here, we review the current literature on what animal behavioral studies have allowed us to elucidate about glycinergic pain modulation, and the progress toward clinical treatments so far. First, we outline the animal pain models that have been used, such as nerve injury models for neuropathic pain, chemogenic pain models for acute and inflammatory pain, and other models that mimic painful human pathologies such as diabetic neuropathy. We then discuss the genetic approaches to animal models that have identified the crucial glycinergic machinery involved in neuropathic and inflammatory pain. Specifically, two glycine receptor (GlyR) subtypes, GlyRα1(β) and GlyRα3(β), and the two glycine transporters (GlyT), GlyT1 and GlyT2. Finally, we review the different pharmacological approaches to manipulating the glycinergic system for pain management in animal models, such as partial vs. full agonism, reversibility, and multi-target approaches. We discuss the benefits and pitfalls of using animal models in drug development broadly, as well as the progress of glycinergic treatments from preclinical to clinical trials.Intestinal ischemia-reperfusion (I/R) is a common pathophysiological process, which can occur in many conditions such as acute enteric ischemia, severe burns, small intestinal transplantation, etc,. Ischemia-reperfusion of the intestine is often accompanied by distal organ injury, especially liver injury. This paper outlined the signal pathways and cytokines involved in acute liver injury induced by intestinal I/R the NF-κB Signaling Pathway, the P66shc Signaling Pathway, the HMGB1 Signaling Pathway, the Nrf2-ARE Signaling Pathway, the AMPK-SIRT-1 Signaling Pathway and other cytokines, providing new ideas for the prevention and treatment of liver injury caused by reperfusion after intestinal I/R.Purpose The aim of the present study was to evaluate the effects of dexmedetomidine compared with propofol in mechanically ventilated patients with sepsis. Methods We searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials comparing the effects of dexmedetomidine versus propofol in septic patients requiring mechanical ventilation from inception to December 2021. The primary outcome was 28/30-day mortality and secondary outcomes were ventilator-free days and the length of ICU stay. Pooled relative risk (RR), mean deviation (MD), along with 95% confidence intervals (CI) were used to express outcomes by the software of Review Manager 5.3. Results Seven studies with a total of 1,212 patients were eligible for meta-analysis. The results primarily showed that dexmedetomidine had no significant effects on the 28/30-day mortality (RR = 1.04 [0.85-1.26], p = 0.70, I2 = 3%). As for secondary outcomes, the administration of dexmedetomidine was not associated with longer-ventilator-free days (MD = 0.50 [-2.15, 3.15], p = 0.71, I2 = 24%) compared with propofol. However, our results revealed dexmedetomidine could shorten the length of ICU stay (MD = -0.76 [-1.34, -0.18], p = 0.01, I2 = 33%). Conclusion Administration of dexmedetomidine for sedation in septic patients who required mechanical ventilation had no effect on 28/30-day mortality and ventilator-free days, but it could shorten the length of ICU stay.[This corrects the article DOI 10.3389/fphar.2021.775084.].Immunotherapy with immune checkpoint inhibitor (ICI) drugs is gradually becoming a hot topic in cancer treatment. To comprehensively evaluate the safety and efficacy of ICI drugs, we employed the Bayesian model and conducted a network meta-analysis in terms of progression-free survival (PFS), overall survival (OS) and severe adverse events (AEs). Linsitinib cell line Our study found that treatment with ipilimumab was significantly worse than standard therapies in terms of PFS, whereas treatment with cemiplimab significantly improved PFS. The results also indicated that cemiplimab was the best choice for PFS. Treatment with nivolumab, pembrolizumab and nivolumab plus ipilimumab significantly improved OS compared to standard therapies. In terms of OS, cemiplimab was found to be the best choice, whereas avelumab was the worst. In terms of severe AEs, atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab all significantly reduced the risk of grade 3 or higher AEs compared to standard therapy. The least likely to be associated with severe AEs were as follows cemiplimab, avelumab, nivolumab, atezolizumab, and camrelizumab, with nivolumab plus ipilimumab to be the worst. Therefore, different ICI drug therapies may pose different risks in terms of PFS, OS and severe AEs. Our study may provide new insights and strategies for the clinical practice of ICI drugs.Ischemic stroke (IS) is an acute neurological injury that occurs when a vessel supplying blood to the brain is obstructed, which is a leading cause of death and disability. Salvia miltiorrhiza has been used in the treatment of cardiovascular and cerebrovascular diseases for over thousands of years due to its effect activating blood circulation and dissipating blood stasis. However, the herbal preparation is chemically complex and the diversity of potential targets makes difficult to determine its mechanism of action. To gain insight into its mechanism of action, we analyzed „Salvianolic acid for injection“ (SAFI), a traditional Chinese herbal medicine with anti-IS effects, using computational systems pharmacology. The potential targets of SAFI, obtained from literature mining and database searches, were compared with IS-associated genes, giving 38 common genes that were related with pathways involved in inflammatory response. This suggests that SAFI might function as an anti-inflammatory agent. Two genes associated with inflammation (PTGS1 and PTGS2), which were inhibited by SAFI, were preliminarily validated in vitro. The results showed that SAFI inhibited PTGS1 and PTGS2 activity in a dose-dependent manner and inhibited the production of prostaglandin E2 induced by lipopolysaccharide in RAW264.7 macrophages and BV-2 microglia. This approach reveals the possible pharmacological mechanism of SAFI acting on IS, and also provides a feasible way to elucidate the mechanism of traditional Chinese medicine (TCM).Neutrophils and other leukocytes invade the mouse uterus at term birth, which is normal for activating the uterus for labor. To better understand the regulation of this migration at term and interleukin (IL)-1β-induced preterm birth, we developed a mouse leukocyte migration assay (mLMA) and used it with rytvela, an IL-1 receptor allosteric antagonist. The mLMA uses term peripheral blood leukocytes that migrate in a Boyden chamber in response to a chemoattractant. We tested several mouse uterine tissues after homogenization and sedimentation of debris for chemoattractant activity. The most active chemoattractant homogenate came from the mouse lower uterus on gestational day (GD) 18.5. Using flow cytometry, we demonstrated that 99% of the cells that migrate are neutrophils. IL-1β administered on GD 16 stimulated neutrophil migration and invasion into the uterus and the fetal brain along with preterm birth on GD 17. Preterm birth and the increased leukocyte invasion of the maternal uterus and fetal brain were all blocked by the co-administration of rytvela. To test where the site of IL-1β action might be, we examined the potency of lower uterine chemoattractant and the activation of leukocytes following IL-1β +/- rytvela administration. IL-1β did not increase lower uterus homogenate chemoattractant activity, but it significantly (p less then 0.05) increased leukocyte activation as defined by cytokine and chemokine expression. Rytvela blocked this activation of leukocytes by IL-1β. We conclude that IL-1β stimulates preterm birth in mice by increasing leukocyte activation leading to increased uterine and fetal brain leukocyte invasion.Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases, accompanied by global alterations in metabolic profiles. In the past 10 years, over hundreds of metabolomics studies have been conducted to unravel metabolic changes in AD, which provides insight into the identification of potential biomarkers for diagnosis, treatment, and prognostic assessment. However, since different species may lead to systemic abnormalities in metabolomic profiles, it is urgently needed to perform a comparative metabolomics analysis between AD animal models and human patients. In this study, we integrated 78 metabolic profiles from public literatures, including 11 metabolomics studies in different AD mouse models and 67 metabolomics studies from AD patients. Metabolites and enrichment analysis were further conducted to reveal key metabolic pathways and metabolites in AD. We totally identified 14 key metabolites and 16 pathways that are both differentially significant in AD mouse models and patients. Moreover, we built a metabolite-target network to predict potential protein markers in AD. Finally, we validated HER2 and NDF2 as key protein markers in APP/PS1 mice. Overall, this study provides a comprehensive strategy for AD metabolomics research, contributing to understanding the pathological mechanism of AD.Purpose This study aimed to disclose the antidiabetic mechanisms of Rehmanniae Radix (RR). Methods The antidiabetic effect of RR was studied in Streptozocin (STZ)-induced diabetes mellitus (DM) rats and HepG2 cells with insulin resistance (IR). Antidiabetic targets and signaling pathways of RR were confirmed by the network pharmacology and transcriptome analysis as well as HK2 cells induced by high glucose (HG). Results After the DM rats were administrated RR extract (RRE) for 4 weeks, their body weight was 10.70 ± 2.00% higher than those in the model group, and the fasting blood glucose (FBG), AUC of the oral glucose tolerance test, and insulin sensitivity test values were 73.23 ± 3.33%, 12.31 ± 2.29%, and 13.61 ± 5.60% lower in the RRE group, respectively. When compared with the model group, an increase of 45.76 ± 3.03% in the glucose uptake of HepG2 cells with IR was seen in the RRE group. The drug (RR)-components-disease (DM)-targets network with 18 components and 58 targets was established. 331 differentially expressed genes (DEGs) were identified. TRPV1 and SCD1 were important DEGs by the intersectional analysis of network pharmacology and renal transcriptome. The TRPV1 overexpression significantly inhibited apoptosis and oxidative stress of the HK2 cells induced by HG, while SCD1 overexpression induced apoptosis and oxidative stress of the HK2 cells induced by low and high glucose. When compared to the HG group, the mRNA and protein expressions of TRPV1 in the presence of RRE (100 μg/ml) increased by 3.94 ± 0.08 and 2.83 ± 0.40 folds, respectively. Conclusion In summary, RR displayed an inspiring antidiabetic effect by reducing FBG and IR, upregulating the mRNA and protein expressions of TRPV1, and downregulating mRNA expression of SCD1. Induction of TRPV1 and inhibition of SCD1 by RR was possibly one of its antidiabetic mechanisms.