Animal Models
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2022 ◽  
Vol 11 (1) ◽  
pp. 40-56
Author(s):  
Udhaya Bharathy Saravanan ◽  
Mayurikaa Namachivayam ◽  
Rajesh Jeewon ◽  
Jian-Dong Huang ◽  
Siva Sundara Kumar Durairajan

2022 ◽  
Author(s):  
Daniel Freilich ◽  
Jennifer Victory ◽  
Paul Jenkins ◽  
James Wheeler ◽  
G Matthew Vail ◽  
...  

Background ACEi/ARB medications have been hypothesized to have potential benefit in COVID-19. Despite concern for increased ACE-2 expression in some animal models, preclinical and observational-retrospective and uncontrolled trials suggested possible benefit. Two RCTs of the ARB losartan from University of Minnesota showed no benefit yet safety signals for losartan in outpatient and hospitalized COVID-19 patients. COVID MED, started early in the pandemic, also assessed losartan in a RCT in hospitalized patients with COVID-19. Methods COVID MED was quadruple-blinded, placebo-controlled, multicenter randomized clinical trial (RCT). Hospitalized COVID-19 patients were randomized to receive standard care and hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued after RCTs showed no benefit. We report data from the losartan arm compared to combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint was the NCOSS slope of change. Slow enrollment prompted early stopping. Results Of 432 screened patients, 14 were enrolled (3.5%), 9 received losartan and 5 combined control (lopinavir/ritonavir [N=2], placebo [N=3]); 1 hydroxychloroquine arm patient was excluded. Most baseline parameters were balanced. Treatment with losartan was not associated with a difference in NCOSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan. Conclusions In this small blinded RCT in hospitalized COVID-19 patients, losartan did not improve outcome vs. control comparisons and was associated with adverse safety signals.


2022 ◽  
Vol 8 (4) ◽  
pp. 263-266
Author(s):  
Raja Chakraverty ◽  
Debalina Sardar ◽  
Pranabesh Chakraborty

The study is aimed at the evaluation of potential activity of and possible interaction with metformin in animal Models of Diabetes Mellitus. Study objectives include study the anti-diabetic effect of for Diabetes Mellitus in animal models and also to study the effect of Abelmoschus esculentus with metformin and explore any interaction. Plant material was collected () followed by extraction of plant materials () Exudate collection of and activity test study was done (acute toxicity study, according to standard OECD guidelines) Experimental animals were divided into groups. Dosing was done for 28 days. Biochemical parameters were studied. Histopathology studies are done. Results showed that in this study administrations of Abelmoschus esculentus extract (2000mg/kg body weight) Metformin with extract (5mg/kg b.w. and 2000mg/kg body weight and Metformin 5mg/kg body weight decreased elevated blood glucose levels significantly from first to fourth week compared to diabetic control rats and showed minimal safety concerns.


Author(s):  
Katarzyna Trzos ◽  
Natalia Pydyn ◽  
Jolanta Jura ◽  
Jerzy Kotlinowski

AbstractMurine models of human diseases are of outmost importance for both studying molecular mechanisms driving their development and testing new treatment strategies. In this review, we first discuss the etiology and risk factors for autoimmune liver disease, including primary biliary cholangitis, autoimmune hepatitis and primary sclerosing cholangitis. Second, we highlight important features of murine transgenic models that make them useful for basic scientists, drug developers and clinical researchers. Next, a brief description of each disease is followed by the characterization of selected animal models.


2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Zhijie Yu ◽  
Jun Xiao ◽  
Xiao Chen ◽  
Yi Ruan ◽  
Yang Chen ◽  
...  

AbstractPulmonary arterial hypertension (PAH) is a progressive and rare disease without obvious clinical symptoms that shares characteristics with pulmonary vascular remodeling. Right heart failure in the terminal phase of PAH seriously threatens the lives of patients. This review attempts to comprehensively outline the current state of knowledge on PAH its pathology, pathogenesis, natural medicines therapy, mechanisms and clinical studies to provide potential treatment strategies. Although PAH and pulmonary hypertension have similar pathological features, PAH exhibits significantly elevated pulmonary vascular resistance caused by vascular stenosis and occlusion. Currently, the pathogenesis of PAH is thought to involve multiple factors, primarily including genetic/epigenetic factors, vascular cellular dysregulation, metabolic dysfunction, even inflammation and immunization. Yet many issues regarding PAH need to be clarified, such as the “oestrogen paradox”. About 25 kinds monomers derived from natural medicine have been verified to protect against to PAH via modulating BMPR2/Smad, HIF-1α, PI3K/Akt/mTOR and eNOS/NO/cGMP signalling pathways. Yet limited and single PAH animal models may not corroborate the efficacy of natural medicines, and those natural compounds how to regulate crucial genes, proteins and even microRNA and lncRNA still need to put great attention. Additionally, pharmacokinetic studies and safety evaluation of natural medicines for the treatment of PAH should be undertaken in future studies. Meanwhile, methods for validating the efficacy of natural drugs in multiple PAH animal models and precise clinical design are also urgently needed to promote advances in PAH. Graphical Abstract


Author(s):  
Tali M. Ball ◽  
Lisa A. Gunaydin

AbstractAvoiding stimuli that predict danger is required for survival. However, avoidance can become maladaptive in individuals who overestimate threat and thus avoid safe situations as well as dangerous ones. Excessive avoidance is a core feature of anxiety disorders, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). This avoidance prevents patients from confronting maladaptive threat beliefs, thereby maintaining disordered anxiety. Avoidance is associated with high levels of psychosocial impairment yet is poorly understood at a mechanistic level. Many objective laboratory assessments of avoidance measure adaptive avoidance, in which an individual learns to successfully avoid a truly noxious stimulus. However, anxiety disorders are characterized by maladaptive avoidance, for which there are fewer objective laboratory measures. We posit that maladaptive avoidance behavior depends on a combination of three altered neurobehavioral processes: (1) threat appraisal, (2) habitual avoidance, and (3) trait avoidance tendency. This heterogeneity in underlying processes presents challenges to the objective measurement of maladaptive avoidance behavior. Here we first review existing paradigms for measuring avoidance behavior and its underlying neural mechanisms in both human and animal models, and identify how existing paradigms relate to these neurobehavioral processes. We then propose a new framework to improve the translational understanding of maladaptive avoidance behavior by adapting paradigms to better differentiate underlying processes and mechanisms and applying these paradigms in clinical populations across diagnoses with the goal of developing novel interventions to engage specific identified neurobehavioral targets.


Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 167-172
Author(s):  
Yang Yang ◽  
Diana Arseni ◽  
Wenjuan Zhang ◽  
Melissa Huang ◽  
Sofia Lövestam ◽  
...  

Hi-res view of human Aβ42 filaments Alzheimer’s disease is characterized by a loss of memory and other cognitive functions and the filamentous assembly of Aβ and tau in the brain. The assembly of Aβ peptides into filaments that end at residue 42 is a central event. Yang et al . used electron cryo–electron microscopy to determine the structures of Aβ42 filaments from human brain (see the Perspective by Willem and Fändrich). They identified two types of related S-shaped filaments, each consisting of two identical protofilaments. These structures will inform the development of better in vitro and animal models, inhibitors of Aβ42 assembly, and imaging agents with increased specificity and sensitivity. —SMH


2022 ◽  
Vol 12 ◽  
Author(s):  
Aifeng Liu ◽  
Jixin Chen ◽  
Juntao Zhang ◽  
Chao Zhang ◽  
Qinxin Zhou ◽  
...  

AimThis study is to investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded with the graphene oxide (GO) granular lubrication on ameliorating inflammatory responses and osteoporosis of the subchondral bone in knee osteoarthritis (KOA) animal models.MethodsThe KOA animal models were established using modified papain joint injection. 24 male New Zealand rabbits were classified into the blank control group, GO group, UCMSCs group, and GO + UCMSCs group, respectively. The concentration in serum and articular fluid nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), type II collagen (COL-II), and glycosaminoglycan (GAG) was detected using ELISA, followed by the dissection of femoral condyles and staining of HE and Micro-CT for observation via the microscope.ResultsGO granular lubrication and UCMSCs repaired the KOA animal models. NO, IL-6, TNF-α, GAG, and COL-II showed optimal improvement performance in the GO + UCMSCs group, with statistical significance in contrast to the blank group (P <0.01). Whereas, there was a great difference in levels of inflammatory factors in serum and joint fluid. Micro-CT scan results revealed the greatest efficacy of the GO + UCMSCs group in improving joint surface damage and subchondral bone osteoporosis. HE staining pathology for femoral condyles revealed that the cartilage repair effect in GO + UCMSCs, UCMSCs, GO, and blank groups were graded down.ConclusionUCMSCs loaded with graphene oxide granular lubrication can promote the secretion of chondrocytes, reduce the level of joint inflammation, ameliorate osteoporosis of the subchondral bone, and facilitate cartilage repair.


2022 ◽  
Author(s):  
Yiwen Qi ◽  
Yue-meng Zhu ◽  
Bin Li

Abstract IntroductionCyclophosphamide (CTX), is reported to be extensively used to establish POI animal model. But the most effective dose has not been systematically concluded yet. This systematic review and network meta-analysis is aimed to compare and rank the different doses of cyclophosphamide in the CTX-induced POI rat model.MethodsRandomized controlled trials of CTX-induced rat POI model were searched in four databases from inception to December, 2021. A network meta-analysis was conducted to analyze the data of included publications. The quality assessment was assessed by SYRCLE’s risk of bias tool. Data were analyzed with STATA 15.0 and Review Manager 5.3.Result205 records were searched and a total of 14 articles met inclusion criteria, Compared by Ovarian morphological changes, estrous cycle and hormone level (FSH, E2, AMH), the loading dose of 200mg/kg CTX with the maintenance dose of 8mg/kg CTX for consecutive 14 days showed the best efficacy in inducing rat POI model.


2022 ◽  
Author(s):  
Daniel Freilich ◽  
Jennifer Victory ◽  
Anne Gadomski

Background In the beginning of the COVID-19 pandemic, many hospitalized patients received empiric hydroxychloroquine/chloroquine (HC/CQ). Although some retrospective-observational trials suggested potential benefit, all subsequent randomized clinical trials (RCTs) failed to show benefit and use generally ceased. Herein, we summarize key studies that clinicians advising patients on HC/CQ efficacy:safety calculus in hospitalized COVID-19 patients would want to know about in a practical one-stop-shopping source. Methods Pubmed and Google were searched on November 4, 2021. Search words included: COVID-19, hydroxychloroquine, chloroquine, in vitro, animal studies, clinical trials, and meta-analyses. Studies were assessed for import and included if considered impactful for benefit:risk assessment. Results These searches led to inclusion of 12 in vitro and animal reports; 12 retrospective-observational trials, 19 interventional clinical trials (17 RCTs, 1 single-arm, 1 controlled but unblinded), and 51 meta-analyses in hospitalized patients. Inconsistent efficacy was seen in vitro and in animal studies for coronaviruses and nil in SARS-CoV-2 animal models specifically. Most retrospective-observational studies in hospitalized COVID-19 patients found no efficacy; QT prolongation and increased adverse events and mortality were reported in some. All RCTs and almost all meta-analyses provided robust data showing no benefit in overall populations and subgroups, yet concerning safety issues in many. Conclusions HC/CQ have inconsistent anti-coronavirus efficacy in vitro and in animal models, and no convincing efficacy yet substantial safety issues in the overwhelming majority of retrospective-observational trials, RCTs, and meta-analyses in hospitalized COVID-19 patients. HC/CQ should not be prescribed for hospitalized COVID-19 patients outside of clinical trials.


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