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Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 126
Author(s):  
Jing Yang ◽  
Xujiao Tang ◽  
Qingqing Wu ◽  
Panpan Ren ◽  
Yishu Yan

To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the “two-hit” strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the “one-hit” model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a “two-hit” strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease.


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Haibo Wu ◽  
Peiqi He ◽  
Yong Ren ◽  
Shiqi Xiao ◽  
Wei Wang ◽  
...  

AbstractA complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


2022 ◽  
Vol 9 ◽  
Author(s):  
Tokio Kinoshita ◽  
Yukihide Nishimura ◽  
Yasunori Umemoto ◽  
Yumi Koike ◽  
Ken Kouda ◽  
...  

Recently, it was reported that children recovering from coronavirus disease (COVID-19) developed multisystem inflammatory syndrome in children (MIS-C), which causes severe inflammation in multiple organs of the body. Because MIS-C is a new disease, the pathophysiology and prognosis are unknown. Owing to a lack of studies on this subject, we herein provide information on rehabilitation for children with MIS-C. A 12-year-old male patient presented with systemic inflammatory symptoms after approximately 2 months since recovery from COVID-19. He was treated with cyclosporine and steroid pulse therapy after admission to our hospital. His general condition improved significantly within approximately 1 week. Thereafter, his lower legs turned dark purple and he experienced intense pain whenever the lower limbs hung below the heart, such as in the sitting position. The patient was referred to the rehabilitation department, as he had difficulties during standing and walking. Because the symptoms improved with elevation of the lower extremities, we considered that the pain was related to venous stasis. The pain reduced when an elastic bandage was applied for the prevention of venous stasis; therefore, exercise therapy was implemented while the patient wore the elastic bandage. The patient's lower extremity symptoms improved in 10 days. He was discharged after 16 days and could independently perform activities of daily living (ADL). The mechanism underlying the patient's pain could not be determined; however, rehabilitation was effective when combined with compression therapy using an elastic bandage.


2022 ◽  
Author(s):  
Celina Reverdy ◽  
Gaetan Gitton ◽  
Xiangying Guan ◽  
Indranil Adhya ◽  
Rama Dumpati ◽  
...  

Among the sirtuin members, Sirt3 is one of the most important deacetylases as it regulates acetylation levels in mitochondria, which are linked to the metabolism of multiple organs and therefore involved in many types of human diseases such as age-related diseases, cancer, heart disease and metabolic diseases. In the current absence of any direct activator of Sirt3, the identification of new modulators could be a key step in the development of new therapeutics. Here we report the discovery of Sirt3 modulators thanks to DNA encoded library technology (ELT). The most enriched compounds after DEL selection against SIRT3 were evaluated according to their activity and affinity. Our best activator seems at least as potent as Honokiol (HKL) while the docking studies tend to show that our modulators probably interact with Sirt3 at an atypical site.


2022 ◽  
Vol 12 ◽  
Author(s):  
Shreya Dogra ◽  
Akanksha Arora ◽  
Aashni Aggarwal ◽  
Gautam Passi ◽  
Akanksha Sharma ◽  
...  

The havoc unleashed by COVID-19 pandemic has paved way for secondary ominous fungal infections like Mucormycosis. It is caused by a class of opportunistic pathogens from the order Mucorales. Fatality rates due to this contagious infection are extremely high. Numerous clinical manifestations result in damage to multiple organs subject to the patient’s underlying condition. Lack of a proper detection method and reliable treatment has made the management of this infection troublesome. Several reports studying the behavior pattern of Mucorales inside the host by modulation of its defense mechanisms have helped in understanding the pathogenesis of this angio-invasive infection. Many recent advances in diagnosis and treatment of this fungal infection have not been much beneficial. Therefore, there is a need to foster more viable strategies. This article summarizes current and imminent approaches that could aid effective management of these secondary infections in these times of global pandemic. It is foreseen that the development of newer antifungal drugs, antimicrobial peptides, and nanotechnology-based approaches for drug delivery would help combat this infection and curb its spread.


2022 ◽  
Author(s):  
Quanyu Zhang ◽  
Huarong Zhang ◽  
Xiaowei Yan ◽  
Sicong Ma ◽  
Xiaohong Yao ◽  
...  

Abstract Background: The pathological features of severe cardiac injury induced by COVID-19 and relevant clinical features is unknown. This post-mortem study intended to determine the pathological findings of hearts from critically ill COVID-19 cases and explore the association of pathological changes and clinical characteristics.Methods: This autopsy cohort study, including hearts from 26 deceased COVID-19 patients admitted in intensive care unit, was conducted at four sites in Wuhan, China. Pathological changes were evaluated using hematoxylin and eosin, and immunohistochemical staining. Cases were divided into neutrophil-infiltration group and no-neutrophil group according to histopathological identification of neutrophilic infiltrates or not. Results: Among 26 cases, four cases had active myocarditis with histopathological examination. All cases with myocarditis accompanied with extensive neutrophil infiltration, while cases without myocarditis did not. Detection rates of interleukin-6 and tumor necrosis factor-α in neutrophil-infiltration group were significantly higher compared to no-neutrophil group. At admission, patients with neutrophil infiltration in myocardium had significantly higher baseline values of aspartate aminotransferase, D dimer and high-sensitivity C reactive protein compared to other 22 patients (P<0.05 for all). During hospitalization, patients with neutrophil infiltration had a significantly higher maximum of creatine kinase (CK)-MB than patients without neutrophil infiltration. Conclusions: In hearts from deceased patients with severe COVID-19, active myocarditis was commonly infiltrated with neutrophils. Cases with neutrophil-infiltrated myocarditis had severe abnormal laboratory tests involving multiple organs at admission, and a high peak value of CK-MB during hospitalization. Role of neutrophil on severe heart injury and even systemic condition in COVID-19 should be emphasized.


2022 ◽  
Vol 11 ◽  
Author(s):  
Jing Bai ◽  
Dan Li ◽  
Peidan Yang ◽  
Kunyan Xu ◽  
Yingnan Wang ◽  
...  

Immune checkpoint inhibitors (ICIs) have substantially changed the treatment of a variety of malignant tumors. With the increasing of their usage, the unique immune-mediated toxicity profile of ICIs has become apparent. We report a case of esophageal squamous cell carcinoma in a patient who received anti-programmed cell death protein 1 (PD-1) (camrelizumab) therapy and the occurrence of sequential immune-related adverse events (irAEs). Although many irAEs have been reported, severe myositis caused by camrelizumab with simultaneous involvement of multiple organs, including the myocardium, respiratory muscles, and skeletal muscles, has rarely been described in literature. This 69-year-old male patient developed a grade 4 camrelizumab-induced adverse reaction according to the Common Terminology Criteria for Adverse Events (CTCAE) and was successfully treated with methylprednisolone and immunoglobulins. The early identification of irAEs, immediate discontinuation of immunotherapy, use of steroids and/or immunosuppressants, and adjuvant supportive treatment are critical to the clinical prognosis of patients. It should be aware that autoimmune complications can occur even when ICI treatment is ceased.


2022 ◽  
Vol 52 (2) ◽  
Author(s):  
Ana Carolina Dal Santo ◽  
Leticia Trevisan Gressler ◽  
Samay Zillmann Rocha Costa ◽  
João Rogério Centenaro ◽  
Isabella Mazzocato Dazzi ◽  
...  

ABSTRACT: Porcine circovirus 2 (PCV2) has a considerable economic impact on the pork industry worldwide for more than two decades. In 2016, a new circovirus, porcine circovirus 3 (PCV3), was described; since then, it has been reported to be associated with diseased or even in clinically healthy swine in several countries. Considering the importance of wild boars as reservoirs of swine pathogens and the extensive distribution of these animals in Rio Grande do Sul and throughout the national territory, we searched for PCV2 and PCV3 in twenty-six wild boars coupled with necropsy and histologic examination of the sampled animals. Using PCR, 182 tissue samples were analyzed, including the heart, kidneys, liver, lung, lymph nodes, spleen, and tonsils. PCV2 and PCV3 were detected in 57.7% (15/26) and 15.4% (4/26) of wild boars, respectively. Furthermore, co-infection with PCV2 and PCV3 was detected in one of these animals, with PCV2 or PCV3 DNA detection in multiple organs. Histological examination showed mild to moderate and multifocal lymphoplasmacytic interstitial nephritis distributed randomly throughout the renal cortex, apparently unrelated to PCV2 or PCV3 detection. The wild boar population in Brazil is extensive, indicating the presence of a larger number of swine pathogen hosts. In the present study, more than half of the wild boars harbored PCV2; and although less frequently, PCV3 was also detected. Therefore, free-living wild boars can serve as reservoirs of swine circoviruses in southern Brazil.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Qiu-Hong Shu ◽  
Yang Yang ◽  
Miao-Miao Wang ◽  
Shu-De Li ◽  
Ming Tian ◽  
...  

Paragonimus species are highly prevalent in various regions of China. The study’s objective is to isolate and identify Paragonimus from natural habitats and compare the phylogenetic diversity of Paragonimus in southern Yunnan province, China. Metacercariae of Paragonimus was isolated from crabs, and morphologic identification was performed by microscopy. Metacercariae were injected into experimental Paragonimus free Sprague Dawley rats. After 114 days, adult worms and eggs were isolated from multiple organs. Morphologic identification confirmed the initial identification. DNA was extracted from 5 adult worms, and molecular characterization was performed by amplification and sequencing of CO1 and ITS2 regions, followed by phylogenetic analysis. Out of 447 crabs captured, 186 crabs were found to be infected. A total of 4 species of Paragonimus was observed from naturally infected crabs. Paragonimus microrchis (2), Paragonimus heterotremus (1), Paragonimus proliferus (1), and Paragonimus skrjabini (1) were isolated and identified. A total of 32 sequences were downloaded from the National Center for Biotechnology Information, and 5 sequences generated in the study were used for phylogenetic analysis. In the phylogenetic tree of the CO1 gene, Paragonimus proliferus, Paragonimus heterotremus, and Paragonimus skrjabini were clustered with the same species, and the confidence values of their branches were >95%. A congruent phylogenetic relationship was observed with the ITS2 phylogenetic tree. In the phylogenetic tree constructed with the combined dataset of CO1 and ITS2 datasets, Paragonimus proliferus, Paragonimus heterotremus, and Paragonimus skrjabini clustered with the same species, and their branch confidence values were >94%. Paragonimus microrchis clustered with Paragonimus bangkokensis in both datasets. Phylogenetic analysis revealed robustness of the double loci method as against the single-locus method with either CO1 or ITS2 alone. Paragonimus species isolated from the southern Yunnan province, China, was phylogenetically diverse, and the analysis revealed the clustering of multiple species of Paragonimus isolated from different geographic locations.


2021 ◽  
Vol 18 (3) ◽  
pp. 49-55
Author(s):  
Sang Ah Lee ◽  
Suk Ju Cho ◽  
Jae Cheol Moon

Atypical antipsychotics are more effective than typical antipsychotics and have fewer side effects such as tardive dyskinesia and extrapyramidal symptoms; therefore, prescriptions of atypical antipsychotics are increasing. However, recently, it has been reported that atypical antipsychotics have a higher incidence of diabetes, hyperglycemia, and obesity than typical antipsychotics. Atypical antipsychotics induce obesity-inhibiting appetite-related receptors such as serotonin and dopamine. Decreased exercise due to improving psychotic symptoms, and genetic characterictics can also cause weight gain. Hyperglycemia and hypoglycemia were another metabolic problem related to treatment with atypical antipsychotics. The mechanisms of hyperglycemia were mainly related obesity, decreased anorexigenic hormones, and increased insulin resistance in multiple organs. There are also reports that genes related to diabetes have an effect on the incidence of diabetes mellitus treated with atypical antipsychotics. On the other hand, although it is not clear why hypoglycemia occurs, it documented in case reports all over the world. There are more reports of atypical antipsychotics than typical antipsychotics and these are frequently reported in Asians. Further research on the mechanism of hypoglycemia related to atypical antipsychotics is strongly recommended.


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