Background: Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the leading cause of end-stage chronic kidney disease. Currently, there are no effective drugs for treating DN. Therefore, novel and effective strategies to ameliorate DN at the early stage should be identified. This study aimed to explore the effectiveness and underlying mechanisms of human umbilical cord mesenchymal stem cells (UC-MSCs) in DN. Methods: We identified the basic biological properties and examined the multilineage differentiation potential of UC-MSCs. Streptozotocin (STZ)-induced DN rats were infused with 2 × 10 6 UC-MSCs via the tail vein at week 6. After 2 weeks, we measured blood glucose level, levels of renal function parameters in the blood and urine, and cytokine levels in the kidney and blood, and analyzed renal pathological changes after UC-MSC treatment. We also determined the colonization of UC-MSCs in the kidney with or without STZ injection. Moreover, in vitro experiments were performed to analyze cytokine levels of renal tubular epithelial cell lines (NRK-52E, HK2) and human renal glomerular endothelial cell line (hrGECs).

Background and aims We aim to assess the safety and immunogenicity of inactivated whole-virion SARS-CoV-2 vaccines in patients with chronic liver diseases (CLD) in this study. Methods This was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Results A total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (36 [8.2%]) was the most frequently reported adverse event. Three participants had Grade 3 aminopherase elevation (defined as alanine aminopherase>5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only one of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in non-cirrhotic CLD group, 78.9% in compensated cirrhotic group, 76.7% in decompensated cirrhotic group (P=0.894 among CLD subgroups) and 90.3% in healthy controls (P=0.008 versus CLD group). Conclusion Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunological response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in non-cirrhotic CLD, compensated cirrhosis and decompensated cirrhosis.

Chronic obstructive pulmonary disease (COPD) is a progressive condition of chronic bronchitis, small airway obstruction, and emphysema that represents a leading cause of death worldwide. While inflammation, fibrosis, mucus hypersecretion, and metaplastic epithelial lesions are hallmarks of this disease, their origins and dependent relationships remain unclear. Here we apply single-cell cloning technologies to lung tissue of patients with and without COPD. Unlike control lungs, which were dominated by normal distal airway progenitor cells, COPD lungs were inundated by three variant progenitors epigenetically committed to distinct metaplastic lesions. When transplanted to immunodeficient mice, these variant clones induced pathology akin to the mucous and squamous metaplasia, neutrophilic inflammation, and fibrosis seen in COPD. Remarkably, similar variants pre-exist as minor constituents of control and fetal lung and conceivably act in normal processes of immune surveillance. However, these same variants likely catalyze the pathologic and progressive features of COPD when expanded to high numbers.

Purified, resting peripheral blood T lymphocytes were previously reported to undergo β1 integrin-dependent activation when cultured with anti-CD3 mAb coimmobilized with fibronectin, but not type I collagen. However, the extravascular T cells that encounter immobilized extracellular matrix proteins and are involved in disease pathogenesis have different properties from resting peripheral blood cells. In this study, we confirm that resting CD4+ and CD8+ T cells from peripheral blood are costimulated by immobilized fibronectin, but not type I collagen. In contrast, Ag- or mitogen-stimulated CD4+ and CD8+ T cell lines, used as models of the effector cells involved in disease, are more potently costimulated by type I collagen than fibronectin. The collagen-induced effects are similar in assays with serum-free medium and in more physiological assays in which anti-CD3 mAb is replaced by a threshold concentration of Ag and irradiated autologous PBMC as APC. The responses are β1 integrin dependent and mediated largely by very late Ag (VLA) 1 and 2, as shown by their up-regulation on the T cell lines as compared with freshly purified resting PBL, and by the effects of blocking mAb. Reversed phase HPLC located the major costimulatory sequence(s) in the α1 chain of type I collagen, the structure of which was confirmed by amino acid sequencing. The results demonstrate the potential importance of type I collagen, an abundant extracellular matrix protein, in enhancing the activation of extravascular effector T cells in inflammatory disease, and point to a new immunotherapeutic target.

Background Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. Methods In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. Results In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child–Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. Conclusions Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child–Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.