The use of inorganic solid-state electrolytes is considered a viable strategy for developing high-energy Li-based metal batteries. However, suppression of parasitic interfacial reactions and growth ...of unfavorable Li metal depositions upon cycling are challenging aspects and not yet fully addressed. Here, to better understand these phenomena, we investigate various sulfide inorganic solid electrolytes (SEs), i.e., Li
PS
Cl
(x = 0.6, 1.0, 1.3, 1.45, and 1.6), via ex situ and in situ physicochemical and electrochemical measurements. We found that the Cl distribution and the cooling process applied during the SE synthesis strongly influence the evolution of the Li|SE interface in terms of microstructure, interphase composition, and morphology. Indeed, for a SE with a moderate chlorine content (i.e., x = 1.3) and obtained via a slow cooling process after sintering, the Cl atoms are located on the surface of the SE grains as interconnected LiCl nanoparticles that form an extended LiCl-based framework. This peculiar microstructure facilitates the migration of the Cl ions to the Li|SE interface during electrochemical cycling, thus, favouring the formation of a LiCl-rich interphase layer capable of improving the battery cycling performances.
Previously, it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions. However, recent data have revealed that neutrophils are heterogeneous and ...are additionally involved in tissue damage and immune regulation. The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer, inflammatory disorders, infections, and other diseases. Currently, neutrophils, with their autocrine, paracrine, and immune modulation functions, have been shown to be involved in liver diseases, including viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, cirrhosis, liver failure, and liver cancer. Accordingly, this review summarizes the role of neutrophils in liver diseases.
Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to ...treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 10
cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.
No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, ...death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non-randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease. The study enrolled 18 hospitalized patients with COVID-19 (n = 9 for each group). The treatment group received three cycles of intravenous infusion of UC-MSCs (3 × 10
cells per infusion) on days 0, 3, and 6. Both groups received standard COVID-treatment regimens. Adverse events, duration of clinical symptoms, laboratory parameters, length of hospitalization, serial chest computed tomography (CT) images, the PaO
/FiO
ratio, dynamics of cytokines, and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed. No serious UC-MSCs infusion-associated adverse events were observed. Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion. Mechanical ventilation was required in one patient in the treatment group compared with four in the control group. All patients recovered and were discharged. Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated. Phase 2/3 randomized, controlled, double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.
Liver fibrosis and its end-stage consequence, cirrhosis, represent the final common pathway of virtually all chronic liver diseases. Research into hepatic stellate cell activation, imbalance of the ...extracellular matrix synthesis and degradation and the contribution of cytokines and chemokines has further elucidated the mechanisms underlying fibrosis. Furthermore, clarification of changes in host adaptive and innate immune systems has accelerated our understanding of the association between liver inflammation and fibrosis. Continued elucidation of the mechanisms of hepatic fibrosis has provided a comprehensive model of fibrosis progression and regression. This review summarizes the current concepts of improvements that have been made in the field of fibrosis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a global pandemic since late 2019 that resulted in more than 360 million population infection. Among them, less than ...7% of infected individuals develop severe or critical illness. Mass vaccination has been carried out, but reinfection and vaccine breakthrough cases still occur. Besides supportive and antiviral medications, much attention has been paid in immunotherapies that aim at reducing pathological changes in the lungs. Mesenchymal stem cells (MSCs) is used as an option because of their immunomodulatory, anti-inflammatory, and regenerative properties. As of January 16, 2022, when ClinicalTrials.gov was searched for “Mesenchymal stem cells and COVID-19,” over 80 clinical trials were registered. MSC therapy was found to be safe and some effective in preclinical and clinical studies. Here, we summarize the major pathological characteristics of COVID-19 and provide scientific and rational evidence for the safety and possible effectiveness of MSCs in COVID-19 treatment.
Abstract
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a global public burden on health authorities. Although the ...virological characteristics and pathogenesis of COVID-19 has been largely clarified, there is currently no specific therapeutic measure. In severe cases, acute SARS-CoV-2 infection leads to immune disorders and damage to both the adaptive and innate immune responses. Having roles in immune regulation and regeneration, mesenchymal stem cells (MSCs) serving as a therapeutic option may regulate the over-activated inflammatory response and promote recovery of lung damage. Since the outbreak of the COVID-19 pandemic, a series of MSC-therapy clinical trials has been conducted. The findings indicate that MSC treatment not only significantly reduces lung damage, but also improves patient recovery with safety and good immune tolerance. Herein, we summarize the recent progress in MSC therapy for COVID-19 and highlight the challenges in the field.
Acute‐on‐chronic liver failure (ACLF) is a severe, life‐threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) ...transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end‐stage liver diseases. We assessed the safety and initial efficacy of umbilical cord‐derived MSC (UC‐MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open‐labeled and controlled study; 24 patients were treated with UC‐MSCs, and 19 patients were treated with saline as controls. UC‐MSC therapy was given three times at 4‐week intervals. The liver function, adverse events, and survival rates were evaluated during the 48‐week or 72‐week follow‐up period. No significant side effects were observed during the trial. The UC‐MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end‐stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC‐MSC transfusions. UC‐MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV‐associated ACLF patients.
This study assessed the safety and initial efficacy of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) transfusions for acute‐on‐chronic liver failure (ACLF) patients associated with hepatitis B virus (HBV) infection. No significant side effects were observed, and the UC‐MSC transfusions significantly increased the survival rates in ACLF patients. It was found that UC‐MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV‐associated ACLF patients.
Decompensated liver cirrhosis (LC), a life‐threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) ...transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord‐derived MSC (UC‐MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC‐MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1‐year follow‐up period. No significant side‐effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC‐MSC transfusion compared with controls (P < 0.05). UC‐MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end‐stage liver disease scores. UC‐MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC‐MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.
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