Principles and practice of infectious diseases

Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on immunoregulation, tissue repair, and regeneration from the bench to the bedside. Increasing evidence demonstrates that extracellular vesicles (EVs) derived from MSCs could contribute to these effects and are considered as a potential replacement for stem cell-based therapies. However, the efficacy and underlying mechanisms of EV-based treatment in hepatic ischemia-reperfusion injury (IRI) remain unclear. Here, we demonstrated that human umbilical cord MSC-EVs (huc-MSC-EVs) could protect against IRI-induced hepatic apoptosis by reducing the infiltration of neutrophils and alleviating oxidative stress in hepatic tissue in vivo. Meanwhile, huc-MSC-EVs reduced the respiratory burst of neutrophils and prevented hepatocytes from oxidative stress-induced cell death in vitro. Interestingly, we found that the mitochondria-located antioxidant enzyme, manganese superoxide dismutase (MnSOD), was encapsulated in huc-MSC-EVs and reduced oxidative stress in the hepatic IRI model. Knockdown of MnSOD in huc-MSCs decreased the level of MnSOD in huc-MSC-EVs and attenuated the antiapoptotic and antioxidant capacities of huc-MSC-EVs, which could be partially rescued by MnSOD mimetic manganese (III) 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP). In summary, these findings provide new clues to reveal the therapeutic effects of huc-MSC-EVs on hepatic IRI and evaluate their preclinical application.-Yao, J., Zheng, J., Cai, J., Zeng, K., Zhou, C., Zhang, J., Li, S., Li, H., Chen, L., He, L., Chen, H., Fu, H., Zhang, Q., Chen, G., Yang, Y., Zhang, Y. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.201800131RR

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response

Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo. In the quest to circumvent these challenges, several modification techniques have been applied to the naive MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated. The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.

/pdf/improved-therapeutics-of-modified-mesenchymal-stem-cells-an-2k7urbozfp.pdf

Improved therapeutics of modified mesenchymal stem cells: an update

Chronic lung diseases pose a tremendous global burden. At least one in four people suffer from severe pulmonary sequelae over the course of a lifetime. Despite substantial improvements in therapeutic interventions, persistent alleviation of clinical symptoms cannot be offered to most patients affected to date. Despite broad discrepancies in origins and pathomechanisms, the important disease entities all have in common the pulmonary inflammatory response which is central to lung injury and structural abnormalities. Mesenchymal stem cells (MSC) attract particular attention due to their broadly acting anti-inflammatory and regenerative properties. Plenty of preclinical studies provided congruent and convincing evidence that MSC have the therapeutic potential to alleviate lung injuries across ages. These include the disease entities bronchopulmonary dysplasia, asthma and the different forms of acute lung injury and chronic pulmonary diseases in adulthood. While clinical trials are so far restricted to pioneering trials on safety and feasibility, preclinical results point out possibilities to boost the therapeutic efficacy of MSC application and to take advantage of the MSC secretome. The presented review summarizes the most recent advances and highlights joint mechanisms of MSC action across disease entities which provide the basis to timely tackle this global disease burden.

MSC Based Therapies-New Perspectives for the Injured Lung.

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.

/pdf/mesenchymal-stem-cell-therapy-for-acute-respiratory-distress-1cl16i26ig.pdf

Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics.

Background With the development of next generation sequencing technology, a lot of research has focused on the role of human microbiome in regulating immunity. The present study evaluated microbiome changes of colorectal cancer patients who received XELOX regimen (capecitabine plus oxaliplatin) without requiring antimicrobials. Methods Stool samples from 7 patients (3 females/4 males) after screening of 11 patients before and after XELOX chemotherapy were subjected to 16S ribosomal RNA (rRNA) sequencing and flora dynamics compared at baseline and after 8 weeks of chemotherapy. Enrolled patients were newly diagnosed with stage IV colorectal cancer and had not received antimicrobial therapy or surgery. XELOX was administered for 2 cycles or 2-weekly treatments for 3 cycles. Results The patterns of relative abundance of all bacteria isolated from stool samples before or after chemotherapy treatment appeared to be different, but there were no significant differences in the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolism pathway between the two groups. The top five pathways in patients were the two-component system, phenylalanine metabolism, degradation of aromatic compounds, beta-lactam resistance and folate biosynthesis. More than 99.6% intestinal flora isolates were bacteria, <0.4% were viruses and Archaea. The relative abundances of the 5 most common bacterial phyla in fecal samples before chemotherapy were Bacteroides, Firmicutes, Proteobacteria, Actinobacteria and Verrucomicrobia. The abundance of Actinomycetes in stools after chemotherapy was increased to 2.5 fold higher than before chemotherapy. Bifidobacterium longum species were significantly elevated in stools after chemotherapy (P<0.05), and changes of relative abundance of Bifidobacterium longum species after chemotherapy from baseline in favorable outcome population (stable disease) was significant higher than them in unfavorable outcome population (progressive disease, PD) (P=0.023). Conclusions The results indicated that Actinomyces in the gut might have a positive clinical outcome for colorectal cancer patients. This idea needs further studies to examine the actions of Actinomyces on inhibition of tumor growth.

https://tcr.amegroups.com/article/download/37938/pdf

Microbiome characteristics and Bifidobacterium longum in colorectal cancer patients pre- and post-chemotherapy

Objective　To investigate the clinical characteristics of patients suffering from acute superior mesenteric venous thrombosis (ASMVT). Methods　Clinical data of 96 ASMVT patients admitted to the PLA General Hospital from January 2000 to December 2013 were retrospectively analyzed. Clinical characteristics and death-associated risk factors were studied, and the influence of treatment strategy and thrombosis location on patients' outcome were analyzed. Results　The patients were divided into survival group (n=83) and death group (n=13) according to the outcome. The mean age was 46.9 years old, and the ratio of male/female was 3:1. Thirty-nine patients presented isolated superior mesenteric venous thrombosis (SMVT) and fiftyseven patients presented combined SMVT. In the death group, higher incidence of severe acute pancreatitis and isolated SMVT were found than the survival group (P<0.01, P=0.004). The patients were again divided into laparotomy group, interventional thrombolysis group, and conservative treatment group according to treatment modality. The interval between symptom onset and treatment was shorter, the incidence of isolated SMVT and mortality rate were higher in the laparotomy group compared with those in interventional thrombolysis group and conservative treatment group. There was no death in the conservative treatment group. In comparison with the combined SMVT group, more patients in the isolated SMVT group presented peritoneal signs and less with history of splenectomy (P<0.001, P=0.002). The proportion of patients with laparotomy and bowel necrosis in the isolated SMVT group was higher than those in the combined SMVT group (P=0.023, P=0.012). Conclusions　Patients with isolated SMVT are more likely to have peritoneal signs and bowel necrosis, surgical treatment is mandatory. Patients with combined SMVT often have a history of splenectomy. ASMVT patients with severe pancreatitis may present higher mortality rate.
		
		DOI: 10.11855/j.issn.0577-7402.2015.05.14

Analysis of clinical characteristics of 96 patients with acute superior mesenteric venous thrombosis

Radiation-induced lung injury (RILI) is a major clinical complication for radiotherapy in thoracic tumors. An immediate effect of lung irradiation is the generation of reactive oxygen that can produce oxidative damage to DNA, lipids, and proteins resulting in lung cell injury or death. Currently, the medical management of RILI remains supportive. Therefore, there is an urgent need for the development of countermeasures. The present study aimed to evaluate the protective effect of manganese superoxide dismutase (MnSOD) gene–modified mesenchymal stem cells (MSCs) to facilitate the improved recovery of RILI. Here, nonobese diabetic/severe combined immunodeficiency mice received a 13 Gy dose of whole-thorax irradiation, and were then transfused intravenously with MnSOD-MSCs and monitored for 30 days. Lung histopathologic analysis, plasma levels of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-10, and tumor necrosis factor-α), profibrotic factor transforming growth factor-β1, and the oxidative stress fa...

Manganese Superoxide Dismutase Gene-Modified Mesenchymal Stem Cells Attenuate Acute Radiation-Induced Lung Injury.

Actinomyces are nonmotile, filamentous, Gram-positive bacteria that cause actinomycosis in immunodeficiency patients. Although the prognosis of actinomycosis is good, the diagnosis of actinomycosis is quite difficult. Recent studies on actinomycosis have shown that Actinomyces play an important role in various biological and clinical processes, such as the formation of dental plaque and the degradation of organics in the gastrointestinal tract. Here, the distribution of Actinomyces in the digestive tract, and different biological effects of actinomycosis, and its clinical association with inflammatory diseases are discussed. Furthermore, an overview of the most commonly used treatment methods and drugs used to treat Actinomyces infected alimentary canal diseases is presented.

/pdf/actinomyces-and-alimentary-tract-diseases-a-review-of-its-ptro7hoeyn.pdf

Actinomyces and Alimentary Tract Diseases: A Review of Its Biological Functions and Pathology.

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Papers

Microbiome characteristics and Bifidobacterium longum in colorectal cancer patients pre- and post-chemotherapy

Analysis of clinical characteristics of 96 patients with acute superior mesenteric venous thrombosis

Manganese Superoxide Dismutase Gene-Modified Mesenchymal Stem Cells Attenuate Acute Radiation-Induced Lung Injury.

Actinomyces and Alimentary Tract Diseases: A Review of Its Biological Functions and Pathology.