Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have great potential for the treatment of various immune diseases due to their unique immunomodulatory properties. However, MSCs exposed to the harsh inflammatory environment of damaged tissue after intravenous transplantation cannot exert their biological effects, and therefore, their therapeutic efficacy is reduced. In this challenging context, an in vitro preconditioning method is necessary for the development of MSC-based therapies with increased immunomodulatory capacity and transplantation efficacy. AIM: To determine whether hypoxia and inflammatory factor preconditioning increases the immunosuppressive properties of MSCs without affecting their biological characteristics. METHODS: Umbilical cord MSCs (UC-MSCs) were pretreated with hypoxia (2% O2) exposure and inflammatory factors (interleukin-1ß, tumor necrosis factor-α, interferon-γ) for 24 h. Flow cytometry, polymerase chain reaction, enzyme-linked immunosorbent assay and other experimental methods were used to evaluate the biological characteristics of pretreated UC-MSCs and to determine whether pretreatment affected the immunosuppressive ability of UC-MSCs in coculture with immune cells. RESULTS: Pretreatment with hypoxia and inflammatory factors caused UC-MSCs to be elongated but did not affect their viability, proliferation or size. In addition, pretreatment significantly decreased the expression of coagulation-related tissue factors but did not affect the expression of other surface markers. Similarly, mitochondrial function and integrity were retained. Although pretreatment promoted UC-MSC apoptosis and senescence, it increased the expression of genes and proteins related to immune regulation. Pretreatment increased peripheral blood mononuclear cell and natural killer (NK) cell proliferation rates and inhibited NK cell-induced toxicity to varying degrees. CONCLUSION: In summary, hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics.

[Start-up of a Three-stage PN/A Granular Sludge Reactor for Treating Wastewater with High Concentrations of Ammonia].

In order to apply partial nitritation-ANAMMOX (PN/A) technology to treat wastewater with high concentrations of ammonia, autotrophic nitrogen-removing granular sludge was crushed and inoculated into a three-stage continuous flow reactor. The nitrogen loading rate (NLR), dissolved oxygen (DO) concentration, and free ammonia (FA) levels in each compartment of the reactor were controlled over a 106-day period. Results showed that the nitritation process occurred with the inoculated granules during the initial phase. A limited aeration strategy was employed in the reactor at relatively high NLRs. Given the effective suppression of nitrite-oxidizing bacteria and the prevention of ANAMMOX bacteria from high DO conditions, the compact structure and nitrogen-removal activity of the granules could be improved. When the ammonia-nitrogen concentration was increased in the influent to 350 mg·L-1, the adverse impacts of high FA concentrations on the functional microbe activity in the first compartment should be eliminated. This occurs by reducing the influent pH and alkalinity dosage. This occurs by reducing the influent pH and degree of alkalinity. As a result, a total nitrogen removal rate of 7.2 kg·(m3·d)-1 was achieved in the reactor, which is 50 to 100 times higher than that of conventional activated sludge systems. The consistent improvement in the nitrogen-removal activity of the granules was demonstrated by batch testing at different aeration intensities. This showed that activity was greatest in the first compartment, which showed the highest granular maturity. In addition, a clear linear correlation (R2>0.97) was observed between the amount of extracellular polymeric substance and the specific nitrogen removal rate. This indicated that the dense granules played a positive role in enhancing the performance of the reactor.

Alterations of pulmonary function in patients with inflammatory bowel diseases.

AIM: The aim of this study was to investigate the alterations of pulmonary function tests (PFTs) and their relationship with disease activity in inflammatory bowel diseases (IBDs). METHODS: Sixty-four IBD patients (31 Crohn's disease [CD] and 33 ulcerative colitis [UC]) and thirty healthy individuals (controls) were studied with regard to the following parameters of PFTs: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio, mid-forced expiratory flow of 25-75% (FEF 25-75), residual volume, total lung capacity, and diffusing capacity of the lung for carbon monoxide (DLCO). The disease activity was calculated using the Crohn's Disease Activity Index for CD and Mayo Clinic Score for UC. Correlation analysis was performed between disease activity and sputum cytology and PFTs. RESULTS: Nineteen of the 31 CD patients (61.29%) and 17 of the 33 UC patients (51.52%) but none of the controls showed at least one abnormal PFTs (P < 0.05). Compared with controls, both CD and UC patients exhibited a significant reduction in FEV1 (P < 0.05), FVC (P < 0.05), FEF 25-75 (P < 0.05), and DLCO (P < 0.05). The majority with decreased measurements of PFTs were in the active phase of diseases (P < 0.05). IBD activity scores correlated negatively with some parameters of PFTs and positively with lymphocytosis and eosinophilia of sputum (P < 0.05). CONCLUSIONS: Pulmonary function disorders are significantly common in IBD patients. The impairment in active disease is significantly greater than in remission.

A case of pulmonary sarcoidosis with endobronchial nodules.

Sarcoidosis is a multisystemic disorder of unknown cause that is characterized pathologically by noncaseating granulomas and predominantly affects the lungs and the lymphatic system, especially intrathoracically. Diagnosis is based on the association of a compatible clinical and radiological presentation, the presence of characteristic histopathological lesions and the exclusion of other potential causes of granuloma. Although the lungs and mediastinal lymph nodes are almost involved, endobronchial nodular lesions of sarcoidosis with lung involvements are rare. We report a case of sarcoidosis with lung involvements and endobronchial nodules as confirmed by bronchial biopsy.

Pulmonary manifestations of inflammatory bowel disease.

Extraintestinal manifestations of inflammatory bowel disease (IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered in the case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.

Pulmonary manifestations of Crohn's disease.

Crohn's disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.

Tracheobronchial nodules and pulmonary infiltrates in a patient with Crohn's disease.

Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been reported to date. We herein report a rare case of tracheobronchial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheobronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.