One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients. However, local inflammation may result and can contribute to worsening of clinical status in these patients. We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients. This initial study sought to investigate the safety of this approach. For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used. Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs. Patients were evaluated 1, 7, 30, and 90 days after therapy. All patients completed the study protocol and 90‐day follow‐up. MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death. No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease. Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes. However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV. EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores. Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy. Stem Cells Translational Medicine
New anti-tuberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis strains and to shorten the current 6–12-month treatment regimen. In this work, we have continued the efforts to develop chalcone-based anti-TB compounds by using an in silico design and QSAR-driven approach. Initially, we developed SAR rules and binary QSAR models using literature data for targeted design of new chalcone-like compounds with anti-TB activity. Using these models, we prioritized 33 compounds for synthesis and biological evaluation. As a result, 10 chalcones-like compounds (4, 8, 9, 11, 13, 17–20, and 23) were found to exhibit nanomolar activity against replicating micobacteria, low micromolar activity against nonreplicating bacteria, and nanomolar and micromolar against rifampin (RMP) and isoniazid (INH) monoresistant strains (rRMP and rINH) (<1 µM and <10 µM, respectively). The series also show low activity against commensal bacteria and generally show good selectivity toward M. tuberculosis, with very low cytotoxicity against Vero cells (SI = 11–545). Our results suggest that our designed chalcone-like compounds, due to their high potency and selectivity, are promising anti-TB agents.
fuels, which represent an important villain for the terrestrial
ecosystem, are non-renewable sources of energy, which prompt many
discussions about how long petroleum will remain available for use.
As an alternative, new energy sources have been explored, including
biofuels, such as biodiesel and ethanol. However, their use can raise
some problems, such as lower storage stability associated with poor
oxidation stability and lower energy availability, which affect consumption,
emissions, and energy efficiency. In this context, a comprehensive
study with structural description, theoretical calculations, and calorific
power test was performed for a new halogen chalcone 4-(4-chlorophenyl)-1-[4-(2-oxo-2-phenylethoxy)phenyl]butan-2-one
to understand its supramolecular arrangement and physicochemical properties.
The structural description was carried out by X-ray diffraction with
the contribution of Hirshfeld surfaces. The theoretical calculations
were carried out using density functional theory with the contribution
of calorific power determined by a calorimetric pump. All observed
results characterize the new chalcone as a potential additive for
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