Development Of Effective Therapeutic Methods Research Articles

Past and future of alveolar organoids for lung regenerative medicine.

The lung is regarded as having limited regenerative capacity, and there are few treatment options for refractory lung diseases, such as interstitial pneumonia. Lung transplantation is the final option available in some scenarios. Research in this area has been slow owing to the complex structure of the lung for efficient gas exchange between the alveolar spaces and capillaries as well as the difficulty in obtaining specimens from patients with progressive lung disease. However, basic research over the past decade in the field of mouse and human embryology using genetic lineage tracing techniques and stem cell biology using primary and pluripotent stem cell-derived alveolar organoids has begun to clarify the tissue response in various intractable lung diseases and the mechanisms underlying remodeling. Advancement in this area may expand potential therapeutic targets for alveolar regeneration, providing alternatives to lung transplantation, and contribute to the development of effective therapeutic methods that activate or repopulate stem cells in the lung. In this review, we cover research focused on alveolar epithelial cells and discuss methods expected to regenerate lungs that are damaged by diseases.

The Hybrid of Cu─TCPP@Mn3 O4 for Inflammation Relief by ROS Scavenging and O2 Production: An Efficient Strategy for Antiviral Therapy.

Seasonal influenza still greatly threatens public health worldwide, leading to significant morbidity and mortality. Antiviral medications for influenza treatment are limited and accompanied by increased drug resistance. In severe influenza virus infection, hyperinflammation and hypoxia may be the significant threats associated with mortality, so the development of effective therapeutic methods to alleviate excessive inflammation while reducing viral damage is highly pursued. Here, a multifunctional MOF-based nanohybrid of Cu─TCPP@Mn3 O4 as a novel drug against influenza A virus infection (MOF = metal-organic framework; TCPP = tetrakis (4-carboxyphenyl) porphyrin) is designed. Cu─TCPP@Mn3 O4 exhibits potent inhibitory capability against influenza A virus infection in vitro and in vivo. The mechanism study reveals that Cu─TCPP@Mn3 O4 inhibits the virus entry by binding to the HA2 subunit of influenza A virus hemagglutinin. In addition, the nanoparticles of Mn3 O4 in Cu─TCPP@Mn3 O4 can scavenge intracellular ROS with O2 generation to downregulate inflammatory factors and effectively inhibit cytokines production. By reconstructing the antioxidant microenvironment, Cu─TCPP@Mn3 O4 features as a promising nanomedicine with anti-inflammatory and anti-viral synergistic effects.

The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain".

Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis.

Tools of the trade: investigations into design strategies of small molecules to target components in Alzheimer's disease.

The growing prevalence of Alzheimer's disease (AD) has warranted the development of effective therapeutic methods. Current available drugs for AD (i.e., acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists) have only offered brief symptomatic relief. Considering that the numbers affected by AD are projected to substantially rise, long-term strategies are urgently needed. The multiple series of small molecules to combat AD have been expanded, with current methods taking aim at factors, such as misfolded protein accumulation, metal ion dyshomeostasis, and oxidative stress. This concept article focuses on describing the design of compounds to target various components of AD and underlining recent advances that have been made.

Mesenchymal stem cell-based angiotensin-converting enzyme 2 in treatment of acute lung injury rat induced by bleomycin

ABSTRACTBackground: Acute lung injury (ALI) is a high incidence disease with no effective therapeutic method (mortality rate > 40%). The aim of this study was to find a new and effective therapeutic method for ALI. Methods: After the isolation of human umbilical cord mesenchymal stem cells (HUMSCs) from cesarean fetus, we transfected the HUMSCs with Lenti-ACE2 (angiotensin-converting enzyme 2) viral particles. Then we evaluated the therapeutic effect of HUMSCs harboring ACE2 on ALI, which induced by bleomycin (BLM) in rat model. Results: Our results showed that HUMSCs harboring ACE2 could attenuate ALI degree through reducing pulmonary inflammatory infiltration and degree of vascular permeability, repressing the mRNA level of pro-inflammatory cytokines, activating the mRNA level of anti-inflammatory cytokines and ACE2. Besides, results also demonstrated that HUMSCs harboring ACE2 gene had higher therapeutic effects to ALI than the single factor of HUMSCs or ACE2. Conclusions: This research provided clues for the development of effective therapeutic methods to ALI using stem cell transplantation and gene therapy.

Structure of Patt1 human proapoptotic histone acetyltransferase

The results of modeling of a novel human histone acetyltransferase Patt1 are presented here. This protein belongs to the GNAT GCN5 family and shows proapoptotic activity in human hepatocellular carcinoma cells. Patt1 is an attractive therapeutic target. The sequence analysis, fold recognition predictions and homology modeling of Patt1 protein structure were performed. N- and C- termini of Patt1 were unstructured. Central part revealed classical GNAT fold–central 7-stranded beta sheet core surrounded by intervening 4 alpha helices. The model was assessed with the methods for protein structure validation PROQ and MetaMQAPII. The all-atom 12 ns molecular dynamics simulation of Patt1 model with TIP3P water model and counterions was conducted. All assessment methods implemented resulted in conviction that the model was of quality that could provide confident structural information to infer sequence-structure-function relationships of Patt1. Phe186 and Cys137 were identified as residues engaged in acetyltransfer reaction and the clues for the identification of reaction mechanism were proposed. The knowledge of detailed molecular architecture of Patt1 is not only the key to understanding its mechanistic functional properties but it also opens the possibility of rational drug and protein design experiments, leading to development of effective therapeutic methods.

Inhibitory effects of TRPV1 blocker on UV-induced responses in the hairless mice

The transient receptor potential vanilloid 1 (TRPV1) channel can be activated by vanilloids, exposure to ultraviolet (UV) irradiation, heat, or protons, and conditions that occur during tissue injury. In the present study, we investigated whether or not TRPV1-specific blocker, 5'-iodoresiniferatoxin (I-RTX), can reduce UV-induced matrix metalloproteinases (MMPs), pro-inflammatory cytokines, cyclooxygenase (COX)-2, and p53 expression in the skin of hairless mice. Our results showed that I-RTX inhibited UV-induced skin thickening, as measured by a caliper, or in hematoxylin and eosin (H&E)-stained sections. UV-induced mRNA and protein expression of MMP-13, MMP-9, MMP-3, and MMP-2 was significantly reduced by I-RTX. We also observed the inhibitory effects of I-RTX on UV-induced mRNA expression of the pro-inflammatory cytokines, interleukin (IL)-1β, IL-2, IL-4, and tumor necrosis factor-α. UV-induced COX-2 and p53 protein expression was also significantly decreased by I-RTX. From the above results, we suggest that TRPV1-specific blocker, I-RTX, could prevent UV-induced skin responses, and provide new insight into development of effective therapeutic methods for photoaging.

Diagnostic and therapeutic problems in heart failure

Heart failure (HF), affecting an increasing number of patients, is associated with several diagnostic, therapeutic, socioeconomic problems. Despite considerable advances, prognosis in HF--both in systolic failure and in that with preserved systolic function--is poor, which in part results from not the fully understood pathophysiology of this disease, and therapeutic approaches used at present. Until recently, efforts of researchers focused on the development of effective therapeutic methods in more advanced stages of the disease, but their results were disappointing. Currently, more emphasis is placed on broadly understood methods of HF prevention. When starting HF treatment upon objective confirmation of the diagnosis, there are some primordial goals to be remembered, that if achieved, may translate into postponing the prospect of death and improving the patient's quality of life. Therapy of HF employs pharmaceuthical agents that reduce mortality (beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonists) and attenuate symptoms (diuretics, digoxin, inotropes). Intensification of therapy depends on the functional NYHA class. In recent years, fate of patients with advanced HF has improved through the use of electrotherapy (cardioverters-defibrillators and [or] resynchronization devices). The key issue is to develop a uniform model of healthcare for HF patients, focused on an outpatient clinic system rather than a hospital.