Notes

From lung fibrosis to be able to modern lung fibrosis: any lethal pathobiological leap.
livery systems for anti-inflammatory therapy.
Both the significant in vitro and in vivo anti-inflammatory results indicated that our oxidation responsive polymeric nanoparticles are promising drug delivery systems for anti-inflammatory therapy.
Home mechanical ventilation (HMV) use in chronic obstructive pulmonary disease (COPD) is becoming increasingly widespread. The aim of this study was to provide an accurate description of the current practices and clinical characteristics of COPD patients on HMV in Portugal.

The study was designed as a cross-sectional, multicenter real-life study of COPD patients established on HMV for at least 30 days. Data related to clinical characteristics, adaptation and ventilatory settings were collected.

The study included 569 COPD patients on HMV from 15 centers. The majority were male, with a median age of 72 years and a high prevalence of obesity (43.2%) and sleep apnea (45.8%). A high treatment compliance was observed (median 8h/day), 48.7% with inspiratory positive airway pressure ≥20 cmH
O and oronasal masks were the preferred interface (91.7%). There was an equal distribution of patients starting HMV during chronic stable condition and following an exacerbation. Patients in stable condition were initiated recent studies and recommendations, there seems to be a move towards higher ventilation pressures, increased use of oronasal masks and an intent to obtain normocapnia. This study shows that chronic hypercapnic and post exacerbation patients do not differ significantly regarding patient characteristics, physiological parameters or ventilatory settings with one exception chronic hypercapnic patients are more often obese and, subsequently, more frequently present OSA.
Chronic mucous hypersecretion (CMH or chronic bronchitis) per se or when associated with chronic inflammatory airway diseases such as asthma or chronic obstructive pulmonary disease (COPD) has several adverse clinical consequences. The sputum fluid phase has several candidate proteins including mucins which have the potential of being therapeutic targets, but has not yet been explored in-depth. This study aimed at exploring the profile of sputum proteins in various airway diseases.

Sputum from thirty-one patients with various airway diseases was collected and the fluid phase analyzed by LC-MS/MS and subsequently by sequential window acquisition of all theoretical fragments ion spectra (SWATH) (n = 15) for protein quantitation. Hierarchical clustering and functional grouping were performed.

A total of 185 proteins were quantitated by SWATH of which 21 proteins were identified which could distinguish between the clinical phenotypes by hierarchical clustering. Functional protein clustering revealed 4 grouppeutic implications of the functional groups of proteins need further evaluation.
Our previous study revealed that a young internal environment ameliorated kidney aging by virtue of an animal model of heterochronic parabiosis and a model of heterochronic renal transplantation. In this research, we used proteome to investigate the effects of donor-recipient age difference in clinical renal transplantation.

This study included 10 pairs of renal transplantation donors and recipients with an age difference of greater than 20 years to their corresponding recipients/donors. All recipients have received transplantation more than 3 years ago. Renal function and the serum/urine proteomes of the donors and recipients were analyzed.

The renal function was similar between the young recipients and the old donors. In contrast, the renal function of the young donors was significantly superior to that of the old recipients. Furthermore, 497 and 975 proteins were identified in the serum and urine proteomes, respectively. The content of SLC3A2 in the blood was found to be related to aging, while the contents of SERPINA1 and SERPINA3 in the urine were related to immune functions after renal transplantation.

This study demonstrated that, in the human body, a younger internal environment could ameliorate kidney aging and provided not only clinical evidence for increasing the age limit of kidney transplant donors but also new information for kidney aging research.
This study demonstrated that, in the human body, a younger internal environment could ameliorate kidney aging and provided not only clinical evidence for increasing the age limit of kidney transplant donors but also new information for kidney aging research.[This corrects the article DOI 10.2147/PPA.S301010.].
Regorafenib is an oral multi-kinase inhibitor approved for the treatment of solid tumours, but the pharmacokinetic profile of regorafenib in the Chinese population is unclear.

The aim of this study was to examine the pharmacokinetics, bioequivalence, and safety of two formulations of regorafenib 40 mg in healthy Chinese volunteers under fed and fasting conditions.

A single-centre, randomised, open-label, two-period, two-way crossover phase 1 trial was conducted by randomising a single oral dose of test (T) or reference (R, Stivarga
) regorafenib (40 mg) to healthy Chinese volunteers under both fasting and fed conditions (high-fat and high-calorie diet). Pharmacokinetic parameters were calculated using non-compartmental methods. Adverse events were recorded to assess drug safety.

Sixty-six participants were enrolled for both fasting and fed treatments. The 90% CIs geometric least-square means of ratio
for regorafenib were completely contained within the equivalence margin of 80-125% under both fasting and fed conditions. Both formulations displayed similar and generally good safety profiles.

Single oral dose of the T (40 mg) and R (40 mg) regorafenib was bioequivalent under fasting and fed conditions and had similar favourable safety profiles among healthy Chinese volunteers.
Single oral dose of the T (40 mg) and R (40 mg) regorafenib was bioequivalent under fasting and fed conditions and had similar favourable safety profiles among healthy Chinese volunteers.
Huai Hua San (HHS), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in treating ulcerative colitis (UC). However, the interaction of bioactives from HHS with the targets involved in UC has not been elucidated yet.

A network pharmacology-based approach combined with molecular docking and in vitro validation was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HHS against UC.

Bioactives and potential targets of HHS, as well as UC-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro experiments were conducted to further verify the findings.

ting diseases.
Our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HHS against UC. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of TCM formulae in treating diseases.
Berberine (BBR) is an active component of Phellodendri Cortex (PC), which is a traditional Chinese medicine that has been prescribed clinically for hyperuricemia (HUA) for hundreds of years. Many studies reported the anti-inflammatory and nephroprotective properties of BBR and PC; however, the therapeutic effects of BBR on HUA have not been explored. This study aims to investigate the efficacy and mechanism of BBR for treating HUA.

The mechanism of BBR in the treatment of HUA were predicted by network pharmacology. A mouse model of HUA established by potassium oxonate and hypoxanthine was used to verify the prediction. The levels of serum uric acid (UA), urea nitrogen (BUN) and creatinine (CRE) were determined by biochemical test kits. Hematoxylin and eosin staining of kidney tissues was used to observe the kidney damage. ELISA kits were applied to detect the levels of interleukin (IL)-1β and IL-18 in serum and kidney tissues. Quantitative real-time PCR and Western blotting were adopted to analyze the exporrecting the aberrant expression of URAT1 in kidney. BBR might be a novel therapeutic agent for treating HUA.
The active-targeted drug delivery systems had attracted more and more attention to efficiently overcome multidrug resistance (MDR) in cancer treatments. The aim of the work was to develop a multifunctional nano-structured liposomal system for co-delivery of doxorubicin hydrochloride (DOX) and celecoxib (CEL) to overcome doxorubicin resistance in breast cancer.

A functional hybrid peptide (MTS-R
H
) with unique cellular penetrability, endo-lysosomal escape and mitochondrial targeting ability was successfully synthesized using solid phase synthesis technology. The peptide modified targeted liposomes (DOX/CEL-MTS-R
H
lipo) for co-delivery of DOX and CEL were formulated to overcome the chemoresistance in MCF/ADR cells.

DOX/CEL-MTS-R
H
lipo showed nanosized shape and displayed high stability for one month. The cytotoxicity effect of the co-delivery of DOX and CEL through peptide modified liposomes had remarkable treatment efficacy on killing MCF/ADR cells. KG-501 molecular weight Targeted liposome exhibited greater cellular entry ability about 5.72-fold stronger than DOX solution. Moreover, as compared with unmodified liposomes, the presence of MTS-R
H
peptide entity on liposome surface enhanced the mitochondrial-targeting ability and achieved effective reactive oxygen species (ROS) production with significant inhibition of P-gp efflux activity.

The study suggested that the DOX/CEL-MTS-R
H
lipo is a promising strategy for overcoming drug resistance in breast cancer treatments with high targeting inhibition efficiency.
The study suggested that the DOX/CEL-MTS-R8H3 lipo is a promising strategy for overcoming drug resistance in breast cancer treatments with high targeting inhibition efficiency.The term idiopathic Parkinson's disease describes an entity of various not well-characterized disorders resembling each other. They are characterized by chronic neuronal dying originating from various disease mechanisms. They result in the onset of motor and related non-motor features, both of which respond to administration of personalized drug combinations and surgical therapies. The unmet need is beneficial disease course modification with repair and neurogenesis. Objectives are to discuss the value of cell secretome based treatments including neuronal graft transplantation and to suggest as an alternative the stimulation of an endogenous available approach for neuronal repair. Chronic neurodegenerative processes result from different heterogeneous, but complementing metabolic, pathological cascade sequences. Accumulated evidence from experimental research suggested neuron transplantation, stem cell application and cell secretome-based therapies as a promising future treatment with cure as an ultimate goal. To date, clinical testing of disease-modifying treatments has focused on substitution or repair of the remaining dopamine synthesizing neurons following diagnosis. At diagnosis, many of the still surviving and functioning, but already affected neurons have lost most of their axons and are primed for cell death. A more promising therapeutic concept may be the stimulation of an existing, endogenous repair system in the peripheral and central nervous systems. The abundant protein repulsive guidance molecule A blocks restoration and neurogenesis, both of which are mediated via the neogenin receptor. Inhibition of the physiological effects of repulsive guidance molecule A is an endogenous available repair pathway in chronic neurodegeneration. Antagonism of this protein with antibodies or stimulation of the neogenin receptor should be considered as an initial repair step. It is an alternative to cell replacement, stem cell or associated cell secretome concepts.
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