Laumathews2997

With the increasingly widespread of central nervous system (CNS) disorders and the lack of sufficiently effective medication, meloxicam (MEL) has been reported as a possible medication for Alzheimer's disease (AD) management. Unfortunately, following the conventional application routes, the low brain bioavailability of MEL forms a significant limitation. The intranasal (IN) administration route is considered revolutionary for CNS medications delivery. The objective of the present study was to develop two types of nanocarriers, poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) and solid lipid nanoparticles (SLNs), for the IN delivery of MEL adapting the Quality by Design approach (QbD). Turning then to further enhance the optimized nanoformulation behavior by chitosan-coating. SLNs showed higher encapsulation efficacy (EE) and drug loading (DL) than PLGA NPs 87.26% (EE) and 2.67% (DL); 72.23% (EE) and 2.55% (DL), respectively. MEL encapsulated into the nanoformulations improved in vitro release, mucoadhesion, and permeation behavior compared to the native drug with greater superiority of chitosan-coated SLNs (C-SLNs). In vitro-in vivo correlation (IVIVC) results estimated a significant in vivo brain distribution of the nanoformulations compared to native MEL with estimated greater potential in the C-SLNs. Hence, MEL encapsulation into C-SLNs towards IN route can be promising in enhancing its brain bioavailability.

Herba taxilli (HT, Sangjisheng in Chinese), which is composed of the dried stems and leaves of Taxillus chinensis (DC.) Danser, has been commonly used to treat inflammation and arthritis in traditional Chinese medicine (TCM). Quercetin (Que) is a major active flavonoid component isolated from HT and is one of the quality control indexes of HT. In the clinical practice of TCM, formulas containing HT are commonly used to treat rheumatoid arthritis (RA). Recent studies have shown that Que exerts antiarthritic effects. However, the mechanism by which Que treatment affects RA is not fully understood.

This study aimed to explore the antiarthritic activity of Que in a collagen-induced arthritis (CIA) mouse model and investigate the underlying mechanisms.

The antiarthritic activity of Que was evaluated in a CIA mouse model by determining the paw clinical arthritis scores and left ankle thicknesses and by conducting micro-PET imaging and histopathological analysis of ankle joint tissues. The proinflammatory cytojoints, and decreased the secretion of IL-6, TNF-α, IL-1β, IL-8, IL-13, and IL-17. Mechanistically, Que treatment improved impaired mitochondrial biogenesis and mitochondrial function by regulating the SIRT1/PGC-1α/NRF1/TFAM pathway and inhibited inflammation via the HMGB1/TLR4/p38/ERK1/2/NF-κB p65 pathway. Notably, epidemiological data revealed correlations between abnormal circulating levels of SIRT1, PGC-1α, NRF1, HMGB1 and RA disease activity in patients.

Our data suggested a potential role of Que as a dietary therapeutic drug for RA treatment that may act through SIRT1 to target mitochondrial biogenesis. Additionally, the role of impaired mitochondrial biogenesis in RA was evaluated.

Our data suggested a potential role of Que as a dietary therapeutic drug for RA treatment that may act through SIRT1 to target mitochondrial biogenesis. Additionally, the role of impaired mitochondrial biogenesis in RA was evaluated.It is unclear how oxidative stress triggered by smoking and vaping may alter specific immune cell subsets. In this study, we showed that tobacco cigarette smoking, but not electronic-cigarette vaping, is associated with increased expression of major proteins in the toll-like receptor 4 (TLR4) inflammasome-interleukin (IL)-6 signalling axis in monocyte subtypes and T cells. TLR4 senses oxidative stress in immune cells caspase-1 is a key protein of inflammasome activation, and IL-6R-α is the receptor for IL-6 that drives proatherogenic IL-6 signalling. These findings implicate the non-nicotine, pro-oxidant toxicants in tobacco cigarette smoke as instigators of increased expression of key proteins in the TLR4-inflammasome-IL-6 axis that contribute to atherogenesis.

To evaluate the potential for identifying overweight people at risk for osteoarthritis from a gut microbiome biomarker.

Osteoarthritis (OA) is the most common form of arthritis, affecting millions of people worldwide. Being overweight increases the load placed on the joints such as the knee, which increases stress and could hasten the breakdown of cartilage. Identifying overweight people at risk for osteoarthritis remains a challenge. However, emerging evidence indicates that microbial dysbiosis in the human gut might play an important role in many inflammatory diseases. see more Considering the role of inflammation in OA development, analysis of the gut microbiome might be a potential non-invasive tool for overweight individuals to evaluate their risk for OA.

In this prospective study, we collected 182 stool samples from overweight OA patients (n=86) and overweight normal people (n=96) (25kg/m

<BMI<30kg/m

). 16S ribosomal RNA gene sequencing for V3 and V4 regions on the Illumina MiSeq platform was used l microbiomes in overweight people to discover and validate microbial biomarkers indicating risk for OA. Our study successfully established a 7 biomarkers prediction panel, moving towards affordable non-invasive early diagnostic biomarkers for OA in stool samples from overweight individuals.

The imbalance of microbial flora is thought to be associated with many diseases. However, the characteristics of the biliary microflora and its relation to in hepatolithiasis are unknown.

This study included 40 patients with hepatolithiasis and 10 control patients. Bile samples were taken during hepatectomy surgeries and 16S rRNA sequencing was performed. The sequencing results were analyzed by operational taxonomic unit (OTU) clustering, species annotation and abundance analyses, sample complexity analyses, diversity analyses, and environmental factor correlation analyses.

There were significant differences in bile microflora between the hepatolithiasis group and the control group. We found that the abundance of microflora in the bile of patients with hepatolithiasis was relatively high (52.4% versus 40.2% and 42.1% versus 29.6%). The diversity of microflora in the bile of patients with hepatolithiasis decreased significantly (Shannon (P=0.004), Observed species (P=0.001), PD-whole-tree (P=0.001)). These differences are mainly associated with Enterococcus(P＜0.