Bioinspired synthetic exosomes according to lipid nanoparticles having let-7b-5p advertise angiogene

Author : Leach Dalby | Published On : 03 May 2025

These results underline the importance of the Ca2+ binding sites predicted in these outer regions for stability and activity of pernisine. KEY POINTS • Aggregation of produced pernisine was prevented by translocation into periplasm. • Thermostability of mature pernisine was increased. • The outer regions of the catalytic core are required for pernisine thermostability.
Angiogenesis is closely related to the pathophysiology of diseases such as cancer or ischemia. Here, we investigated the effect of lidocaine at clinically effective blood concentrations on vascular endothelial growth factor A (VEGF-A)-induced angiogenesis. In addition, we aimed to clarify the mechanisms by which lidocaine could inhibit angiogenesis.

Angiogenesis was analyzed using commercially available in vitro assay kits in human umbilical vein endothelial cells (HUVECs)/normal human dermal fibroblast co-culture systems. The effects of lidocaine on cytotoxicity, VEGF-induced cell migration, and VEGF-induced cell proliferation were examined in HUVECs using lactate dehydrogenase cytotoxic, Boyden chamber, and WST-8 assays, respectively. The VEGF signaling pathway via VEGF receptor 2 (VEGFR-2) was analyzed by western blotting.

Lidocaine elicited a significant dose-dependent, angiogenesis-inhibitory effect at a concentration range of 1-10μg/ml. At this concentration range, cell death was not observed. Lidocaine, at a concentration of 10μg/ml, significantly inhibited cell proliferation but not cell migration, induced by VEGF-A in HUVECs. Furthermore, lidocaine, in a dose-dependent manner, significantly inhibited the VEGF-A-induced phosphorylation of VEGFR-2 at 3 and 10μg/ml.

We demonstrated that lidocaine has an anti-angiogenesis effect on clinically effective blood concentrations without causing cell death. This finding could represent a new avenue for future research into anesthesia, cancer-related analgesia, and revascularization therapy.
We demonstrated that lidocaine has an anti-angiogenesis effect on clinically effective blood concentrations without causing cell death. This finding could represent a new avenue for future research into anesthesia, cancer-related analgesia, and revascularization therapy.The neuro-inflammation is well known to be an inflammatory response in the brain tissue. Anti-inflammatory therapy in ischemia/reperfusion (I/R) pathogenesis is a potential therapeutic strategy for post-I/R injury. Currently, we made attempt to scrutinize the neuro-protective effect of tangeretin against I/R injury in the brain of experimental rats. I/R injury is induced in the brain via transient middle cerebral artery occlusion (2 h) and reperfusion (20 h). The infarction area, brain water content and neurofunctional parameters were also estimated. Inflammatory cytokines and brain injury markers were scrutinized at the end of the study. mRNA expression of interleukin 6 (IL-6), toll-like receptor-4 (TLR-4), interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), interferon-γ (IFNG-γ), and transforming growth factor-β1 (TGF-β1) was estimated using the qRT-PCR. Tangeretin significantly (P  less then  0.001) decreased brain water content, infarct volume, neurological score, brain edema, and Evans blue leakage. Tangeretin significantly (P  less then  0.001) down-regulated the inflammatory and pro-inflammatory cytokines and oxidative stress parameters in the serum and brain tissue of experimental rats. qRT-PCR data demonstrated that rats treated with tangeretin could significantly (P  less then  0.001) suppress the IL-1β, TLR-4 TNF-α, IFNG-γ, and IL-6 and boost the expression of TGF-β1 compared with I/R injury rats. The result clearly showed tangeretin neuro-protective and anti-inflammatory effect against I/R injury in rats through suppressed inflammatory reaction.
The authors assess the impact of Ghanaian diaspora-based psychiatrists' participation in clinical teaching in Ghana on the attitudes of medical students toward careers in psychiatry.

This quantitative cross-sectional study involved fifth- and sixth-year medical students of the four public medical schools in Ghana. Data were analyzed with descriptive and inferential statistics.

About half (49.7%) of clinical year medical students in Ghana reported that diaspora-based Ghanaian psychiatrists participated in their teaching during their clinical psychiatry rotation. A significantly higher proportion of medical students who had diaspora-based psychiatrists participate in their clinical training expressed that the depth of clinical teaching (54.4% vs. 45.6%, p = 0.003) and the extent of experience gained during their psychiatric rotations (54.7% vs. 45.3%, p = 0.001) were adequate or somewhat adequate when compared with medical students who did not have diaspora psychiatrists participate in their clinical training. Medical students who had diaspora-based Ghanaian psychiatrists participate in their teaching were significantly more likely to consider careers in psychiatry after their clinical rotation (42.2% versus 25.6%, χ
 = 16.2, p = 0.00).

In a low-resource country with few psychiatrists, the involvement of diaspora-based psychiatrists in the teaching of clinical year medical students has the potential to improve the global experience and attitude of the medical students toward psychiatry.
In a low-resource country with few psychiatrists, the involvement of diaspora-based psychiatrists in the teaching of clinical year medical students has the potential to improve the global experience and attitude of the medical students toward psychiatry.Cystic Fibrosis (CF) is caused most often by removal of amino acid 508 (Phe508del, deltaF508) within CFTR, yet dozens of additional CFTR variants are known to give rise to CF and many variants in the genome are known to contribute to CF pathology. To address CFTR coding variants, we developed a sequence-to-structure-to-dynamic matrix for all amino acids of CFTR using 233 vertebrate species, CFTR structure within a lipid membrane, and 20 ns of molecular dynamic simulation to assess known variants from the CFTR1, CFTR2, ClinVar, TOPmed, gnomAD, and COSMIC databases. Surprisingly, we identify 18 variants of uncertain significance within CFTR from diverse populations that are heritable and a likely cause of CF that have been understudied due to nonexistence in Caucasian populations. check details In addition, 15 sites within the genome are known to modulate CF pathology, where we have identified one genome region (chr1134754985-34836401) that contributes to CF through modulation of expression of a noncoding RNA in epithelial cells.