real-time-sampling-rat-femoral-arteriovenous-adventitial-interstitial

Real-Time Sampling of Rat Femoral Arteriovenous Adventitial Interstitial Fluid by Placement of a Microdialysis Probe

Interstitial fluid (ISF) is a vital element of the extracellular microenvironment, facilitating metabolic exchange and intercellular communication. ...

Chinese Academy of Medical Sciences

Peking Union Medical College

To analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC.

[Association of serum EGFR protein concentration with the efficacy of Gefitinib in the treatment of advanced non-small cell lung cancer].

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC. 

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.

Chronic pain is a pathological condition that results in significant loss of life quality, but so far no specific treatment for chronic pain has been developed. Currently available analgesia drugs are either not specific enough or have severe side effects. Therefore a non-invasive approach with high specificity to inhibit nociception becomes essential. In this study, a recombinant virus (AAV5-TRPV1-ArchT-eGFP) was constructed and injected into the mouse dorsal root ganglion (DRG). The Transient Receptor Potential Vanilloid type 1 (TRPV1) channel promoter was used to selectively express inhibitory light-sensitive pump ArchT (the archaerhodopsin from Halorubrum strain TP009) in nociceptive DRG neurons. The successful transfer of ArchT gene was confirmed by a robust expression of green florescent protein in the DRG neurons. In vivo behavioral tests demonstrated that both the mechanical paw withdrawal threshold and the radiant heat evoked paw withdrawal latency were significantly increased upon illumination by a 532 nm green laser light to the paw of a viral-vector injected mice, while the same laser light did not induce any observable change in naïve mice. In conclusion, we have established a novel analgesic approach that can noninvasively and selectively inhibit pain transmission using an acute and controllable optogenetics method. This study may shed light on the application of a novel optogenetic strategy for the treatment of pain.

A novel analgesic approach to optogenetically and specifically inhibit pain transmission using TRPV1 promoter.

Pharmacological autophagy enhancement constitutes a preclinically validated strategy for preventing or treating most major age-associated diseases. Driven by this consideration, we performed a high-content/high-throughput screen on 65 000 distinct compounds on a robotized fluorescence microscopy platform to identify novel autophagy inducers.

IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms.

Interstitial fluid (ISF) flow through vascular adventitia has been discovered recently. However, its kinetic pattern was unclear. We used histological and topographical identification to observe ISF flow along venous vessels in rabbits. By magnetic resonance imaging (MRI) in live subjects, the inherent pathways of ISF flow from the ankle dermis through the legs, abdomen, and thorax were enhanced by paramagnetic contrast. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACTs) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis, which coincided with the findings by MRI. The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow. By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues, consisting of longitudinally assembled fibers. Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow: one along adventitial fibers and another one between the vascular adventitia and its covering fascia. Using nanoparticles and surfactants, a PACT pathway was found to be accessible by a nanoparticle of <100 nm and contained two parts: a transport channel and an absorptive part. The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6‒15.6 mm/s. These data revealed that a PACT pathway was a "slit-shaped" porous biomaterial, comprising a longitudinal transport channel and an absorptive part for imbibition. The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels. A hypothetical "gel pump" is proposed based on interfacial tension and interactions to regulate ISF flow. These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.

Layers of interstitial fluid flow along a "slit-shaped" vascular adventitia.

The pyrethroids (PYRs) were extensively used to increase agriculture outputs. However, the cumulative exposures of PYRs would bring about potential risks through food intake. It is an urgent requirement to explore the cumulative exposures on the fruits and vegetables. In this study, a total of 1720 samples incorporating eight primary fruits and vegetables collected around China were investigated to assess the health risk for adults and children from eight PYRs. The relative potency factor (RPF) method was employed to reveal both chronic and acute cumulative exposure. As a result, the hazard index (HI) were 0.004 ~ 0.200% and 11.85 ~ 99.19% for chronic and acute cumulative dietary exposure, respectively. The national wide investigation indicated the cumulative assessments were not hazardous. Besides, the acute intake of pear, grape, and lettuce should be paid on more attention, particularly. This study provides compelling evidence to develop relative policy and regulation to improve the food quality and safety.

Dietary exposure risk assessment of pyrethroids in fruits and vegetables: a national scale investigation.

Three new monoterpene phenol dimers, bisbakuchiols V-X (), and two bakuchiol ethers ( and ), along with four known compounds (-) were isolated from the fruits of . Their structures were elucidated based on extensive spectral analysis. The absolute configurations of , , , and  were specified by quantum chemical calculations of ECD spectra.

New monoterpene phenol dimers from the fruits of .

Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

Regulation of interstitial fluid flow in adventitia along vasculature by heartbeat and respiration.

Four undescribed sesquiterpenes, atramacrolodes A-D (1-4), along with six known compounds 5-10 were isolated from the rhizome of Atractylodes macrocephala. Compound 3 possessed a new skeleton based on an unprecedented carton-carton connection. Their structures were determined by UV, IR, HRESIMS, NMR spectra, C NMR calculation with DP4 analysis, and the comparison of experimental and calculated ECD spectra. Compounds 5 and 8 showed protective effects against paracetamol-induced liver cell injury.

Atramacrolodes A-D (1-4), Four Undescribed Eudesmane-Type Sesquiterpenes from the Rhizome of Atractylodes macrocephala.

Atractylodimers A-D (1-4), sesquiterpenoid dimers (SDs) featuring a unique cage-like structure, were isolated from the rhizomes of Atractylodes macrocephala. The most distinctive characteristic of these isolates was the highly twisted "cap" structure based on highly twisted five-membered oxygen heterocyclic rings. Notably, compound 1 contained a furo[2,3b]furan ring, a caged 3,10-oxa-tricyclo[5.2.1.0]decane moiety, and 6/6/5/5/5/5/6/6 octocyclic skeleton. Compounds 2-3 exhibited a spirotetrahydrofuran ring, while compound 4 incorporated a caged spiro2,5,9-oxa-tricyclo[5.2.1.0]decane scaffold for unit linkage. Their structures were definitively established through spectroscopic methods and X-ray diffraction experiments. Plausible biosynthetic pathways of compounds 1-4 were proposed. Compounds 1 and 2 demonstrated significant neuroprotective effects against serum deprivation-induced PC12 cell damage.

Atractylodimers A-D, unprecedented sesquiterpenoid dimers with cage-like skeletons from Atractylodes macrocephala and their neuroprotective activities.

Article	Year
[Association of serum EGFR protein concentration with the efficacy of Gefitinib in the treatment of advanced non-small cell lung cancer]. Zhonghua zhong liu za zhi [Chinese journal of oncology]\| PubMed ID: 21875483	2011
Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. Nature genetics\| PubMed ID: 25129146	2014
A novel analgesic approach to optogenetically and specifically inhibit pain transmission using TRPV1 promoter. Brain research\| PubMed ID: 25797803	2015
IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms. Journal for immunotherapy of cancer\| PubMed ID: 34127545	2021
Layers of interstitial fluid flow along a "slit-shaped" vascular adventitia. Journal of Zhejiang University. Science. B\| PubMed ID: 34414700	2021
Dietary exposure risk assessment of pyrethroids in fruits and vegetables: a national scale investigation. Environmental science and pollution research international\| PubMed ID: 37369895	2023
New monoterpene phenol dimers from the fruits of . Journal of Asian natural products research\| PubMed ID: 38509697	2024
Regulation of interstitial fluid flow in adventitia along vasculature by heartbeat and respiration. iScience\| PubMed ID: 38532885	2024
Atramacrolodes A-D (1-4), Four Undescribed Eudesmane-Type Sesquiterpenes from the Rhizome of Atractylodes macrocephala. Chemistry & biodiversity\| PubMed ID: 38775105	2024
Atractylodimers A-D, unprecedented sesquiterpenoid dimers with cage-like skeletons from Atractylodes macrocephala and their neuroprotective activities. Chinese journal of natural medicines\| PubMed ID: 41435590	2025

Bei Li

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