Intratumoral Microbiota: Metabolic Influences and Biomarker Potential in Gastrointestinal Cancer.

Gastrointestinal (GI) cancers impose a substantial global health burden, highlighting the necessity for deeper understanding of their intricate pathogenesis and treatment strategies. This review explores the interplay between intratumoral microbiota, tumor metabolism, and major types of GI cancers (including esophageal, gastric, liver, pancreatic, and colorectal cancers), summarizing recent studies and elucidating their clinical implications and future directions. Recent research revealed altered microbial signatures within GI tumors, impacting tumor progression, immune responses, and treatment outcomes.

Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury.

Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin.

Activation of the M3AChR and Notch1/HSF1 Signaling Pathway by Choline Alleviates Angiotensin II-Induced Cardiomyocyte Apoptosis.

Angiotensin II- (Ang II-) induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure. Choline exerts cardioprotective effects; however, its effects on Ang II-induced cardiomyocyte apoptosis are unclear. In this study, the role and underlying mechanism of choline in regulating Ang II-induced cardiomyocyte apoptosis were investigated using a model of cardiomyocyte apoptosis, which was induced by exposing neonatal rat cardiomyocytes to Ang II (10 M, 48 h).

Joint effect of alcohol drinking and tobacco smoking on all-cause mortality and premature death in China: A cohort study.

Background: Tobacco smoking and alcohol drinking are associated with several diseases, and studies on the joint effects of smoking and drinking are rare.

Objective: This study investigates the joint effects of tobacco smoking and alcohol drinking on all-cause and premature mortality in a contemporary cohort.

Methods: The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative survey of subjects aged over 45 years in China that was performed every two years for a total of three waves from 2011 to 2015 in China.

A mitochondrial-targetable dual functional near-infrared fluorescent probe to monitor pH and HO in living cells and mice.

A lower pH level and high hydrogen peroxide (HO) concentration in mitochondria is closely associated with a variety of diseases including cancer and inflammation. Thus, determination of changes in the level of acidic pH and HO is of great importance and could provide new insights into the key functions under both physiological and pathological conditions. Herein, we present a novel mitochondria-targetable probe NIR-pH-HO, as the first near infrared (NIR) fluorescent small molecule, to monitor changes of endogenous pH (p = 6.

[miR-153-3p inhibits proliferation and migration of breast cancer cells via down-regulating ROCK1].

Objective To investigate the molecular mechanism of miR-153-3p regulating the proliferation, migration and invasion of human breast cancer cells. Methods Bioinformatics software was used to predict the candidate target gene of miR-153-3p. The double-luciferase reporter assay was used to validate the targeting relationship between miR-153-3p and candidate genes.

Design, synthesis and biological activity of 4-(4-benzyloxy)phenoxypiperidines as selective and reversible LSD1 inhibitors.

Lysine specific demethylase 1 (LSD1) plays a vital role in epigenetic regulation of gene activation and repression in several human cancers and is recognized as a promising antitumor therapeutic target. In this paper, a series of 4-(4-benzyloxy)phenoxypiperidines were synthesized and evaluated. Among the tested compounds, compound 10d exhibited the potent and reversible inhibitory activity against LSD1 in vitro (IC = 4 μM).

DT-13 Ameliorates TNF-α-Induced Vascular Endothelial Hyperpermeability Non-Muscle Myosin IIA and the Src/PI3K/Akt Signaling Pathway.

DT-13(25(R,S)-ruscogenin-1[β-d-glucopyranosyl-(1→2)][β-d-xylopyranosyl-(1→3)]-β-d-fucopyranoside) has been identified as an important factor in TNF-α-induced vascular inflammation. However, the effect of DT-13 on TNF-α-induced endothelial permeability and the potential molecular mechanisms remain unclear. Hence, this study was undertaken to elucidate the protective effect of DT-13 on TNF-α-induced endothelial permeability and the underlying mechanisms and .

Choline ameliorates cardiovascular damage by improving vagal activity and inhibiting the inflammatory response in spontaneously hypertensive rats.

Autonomic dysfunction and abnormal immunity lead to systemic inflammatory responses, which result in cardiovascular damage in hypertension. The aim of this report was to investigate the effects of choline on cardiovascular damage in hypertension. Eight-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were intraperitoneally injected with choline or vehicle (8 mg/kg/day).

Inhibition of the mitochondrial unfolded protein response by acetylcholine alleviated hypoxia/reoxygenation-induced apoptosis of endothelial cells.

The mitochondrial unfolded protein response (UPR(mt)) is involved in numerous diseases that have the common feature of mitochondrial dysfunction. However, its pathophysiological relevance in the context of hypoxia/reoxygenation (H/R) in endothelial cells remains elusive. Previous studies have demonstrated that acetylcholine (ACh) protects against cardiomyocyte injury by suppressing generation of mitochondrial reactive oxygen species (mtROS).

Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats.

Background: Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis.

Acetylcholine Inhibits LPS-Induced MMP-9 Production and Cell Migration via the α7 nAChR-JAK2/STAT3 Pathway in RAW264.7 Cells.

Background: Excessive activation of matrix metalloproteinase 9 (MMP-9) has been found in several inflammatory diseases. Previous studies have shown that acetylcholine (ACh) reduced the levels of pro-inflammatory cytokines and decreased tissue damage. Therefore, this study was designed to explore the potential effects and mechanisms of ACh on MMP-9 production and cell migration in response to lipopolysaccharide (LPS) stimulation in RAW264.

Acetylcholine Attenuated TNF-α-Induced Apoptosis in H9c2 Cells: Role of Calpain and the p38-MAPK Pathway.

Background: Previous studies have shown that inflammation is associated with excessive activation of calpains. Acetylcholine (ACh) has been reported to inhibit pro-inflammatory cytokine release and protect against cardiomyocyte injury. However, there is no direct evidence regarding whether ACh can regulate calpains to exert cardioprotection.

Acetylcholine ameliorates endoplasmic reticulum stress in endothelial cells after hypoxia/reoxygenation via M3 AChR-AMPK signaling.

Endoplasmic reticulum (ER) stress is associated with various cardiovascular diseases. However, its pathophysiological relevance and the underlying mechanisms in the context of hypoxia/reoxygenation (H/R) in endothelial cells are not fully understood. Previous findings have suggested that acetylcholine (ACh), the major vagal nerve neurotransmitter, protected against cardiomyocyte injury by activating AMP-activated protein kinase (AMPK).

Reduction of Mitochondria-Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury.

Objective: We explored the role of endoplasmic reticulum (ER)-mitochondria Ca(2+) cross talk involving voltage-dependent anion channel-1 (VDAC1)/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 in endothelial cells during hypoxia/reoxygenation (H/R), and investigated the protective effects of acetylcholine.

Approach And Results: Acetylcholine treatment during reoxygenation prevented intracellular and mitochondrial Ca(2+) increases and alleviated ER Ca(2+) depletion during H/R in human umbilical vein endothelial cells. Consequently, acetylcholine enhanced mitochondrial membrane potential and inhibited proapoptotic cascades, thereby reducing cell death and preserving endothelial ultrastructure.

Activation of M3 cholinoceptors attenuates vascular injury after ischaemia/reperfusion by inhibiting the Ca2+/calmodulin-dependent protein kinase II pathway.

Background And Purpose: The activation of M3 cholinoceptors (M3 receptors) by choline reduces cardiovascular risk, but it is unclear whether these receptors can regulate ischaemia/reperfusion (I/R)-induced vascular injury. Thus, the primary goal of the present study was to explore the effects of choline on the function of mesenteric arteries following I/R, with a major focus on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) regulation.

Experimental Approach: Rats were given choline (10 mg · kg(-1), i.

Acetylcholine protects mesenteric arteries against hypoxia/reoxygenation injury via inhibiting calcium-sensing receptor.

The Ca(2+)-sensing receptor (CaSR) plays an important role in regulating vascular tone. In the present study, we investigated the positive effects of the vagal neurotransmitter acetylcholine by suppressing CaSR activation in mesenteric arteries exposed to hypoxia/reoxygenation (H/R). The artery rings were exposed to a modified 'ischemia mimetic' solution and an anaerobic environment to simulate an H/R model.

Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases.

Cardiovascular disease remains a major cause of disability and death worldwide. Autonomic imbalance, characterized by suppressed vagal (parasympathetic) activity and increased sympathetic activity, correlates with various pathological conditions, including heart failure, arrhythmia, ischaemia/reperfusion injury and hypertension. Conventionally, pharmacological interventions, such as β-blocker treatment, have primarily targeted suppressing sympathetic over-activation, while vagal modulation has always been neglected.

Acetylcholine inhibits tumor necrosis factor α activated endoplasmic reticulum apoptotic pathway via EGFR-PI3K signaling in cardiomyocytes.

Previous findings have shown that acetylcholine (ACh) decreased hypoxia-induced tumor necrosis factor alpha (TNF α) production, thus protected against cardiomyocyte injury. However, whether and how ACh affects TNF α-induced endoplasmic reticulum (ER) stress and cell apoptosis remain poorly defined. This study was aimed at determining the effect of ACh in H9c2 cells after TNF α stimulation.

Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.

Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction.

Pyridostigmine prevents peripheral vascular endothelial dysfunction in rats with myocardial infarction.

1. Myocardial infarction (MI) is characterized by the withdrawal of vagal activity and increased sympathetic activity. We have shown previously that pyridostigmine (PYR), an acetylcholinesterase inhibitor, was able to improve vagal activity and ameliorate cardiac dysfunction following MI.

Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion.

Myocardial ischemia/reperfusion (I/R) induces inflammatory response that may lead to remote vascular injury. Vagal nerve elicits the cholinergic anti-inflammatory pathway by activating α7 nicotinic acetylcholine receptors (α7nAChR). Nevertheless, the role of vagal nerve-mediated anti-inflammatory pathway in the vasculature has not been studied previously.

Role of endothelial nitric oxide synthase and vagal activity in the endothelial protection of atorvastatin in ischemia/reperfusion injury.

Vascular endothelial dysfunction plays a pivotal role in the development and maintenance of ischemia/reperfusion (I/R) injury. Statins, developed as lipid-lowering drugs, partially restore vagal activity and exhibit pleiotropic effects. This study was aimed at determining the effect of atorvastatin (ATV) on endothelial dysfunction in peripheral resistance arteries after I/R injury.