A Novel "Endocrine Hormone": The Diverse Role of Extracellular Vesicles in Multiorgan Insulin Resistance.

Insulin resistance is the primary contributor to the disruption in glucose homeostasis in the body, playing a significant causative role in many metabolic diseases. Insulin resistance is characterized by compensatory insulin secretion and reduced insulin responsiveness in target organs. Dysregulation of the interaction between insulin-secreting cells and insulin-responsive target organs is an important factor driving the progression of insulin resistance. Circulating endocrine hormones are important mediators mediating the interaction between insulin-secreting cells and insulin-responsive target organs. In addition to the classical hormones secreted by endocrine glands and organ-specific hormones secreted by metabolism-related organs (adipose tissue, muscle, liver, etc.), extracellular vesicles have been recognized as a novel class of endocrine hormones with a complex composition. Extracellular vesicles can transport signaling molecules, such as miRNAs and LncRNAs, to vital organs related to insulin resistance, in a manner akin to conventional hormones. The significant role in regulating the development of insulin resistance underscores the increasing interest in extracellular vesicles as essential contributors to this process. In this review, we summarize the three types of hormones (classical hormones, organokines and extracellular vesicles) that play a regulatory role in insulin resistance, and focus on the novel endocrine hormones, extracellular vesicles, to elaborate the mechanism of extracellular vesicles' regulation of insulin resistance progress from two aspects: the impact on insulin-secreting cells and the influence on insulin-responsive target organs. In addition, this paper outlines the clinical applications of extracellular vesicles in insulin resistance. A comprehensive understanding of the regulatory mechanisms and diagnostic status of the inter-organ network in insulin resistance has great potential to advance targeted therapeutic interventions and diagnostic markers, thereby benefiting both the prevention and treatment of insulin resistance.

The mechanism of Girdin in degenerative brain disease caused by high glucose stimulation.

Girdin, as an actin-binding protein, plays a major role in maintaining the stability of the actin skeleton structure and affects the growth, development, and migration of neurons. This study discusses the mechanism of Girdin in brain degeneration caused by high glucose stimulation. We examined the expression of Girdin in diabetic patients. The positive expression rate of Girdin in the diabetic group was 17.2% (5/29), which was obviously lower than the positive expression rate of 83.3% (20/24) in the non-diabetic group. We examined the expression of Girdin and its signaling pathway-related proteins Akt and STAT3 in hippocampal neurons induced by high glucose. The results showed that, in contrast to the control group (glucose concentration = 25 mmol/L), the expression of Girdin in the high-glucose group (glucose concentration = 225 mmol/L) was reduced (P < 0.05); the phosphorylation levels of Akt and STAT3 related to Girdin signaling pathway were also reduced (P < 0.05). Under high-glucose stimulation, the structure of neurons is abnormal, such as the reduction or disappearance of dendritic spines, and the number of neurons is reduced. In addition, Girdin and Akt were less expressed in neurons and synapses, especially the most obvious reduction in synaptic terminals. The activity of Girdin and its signaling pathway-related proteins Akt and STAT3 decreased in neurons under high glucose stimulation, indicating that the mechanism of Girdin in brain degeneration caused by high glucose stimulation was closely related to the Akt and STAT3 pathways. Graphic Abstract: The mechanism of Girdin in degenerative brain disease caused by high glucose stimulation. This article discusses the mechanism of Girdin in brain degeneration induced by high glucose stimulation. The expression of Girdin in the diabetic group was significantly lower than that in the non-diabetic group. The expression of Girdin and its signaling pathway-related proteins Akt and STAT3 in hippocampal neurons was significantly reduced under high glucose stimulation. Under high glucose stimulation, the structure of neurons is abnormal and the number decreases; synapses become shorter. It indicates that the mechanism of brain degeneration caused by high glucose stimulation by Girdin is closely related to the Akt and STAT3 pathways.

A Potential Target for Clinical Atherosclerosis: A Novel Insight Derived from TPM2.

Atherosclerosis (AS) is a potential inducer of numerous cardio-cerebrovascular diseases. However, little research has investigated the expression of TPM2 in human atherosclerosis samples. A total of 34 clinical samples were obtained, including 17 atherosclerosis and 17 normal artery samples, between January 2018 and April 2021. Bioinformatics analysis was applied to explore the potential role of TPM2 in atherosclerosis. Immunohistochemistry, immunofluorescence, and western blotting assays were used to detect the expression of TPM2 and α-SMA proteins. The mRNA expression levels of TPM2 and α-SMA were detected using RT-qPCR. A neural network and intima-media thickness model were constructed. A strong relationship existed between the intima-media thickness and relative protein expression of TPM2 (P<0.001, R=-0.579). The expression of TPM2 was lower in atherosclerosis than normal artery (P<0.05). Univariate logistic regression showed that TPM2 (OR=0.150, 95% CI: 0.026-0.868, P=0.034) had clear correlations with atherosclerosis. A neural network model was successfully constructed with a relativity of 0.94434. TPM2 might be an independent protective factor for arteries, and one novel biomarker of atherosclerosis.

Labor productivity of small-scale agriculture and its influence on agricultural landscape conservation in mountainous areas in China: a case study of rice farming in Hani terraced region.

Small-scale agriculture (SA) is regarded as unsustainability because of its low benefit. To protect traditional agricultural landscapes like terraces through SA will be difficult. However, in China, terraces are still maintained well by smallholders now. This study takes the family as a basic unit and SA in Hani terraced region as an object to explore its sustainability from the perspective of labor productivity (LP) through the questionnaire method. The findings are that peasant households work on both farm and non-farm jobs. They get a low income (3854.5 yuan RMB) from hybrid-rice-cropping and a high income (44,665.8 yuan RMB) from non-farm jobs but spend a small part of labors (34.23 person•days) in growing hybrid-rice and expended lots of labor (522 person•days) for non-farm jobs. In conclusion, LP of hybrid-rice-cropping is 1.32 times that of non-farm jobs for a household. The result shows SA in Hani terraced region has a higher return of labor investment than non-farm jobs. It is different from the common impression of the low benefit of SA and also explains why SA still continues to exist in the mountainous area in China now. However, SA in Hani terraced region also faces challenges with salary level rise of non-farm jobs and part-time farmers' requirement for living quality improvement. In the future, promoting industrial integration development in this region to add local employment for improving farmers' income is a feasible approach to protect terraced landscapes.

The research of the possible mechanism and the treatment for capsaicin-induced cough.

Unexplained chronic cough (UCC) affects millions of patients worldwide. New therapeutic approaches to this condition are urgently needed, since current treatment options provide only symptomatic relief. Cough reflex hypersensitivity has been shown to play an important role in the pathogenesis of UCC. The transient receptor potential vanilloid type 1 (TRPV1) is present on peripheral terminals of airway sensory nerves and modulation of its activity represents a potential target for the pharmacological treatment of UCC. The aim of this study was to explore the efficacy and the possible mechanism of SB705498, a TRPV1 antagonist, for cough in a capsaicin-induced cough animal model (i.e. guinea pigs). Induction of cough by capsaicin was successfully implemented in the guinea pigs, and the animals that met the inclusion criteria were randomly divided into four treatment groups: (1) Saline inhalation group (NSInh group, N = 10, negative control group), (2) Codeine phosphate intraperitoneal injection group (CPInp group, N = 10, positive control group), (3) SB705498 inhalation group (SBInh group, N = 10), (4) SB705498 intragastric administration group (SBIng group, N = 10). After treatment with above compounds, the capsaicin-induced cough experiment was performed again. The cough numbers and the cough incubation periods were recorded to evaluate the antitussive effect of SB705498. Enzyme-linked immunosorbent assay (ELISA) testing and Immunohistochemistry (IHC) staining for substance P (SP), calcitonin gene related peptide (CGRP) and neurokinin A (NKA) expression in lung and brain tissues were performed as an indication of neurogenic inflammation. Hematoxylin-Eosin (H&E) staining was used to observe the pathology morphology of lung and brain tissues. When the CPInp, SBInh and SBIng groups were compared to the NSInh group, the cough numbers were significantly reduced (p < .001), while the cough incubation periods were significantly prolonged (P < .001). In addition, the expression of SP, CGRP and NKA in lung and brain tissue was reduced (P < .05). None of the animals in the four groups exhibited lung and brain parenchymal inflammation. The results from this study showed that SB705498 had a significant antitussive effect, could reduce the neurogenic inflammation by reducing the expression of SP, CGRP and NKA in a capsaicin-induced cough model of guinea pigs. The results further indicated that TRPV1 played an important role in UCC and SB705498 might be a promising therapeutic agent for UCC.

[Expression of Girdin in brain tissues of Alzheimer's disease].

OBJECTIVE: To investigate the expression of Girdin and its significance in Alzheimer's disease (AD). METHODS: Fifty-nine autopsy cases from Department of Pathology, Beijing Hospital from January 1988 to December 2013, including 35 AD cases and 24 non-AD cases as control. Girdin and amyloid ß-protein (Aß) expression was evaluated immunohistochemically by EnVision method. The correlation between Girdin and Aß was analyzed. RESULTS: Girdin expression was localized in the nucleus and/or cytoplasm. The expression rates of Girdin were 20.0% (7/35) in the AD group and 83.3% (20/24) in the non-AD group, respectively. The difference was significant (Yates's correction for continuity χ(2)=20.527, P<0.05). Girdin expression and Aß deposition also correlated significantly (P<0.05). CONCLUSIONS: Girdin shows reduced expression in AD, and is correlated positively with Aß deposition. This suggests that Girdin may play an important role in the occurrence and development of AD.