Exploring the role of ITGB6: fibrosis, cancer, and other diseases.

Integrin ß6 (ITGB6), a member of the integrin family of proteins, is only present in epithelial tissues and frequently associates with integrin subunit αv to form transmembrane heterodimers named integrin αvß6. Importantly, ITGB6 determines αvß6 expression and availability. In addition to being engaged in organ fibrosis, ITGB6 is also directly linked to the emergence of cancer, periodontitis, and several potential genetic diseases. Therefore, it is of great significance to study the molecular-biological mechanism of ITGB6, which could provide novel insights for future clinical diagnosis and therapy. This review introduces the structure, distribution, and biological function of ITGB6. This review also expounds on ITGB6-related diseases, detailing the known biological effects of ITGB6.

Clinical Characteristics of Human Papillomavirus Infection in the Male Genital Tract.

Objective: This study aims to understand the clinical characteristics of male HPV infection and provide data and information for the prevention and health of the male and female reproductive tracts in the region. Methods: A total of 390 male patients who underwent HPV examinations in outpatient clinics and physical examinations in 363 hospitals from December 2017 to May 2022 were selected. Samples were collected, and HPV genotyping was performed using multiplex fluorescent PCR. The HPV infection rate, genotype distribution, age distribution, and clinical symptom distribution were analyzed. Results: Out of 3,816 samples, the total HPV infection rate was 47.44% (185/390). The HPV infection rate in the symptomatic group was 57.09% (141/247), significantly higher than that in the asymptomatic group (P < .01). Among the subtypes, HPV6 accounted for the highest proportion (31.03%, 90/290), followed by HPV11 (14.14%, 41/290) and HPV52 (8.62%, 25/290). Types 6 and 11 were mainly concentrated in the symptomatic group (91.11%, 85.37%). The highest positive rate was observed in the 17-30-year-old group (45.41%, 85/185), followed by the 31-40-year-old group (28.11%, 52/185). The proportion of HPV infections with clinical symptoms of abnormal growth was 84.40% (119/141). HPV6 or/and HPV11 infections were mainly concentrated in the abnormal growth group, accounting for 90.76% (108/113). Conclusions: The rates of male HPV infection are high, particularly among individuals aged 17-40. Low-risk infections (types 6 and 11) cause male reproductive tract symptoms, including abnormal growth. High-risk infection (HPV52) correlates with local women's HPV subtype distribution and potential transmission. Therefore, screening for male HPV infection is crucial in preventing cervical cancer. Authorities should promote the development and early use of male HPV vaccines.

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases.

Silent information regulator 1 (SIRT1), a highly conserved NAD+-dependent deacetylase, is a cellular regulator that has received extensive attention in recent years and regarded as a sensor of cellular energy and metabolism. The accumulated evidence suggests that SIRT1 is involved in the development of endocrine and metabolic diseases. In a variety of organisms, SIRT1 regulates gene expression through the deacetylation of histone, transcription factors, and lysine residues of other modified proteins including several metabolic and endocrine signal transcription factors, thereby enhancing the therapeutic effects of endocrine and metabolic diseases. These evidences indicate that targeting SIRT1 has promising applications in the treatment of endocrine and metabolic diseases. This review focuses on the role of SIRT1 in endocrine and metabolic diseases. First, we describe the background and structure of SIRT1. Then, we outline the role of SIRT1 in endocrine and metabolic diseases such as hyperuricemia, diabetes, hypertension, hyperlipidemia, osteoporosis, and polycystic ovarian syndrome. Subsequently, the SIRT1 agonists and inhibitors in the above diseases are summarized and future research directions are proposed. Overall, the information presents here may highlight the potential of SIRT1 as a future biomarker and therapeutic target for endocrine and metabolic diseases.

CTRP family in diseases associated with inflammation and metabolism: molecular mechanisms and clinical implication.

C1q/tumor necrosis factor (TNF) related proteins (CTRPs) is a newly discovered adipokine family with conservative structure and ubiquitous distribution and is secreted by adipose tissues. Recently, CTRPs have attracted increasing attention due to the its wide-ranging effects upon inflammation and metabolism. To-date, 15 members of CTRPs (CTRP1-15) with the characteristic C1q domain have been characterized. Earlier in-depth phenotypic analyses of mouse models of CTRPs deficiency have also unveiled ample function of CTRPs in inflammation and metabolism. This review focuses on the rise of CTRPs, with a special emphasis on the latest discoveries with regards to the effects of the CTRP family on inflammation and metabolism as well as related diseases. We first introduced the structure of characteristic domain and polymerization of CTRPs to reveal its pleiotropic biological functions. Next, intimate association of CTRP family with inflammation and metabolism, as well as the involvement of CTRPs as nodes in complex molecular networks, were elaborated. With expanding membership of CTRP family, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.

[Effects of Hematocrit on the Parameters of Thromboelastography in Healthy Adults].

OBJECTIVE: To explore the effects of hematocrit (HCT) on the parameters of thromboelastography (TEG) in healthy adults, so as to judge coagulation and fibrinolysis more accurately. METHODS: Three hundred and ninety-three healthy adults examined in Chengdu 363 Hospital Affiliated to Southwest Medical University from May 2018 to May 2019 were selected. HCT and TEG were detected at the same time. The differences of TEG parameters between the high HCT group and the low HCT group were compared. The correlation between HCT and TEG parameters was analyzed. The differences of TEG parameters between the healthy adults in Plateau and plain areas were compared. RESULTS: Among the parameters of TEG, R and K in high HCT group were significantly higher, and Angle, MA and CI were significantly lower than those in low HCT group, which showed statistically significance (P<0.05). There was no significant difference in LY30 and EPL between the two groups (P>0.05). R and K positively correlated with HCT (r=0.112, 0.517, P=0.027, 0.000), and Angle, MA and CI negatively correlated with HCT (r=-0.490, -0.408, -0.414, P=0.000). LY30 and EPL not correlated with HCT (P>0.05). HCT in plateau area was significantly higher than that in plain area (P<0.05). Among the parameters of TEG, K value was significantly higher, and Angle, MA and CI were significantly lower than those in plain area (P<0.05). R, LY30 and EPL were not significantly different from those in plain area (P>0.05). CONCLUSION: The difference of HCT may affect the values of R, K, Angle, MA and CI in TEG parameters. R and K positively correlate with HCT, while Angle, MA and CI negatively correlate with HCT. It is suggested that a suitable TEG reference range for the local population should be established, in plateau area especially K, Angle, MA and CI, which will be more conducive to the accurate evaluation of patients' coagulation and fibrinolysis status.

Ultrasound/Optical Dual-Modality Imaging for Evaluation of Vulnerable Atherosclerotic Plaques with Osteopontin Targeted Nanoparticles.

Because of the high mortality of coronary atherosclerotic heart diseases, it is necessary to develop novel early detection methods for vulnerable atherosclerotic plaques. Phenotype transformation of vascular smooth muscle cells (VSMCs) plays a vital role in progressed atherosclerotic plaques. Osteopontin (OPN) is one of the biomarkers for phenotypic conversion of VSMCs. Significant higher OPN expression is found in foam cells along with the aggravating capacity of macrophage recruitment due to its arginine-glycine-aspartate sequence and interaction with CD44. Herein, a dual-modality imaging probe, OPN targeted nanoparticles (Cy5.5-anti-OPN-PEG-PLA-PFOB, denoted as COP-NPs), is constructed to identify the molecular characteristics of high-risk atherosclerosis by ultrasound and optical imaging. Characterization, biocompatibility, good binding sensibility, and specificity are evaluated in vitro. For in vivo study, apolipoprotein E deficien (ApoE-/- ) mice fed with high fat diet for 20-24 weeks are used as atherosclerotic model. Ultrasound and optical imaging reveal that the nanoparticles are accumulated in the vulnerable atherosclerotic plaques. OPN targeted nanoparticles are demonstrated to be a good contrast agent in molecular imaging of synthetic VSMCs and foam cells, which can be a promising tool to identify the vulnerable atherosclerotic plaques.

Activation of cannabinoid receptor type II by AM1241 protects adipose-derived mesenchymal stem cells from oxidative damage and enhances their therapeutic efficacy in myocardial infarction mice via Stat3 activation.

The poor survival of cells in ischemic sites diminishes the therapeutic efficacy of stem cell therapy. Previously we and others have reported that Cannabinoid receptor type II (CB2) is protective during heart ischemic injury for its anti-oxidative activity. However, whether CB2 activation could improve the survival and therapeutic efficacy of stem cells in ischemic myocardium and the underlying mechanisms remain elusive. Here, we showed evidence that CB2 agonist AM1241 treatment could improve the functional survival of adipose-derived mesenchymal stem cells (AD-MSCs) in vitro as well as in vivo. Moreover, AD-MSCs adjuvant with AM1241 improved cardiac function, and inhibited cardiac oxidative stress, apoptosis and fibrosis. To unveil possible mechanisms, AD-MSCs were exposed to hydrogen peroxide/serum deprivation to simulate the ischemic environment in myocardium. Results delineated that AM1241 blocked the apoptosis, oxidative damage and promoted the paracrine effects of AD-MSCs. Mechanistically, AM1241 activated signal transducers and activators of transcription 3 (Stat3) through the phosphorylation of Akt and ERK1/2. Moreover, the administration of AM630, LY294002, U0126 and AG490 (inhibitors for CB2, Akt, ERK1/2 and Stat3, respectively) could abolish the beneficial actions of AM1241. Our result support the promise of CB2 activation as an effective strategy to optimize stem cell-based therapy possibly through Stat3 activation.

ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells.

The proliferation of vascular smooth muscle cells (VSMCs) is one of the key events during the progress of atherosclerosis. The activated liver X receptor (LXR) signalling pathway is demonstrated to inhibit platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation. Notably, following PDGF-BB stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by VSMCs increases significantly. In this study, anti-ICAM-1 antibody-conjugated liposomes were fabricated for targeted delivery of a water-insoluble LXR agonist (T0901317) to inhibit VSMC proliferation. The liposomes were prepared by filming-rehydration method with uniform size distribution and considerable drug entrapment efficiency. The targeting effect of the anti-ICAM-T0901317 liposomes was evaluated by confocal laser scanning microscope (CLSM) and flow cytometry. Anti-ICAM-T0901317 liposomes showed significantly higher inhibition effect of VSMC proliferation than free T0901317 by CCk8 proliferation assays and BrdU staining. Western blot assay further confirmed that anti-ICAM-T0901317 liposomes inhibited retinoblastoma (Rb) phosphorylation and MCM6 expression. In conclusion, this study identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression.