Hapln2 in neurological diseases and its potential as therapeutic target

Hyaluronan and proteoglycan link protein 2 (Hapln2) is important for the binding of chondroitin sulfate proteoglycans to hyaluronan. Hapln2 deficiency leads to the abnormal expression of extracellular matrix (ECM) proteins and dysfunctional neuronal conductivity, demonstrating the vital role of Hapln2 in these processes. Studies have revealed that Hapln2 promotes the aggregation of α-synuclein, thereby contributing to neurodegeneration in Parkinson’s disease (PD), and it was recently suggested to be in intracellular neurofibrillary tangles (NFTs). Additionally, the expression levels of Hapln2 showed lower in the anterior temporal lobes of individuals with schizophrenia than those of healthy subjects. Together, these studies implicate the involvement of Hapln2 in the pathological processes of neurological diseases. A better understanding of the function of Hapln2 in the central nervous system (CNS) will provide new insights into the molecular mechanisms of these diseases and help to establish promising therapeutic strategies. Herein, we review the recent progress in defining the role of Hapln2 in brain physiology and pathology

Natural history of small asymptomatic kidney and residual stones over a long-term follow-up: systematic review over 25 years

Objective: To systematically review the natural history of small asymptomatic kidney and residual stones, as the incidental identification of small, asymptomatic renal calculi has risen with increasing use of high-resolution imaging. Materials and methods: We reviewed the natural history of small asymptomatic kidney and residual stones using the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We searched MEDLINE, Scopus, EMBASE, EBSCO, Cochrane library and Clinicaltrials.gov using themes of ‘asymptomatic’, ‘nephrolithiasis’, ‘observation’, ‘symptoms’, ‘admission’, ‘intervention’ and similar allied terms for all English language articles from 1996 to 2020 (25 years). Inclusion criteria were studies with ≥50 patients, stones ≤10 mm, and a mean follow-up of ≥24 months. Primary outcomes were occurrence of symptoms, emergency admission, and interventions. Results: Our literature search returned 2247 results of which 10 papers were included in the final review. Risk of symptomatic episodes ranged from 0% to 59.4%. Meta-analysis did not identify any significant difference in the likelihood of developing symptoms when comparing stones 5 mm, nor those 10 mm. Risk of admission varied from 14% to 19% and the risk of intervention from 12% to 35%. Meta-analysis showed a significantly decreased likelihood of intervention for stones 5 mm and 10 mm. Studies had variable risk of bias due to heterogeneous reporting of outcome measures with significant likelihood that observed differences in results were compatible with chance alone (Symptoms: I2=0%, Cochran’s Q = 3.09, P = 0.69; Intervention: I2=0%, Cochran’s Q = 1.76, P = 0.88). Conclusions: The present systematic review indicates that stone size is not a reliable predictor of symptoms; however, risk of intervention is greater for stones >5mm vs 10 vs <10 mm. This review will inform urologists as they discuss management strategies with patients who have asymptomatic renal stones and offer insight to committees during the development of evidence-based guidelines

Male Patients With Dilated Cardiomyopathy Exhibiting a Higher Heart Rate Acceleration Capacity or a Lower Deceleration Capacity Are at Higher Risk of Cardiac Death

The effects of dilated cardiomyopathy (DCM) on cardiac autonomic regulation and electrophysiology, and the consequences of such changes, remain unclear. We evaluated the associations between heart rate acceleration capacity (AC) and deceleration capacity (DC), heart structural and functional changes, and cardiac death in 202 healthy controls and 100 DCM patients. The DC was lower and the AC was higher in DCM patients (both males and females). Multivariable, linear, logistic regression analyses revealed that in males, age was positively associated with AC in healthy controls (N = 85); the left atrial diameter (LAD) was positively and the left ventricular ejection fraction (LVEF) was negatively associated with AC in DCM patients (N = 65); age was negatively associated with DC in healthy controls (N = 85); and the LAD was negatively and the LVEF was positively associated with DC in DCM patients (N = 65). In females, only age was associated with either AC or DC in healthy controls (N = 117). Kaplan–Meier analysis revealed that male DCM patients with greater LADs (≥46.5 mm) (long-rank chi-squared value = 11.1, P = 0.001), an elevated AC (≥-4.75 ms) (log-rank chi-squared value = 6.8, P = 0.009), and a lower DC (≤4.72 ms) (log-rank chi-squared value = 9.1, P = 0.003) were at higher risk of cardiac death within 60 months of follow-up. In conclusion, in males, DCM significantly affected both the AC and DC; a higher AC or a lower DC increased the risk of cardiac death

Secular trend of the leading causes of death in China from 2003 to 2013

Background: To analyze the epidemiological characteristics and secular trends of the leading causes of death in China.Methods: Data on the leading causes of death was collected from the Statistical Yearbook of China. Data for 11 years, from 2003 to 2013, was analyzed by regression analysis and chi-square test.Results: The top 3 causes of death from 2009 to 2013 were cancer, cerebrovascular disease, and cardiopathy, with the role of cardiopathy increasing over time (P&lt;0.01). The proportion of deaths related to cardio-cerebrovascular diseases in urban and rural areas increased to 41.9% and 44.8%, respectively, in 2013, and was significantly higher than that for cancer, 25.5% and 22.4% (both P&lt;0.01). Injury and poisoning in urban or rural areas represented the fifth leading cause of death. In 2006, endocrine, nutritional, and metabolic diseases were the sixth main cause of death, with 3.3% in urban areas. The role of genito-urinary,respiratory, and digestive system diseases in urban areas and genito-urinary system diseases in rural areas decreased during this period (all P&lt;0.05).Conclusion: Cancer, cerebrovascular disease, and cardiopathy accounted for more than 67% of all deaths from 2007 to 2013 in China, and significantly increased in proportion from 2003 to 2013.Keywords: Causes of death; China; cancer; cardiovascular diseas

Transmembrane peptide 4 and 5 of APJ are essential for its heterodimerization with OX1R

Increasing evidence indicates some G protein-coupled receptors function as a heterodimer, which provide a novel target for therapeutics investigation. However, study on the receptor-receptor interaction interface, a potent target on interfering dimer formation, are still limited. Here, using bioluminescence resonance energy transfer (BRET) combined with co-immunoprecipitation (Co-IP), we found a new constitutive GPCR heterodimer, apelin receptor (APJ)-orexin receptor type 1 (OX1R). Both APJ and OX1R co-internalized when constantly subjected to cognate agonist (apelin-13 or orexin-A) specific to either protomer. Combined with BRET and immunostaining, the in vitro synthesized transmembrane peptides (TMs) interfering experiments suggests that TM4 and 5 of APJ act as the interaction interface of the APJ-OX1R heterodimer, and co-internalization could be disrupted by these peptides as well. Our study not only provide new evidence on GPCR heterodimerization, but address a novel heterodimerization interface, which can be severed as a potential pharmacological target

Secular trend of the leading causes of death in China from 2003 to 2013.

Background: To analyze the epidemiological characteristics and secular trends of the leading causes of death in China. Methods: Data on the leading causes of death was collected from the Statistical Yearbook of China. Data for 11 years, from 2003 to 2013, was analyzed by regression analysis and chi-square test. Results: The top 3 causes of death from 2009 to 2013 were cancer, cerebrovascular disease, and cardiopathy, with the role of cardiopathy increasing over time (P&lt;0.01). The proportion of deaths related to cardio-cerebrovascular diseases in urban and rural areas increased to 41.9% and 44.8%, respectively, in 2013, and was significantly higher than that for cancer, 25.5% and 22.4% (both P&lt;0.01). Injury and poisoning in urban or rural areas represented the fifth leading cause of death. In 2006, endocrine, nutritional, and metabolic diseases were the sixth main cause of death, with 3.3% in urban areas. The role of genito-urinary, respiratory, and digestive system diseases in urban areas and genito-urinary system diseases in rural areas decreased during this period (all P&lt;0.05). Conclusion: Cancer, cerebrovascular disease, and cardiopathy accounted for more than 67% of all deaths from 2007 to 2013 in China, and significantly increased in proportion from 2003 to 2013

Optimized protocol for live imaging of overnutrition-elicited interactions between immune cells and β cells in zebrafish

Summary: Here, we provide an optimized protocol to observe the interactions between infiltrating immune cells and islet β cells using live imaging. This protocol is useful for the characterization of cell-cell interactions and for the direct visualization of immune cell migration to the principal pancreatic islet during islet inflammation. We describe the preparation of zebrafish transgenic lines and detail steps for setting up the fish for live confocal imaging.For more details on the use and execution of this protocol, please refer to Yang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Systematic genome editing of the genes spanning an entire chromosome by CRISPR/Cas9 in a vertebrate——zebrafish (Danio rerio)

Deciphering the biological functions of each gene in the genome is fundamental for understanding the molecular mechanisms underlying normal development, physiology,and behavior, as well as diseases. One common approach to determine gene function is to disrupt individual genes and assess the consequences. Zebrafish (Danio rerio) has been gaining popularity as a model organism to analyze gene function. This is particularly true in China

2&prime;-Fucosyllactose Suppresses Angiogenesis and Alleviates Toxic Effects of 5-Fu in a HCT116 Colon Tumor-Bearing Model

The present study was aimed at examining the anti-tumor effects and molecular mechanisms of 2&prime;-fucosyllactose (2&prime;-FL). At the beginning, the viabilities of four types of colon cancer cells were analyzed after exposure to increasing concentrations of 2&prime;-FL, and HCT116 cells were selected as the sensitive ones, which were applied in the further experiments; then, interestingly, 2&prime;-FL (102.35 &micro;M) was found to induce apoptosis of HCT116 cells, which coincides with significant changes in VEGFA/VEGFR2/p-PI3K/p-Akt/cleaved Caspase3 proteins. Next, in a tumor-bearing nude mouse model, HCT116 was chosen as the sensitive cell line, and 5-fluorouracil (5-Fu) was chosen as the positive medicine. It was noteworthy that both 2&prime;-FL group (2.41 &plusmn; 0.57 g) and 2&prime;FL/5-Fu group (1.22 &plusmn; 0.35 g) had a significantly lower tumor weight compared with the control (3.87 &plusmn; 0.79 g), suggesting 2&prime;-FL could inhibit colon cancer. Since 2&prime;-FL reduced the number of new blood vessels and the malignancy of tumors, we confirmed that 2&prime;-FL effectively inhibited HCT116 tumors, and its mechanism was achieved by regulating the VEGFA/VEGFR2/PI3K/Akt/Caspase3 pathway. Moreover, though HE staining and organ index measurement, 2&prime;-FL was validated to alleviate toxic effects on liver and kidney tissue when combining with 5-Fu. In conclusion, 2&prime;-FL had certain anti-tumor and detoxification effects