Global trends in the burden of chronic kidney disease attributable to type 2 diabetes: An age-period-cohort analysis.

AIM: To assess temporal trends of chronic kidney disease (CKD) attributable to type 2 diabetes (T2D) globally and in five sociodemographic index (SDI) regions. MATERIALS AND METHODS: We extracted the population data and CKD burden attributable to T2D from the Global Burden of Disease Study 2019. We evaluated the trends of disability-adjusted life years (DALYs), mortality, prevalence and incidence through age-period-cohort modelling, and calculated net drifts (overall annual percentage changes), local drifts (annual percentage changes in each age group), longitudinal age curves (fitted longitudinal age-specific rates), period relative risks (RRs) and cohort RRs. RESULTS: From 1990 to 2019, the global burden of CKD attributable to T2D showed increasing trends in general. The burden of CKD attributable to T2D was highest in the middle SDI region and lowest in the low SDI region. Age effects increased with age, and peaked at the ages of 75-79 and 80-84 years for incidence and prevalence, respectively. Period RRs in the burden of CKD attributable to T2D increased, with the high SDI being the most remarkable in DALYs and mortality, and the middle SDI being the most notable in incidence. Cohort RRs showed unfavourable trends in incidence and prevalence among recent cohorts. CONCLUSIONS: After a lengthy period of multi-initiative diabetes management, the high-middle SDI region exhibited improvement. However, unresolved issues and improvement gaps were still remarkable. Future efforts to reduce the burden of CKD attributable to T2D in the population should prioritize addressing the unfavourable patterns identified.

Effect of FoxO1 on Cardiomyocyte Apoptosis and Inflammation in Viral Myocarditis via Modultion of the TLR4/NF-κB Signaling Pathway.

To investigate the possible effect of FoxO on coxsackievirus B3 (CVB3) -induced cardiomyocyte inflammation and apoptosis via modulation of the TLR4/NF-κB signaling pathway.Viral myocarditis (VMC) models were establied via CVB3 infection both in vivo and in vitro. Western blotting was adopted to detect FoxO1 and TLR4 expressions in myocardial tissues and cells. Cardiomyocytes of suckling mouse were divided into the control, CVB3, CVB3 + pcDNA, CVB3 + pcDNA-FoxO1, CVB3 + TLR4 siRNA, and CVB3 + pcDNA-FoxO1 + TLR4 siRNA groups. Flow cytometry was employed to evaluate cell apoptosis. The expressions of inflammatory factors including TNF-α, IL-1ß, and IL-6 were detected via quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Then, TLR4/NF-κB pathway-related proteins were determined via Western blotting.VMC mice had increased FoxO1 and TLR4 expressions in myocardial tissues. Cardiomyocytes with CVB3 infection also had upregulated protein expressions of p-FoxO1/FoxO1 and TLR4. Compared with those in the control group, the cardiomyocytes in the CVB3 group were increased in LDH and CK-MB levels, cell apoptosis rate and inflammatory factors (TNF-α, IL-1ß and IL-6), as well as protein expressions of TLR4 and p-p65/p65. Compared with those in the CVB3 group, the cardiomyocytes in the CVB3 + pcDNA-FoxO1 group were further upregulated whereas those in the CVB3 +TLR4 siRNA group were downregulated in the aforementioned indicators. Furthermore, TLR4 siRNA can reverse the effect of pcDNA-FoxO1 on the aggravation of cardiomyocyte injury induced by CVB3 infection.FoxO1 can upregulate the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced VMC.

Where does fear originate in the brain? A coordinate-based meta-analysis of explicit and implicit fear processing.

Processing of fear is of crucial importance for human survival and it can generally occur at explicit and implicit conditions. It is worth noting that explicit and implicit fear processing produces different behavioral and neurophysiological outcomes. The present study capitalizes on the Activation Likelihood Estimation (ALE) method of meta-analysis to identify: (a) the "core" network of fear processing in healthy individuals; (b) common and specific neural activations associated with explicit and implicit processing of fear. Following PRISMA guidelines, a total of 92 fMRI and PET studies were included in the meta-analysis. The overall analysis show that the core fear network comprises the amygdala, pulvinar, and fronto-occipital regions. Both implicit and explicit fear processing activated amygdala, declive, fusiform gyrus, and middle frontal gyrus, suggesting that these two types of fear processing share a common neural substrate. Explicit fear processing elicited more activations at the pulvinar and parahippocampal gyrus, suggesting visual attention/orientation and contextual association play important roles during explicit fear processing. In contrast, implicit fear processing elicited more activations at the cerebellum-amygdala-cortical pathway, indicating an 'alarm' system underlying implicit fear processing. These findings have shed light on the neural mechanism underlying fear processing at different levels of awareness.

Phosphorylation of 5-LOX: The Potential Set-point of Inflammation.

Inflammation secondary to tissue injuries serves as a double-edged sword that determines the prognosis of tissue repair. As one of the most important enzymes controlling the inflammation process by producing leukotrienes, 5-lipoxygenase (5-LOX, also called 5-LO) has been one of the therapeutic targets in regulating inflammation for a long time. Although a large number of 5-LOX inhibitors have been explored, only a few of them can be applied clinically. Surprisingly, phosphorylation of 5-LOX reveals great significance in regulating the subcellular localization of 5-LOX, which has proven to be an important mechanism underlying the enzymatic activities of 5-LOX. There are at least three phosphorylation sites in 5-LOX jointly to determine the final inflammatory outcomes, and adjustment of phosphorylation of 5-LOX at different phosphorylation sites brings hope to provide an unrecognized means to regulate inflammation. The present review intends to shed more lights into the set-point-like mechanisms of phosphorylation of 5-LOX and its possible clinical application by summarizing the biological properties of 5-LOX, the relationship of 5-LOX with neurodegenerative diseases and brain injuries, the phosphorylation of 5-LOX at different sites, the regulatory effects and mechanisms of phosphorylated 5-LOX upon inflammation, as well as the potential anti-inflammatory application through balancing the phosphorylation-depended set-point.

[Expression of the Ces5a gene in the rat testis].

OBJECTIVE: To study the expression of the Ces5a gene in the development of the rat testis. METHODS: Using RT-PCR, Western blot, immunohistochemistry and HE staining, we determined the mRNA transcription level, protein expression and localization of the Ces5a gene in the testes of three litters of rats at different postnatal (PN) days. RESULTS: The expression of Ces5a mRNA was found in the testis tissue of the rats at 2－65 PN days, low at 2－12 days, decreased to the lowest level at 14－16 days (P < 0.05), but significantly increased at 20－35 days (P < 0.05), and elevated to the highest level at 40－65 days (P < 0.05). The expression of the Ces5a protein was also observed in the testis tissue of the rats at 2－65 PN, low at 2－12 days, with no significant change at 14－16 days (P > 0.05), but markedly increased at 20－35 days (P < 0.05), and again with no significant change at 40－65 days (P > 0.05). The Ces5a protein was expressed in the spermatogonia, spermatocytes and round sperm cells. CONCLUSIONS: The Ces5a gene may be involved in the proliferation and meiosis of rat spermatogonia and play a special role in round spermatogenesis and sperm deformation.

[Expression of the MYL2 gene in the development of rat testis tissue].

OBJECTIVE: To study the expression of the gene of myosin regulatory light chain-2 (MYL2) in the development of rat testis tissue. METHODS: Using real-time PCR and immunohistochemistry, we determined the mRNA transcription level and protein expression of MYL2 in the rat testis. RESULTS: The mRNA expression of the MYL2 gene changed in an age-dependent manner, reaching the highest value on postnatal day (PND) 2, then dropped rapidly till PND 8, increased slowly on PNDs 10 and 12, decreased on PND 14, rose slightly from PND 15 and rapidly on PNDs 20 and 25, and declined slowly from PND 65. Immunohistochemistry showed that the MYL2 protein was mainly expressed in testicular sperm cells. CONCLUSIONS: The MYL2 gene may be involved in the proliferation of spermatogonial stem cells and the process of sperm cells developing into mature sperm.

Assessment of prognostic role of a novel 7-lncRNA signature in HCC patients.

Background: Hepatocellular carcinoma (HCC) is characterized by extensive risk factors, high morbidity and mortality. Clinical prognostic evaluation assay assumes a nonspecific quality. Better HCC prognostics are urgently needed. Long noncoding RNAs (lncRNAs) exerts a crucial role in tumorigenesis and development. Excavating specific lncRNAs signature to ameliorate the high-risk survival prediction in HCC patients is worthwhile. Methods: Differentially expressed lncRNAs (DElncRNAs) profile was acquired from The Cancer Genome Atlas database (TCGA). Then, the lncRNAs high-risk survival prognostic model was established using the least absolute shrinkage and selection operator (LASSO)-Cox regression algorithm. The lncRNAs were evaluated in clinical specimen by PCR. The receiver operating characteristic curve (ROC) analysis was further conducted to assess the potential prognostic value of the model. Moreover, a visible nomogram containing clinicopathological features and prognostic model was developed for prediction of survival property. Potential molecular mechanism was assessed by GO, KEGG, GSEA enrichment analysis and CIBERSORT immune infiltration analysis. Results: A novel 7-lncRNA risk model (AL161937.2, LINC01063, AC145207.5, POLH-AS1, LNCSRLR, MKLN1-AS, AC105345.1) was constructed and validated for HCC prognosis prediction. Kaplan-Meier analysis revealed that patients in the high-risk group suffered a poor prognosis (p = 1.813 × 10-8). These genes were detected by PCR, and the expression trend was in accordance with TCGA database. Interestingly, the risk score served as an independent risk factor for HCC patients (HR: 1.166, 95% CI:1.119-1.214, p < 0.001). The nomogram was established, and the predictive accuracy in the nomogram was prior to the TNM stage according to the ROC curve analysis. Cell proliferation related pathway, decreased CD4+ T cell, CD8+ T cell, NK cell and elevated Neutrophil, Macrophage M0 were observed in high-risk group. Besides, suppression of MKLN1-AS expression inhibited cell proliferation of HCC cells by CCK8 assay in vitro. Conclusion: The 7-lncRNA signature may exert a particular prognostic prediction role in HCC and provide new insight in HCC carcinogenesis.

The role of calcium-sensitive receptor in ovalbumin-induced airway inflammation and hyperresponsiveness in juvenile mice with asthma.

The role of the calcium-sensitive receptor (CaSR) was assessed in a juvenile mouse model of asthma induced by ovalbumin (OVA). The experiment was divided into normal control, OVA, and OVA +2.5/5 mg/kg NPS2143 (a CaSR antagonist) groups. OVA induction was performed in all groups except the normal control, followed by assessing airway hyperresponsiveness (AHR) and lung pathological changes. Serum OVA-specific IgE and IgG1 were detected with an enzyme-linked immunosorbent assay (ELISA), and inflammatory cells were counted in bronchoalveolar lavage fluid (BALF). Real-time quantitative polymerase chain reaction, ELISA, and western blotting were performed to detect gene and protein expression. NPS2143 improved the OVA-induced AHR in mice, and AHR was higher in the OVA +2.5 mg/kg NPS2143 group than in the OVA +5 mg/kg NPS2143 group. Furthermore, NPS2143 reduced the production of OVA-specific IgE and IgG1 in serum and the number of eosinophils and lymphocytes in BALF in OVA mice with reduced CaSR expression in lung tissues. Besides, OVA-induced mice exhibited peribronchial and perivascular inflammatory cell infiltration, which was accompanied by severe goblet cell hyperplasia/hyperplasia and airway mucus hypersecretion. Furthermore, these mice exhibited increased levels of Interleukin (IL)-5, IL-13, MCP-1, and eotaxin, which were alleviated by NPS2143. The 5 mg/kg NPS2143 showed more effective than the 2.5 mg/kg treatment. CaSR expression was elevated in the lung tissues of OVA-induced asthmatic juvenile mice, whereas the CaSR antagonist NPS2143 reduced AHR and attenuated the inflammatory response in OVA-induced juvenile mice, possibly exerting therapeutic effects on childhood asthma.

[Comparative study of two high-efficiency methods for purifying spermatogonial stem cells].

Objective: To compare the advantages and disadvantages of the differential attachment method and immunomagnetic bead method for purification of mouse spermatogonial stem cells (mSSCs). Methods: Ten male C57BL/6 mice aged 12～15 days were selected and sacrificed by cervical dislocation. Testes were collected and the seminiferous tubule single cell suspension was obtained by enzymatic digestion. mSSCs were purified by using the differential attachment method and immunomagnetic bead method respectively. Then a detailed comparison of the two methods in terms of cell number, separation efficiency, and impact on cell proliferation and growth was conducted. Results: Both of the methods could isolate and purify stem cells from single cell suspension of mouse seminiferous tubules. mSSCs showed typical grape cluster-like clones in vitro culture, which could be continuously cultured and proliferated for over 3 months in vitro. The testes of 10 mice could obtain 3×105±0.4×105 mSSCs (n=5) by differential attachment method, cell recovery rate (the number of cells after purification/the number of cells of the single cell suspension of seminiferous tubules) was 1.5%±0.1%; 6×105±0.4×105 mSSCs (n= 5) could be obtained by immunomagnetic bead method. The recovery rate was about 3%±0.1%, and the number of stem cells obtained by the immunomagnetic bead method was higher. The stem cells obtained by the differential attachment method were more pure, because the stem cell colonies were preferentially obtained after 5 days of in vitro culture, while the stem cells obtained by the immunomagnetic bead method needed to be cultured for about 10 days before the obvious cell colonies could be observed, but the two types of purification method had no obvious effect on the long-term growth of cells in vitro. Conclusion: Both methods can get high quality mSSCs, but both methods have their own advantages and disadvantages. The differential attachment method is more economical and practical than the other, it does not require special equipment, but the stem cell number obtained is relatively lower and the time needed is longer.

[Effect of dopamine receptor agonist apomorphine on scopolamine induced memory deficits in mice].

OBJECTIVE: To research the mechanism of dopamine (DA) controlled memory in mice. METHODS: Mice received i.p. injection of scopolamine (0.3 mg/kg, SCOP 0.3, and 3.0mg/kg, SCOP 3.0, respectively, n = 10) and saline (NS, n = 10) for 60 days in experiment 1. Memory of mice was detected by dark avoidance behavior in the 53" d and the 60"' d. Animals were sacrificed after the memory test; brain tissues were processed for Fos-ir and TH-ir by immunohistochemistry. Mice were divided into four groups according results of expri-ment 1, they received i.p. injection of apomorphine (0.1 mg/kg, APO 0.1, 0.5 mg/kg, APO 0.5, and 2.0 mg/kg, APO2.0 respectively, n = 10). RESULTS: Memory was inhibited in mice injected scopolamine 3.0 mg/kg. Latency was significantly less than in NS group, only 1/ 4 that of NS group (P > 0.05). The number of mistake of SCOP 3.0 group increased about four times than that of NS group (P > 0.05). But there was no difference of latency and number of mistake between SCOP 0.3 and NS group in expriment 1. Scopolamine-induced memory deficit was associated with decreased cellular activation, indicated by Fos immunoreactive (ir) staining, in NAcc CA1 and CA3 (P < 0.05), and also associated with decreases in the number of cells labeled for tyrosine hydroxylase (TH-ir), the rate limiting enzyme for dopamine conversion (P < 0.01) and the number of cells co-labeled for TH-ir/Fos-ir (P <0.01) in the ventral tegmental area(VTA), apomorphine lessened scopolamine-induced memory deficit in experiment 2. The number of cells co-labeled for TH-ir/Fos-ir (P <, 0.05) was increased in VTA after apomorphine treatment. CONCLUSION: Apomorphine lessened scopolamine-induced memory deficit in mice by increasing DA activities in VTA.

Application of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology for the diagnosis of colorectal adenoma.

The aim of the present study was to identify a specific biological marker for the diagnosis of colorectal adenomas through the analysis of variations in serum protein profiling in colorectal adenoma patients. The study was conducted at the Renmin Hospital of Wuhan University (Wuhan, China) between September 2011 and May 2012. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was performed to compare the serum protein profiles of 50 patients with colorectal adenoma and 50 healthy individuals. The obtained protein profiles were analyzed using Biomarker Wizard software. Twenty protein peaks were identified to exhibit differences in average intensity between colorectal adenomas compared with normal controls, including peaks 8,565.84, 8,694.51 and 5,910.50 Da, in which the intensity between the patients and control individuals was significantly different. Two peaks, 8,565.84 and 8,694.51 Da, were observed to be highly expressed in the colorectal adenomas, however, expression was low in the control samples. By contrast, 5,910.50 Da expression was low in the colorectal adenomas and high in the controls. The results of the current study indicate that the three protein peaks may represent specific biomarkers for colorectal adenomas.