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Objective To investigate whether junctional adhesion molecule-like protein (JAML) influences lipid homeostasis imbalance in podocytes affected by diabetic kidney disease through cell⁃death⁃inducing DNA⁃fragmentation⁃factor⁃like effector⁃B (CIDE⁃B). Methods The Cre-floxp system was used to generate JAML podocyte-specific knockout mice, thereby establishing a mouse model of diabetic kidney disease. The effects of JAML on lipid droplets and the regulation of CIDE⁃B family proteins in kidney cells were assessed with immunohistochemistry, immunofluorescence, and western blot. The impact of CIDE⁃B knockout on lipid droplets in podocytes exposed to high glucose levels was evaluated through BODIPY staining, as well as triglyceride and cholesterol assays. Results JAML deletion leads to a reduction in CIDE⁃B expression in the context of diabetic kidney disease. Furthermore, the deletion of CIDE⁃B in podocytes significantly mitigates the enlargement of lipid droplets and lipid deposition induced by high glucose. Conclusion JAML facilitates increases lipid droplet fusion in podocytes of diabetic kidney disease mice via CIDE⁃B, resulting in a disruption of lipid metabolism homeostasis and exacerbation of kidney damage.
Objective To observe the effects of splenic irradiation on tumor growth in tumor-bearing mice and to investigate the underlying mechanisms. Methods MC38 tumor cells were injected into the right back of mice to establish a unilateral subcutaneous tumor model. When the tumors reached a maximum diameter of 8-10 mm, the mice were randomly divided into the control group and the splenic irradiation group. A naive group of mice was set up to observe the changes in the spleen.The control group received no treatment, while the splenic irradiation group received 2 Gy of irradiation to the spleen per day for 5 days. At the end of the experiment, the mice were sacrificed and their tumor and spleen were collected and changes in immune cell composition and function were analyzed by flow cytometry. Results Compared with the control group, splenic irradiation inhibited tumor growth [(586.1 ± 61.3) mm3vs.(945.7 ± 116.5)mm3,P < 0.001] and significantly reduced tumor weight [(1 130 ± 143.4)mg vs.(1 800 ± 535.3)mg, P = 0.047].Spleen weight was significantly increased in tumor-bearing mice(149.6 ± 38.6)mg compared to naive mice(63.2 ± 7.8)mg,P = 0.007, whereas it was significantly reduced after splenic irradiation [(66.9 ± 6.2)mg vs.(149.6 ± 38.6)mg,P = 0.008], with a positive correlation between spleen weight and tumor weight (r = 0.659, P = 0.038). Flow cytometry results showed a significant increase in the proportion of CD8⁺ T cells in the spleen and tumor microenvironment (TME) after splenic irradiation [spleen:(8.1 ± 0.5)% vs.(5.2 ± 0.6)%, P < 0.001; TME:(16.2 ± 3.0)% vs.(11.7 ± 2.2)%, P = 0.028]. The killing (GZMB) and proliferative (Ki-67) capacities of CD8⁺ T cells were also significantly increased in spleen(GZMB:P = 0.030, Ki-67:P = 0.033)and TME (GZMB:P = 0.031, Ki-67:P = 0.027).In addition, neutrophils were significantly increased in the spleen of tumor-bearing mice [(34.3 ± 9.6)% vs.(18.5 ± 4.0)%, P = 0.010], whereas splenic irradiation resulted in a significant decrease in the proportion of neutrophils in the spleen [(21.2 ± 4.9)% vs.(34.3 ± 9.6)%, P = 0.027] and the TME [(9.4 ± 1.8)% vs.(17.4 ± 5.2)%, P = 0.012]. Conclusion Splenic irradiation effectively inhibited tumor growth by inhibiting the development of EMH in tumor-bearing mice, thereby decreasing the proportion of neutrophils and increasing the proportion and function of CD8⁺ T lymphocytes in the spleen and TME.
Objective To investigate the changes of peripheral and central natriuretic peptides (NPs) and their receptors in spontaneously hypertensive rats (SHR). Methods SHR and Wistar-Kyoto (WKY) rats aged 3,5,7 and 9 months were used in this study. Non-invasive blood pressure measurement, echocardiography and transcranial Doppler ultrasound were used to evaluate the function of heart and brain. The levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) in serum and cerebrospinal fluid were measured by ELISA. Western blot was used to analyze the expression of NPs receptors in heart and brain tissues. Results The blood pressure of SHR began to rise from 3 months old and continued to rise with age, which was significantly higher than that of WKY rats of the same age. Echocardiography showed that since 5 months of age, the cardiac function indexes such as ejection fraction and fractional shortening in SHR group were significantly lower than those in WKY group. Transcranial Doppler ultrasound showed that the resistance index and pulsatility index of SHR increased significantly. ELISA results showed that the contents of ANP, BNP and CNP in serum and cerebrospinal fluid of SHR were significantly increased. Western blot results showed that the expression of NPR-A and NPR-C protein in heart and brain tissue of SHR decreased significantly from 5 months old, and the level of NPR-B protein in 9 months old SHR group decreased significantly. Conclusion NPs and their receptors are essential in hypertension, cardiac dysfunction and cerebral blood flow changes in SHR, and may play a potential role in the prevention and treatment of hypertension and its complications.
Objective To assess whether drug-coated balloon treatment of lower limb arteriosclerosis obliterans, postoperative non-NHLBI type F entrapment, all without stent implantation, is safe and effective at 12-month follow-up, and the risk factors affecting the patency rate at one year postoperatively. Methods From October 2020 to November 2021, the clinical data of 131 patients were retrospectively analyzed for the application of drug-coated balloon for the treatment of superficial femoral atherosclerotic occlusion in the Department of Vascular Surgery of the Second Affiliated Hospital of Shandong First Medical University, and a total of 65 patients were entered into the analysis according to the exclusion criteria. According to the NHLBI sandwich classification, it is divided into two groups: NHLBI A/B group and NHLBI C/D/E group, comparing the acute occlusion rate, phase I patency rate, freedom from clinically driven target lesion revascularisation (CD-TLR), CD-TLR of patients in the two groups during the 12-month follow-up period. change in ankle-brachial index (ABI), change in Rutherford classification, and major adverse events (MAEs): amputation rate and mortality. The Kaplan-Meier method was used to assess the first-stage patency rate and CD-TLR, and the Cox proportional risk model was used to determine the risk factors affecting the first-stage patency rate. Results No acute occlusive events occurred during hospitalisation. During the 12-month follow-up, the one-stage patency rate was 71.0% in the NHLBI A/B group and 67.6% in the NHLBI C/D/E group (P = 0.753).The free CD-TLR rate was 74.2% in the NHLBI A/B group and 73.5% in the NHLBI C/D/E group (P = 0.890). Postoperative ankle-brachial index and Rutherford classification were significantly higher in both groups compared with those in preoperative period. No patients were found to have amputation and death during the follow-up period.TASC type C/D (HR = 0.292, 95% CI:0.111-0.771, P < 0.05) versus preoperative Rutherford grading of stage 4/5/6 (HR = 0.124, 95% CI:0.028-0.537, P < 0. 05) was found to be an independent risk factor for it. Conclusion Non-NHLBI F clips arising after drug-coated balloon dilatation for superficial femoral atherosclerotic occlusive disease may be safe and effective without stenting at 12-month follow-up. And TASC staging and Rutherford staging may be important factors influencing the one-stage postoperative patency rate.
Objective To examine the dynamic patterns of injury and subsequent repair in the central corneal sub-basal nerve plexus in patients with diabetes and cataracts, both prior to and following phacoemulsification surgery. Methods A total of 102 cases (115 eyes) of patients scheduled for phacoemulsification cataract surgery was collected from October 2023 to September 2024 at the department of ophthalmology, The Second Affiliated Hospital of Shandong First Medical University. The patients were categorized into a diabetes group (59 eyes) and a control group (56 eyes) based on the presence of type 2 diabetes. One week, one month, and three months before and after the surgery, images of the sub-basal nerve plexus in the central cornea were obtained using in vivo confocal microscopy. Various parameters, including corneal nerve branch density (CNBD), corneal nerve fiber area (CNFA), corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve fiber width (CNFW), corneal nerve total branch density (CTBD) and corneal nerve fractal dimension (CNFrD) were quantified using ACCMetrics software. It was aimed to compare the dynamic differences in these parameters between the two groups at the specified time points. In the diabetic cohort, the restoration of CNBD, CNFD, and CNFL was protracted relative to the control cohort. One week and three months after the surgery, CNBD and CNFD levels in the diabetic cohort were significantly lower than those in the control cohort (P < 0.05). Similarly, one month after surgery, CNBD and CNFL levels were also significantly reduced in the diabetic cohort compared to those in the control cohort (P < 0.05). Interaction analysis revealed that CNBD in the diabetic cohort exhibited a more rapid decline and a slower recovery, with statistically significant differences (P < 0.05), whereas the trajectories of other parameters were analogous between the two cohorts. Furthermore, comparative analysis of CNFA, CNFrD, CNFW and CTBD between the cohorts did not reveal any statistically significant differences (P > 0.05). Results A comparative analysis of preoperative and intraoperative parameters, including gender, age, ultrasonic energy consumption, and various corneal nerve metrics, revealed no statistically significant differences between the two groups (P > 0.05). A temporal effect was observed on the alterations in CNFD, CNBD, CNFL, CNFrD and CTBD, with these parameters exhibiting significant reductions both one week and one month after surgery compared to preoperative values (P < 0.05). Notably, CNFD and CNFrD demonstrated significant increases one month after surgery relative to one week after surgery (P < 0.05). Three months after surgery, most parameters had returned to their baseline preoperative levels. Conclusion Cataract surgery may induce reversible alterations in corneal nerves, evidenced by a temporary reduction in corneal nerve parameters during the initial postoperative period; however, these alterations are capable of self-limited recovery. In patients with diabetes, the extent of corneal nerve damage post-surgery is more pronounced, and the subsequent repair process is comparatively protracted.
Noise-induced hearing loss (NIHL) is a common form of sensorineural hearing impairment with an incompletely understood pathogenesis. In recent years, the role of mitochondria in cochlear hair cell damage has gained increasing attention, establishing it as a focal point in NIHL research. As the energy supply and regulatory center of the cell, mitochondria play a crucial role in cochlear hair cell injury through mechanisms such as oxidative stress, autophagy and apoptosis. This review summarizes the multifaceted roles of mitochondria in NIHL, focusing on oxidative stress induced by ROS accumulation, both caspase-dependent and caspase-independent apoptosis pathways, autophagy dysregulation, and the interaction between mitochondrial function and cochlear blood flow. Additionally, this paper highlights mitochondria-targeted intervention strategies, including antioxidants, autophagy modulators and gene-editing approaches, providing new perspectives for developing effective preventive and therapeutic measures against NIHL. A more comprehensive understanding of mitochondria-related molecular mechanisms will lay an essential foundation for the prevention, research, and clinical management of NIHL.
There is a growing interest in the role of gut flora and metabolites in neurological disorders. Trimethylamine N-oxide (TMAO), a crucial metabolite of gut microbiota, has been confirmed to be closely associated with cardiovascular diseases, chronic kidney disease, and neurodegenerative disorders. White matter lesion (WML) is a common pathological feature of various neurological diseases, whose underlying mechanisms are incompletely understood. This article reviews the production and excretion pathways of TMAO with its possible effects on cerebral white matter and potential molecular mechanisms, providing outlook on TMAO-targeted therapeutic strategies.
Liver fibrosis (LF) is a pathologic tissue-repairing response to chronic liver injury featuring overproduction of extracellular matrix by myofibroblasts, and it is also a transitional stage in the progression of chronic liver disease to cirrhosis. Despite the situation of the growing population of chronic liver disease and the high mortality rate of cirrhosis, there is still no FDA-approved drug for the treatment of LF. In recent years, with the in-depth study on the roles of microRNAs (miRNAs) in LF, multiple miRNAs are increasingly being studied in LF. This review introduces the latest understanding of the pathogenesis of LF, focusing on the roles of miRNAs in the occurrence and development of LF as well as the related applications in diagnosis and treatment in recent years.


