Objective To conduct a visual analysis of the literature related to Mendelian randomization (MR) studies in the field of cancer based on CiteSpace software. Methods English literature on MR studies in the field of cancer was searched in the Web of Science Core Collection database, and Chinese literature was searched in CNKI, Wanfang Data, and VIP databases. The search period ranged from the inception of the databases to April 18, 2024. CiteSpace 6.3.R1 software was used to perform a visual analysis of the publication trends, authors, institutions, and keywords of the included literature through knowledge mapping. Results A total of 964 English articles and 121 Chinese articles were included in this study. The annual publication of English and Chinese literature on MR studies in the field of cancer showed an overall upward trend, but there was limited collaboration among authors and institutions. The analysis of keywords in both English and Chinese literature revealed that breast cancer, colorectal cancer, lung cancer, prostate cancer, and gastric cancer were the key cancer types, with sex hormones and low back pain as the main associated factors. Research hotspots lasting for more than five years included genetic polymorphism, colorectal cancer, and genome-wide association studies. The recent research hotspots focused on insulin, renal cell carcinoma, and endometrial cancer. Conclusion MR studies have been extensively conducted in the field of cancer and have become a research hotspot. However, collaboration among authors and institutions still need to be strengthened. The inherent limitations of the research methodology itself can lead to issues such as insufficiency of MR study evidence and conflicting results among different studies. Future MR studies should integrate other disciplines and epidemiological research methods to provide more comprehensive causal evidence.

ObjectiveTo investigate the single nucleotide polymorphisms (SNPS) in the coding regions of the human ABCA2 gene and to determine the association of some of these SNPs with gallstone disease in a Chinese population. MethodsThe exons and part of the introns of the ABCA2 gene were sequenced using a fluorescent labeling automatic method in 24 patients with gallstone disease to identify and characterize the SNPs in a Chinese population. For SNPs in the exons, case-control studies were performed on patients and controls. ResultsTwelve SNPs were found within a 16911 bp region of the ABCA2 gene. Among them, two were in the exons, ten in the introns and five were novel SNPs. There was no significant difference in the SNPs genotype between the patients and the controis. ConclusionsThere is an important ethnic difference in the SNPs distribution of the human ABCA2 gene. The distribution of SNPs in the coding regions of the human ABCA2 gene is not significantly different between the patients and the controls.

With the acceleration of population aging in China, the issue of population aging is becoming increasingly severe.The investigation of the pathogenesis of aging-related diseases has become a focal point in the field of modern geriatrics.Iron is an essential trace element in the human body and plays a crucial role in maintaining normal physiological functions.Numerous studies have demonstrated the association between the disruption of iron metabolism and the occurrence and progression of various aging-related diseases.This review aims to briefly summarize the potential mechanisms of iron metabolism disorders in common aging-related diseases, and provide a theoretical basis for the diagnosis and treatment of such diseases.

BACKGROUND:Diabetic nephropathy is an important cause of end-stage renal disease,and intestinal barrier damage plays an important role in the occurrence and development of diabetic nephropathy. OBJECTIVE:To observe the protective effect of human umbilical cord mesenchymal stem cells on the intestinal barrier in rats with diabetic nephropathy. METHODS:Thirty 8-week-old male SD rats were randomly assigned to healthy control group,model group and human umbilical cord mesenchymal stem cell group,with 10 rats in each group.Rats in the human umbilical cord mesenchymal stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for 4 weeks after the model establishment of diabetic nephropathy.Rats in the healthy control group and the model group were injected with an equal volume of PBS at the same time.1 week after the last injection,the histomorphological changes in the kidney and colon were observed under a light microscope.The expressions of ZO-1 and Occludin in the colon tissue of rats were detected by immunohistochemistry.Serum D-lactic acid and lipopolysaccharide levels were detected by ELISA.In addition,the distribution of human umbilical cord mesenchymal stem cells labeled with DiR dye in rats was observed by in vivo imaging system.The expression of human mesenchymal stem cell surface marker antigens CD44 and CD90 in colon tissue was detected by immunohistochemistry. RESULTS AND CONCLUSION:(1)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly inhibited the increase of urea nitrogen,serum creatinine,24-hour urine protein level and urinary albumin/creatinine ratio in diabetic nephropathy rats(all P<0.05).(2)The expression of human mesenchymal stem cell surface markers CD44 and CD90 was found in the colon of diabetic nephropathy rats.(3)Compared with the healthy control group,the expression levels of tight junction proteins Occludin and ZO-1 in the colon tissue of the model group were significantly reduced,while the expressions of Occludin and ZO-1 were significantly increased after treatment with human umbilical cord mesenchymal stem cells.(4)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly reduced serum D-lactic acid and lipopolysaccharide levels in diabetic nephropathy rats.(5)The results suggest that human umbilical cord mesenchymal stem cells may protect the intestinal barrier function by enhancing the expression of intestinal tight junction proteins in diabetic nephropathy rats.

Objective:To establish a cell line stably expressing the transient receptor potential melastatin 2(TRPM2)channel for screening TRPM2 inhibitors based on PiggyBac transposition system.Methods:A plasmid PiggyBac-human TRPM2(pPB-hTRPM2)eukaryotic expression vector was constructed using PiggyBac transposition system.The plasmid and a helper plasmid were co-transfected into HEK293T cells to express TRPM2,which was identified by fluorescence and patch-clamp assays.The high throughput screening performance was assessed with the Z'factor.Calcium imaging and patch clamp techniques were employed to assess the initial activity of eleven compound molecules,confirming the inhibitory effects of the primary molecules on TRPM2.The protective effect of the screened compounds on damaged cells was validated using the oxygen-glucose deprivation/reperfusion(OGD/R)injury model and CCK-8 kit.The level of cellular reactive oxygen species(ROS)was detected by flow cytometry.The neuroprotective effects of the compounds were evaluated using a transient middle cerebral artery occlusion(tMCAO)mouse model.Results:The HEK293T cells transfected with pPB-hTRPM2-EGFP showed high TRPM2 expression.Puromycin-resistant cells,selected through screening,exhibited robust fluorescence.Whole-cell patch results revealed that induced cells displayed classical TRPM2 current characteristics comparable to the control group,showing no significant differences(P＞0.05).With a Z'factor of 0.5416 in calcium imaging,the model demonstrated suitability for high-throughput screening of TRPM2 inhibitors.Calcium imaging and electrophysiological experiments indicated that compound 6 significantly inhibited the TRPM2 channel.Further experiments showed that 1.0 μmol/L of compound 6 enhanced cell viability(P＜0.05)and reduced the level of ROS(P＜0.05)of SH-SY5Y under OGD/R injury.0.3 and 1.0 mg/kg of compound 6 reduced the cerebral infarction volume in tMCAO mice(both P＜0.05).Conclusions:A stable TRPM2 gene expressing cell line has been successfully established using PiggyBac gene editing in this study.TRPM2 channel inhibitors were screened through calcium imaging and patch clamp techniques,and an inhibitor compound 6 was identified.This compound can alleviate cell damage after OGD/R by reducing cellular ROS levels and has a protective effect against cerebral ischemia-reperfusion injury in mice.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*