Exploring the crosstalk molecular mechanisms between IgA nephropathy and Sjögren's syndrome based on comprehensive bioinformatics and immunohistochemical analyses.

IgA nephropathy (IgAN) and Sjogren's syndrome (SS) are two autoimmune diseases with undetermined etiology and related to abnormal activation of lymphocytes. This study aims to explore the crucial genes, pathways and immune cells between IgAN and SS. Gene expression profiles of IgAN and SS were obtained from the Gene Expression Omnibus and Nephroseq data. Differentially expressed gene (DEG) and weighted gene co-expression network analyses (WGCNA) were done to identify common genes. Enrichment analysis and protein-protein interaction network were used to explore potential molecular pathways and crosstalk genes between IgAN and SS. The results were further verified by external validation and immunohistochemistry (IHC) analysis. Additionally, immune cell analysis and transcription factor prediction were also conducted. The DEG analysis revealed 28 commonly up-regulated genes, while WGCNA identified 98 interactively positive-correlated module genes between IgAN and SS. The enrichment analysis suggested that these genes were mainly involved in the biological processes of response to virus and antigen processing and presentation. The external validation and IHC analysis identified 5 hub genes (PSMB8, PSMB9, IFI44, ISG15, and CD53). In the immune cell analysis, the effector memory CD8 T and T follicular helper cells were significantly activated, and the corresponding proportions showed positively correlations with the expressions of the 5 hub genes in the two autoimmune diseases. Together, our data identified the crosstalk genes, molecular pathways, and immune cells underlying the IgAN and SS, which provides valuable insights into the intricate mechanisms of these diseases and offers potential intervention targets.

LncRNA KCNQ1OT1 promotes NLRP3 inflammasome activation in Parkinson's disease by regulating pri-miR-186/mature miR-186/NLRP3 axis.

Increasing evidence indicated that neuroinflammation was involved in progression of Parkinson's disease (PD). Long noncoding RNAs (lncRNAs) played important roles in regulating inflammatory processes in multiple kinds of human diseases such as cancer diabetes, cardiomyopathy, and neurodegenerative disorders. The mechanisms by which lncRNAs regulated PD related inflammation and dopaminergic neuronal loss have not yet been fully elucidated. In current study, we intended to explore the function and potential mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in regulating inflammasome activation in PD. Functional assays confirmed that knockdown of KCNQ1OT1 suppress microglial NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and attenuated dopaminergic neuronal loss in PD model mice. As KCNQ1OT1 located in both cytoplasm and nucleus of microglia, we demonstrated that KCNQ1OT1 promoted microglial NLRP3 inflammasome activation by competitive binding with miR-186 in cytoplasm and inhibited pri-miR-186 mediated NLRP3 silencing through recruitment of DiGeorge syndrome critical region gene 8 (DGCR8) in nucleus, respectively. Our study found a novel lncRNA-pri-miRNA/mature miRNA-mRNA regulatory network in microglia mediated NLRP3 inflammasome activation and dopaminergic neuronal loss, provided further insights for the treatment of Parkinson's disease.

Lipid-associated macrophages for osimertinib resistance and leptomeningeal metastases in NSCLC.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

Screening of monoamine oxidase B inhibitors in Tibetan strawberry by ligand fishing based on enzyme functionalized cellulose filter paper.

Tibetan strawberry (Fragaria nubicola) is a wild medicinal and edible plant in Tibet possessing various health benefits such as neuroprotection and anti-oxidation. However, there has been little study reported on its chemical constituents. To investigate the inhibitors of monoamine oxidase B (MAO-B) in Tibetan strawberry, we immobilized the enzyme onto cellulose filter paper for the first time to develop a new screening method. Two known glycosides (compounds 1 and 2) and one new iridoid glucoside (Compound 3) were fished out by this method, which was found to effectively inhibit MAO-B with IC50 values of 16.95 ± 0.93, 24.69 ± 0.20, and 46.77 ± 0.78 µM, respectively. Molecular docking and kinetic analysis were performed to reveal the inhibition mechanism of these compounds. Furthermore, compound 1 exhibited neuroprotective effects against 6-OHDA-induced injury on PC12 cells. The developed method exhibits the advantages of rapidness and effectiveness in screening of MAO-B inhibitors from complex herbal extracts.

Efficient Dlx2-mediated astrocyte-to-neuron conversion and inhibition of neuroinflammation by NeuroD1.

In vivo astrocyte-to-neuron (AtN) conversion induced by overexpression of neural transcriptional factors has great potential for neural regeneration and repair. Here, we demonstrate that a single neural transcriptional factor, Dlx2, converts mouse striatal astrocytes into neurons in a dose-dependent manner. Lineage-tracing studies in Aldh1l1-CreERT2 mice confirm that Dlx2 can convert striatal astrocytes into DARPP32+ and Ctip2+ medium spiny neurons (MSNs). Time-course studies reveal a gradual conversion from astrocytes to neurons in 1 month, with a distinct intermediate state in between astrocytes and neurons. Interestingly, when Dlx2-infected astrocytes start to lose astrocytic markers, the other local astrocytes proliferate to maintain astrocytic levels in the converted areas. Unexpectedly, although Dlx2 efficiently reprograms astrocytes into neurons in the gray matter striatum, it also induces partial reprogramming of astrocytes in the white matter corpus callosum. Such partial reprogramming of white matter astrocytes is associated with neuroinflammation, which can be suppressed by the addition of NeuroD1. Our results highlight the importance of investigating AtN conversion in both the gray matter and white matter to thoroughly evaluate therapeutic potentials. This study also unveils the critical role of anti-inflammation by NeuroD1 during AtN conversion.

Interaction of Th17 differentiations-related gene polymorphisms and environmental factors contributing to the disease classification, complications, and surgical risks of Crohn's disease in the Chinese Han population.

OBJECTIVES: Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS: We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS: Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS: This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.

Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through MALAT1/miR-138-5p/SLC7A11 Coexpression Regulation.

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.

Cepharanthine triggers ferroptosis through inhibition of NRF2 for robust ER stress against lung cancer.

BACKGROUND: Severe endoplasmic reticulum (ER) stress elicits apoptosis to suppress lung cancer. Our previous research identified that Cepharanthine (CEP), a kind of phytomedicine, possessed powerful anti-cancer efficacy, for which the underlying mechanism was still uncovered. Herein, we investigated how CEP induced ER stress and worked against lung cancer. METHODS: The differential expression genes (DEGs) and enrichment were detected by RNA-sequence. The affinity of CEP and NRF2 was analyzed by cellular thermal shift assay (CETSA) and molecular docking. The function assay of lung cancer cells was measured by western blots, flow cytometry, immunofluorescence staining, and ferroptosis inhibitors. RESULTS: CEP treatment enriched DEGs in ferroptosis and ER stress. Further analysis demonstrated the target was NRF2. In vitro and in vivo experiments showed that CEP induced obvious ferroptosis, as characterized by the elevated iron ions, ROS, COX-2 expression, down-regulation of GPX4, and atrophic mitochondria. Moreover, enhanced Grp78, CHOP expression, ß-amyloid mass, and disappearing parallel stacked structures of ER were observed in CEP group, suggesting ER stress was aroused. CEP exhibited excellent anti-lung cancer efficacy, as evidenced by the increased apoptosis, reduced proliferation, diminished cell stemness, and prominent inhibition of tumor grafts in animal models. Furthermore, the addition of ferroptosis inhibitors weakened CEP-induced ER stress and apoptosis. CONCLUSION: In summary, our findings proved CEP drives ferroptosis through inhibition of NRF2 for induction of robust ER stress, thereby leading to apoptosis and attenuated stemness of lung cancer cells. The current work presents a novel mechanism for the anti-tumor efficacy of the natural compound CEP.

Enabling long-distance hydrogen spillover in nonreducible metal-organic frameworks for catalytic reaction.

Hydrogen spillover is an extraordinary effect in heterogeneous catalysis and hydrogen storage, which refers to the surface migration of metal particle-activated hydrogen atoms over the solid supports. Historical studies on this phenomenon have mostly been limited to reducible metal oxides where the long-distance proton-electron coupled migration mechanism has been established, yet the key question remains on how to surmount short-distance and defect-dependent hydrogen migration on nonreducible supports. By demerging hydrogen migration and hydrogenation reaction, here we demonstrate that the hydrogen spillover in nonreducible metal-organic frameworks (MOFs) can be finely modulated by the ligand functional groups or embedded water molecules, enabling significant long-distance (exceed 50 nm) movement of activated hydrogen. Furthermore, using sandwich nanostructured MOFs@Pt@MOFs as catalysts, we achieve highly selective hydrogenation of N-heteroarenes via controllable hydrogen spillover from Pt to MOFs-shell. We anticipate that this work will enhance the understanding of hydrogen spillover and shed light on de novo design of MOFs supported catalysts for many important reactions involving hydrogen.

Comparison of efficacy and safety between robotic-assisted versus laparoscopic surgery for locally advanced mid-low rectal cancer following neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: To some extent, robotic technique does offer certain benefits in rectal cancer surgery than laparoscopic one, while remains a topic of ongoing debate for rectal cancer patients who had undergone neoadjuvant chemoradiotherapy (NCRT). METHODS: Potential studies published until January 2024 were obtained from Web of Science, Cochrane Library, Embase and PubMed. Dichotomous and continuous variables were expressed as odds ratios (ORs) and weighted mean differences (WMDs) with 95% their confidence intervals (CIs), respectively. A random effects model was used if I2 statistic >50%, otherwise a fixed effects model. RESULTS: Eleven studies involving 1079 patients were analyzed. The robotic-assisted group had an 0.4 cm shorter distance from anal verge (95% CI: -0.680 to -0.114, P=0.006) and 1.94 times higher complete total mesorectal excision (TME) rate (OR=1.936, 95% CI: 1.061 to 3.532, P=0.031). However, the operation time in the robotic-assisted group was 54 minutes longer (95% CI: 20.489 to 87.037, P=0.002) than laparoscopic group. In addition, the robotic-assisted group had a lower open conversion rate (OR=0.324, 95% CI: 0.129 to 0.816, P=0.017) and a shorter length of hospital stay (WMD=-1.127, 95% CI: -2.071 to -0.184, P=0.019). CONCLUSION: Robot-assisted surgery offered several advantages over laparoscopic surgery for locally advanced mid-low rectal cancer following NCRT in terms of resection of lower tumours with improved TME completeness, lower open conversion rate and shorter hospital stay, despite longer operative time.

Long Non-Coding RNAs in Drug Resistance of Gastric Cancer: Complex Mechanisms and Potential Clinical Applications.

Gastric cancer (GC) ranks as the third most prevalent malignancy and a leading cause of cancer-related mortality worldwide. However, the majority of patients with GC are diagnosed at an advanced stage, highlighting the urgent need for effective perioperative and postoperative chemotherapy to prevent relapse and metastasis. The current treatment strategies have limited overall efficacy because of intrinsic or acquired drug resistance. Recent evidence suggests that dysregulated long non-coding RNAs (lncRNAs) play a significant role in mediating drug resistance in GC. Therefore, there is an imperative to explore novel molecular mechanisms underlying drug resistance in order to overcome this challenging issue. With advancements in deep transcriptome sequencing technology, lncRNAs-once considered transcriptional noise-have garnered widespread attention as potential regulators of carcinogenesis, including tumor cell proliferation, metastasis, and sensitivity to chemo- or radiotherapy through multiple regulatory mechanisms. In light of these findings, we aim to review the mechanisms by which lncRNAs contribute to drug therapy resistance in GC with the goal of providing new insights and breakthroughs toward overcoming this formidable obstacle.

A biomimetic lubricating nanosystem for synergistic therapy of osteoarthritis.

Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core-shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications.

The association of systemic immune-inflammation index with lung function, risk of COPD and COPD severity: A population-based study.

PURPOSE: The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were not fully understood. We conducted this cross-sectional, population-based study to investigate the complex association between SII and COPD, lung function, and COPD severity among the US adults. METHODS: Overall, 18,349 participants were included in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The exposure variable was SII, calculated from platelet counts, neutrophil counts, and lymphocyte counts. Weighted univariable and multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were performed to assess the relationship between COPD, lung function, COPD severity and SII. Last, we used a propensity score matching (PSM) analysis to reduce selective bias and validate these relationships. RESULTS: Approximately 1,094 (5.96%) of the participants were diagnosed as COPD. The multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) for the Q2 group (Log-SII > 2.740) was 1.39 (1.16 to 1.68). Before and after matching, multivariable logistic regression models revealed that increased Log-SII levels (SII Logarithmic transformation) associated positively with the risk of COPD. The subgroup analysis showed no interaction between Log-SII and a variety of variables (P for interaction > 0.05). RCS showed a reversed L-shaped relationship between Log-SII with COPD (P for nonlinear = 0.001) in individuals. In addition, we observed negative significant correlations between forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) %, FEV1/FVC% predicted and SII, and reversed U-shaped curve relationships between FEV1, FEV1% predicted and SII. High SII level is associated with severity of COPD, especially at Global Initiative on Obstructive Lung Disease (GOLD) 1 and GOLD 3. CONCLUSIONS: In summary, the Log-SII level is associated with COPD risk, lung function, and COPD severity.

The Microbiome Protocols eBook initiative: Building a bridge to microbiome research.

The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.

[Effects of Different Modified Materials on Soil Fungal Community Structure in Saline-Alkali Soil].

Studying the effects of different modified materials on the physicochemical properties and fungal community structure of saline-alkali soil can provide theoretical basis for reasonable improvement of saline-alkali soil. High-throughput sequencing technology was used to explore the effects of five treatments, namely, control (CK), desulfurization gypsum (T1), soil ameliorant (T2), organic fertilizer (T3), and desulfurization gypsum compounds soil ameliorant and organic fertilizer (T4), on soil physicochemical properties and fungal community diversity, composition, and structure of saline-alkali soil in Hetao Plain, Inner Mongolia. The results showed that compared with those in CK, the contents of available phosphorus, available potassium, organic matter, and alkali hydrolysis nitrogen were significantly increased in modified material treatments, and the T4 treatment significantly decreased soil pH. Modified treatments increased the Simpson and Shannon indexes of fungi but decreased the Chao1 index. The dominant fungi were Ascomycota, Basidiomycota, and Mortierellomycota, and the dominant genera were Mortierella, Conocybe, Botryotrichum, Fusarium, and Pseudogymnoascus. The application of modified materials increased the relative abundance of Ascomycota, Basidiomycota, Fusarium, and Pseudogymnoascus, while decreasing the relative abundance of Mortierellomycota, Chytridiomycota, and Mortierella. LEfSe analysis showed that modified treatments altered the fungal community biomarkers. Correlation analysis showed that pH and available potassium were the main environmental factors affecting fungal community structure. The results can provide scientific basis for improving saline-alkali soil and increasing soil nutrients in Hetao Plain, Inner Mongolia.

Defect-induced discrete breather in dissipative optical lattices with weak nonlinearity.

It is widely believed that the discrete breather (DB) can only be created when the nonlinearity is strong in nonlinear systems. However, we here establish that this belief is incorrect. In this work, we systemically investigate the generation of DBs induced by coupling of the defects and nonlinearity for Bose-Einstein condensates in dissipative optical lattices. The results show that, only in a clean lattice is strong nonlinearity a necessary condition for generating of DB; whereas, if the lattice has a defect, the DBs can also be discovered even in weak nonlinearity, and its generation turns out to be controllable. In addition, we further reveal a critical interval of the defect in weak nonlinearity, within which DBs can be found, while outside DBs do not exist. Furthermore, we also explore the impact of multiple defects on the generation of DBs, and analyze the underlying physical mechanisms of these interesting phenomena. The results not only have the potential to be used for more precise engineering in the DB experiments, but also suggest that the DB may be ubiquitous since the defects and dissipation are unavoidable in real physics.

Improved therapeutic effects on vascular intimal hyperplasia by mesenchymal stem cells expressing MIR155HG that function as a ceRNA for microRNA-205.

Coronary artery bypass grafting (CABG) is an effective treatment for coronary heart disease, with vascular transplantation as the key procedure. Intimal hyperplasia (IH) gradually leads to vascular stenosis, seriously affecting the curative effect of CABG. Mesenchymal stem cells (MSCs) were used to alleviate IH, but the effect was not satisfactory. This work aimed to investigate whether lncRNA MIR155HG could improve the efficacy of MSCs in the treatment of IH and to elucidate the role of the competing endogenous RNA (ceRNA). The effect of MIR155HG on MSCs function was investigated, while the proteins involved were assessed. IH was detected by HE and Van Gieson staining. miRNAs as the target of lncRNA were selected by bioinformatics analysis. qRT-PCR and dual-luciferase reporter assay were performed to verify the binding sites of lncRNA-miRNA. The apoptosis, Elisa and tube formation assay revealed the effect of ceRNA on the endothelial protection of MIR155HG-MSCs. We observed that MIR155HG improved the effect of MSCs on IH by promoting viability and migration. MIR155HG worked as a sponge for miR-205. MIR155HG/miR-205 significantly improved the function of MSCs, avoiding apoptosis and inducing angiogenesis. The improved therapeutic effects of MSCs on IH might be due to the ceRNA role of MIR155HG/miR-205.

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital.

BACKGROUND: Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM: To improve overall understanding of this disease's diagnosis and prognosis. METHODS: We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS: Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION: Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury.

Testicular torsion is a critical urologic condition for which testicular detorsion surgery is considered irreplaceable as well as the golden method of reversal. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat blood reperfusion injuries. Salidroside (SAL) is one of the main effective substances in rhodiola, which has been shown to have antioxidant and antiapoptosis activities. This study was designed to determine whether SAL exerted a protective effect on testicular ischemia-reperfusion (I/R) injury. In this study, the I/R injury model of the testes and reoxygenation (OGD/R) model were used for verification, and SAL was administered at doses of 100 mg/kg and 0.05 mmol/L, respectively. After the experiments, the testicular tissue and TM4 Sertoli cells were collected for histopathologic and biochemical analyses. The results revealed that SAL improves the structure of testicular tissue and regulates the oxidation-antioxidation system. To further understand the molecular mechanisms of SAL in treating testicular I/R injuries, transcriptomics and metabonomics analyses were integrated. The results show that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway is enriched significantly, indicating that it may be the main regulatory pathway for SAL in the treatment of testicular I/R injuries. Thereafter, transfection with Nrf2 plasmid-liposome was used to reverse verify that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway was the main pathway for SAL anti-testicular I/R injury treatment. Thus, it is suggested that SAL can protect against testicular I/R injuries by regulating the Nfr2/HO-1/GPX4 signaling pathway to inhibit ferroptosis and that SAL may be a potential drug for the treatment of testicular I/R injuries.