Objective: To explore the association between mediterranean diet (MD) patterns and dental caries among children and adolescents with neurodevelopmental disorders (NDD), so as to provide a basis for developing scientific anti caries strategies related to diet. Methods: From December 2021 to June 2024, a questionnaire survey, a three day 24 hour dietary review survey, oral health examination, physical development measurement and Childhood Autism Rating Scale (CARS) evaluation were conducted involving 147 children and adolescents aged 2-22 years with NDD from nine special education schools and rehabilitation institutions in Tianjin. Group comparisons were carried out using the Mann-Whitney U test, Chi-square test, or Fisher s exact probability method. The correlation between dietary quality and dental caries was analyzed by adopting multiple linear regression analysis and restricted cubic spline. Results: There were 46 children and adolescents (31.3%) in the non dental caries group and 101 children and adolescents (68.7%) in the dental caries group. The number of decayed missing and filled teeth (dmft) was 2.0 (4.0), and the MD score was 4.0 (2.0) points. There were 62 children and adolescents (42.2%) in the low MD scores group and 85 children and adolescents (57.8%) in the high MD scores group. There was no significant difference in MD scores between NDD children in the non dental caries group and those in the dental caries group [nondental caries group:4.0(2.0), dental caries group:4.0(2.0), Z= -0.14, P >0.05]. The MD scores and dmft exhibited increasing and then decreasing trend ( P total =0.02, P non lineary = 0.04 ). Children and adolescents with NDD in the MD high scores group had a lower number of dmft than those in the MD low scores group ( β= -2.00 , 95%CI =-3.39 to -0.62, P <0.05). However, in children and adolescents with NDD and CARS scores ≥30, the above association was insignificant ( β=-0.63, 95%CI=-0.29-0.15, P >0.05). Conclusion Children and adolescents with NDD who have dietary patterns similar to the Mediterranean diet, are found to have fewer dental caries, and this is observed among those with no or mild symptoms of autism spectrum disorder.

Objective To investigate the impact of Qizhi Jiangtang Capsule (QZJT) on renal damage in diabetic nephropathy (DN) mice via NOD like receptors family pyrin domain containing 3/caspase-1/ Gasdermin D (NLRP3/caspase-1/GSDMD) signaling pathway. Methods Mice were randomly allocated into six experimental groups: a normal control group (NC), a diabetic nephropathy model group (DN), a low-dose QZJT treatment group (L-QZJT), a high-dose QZJT treatment group (H-QZJT), a positive control group administered Shenqi Jiangtang Granules (SQJT), and an ML385 group (treated with an inhibitor of nuclear factor erythroid 2-related factor 2, Nrf2). Upon successful model induction, therapeutic interventions were commenced. Renal function impairment in the mice was evaluated through quantification of fasting blood glucose (FBG), 24-hour urinary albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney-to-body mass ratio (K/B). Renal tissue pathology was evaluated using HE and PAS staining. Serum levels of inflammatory cytokines IL-1β and IL-18 were quantified by ELISA. Levels of podocyte markers and proteins involved in relevant pathways were assessed using Western blot analysis. Results Compared with the NC group, FBG, 24 h UAlb, SCr, and BUN were increased in the DN group, and the K/B mass ratio was also increased. In contrast, compared with the DN group, FBG, 24 h UAlb, SCr, and BUN in both the low-dose (L-QZJT) and high-dose Quanzhou Jintang (H-QZJT) groups were decreased, and the K/B mass ratio was decreased as well. The therapeutic efficacy of H-QZJT was comparable to that of Shenqi Jiangtang Granules. QZJT ameliorated renal histopathological injury in DN mouse, increased the protein levels of Nephrin (a podocyte marker), and decreased the protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, and GSDMD-N. After ML385 treatment, renal cells exhibited swelling and morphological changes, the inflammatory infiltrate area was enlarged, the protein levels of NLRP3, ASC, pro-caspase-1, and GSDMD-N were up-regulated, and the levels of IL-1β and IL-18 were increased. Conclusion QZJT may inhibit podocyte pyroptosis by acting on the Nrf2 to regulate the NLRP3/caspase-1/GSDMD pathway, thus improving renal damage in DN mouse.
Animals ; Diabetic Nephropathies/pathology* ; Podocytes/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Pyroptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Signal Transduction/drug effects* ; Mice ; Phosphate-Binding Proteins/genetics* ; Male ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Kidney/pathology* ; Gasdermins

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

Tissue engineering has provided wide applications in the field of breast reconstruction for breast cancer patients. A sufficient blood supply is critical to long-term tissue survival, which is also the key to creating large volume tissue-engineered breasts. Compared with traditional three-dimensional(3D) printing, 3D bioprinting uses bioactive bioinks to print tissue or organ structures to bring related biofunctions. It has become a promising developing direction for recreating functional vascular networks in vitro. The article summarized the recent findings of studies on bioprinting in fabricating vascularized tissue-engineered breasts. Moreover, it has highlighted the possible mechanisms of precise bioprinting of vascular networks and angiogenesis.

Tissue engineering has provided wide applications in the field of breast reconstruction for breast cancer patients. A sufficient blood supply is critical to long-term tissue survival, which is also the key to creating large volume tissue-engineered breasts. Compared with traditional three-dimensional(3D) printing, 3D bioprinting uses bioactive bioinks to print tissue or organ structures to bring related biofunctions. It has become a promising developing direction for recreating functional vascular networks in vitro. The article summarized the recent findings of studies on bioprinting in fabricating vascularized tissue-engineered breasts. Moreover, it has highlighted the possible mechanisms of precise bioprinting of vascular networks and angiogenesis.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

Objective To explore the diagnostic value of serum ficolin-3(FCN3)and collagen triple helix repeat containing-1(CTHRC1)in non-small cell lung cancer(NSCLC)and their relationship with clinicopathological characteristics.Methods From July 2021 to August 2022,73 patients with NSCLC who were admitted to the our Hospital were selected as the study group,and 55 healthy people who came to our hospital for physical examination were regarded as the control group.the serum levels of FCN3 and CTHRC1 were measured by enzyme-linked immunosorbent assay(ELISA);Pearson method was applied to analyze the correlation of serum FCN3 and CTHRC1 levels in NSCLC patients;Logistic regression analysis was applied to analyze the influencing factors of NSCLC;the diagnostic value of serum FCN3 and CTHRC1 levels on the occurrence of NSCLC was analyzed by the ROC curve.Results The levels of serum FCN3 and CTHRC1 in the study group were obviously higher than those in the control group(P＜0.05);the levels of serum FCN3 and CTHRC1 were correlated with the degree of cancer cell differentiation,TNM stage and lymph node metastasis in NSCLC patients(P＜0.05);Pearson method analysis showed that there was a positive correlation between serum FCN3 and CTHRC1 levels in NSCLC patients(r=0.258,P=0.028);Logistic regression analysis showed that serum FCN3 and CTHRC1 were the influencing factors of NSCLC(P＜0.05);the area under the ROC curve of serum FCN3 and CTHRC1 levels in diagnosis of NSCLC was 0.869 and 0.810,respectively,the area under the ROC curve of NSCLC was 0.881,which were better than those of serum FCN3 and CTHRC1.Conclusion The levels of serum FCN3 and CTHRC1 in patients with NSCLC increase,which are related to the degree of cancer cell differentiation,TNM stage and lymph node metastasis,they are risk factor for NSCLC,and the combination of the two is more valuable in diagnosis of NSCLC.