static-strength-training-method-for-type-2-diabetic-mice

Static Strength Training Method for Type 2 Diabetic Mice

The treatment of type 2 diabetes mellitus (T2DM) is a major difficulty in improving patient health. Exercise is one of the main interventions for T2DM. ...

Nanjing University of Chinese Medicine

Currently, few herbal pharmacokinetic (PK) parameters have been applied successfully for therapeutic monitoring because of the complexity of consistency when there are multiple chemicals and efficacies.

Pharmacokinetic study of precisely representative antidepressant, prokinetic, anti-inflammatory and anti-oxidative compounds from Fructus aurantii and Magnolia Bark.

Endoscopic ultrasound-guided gallbladder fistulization for cholecystolithotomy after endoscopic transpapillary cannulation of the gallbladder in patients with gallstones and common bile duct stones.

The aim of the study was to investigate the clinical effects of abdominal massage on patients with type 2 diabetes mellitus (T2DM) and its influence on the intestinal microflora. We conducted a randomized, controlled clinical trial. A total of 60 patients with T2DM, who met the inclusion criteria, were randomly allocated to the control group, the routine massage group, and the abdominal massage group. The control group received health education and maintained their hypoglycemic drug treatment plan. The routine massage group and the abdominal massage group received different massage interventions. In addition to glucose and lipid metabolism indicators, we quantitatively analyzed the gut microbiota to assess the effects of massage on the intestinal microflora of patients with T2DM. Compared with the control group, the abdominal massage improved levels of glycated hemoglobin, total cholesterol, Enterobacter, and Bifidobacteria with significant differences ( = 0.02,  = 0.03,  = 0.03, and  = 0.03). The comparison within group showed that the levels of the four bacterial genera in the abdominal massage group revealed significant differences before and after treatment ( = 0.006,  < 0.001,  < 0.001, and  = 0.002). The comparison between the routine massage group and the abdominal massage group was not significantly different in all levels of test indices. The abdominal massage group regulated levels of Enterobacter and Lactobacilli to a greater extent than the routine massage group. Additionally, abdominal massage decreased Enterococcus levels. The results of this study showed that abdominal massage has clinical advantages over routine massage. Specifically, this intervention may correct microflora disturbances to a certain extent.

Clinical Effect of Abdominal Massage Therapy on Blood Glucose and Intestinal Microbiota in Patients with Type 2 Diabetes.

Estrogen receptor-positive (ER) breast cancer accounts for the majority of breast cancers diagnosed, and nearly 20% of patients do not respond to endocrine therapy. The pathogenesis of ER breast cancer has not been well elucidated. The enhancer is a -regulatory element that promotes gene transcription and plays an important role in the spatiotemporal expression of cellular genes. Nevertheless, the oncogenic enhancer and its role in the occurrence and progression of cancer remain unclear. Here, we report a novel oncogenic enhancer (named αE  ) for  and reveal its activation mechanism in ER breast cancer. The results demonstrated that αE  enhanced the transcription of downstream genes more than 20-fold. The deletion of the 7-bp region () in αE  significantly downregulated the expression of , resulting in cell nuclear changes, cell-cycle arrest, cell apoptosis, and finally, remarkable inhibition of cell proliferation. In conclusion, the present study discovers a novel oncogenic enhancer αE  (801 base pairs [bp], at Chr8: 127668529-127669329) and offers a remarkable core enhancer target () of αE  for gene therapy of ER breast cancer.

A novel oncogenic enhancer of estrogen receptor-positive breast cancer.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by chronic low-grade inflammation. Previous studies have demonstrated that the gut microbiome can affect the host tissue cells' mRNA N6-methyladenosine (m6A) modifications. This study aimed to understand the role of intestinal flora in ovarian cells inflammation by regulating mRNA m6A modification particularly the inflammatory state in PCOS. The gut microbiome composition of PCOS and Control groups was analyzed by 16S rRNA sequencing, and the short chain fatty acids were detected in patients' serum by mass spectrometry methods. The level of butyric acid was found to be decreased in the serum of the obese PCOS group (FAT) compared to other groups, and this was correlated with increased Streptococcaceae and decreased Rikenellaceae based on the Spearman's rank test. Additionally, we identified FOSL2 as a potential METTL3 target using RNA-seq and MeRIP-seq methodologies. Cellular experiments demonstrated that the addition of butyric acid led to a decrease in FOSL2 m6A methylation levels and mRNA expression by suppressing the expression of METTL3, an m6A methyltransferase. Additionally, NLRP3 protein expression and the expression of inflammatory cytokines (IL-6 and TNF-α) were downregulated in KGN cells. Butyric acid supplementation in obese PCOS mice improved ovarian function and decreased the expression of local inflammatory factors in the ovary. Taken together, the correlation between the gut microbiome and PCOS may unveil crucial mechanisms for the role of specific gut microbiota in the pathogenesis of PCOS. Furthermore, butyric acid may present new prospects for future PCOS treatments.

Short-chain fatty acid-butyric acid ameliorates granulosa cells inflammation through regulating METTL3-mediated N6-methyladenosine modification of FOSL2 in polycystic ovarian syndrome.

Gene therapy offers potentially transformative strategies for major human diseases. However, one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue. Here, we report a novel virus-like nanoparticle, the bioorthgonal engineered virus-like recombinant biosome (reBiosome), for efficient gene therapies of cancer and inflammatory diseases. The mutant virus-like biosome (mBiosome) is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site, and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry. The results show that the reBiosome exhibits reduced virus-like immunogenicity, prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci (like tumor and arthritic tissue). Furthermore, reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems, respectively. In conclusion, this study develops a universal, safe and efficient platform for gene therapies for cancer and inflammatory diseases.

Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy.

This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1β, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1β, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.

[Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation].

Triptolide (TP) is an epoxy diterpene lactone compound isolated and purified from the traditional Chinese medicinal plant  Hook. f., which has been shown to inhibit the proliferation of hepatocellular carcinoma. However, due to problems with solubility, bioavailability, and adverse effects, the use and effectiveness of the drug are limited. In this study, a transferrin-modified TP liposome (TF-TP@LIP) was constructed for the delivery of TP. The thin-film hydration method was used to prepare TF-TP@LIP. The physicochemical properties, drug loading, particle size, polydispersity coefficient, and zeta potential of the liposomes were examined. The inhibitory effects of TF-TP@LIP on tumor cells in vitro were assessed using the HepG2 cell line. The biodistribution of TF-TP@LIP and its anti-tumor effects were investigated in tumor-bearing nude mice. The results showed that TF-TP@LIP was spherical, had a particle size of 130.33 ± 1.89 nm and zeta potential of -23.20 ± 0.90 mV, and was electronegative. Encapsulation and drug loading were 85.33 ± 0.41% and 9.96 ± 0.21%, respectively. The preparation was stable in serum over 24 h and showed biocompatibility and slow release of the drug. Flow cytometry and fluorescence microscopy showed that uptake of TF-TP@LIP was significantly higher than that of TP@LIP ( < 0.05), while MTT assays indicated mean median inhibition concentrations (IC) of TP, TP@LIP, and TF-TP@ of 90.6 nM, 56.1 nM, and 42.3 nM, respectively, in HepG2 cell treated for 48 h. Real-time fluorescence imaging indicated a significant accumulation of DiR-labeled TF-TP@LIPs at tumor sites in nude mice, in contrast to DiR-only or DiR-labeled, indicating that modification with transferrin enhanced drug targeting to the tumor tissues. Compared with the TP and TP@LIP groups, the TF-TP@LIP group had a significant inhibitory effect on tumor growth. H&E staining results showed that TF-TP@LIP inhibited tumor growth and did not induce any significant pathological changes in the heart, liver, spleen, and kidneys of nude mice, with all liver and kidney indices within the normal range, with no significant differences compared with the control group, indicating the safety of the preparation. The findings indicated that modification by transferrin significantly enhanced the tumor-targeting ability of the liposomes and improved their anti-tumor effects in vivo. Reducing its distribution in normal tissues and decreasing its toxic effects suggest that the potential of TF-TP@LIP warrants further investigation for its clinical application.

Transferrin-Modified Triptolide Liposome Targeting Enhances Anti-Hepatocellular Carcinoma Effects.

Virus-like particles (VLPs) have natural structural antigens similar to those found in viruses, making them valuable in vaccine immunization. Furthermore, VLPs have demonstrated significant potential in drug delivery, and emerged as promising vectors for transporting chemical drug, genetic drug, peptide/protein, and even nanoparticle drug. With virus-like permeability and strong retention, they can effectively target specific organs, tissues or cells, facilitating efficient intracellular drug release. Further modifications allow VLPs to transfer across various physiological barriers, thus acting the purpose of efficient drug delivery and accurate therapy. This article provides an overview of VLPs, covering their structural classifications, deliverable drugs, potential physiological barriers in drug delivery, strategies for overcoming these barriers, and future prospects.

Overcoming biological barriers by virus-like drug particles for drug delivery.

Decreased ovarian reserve function is mainly characterized by female endocrine disorders and fertility decline. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been shown to regulate the function of granulosa cells (GCs). The present study explored differentially expressed miRNAs (DEmiRNAs) in patients with diminished ovarian reserve (DOR).

Differential expression of follicular fluid exosomal microRNA in women with diminished ovarian reserve.

PD-1 blockade therapy has made great breakthroughs in treatment of multiple solid tumors. However, patients with microsatellite-stable (MSS) colorectal cancer (CRC) respond poorly to anti-PD-1 immunotherapy. Although CRC patients with microstatellite instability (MSI) or microsatellite instability-high (MSI-H) can benefit from PD-1 blockade therapy, there are still some problems such as tumor recurrence. Tumor-associated macrophages (TAMs), most abundant immune components in tumor microenvironment (TME), largely limit the therapeutic efficacy of anti-PD-1 against CRC. The CSF1/CSF1R pathway plays a key role in regulating macrophage polarization, and blocking CSF1R signaling transduction may be a potential strategy to effectively reprogram macrophages and remodel TME. Here, we found that increasing expression of CSF1R in macrophages predicted poor prognosis in CRC cohort. Furthermore, we discovered a novel potent CSF1R inhibitor, PXB17, which significantly reprogramed M2 macrophages to M1 phenotype. Mechanically, PXB17 significantly blocked activation of PI3K/AKT/mTORC1 signaling, resulting in inhibition of cholesterol biosynthesis. Results from 3D co-culture system suggested that PXB17-repolarized macrophages could induce infiltration of CD8 T lymphocytes in tumors and improve the immunosuppressive microenvironment. In vivo, PXB17 significantly halted CRC growth, with a stronger effect than PLX3397. In particular, PXB17 potently enhanced therapeutic activity of PD-1 mAb in CT-26 (MSS) model and prevented tumor recurrence in MC-38 (MSI-H) model by promoting formation of long-term memory immunity. Our study opens a new avenue for CSF1R in tumor innate and adaptive anti-tumor immunomodulatory activity and suggests that PXB17 is a promising immunotherapy molecule for enhancing the efficacy of PD-1 mAb or reducing tumor recurrence of CRC.

Article	Year
Pharmacokinetic study of precisely representative antidepressant, prokinetic, anti-inflammatory and anti-oxidative compounds from Fructus aurantii and Magnolia Bark. Chemico-biological interactions\| PubMed ID: 31614129	2020
Endoscopic ultrasound-guided gallbladder fistulization for cholecystolithotomy after endoscopic transpapillary cannulation of the gallbladder in patients with gallstones and common bile duct... Journal of digestive diseases\| PubMed ID: 32314462	2020
Clinical Effect of Abdominal Massage Therapy on Blood Glucose and Intestinal Microbiota in Patients with Type 2 Diabetes. Oxidative medicine and cellular longevity\| PubMed ID: 35965680	2022
A novel oncogenic enhancer of estrogen receptor-positive breast cancer. Molecular therapy. Nucleic acids\| PubMed ID: 36159594	2022
Short-chain fatty acid-butyric acid ameliorates granulosa cells inflammation through regulating METTL3-mediated N6-methyladenosine modification of FOSL2 in polycystic ovarian syndrome. Clinical epigenetics\| PubMed ID: 37179374	2023
Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy. Nano-micro letters\| PubMed ID: 37572220	2023
[Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 37802787	2023
Transferrin-Modified Triptolide Liposome Targeting Enhances Anti-Hepatocellular Carcinoma Effects. Biomedicines\| PubMed ID: 37893242	2023
Overcoming biological barriers by virus-like drug particles for drug delivery. Advanced drug delivery reviews\| PubMed ID: 37926218	2023
Differential expression of follicular fluid exosomal microRNA in women with diminished ovarian reserve. Journal of assisted reproduction and genetics\| PubMed ID: 38321265	2024
CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer. Pharmacological research\| PubMed ID: 38432446	2024

Ying Xie

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