Mulberry leaf and konjac flour compound dietary fiber improves digestion and metabolism in elderly mice with high-fish-protein diet by regulating gut microbiota structure and intestinal tissue repair.

Ensuring sufficient protein intake, efficient digestion, and optimal absorption are crucial for the elderly. This study aims to investigate the potential of a compound dietary fiber, consisting of mulberry leaf and konjac flour (CMK), to enhance the digestion and absorption of a high-fish-protein diet in elderly mice. Results showed that CMK effectively reduced the number of unique peptide segments, generated short-chain fatty acids (SCFA) in feces, improved the content of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), amino acid, and urea nitrogen in serum, activated the contents of pepsin, trypsin, and erepsin, and enhanced the expression of glutamate dehydrogenase (GDH), peptide transporter 1 (PepT1), and aminopeptidase N (APN). Furthermore, CMK demonstrated its ability to decrease the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), lipopolysaccharide (LPS), and lipopolysaccharide binding protein (LBP), while increase the abundance of beneficial bacteria, such as Lactobacillus and Blautia. In conclusion, CMK proved effective in enhancing the digestion and metabolism of protein in elderly mice through the regulation of gut microbiota structure and intestinal tissue repair.

Characterization of T cell receptor repertoire in penile cancer.

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.

Research progress on rodent models and its mechanisms of liver injury.

The liver is the most important organ for biological transformation in the body and is crucial for maintaining the body's vital activities. Liver injury is a serious pathological condition that is commonly found in many liver diseases. It has a high incidence rate, is difficult to cure, and is prone to recurrence. Liver injury can cause serious harm to the body, ranging from mild to severe fatty liver disease. If the condition continues to worsen, it can lead to liver fibrosis and cirrhosis, ultimately resulting in liver failure or liver cancer, which can seriously endanger human life and health. Therefore, establishing an rodent model that mimics the pathogenesis and severity of clinical liver injury is of great significance for better understanding the pathogenesis of liver injury patients and developing more effective clinical treatment methods. The author of this article summarizes common chemical liver injury models, immune liver injury models, alcoholic liver injury models, drug-induced liver injury models, and systematically elaborates on the modeling methods, mechanisms of action, pathways of action, and advantages or disadvantages of each type of model. The aim of this study is to establish reliable rodent models for researchers to use in exploring anti-liver injury and hepatoprotective drugs. By creating more accurate theoretical frameworks, we hope to provide new insights into the treatment of clinical liver injury diseases.

Hepatoprotective effect of syringin combined with costunolide against LPS-induced acute liver injury in L-02 cells via Rac1/AKT/NF-κB signaling pathway.

Acute liver injury (ALI) leads to abnormal liver function and damage to liver cells. Syringin (syr) and costunolide (cos) are the major extracts from Dolomiaea souliei (Franch.) C.Shih (D. souliei), showing diverse biological functions in various biological processes. We explored the underlying hepatoprotective effects of syr+cos against LPS-induced ALI. Cell viability and proliferation were assessed using an MTT assay and immunofluorescence staining. Flow cytometry analysis was used to detect cell cycle distribution and apoptosis. ELISA was utilized to measure liver function and antioxidant stress indexes. qRT-PCR and western blotting was performed to determine mRNA and protein levels respectively. Using shRNA approach to Rac1 analyzed transcriptional targets. The results showed that syr+cos promoted L-02 cell proliferation, inhibiting the cell apoptosis and blocking cell cycle in G1 and G2/M phase. Syr+cos decreased the production of ALT, AST, LDH, MDA and ROS while increased SOD and CAT activities. Pretreated with syr+cos may decrease expressions of caspase-3,7,9, NF-κB, TNF-α proteins, Cyclin B, CDK1 and p-IκB proteins while p-IκB increased. Silencing of Rac-1 may protect the liver by increasing AKT, S473, T308 and reducing p-AKT proteins. Syr+cos exhibits anti-ALI activity via Rac1/AKT/NF-κB signaling pathway which might act as an effective candidate drug for the treatment of ALI.

Systematic pharmacology-based strategy to explore the mechanism of Semen Strychni for treatment of papillary thyroid carcinoma.

The aim of the study was to investigated the mechanism of Strychnos nux-vomica L. (Semen Strychni, SS) against papillary carcinoma thyroid (PTC) by combined of network pharmacology and experimental verification. By searching the TCMSP, SEA and SwissTarget Prediction database, the main active ingredients and related targets were obtained. Utilizing Venny 2.1.0 String database and Cytoscape 3.7.2 to screened the intersection target and constructed protein-protein interaction (PPI) network diagram. Using R 4.0.4 software carried out the enrichment analysis of GO and KEGG. HPLC was carried out using LC-20A modular HPLC system to identify the bioactive compound brucine present in SS. Molecular docking was performed using Discovery 2019 software. The inhibition rate was detected by CCK8 method. Western blot was used to detect the expression levels of brucine anti-PTC related pathway proteins. 14 active components were screened out, of which 4 main components showed tight relationship with PTC. SS may play the anti-PTC role by acting on two main pathways (TNF signaling pathway and MAPK signaling pathway) and mediating various biological functions. HPLC analysis revealed that brucine was a suitable marker for standardization of the SS. 4 active components exhibit strong binding energy with core protein. Brucine could significantly reduce the activity of BCPAP cells compared with isobrucine, stigmasterol, (+)-catechin. Brucine may reduce the protein expression levels of IL-6, VEGFA, JUN, TP53, 1L1B, PTGS2, BCL2, CASP3, CASP8, and CASP9 while increase the protein expression levels of BAD, cleaved-CASP3, cleaved-CASP8, and cleaved-CASP9 in BCPAP cells, respectively. The active components of SS against PTC mainly include isobrucine, stigmasterol, (+)-catechin, brucine. Among them, brucine exhibits the strongest anti-PTC activity in BCPAP cells, which may reduce the PTC-related protein expression levels. Therefore, SS may exhibits the anti-PTC activities through multiple targets and pathways.

IL-4 functionalized titanium dioxide nanotubes modulate the inflammatory response of macrophages.

Inflammatory response is an essential part of optimal tissue-implant integration and the regeneration process. Due to their highly plastic properties, macrophages display phenotypic changes during inflammatory signaling. Investigating these changes on implant surfaces is essential for evaluating implant stability and longevity. In order to control macrophage polarization, IL-4 was conjugated to titanium dioxide nanotubes (TNTs) through polydopamine, and successful fabrication was checked by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle, respectively. In vitro experiments including immunofluorescence staining, cell proliferation, the expression of genes associated with pro-inflammatory M1 phenotype (tumor necrosis factor-alpha (TNF-α), Interleukin-18 (IL-18)) and cytokines related to the anti-inflammatory M2 phenotype (IL-4 and IL-10), and the production of nitric oxide (NO) and cytokines TNF-α, IL-10 were detected. Macrophage response showed that IL-4 functionalized TNTs favored macrophage polarization towards an anti-inflammatory M2-phenotype. This study provides a new strategy for use in medical devices and the development of advanced nano-biomaterials in immunotherapy applications.

A natural polysaccharide mediated MOF-based Ce6 delivery system with improved biological properties for photodynamic therapy.

Chlorin e6 (Ce6) is a second generation photosensitizer for photodynamic therapy (PDT). However, free Ce6 still has some defects leading to reduced clinical efficacy, such as easy agglomeration in a physiological environment and poor accumulation in tumor tissue. In order to solve these problems, a hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) based Ce6 (ZIF-8@Ce6-HA) therapeutic agent is constructed for PDT by one-pot encapsulation and self-assembly. ZIF-8@Ce6-HA exhibits acceptable encapsulation efficiency, effective cell uptake and good biocompatibility. Moreover, the results of in vitro anticancer experiments demonstrated that the ZIF-8@Ce6-HA group exhibited greater cytotoxicity after irradiation than the free Ce6 group, which caused about 88.4% of HepG2 cells to die since ROS is produced by PDT. Additionally, the data of inductively coupled plasma mass spectrometry indicated that modification of HA increased the blood circulation time and reduced the systemic toxicity of ZIF-8@Ce6. In summary, this work created an interesting Ce6 therapeutic agent for PDT and provided the data for HA regarding the improvement in biocompatibility and biological half-life of metal organic frameworks.

Identification of recombinant intermediates of hepatitis B virus between genotype B and C in vitro.

OBJECTIVE: To detect the recombinant intermediates of hepatitis B virus (HBV) between genotype B and C in vitro. METHODS: Vector Plenti6/V5-D-topo-X was genetically modified by genotype B and C to transfect HepG2 cells. Then the HepG2 cells were amplified and sequence of the nucleic acid after the transinfection was tested and compared with RDP3Beta40 software package and bootscanning procedure in SimPlot program package. RESULTS: Three recombinant intermediates of HBV between genotype B and C were identified in vitro. Genotype C in the precore region plus the core gene spanning nucleotide positions from 1740-1838 to 2443-2485 contributed to the recombination with genotype B. Isolate R1 recombinant intermediate had 2 break points at nt2170-2172 and nt2188-2189. Nucleic acid changed from CAC to TGT and from GA to AC, respectively. Isolate R2 recombinant intermediate had a break point at nt1740-1 838, and 3 bases changed in different nucleic acid sites: from A to T at nt1740, from C to T at nt1753, and from G to A at nt1838, respectively. Isolate R3 recombinant intermediate had a break point at nt2443-2483, and 4 bases changed in different nucleic acid sites: from C to T at nt2443, from A to G at nt2452, from T to C at nt2480, and from C to T at nt2483, respectively. CONCLUSION: The recombinant intermediates of HBV between genotype B and C have been detected in vitro and the changes have been identified in the precore region plus the core gene in genotype B and C.