Red ginseng ameliorates lipotoxicity-induced renal fibrosis in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. AIM OF THE STUDY: This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. MATERIALS AND METHODS: A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-ß1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RESULTS: RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-ß1, and α-SMA, and up-regulated OAT1 and E-cadherin. CONCLUSIONS: RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis.

Experimental analysis of low-dip reverse fault dislocation effects on tunnel site models with different soil properties.

The fortification system of the tunnel structure spanning the active fault, such as the failure mechanism and fault-resistant design (measures), has not been thoroughly established. In this study, the self-developed cross-fault large-scale bedrock dislocation loading device platform is utilized to carry out the model test of the tunnel structure and soil site of sand and cohesive soil when the low-angle reverse fault dislocation occurs, based on the earthquake damage. The results demonstrate that: (1) When the fault is staggered, the segmented flexible joint tunnel segment is more favorable in the cohesive soil site. (2) When compared to the cohesive soil tunnel structure site, the strain change of the tunnel structure in the sandy soil site is greater, with the vault increasing by roughly two times and the arch bottom increasing by nearly six times. After the tunnel is buried, the uplift range of the sand cover layer grows, revealing uneven deformation, and the rupture zone migrates to the footwall; hence, the sand site plays a "add seismic" role in the cross-fault tunnel structure. (3) Knowing the location and shape of the rupture range of the overburden soil caused by bedrock dislocation under different inclination angles and soil properties is required in the design in order to place the buried depth and segment length of the tunnel reasonably and take fault-resistant measures.

Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored.

Inflammatory bowel disease (IBD) is a complex multifactorial chronic inflammatory disease, that includes Crohn's disease (CD) and ulcerative colitis (UC), having progressively increasing global incidence. Disturbed intestinal flora has been highlighted as an important feature of IBD and offers promising strategies for IBD remedies. A brief overview of the variations occurring in intestinal flora during IBD is presented, and the role of the gut microbiota in intestinal barrier maintenance, immune and metabolic regulation, and the absorption and supply of nutrients is reviewed. More importantly, we review drug research on gut microbiota in the past ten years, including research on clinical and natural drugs, as well as adjuvant therapies, such as Fecal Microbiota Transplantation and probiotic supplements. We also summarize the interventions and mechanisms of these drugs on gut microbiota.

Expression Pattern and Prognostic Analysis of Branched-Chain Amino Acid Catabolism-Related Genes in Non-Small Cell Lung Cancer.

BACKGROUND: The purpose of our study is to analyze the expression pattern and prognostic value of catabolism-related enzymes of branched-chain amino acids (BCAAs) in non-small cell lung cancer (NSCLC). METHODS: Differential expression analysis, mutation, copy number variation (CNV), methylation analysis, and survival analysis of BCAAs catabolism-related enzymes in NSCLC were performed using the Cancer Genome Atlas (TCGA) database. RESULTS: Six and seven differentially expressed genes were obtained in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. IL4I1 was located at the core regulatory nodes in the gene co-expression networks of both LUAD and LUSC. The AOX1 mutation rate was the highest in both LUAD and LUSC. For CNV, IL4I1 was up-regulated in both LUAD and LUSC with an increase in copy number, whereas AOX1 and ALDH2 were differentially regulated in the two subtypes of lung cancer. In patients with NSCLC, high expression of IL4I1 was associated with lower overall survival (OS), and low expression of ALDH2 predicted shorter disease-free survival (DFS). ALDH2 expression was related with LUSC survival. CONCLUSIONS: This study explored the biomarkers of BCAAs catabolism related to the prognosis of NSCLC, which provided a theoretical foundation to guide the clinical diagnosis and treatment of NSCLC.

"Platelet-coated bullets" biomimetic nanoparticles to ameliorate experimental colitis by targeting endothelial cells.

Intestinal vascular impairment is critical to the recovery of inflammatory bowel disease (IBD), and targeting vascular endothelial cells is a promising emerging therapeutic option. Considering the natural homing properties of platelets to activated vascular endothelium, platelet membrane-mimetic nanoparticles are expected to achieve precise treatment of IBD. Patchouli alcohol (PA) has proven efficacy in experimental colitis, yet its pharmacochemical properties require improvement to enhance efficacy. The rationale for targeting vascular lesions in IBD was analyzed by network pharmacology, and PA-affecting pathways were predicted. PA-encapsulated bio-nanoparticles (PNPs) were constructed to investigate the efficacy of agents on mouse intestinal microvascular endothelial cells (MIMVEC) inflammation model and dextran sulfate sodium (DSS)-induced acute mouse colitis model. PNPs were endocytosed by MIMVEC in vitro and efficiently enriched in inflamed colon. PNPs significantly alleviated the symptoms of experimental colitis and improved neutrophil infiltration. PNPs down-regulated LPS-induced aberrant elevation of il1ß, tnfα and il6 mRNAs and reduced p65 phosphorylation in MIMVEC. Intracellular calcium expression, mitochondrial respiration and reactive oxygen species expression were also downregulated by PNPs. PNPs amplified the potency of PA as a calcium antagonist, restrained intracellular Ca2+ perturbations to prevent endothelial activation, which may block leukocyte recruitment in vivo to improve colitis.

Tackling Inflammatory Bowel Diseases: Targeting Proinflammatory Cytokines and Lymphocyte Homing.

Inflammatory bowel diseases (IBDs) are characterized by chronic inflammatory disorders that are a result of an abnormal immune response mediated by a cytokine storm and immune cell infiltration. Proinflammatory cytokine therapeutic agents, represented by TNF inhibitors, have developed rapidly over recent years and are promising options for treating IBD. Antagonizing interleukins, interferons, and Janus kinases have demonstrated their respective advantages in clinical trials and are candidates for anti-TNF therapeutic failure. Furthermore, the blockade of lymphocyte homing contributes to the excessive immune response in colitis and ameliorates inflammation and tissue damage. Factors such as integrins, selectins, and chemokines jointly coordinate the accumulation of immune cells in inflammatory regions. This review assembles the major targets and agents currently targeting proinflammatory cytokines and lymphatic trafficking to facilitate subsequent drug development.

Combating liver cancer through GO-targeted biomaterials.

Hydroxycamptothecin (HCPT) is a topoisomerase I inhibitor, and it has been widely used clinically in the treatment of primary liver cancer, gastric cancer, and other tumors. The clinical application of HCPT is limited by its water solubility, and it has certain toxicity to patients with tumor. Therefore, the effective tumor site accumulation of HCPT is necessary. This work studied the inhibitory effect of HCPT on the proliferation and migration of human liver cancer cells (HepG-2) and used carboxymethyl chitosan (CMC) and hyaluronic acid (HA) to modify graphene oxide (GO) as nano-carrier materials, which load HCPT to achieve a drug delivery system for liver tumors with good biocompatibility and high drug loading. HCPT can significantly inhibit proliferation and migration of HepG-2, enhance the release of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The GO-CMC-HA/HCPT drug delivery system enabled HepG-2 to uptake more HCPT, thereby inhibiting its proliferation and improving the efficacy of HCPTin vivoandin vitro. This study explored a potential therapy strategy by preparing a GO-based tumor-targeted drug delivery system.

Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer.

AIM OF THE STUDY: CHE can inhibit the proliferation of lung cancer cells and induce apoptosis. However, despite having in vivo toxicity, CHE has not been thoroughly investigated in term of its in vivo antitumor effect. The present study evaluated the antitumor effect of CHE on non-small cell lung cancer cell line HCC827. METHODS: The antitumor effect of CHE on HCC827 was evaluated, and its potential work mechanism was investigated. CHE long circulation liposomes (CHELPs) modified with polyethylene glycol have been optimized and characterized by in vivo pharmacokinetic studies. A HCC827 xenograft model was developed on BALB/c nude mice for the assessment of the effects of CHE and CHELP. RESULTS: CHE might inhibit HCC827 growth through the ROS/PKC-ϵ/caspase 3 pathway and glycolysis. The optimized CHELP remained stable after storage for 10 days at 4°C and exhibited sustained drug release, showing approximately one-fifteenth of the in vivo clearance rate and 86 times the absorption concentration of free drug. While increasing the bioavailability of CHE, CHELP showed a good therapeutic effect on HCC827 tumor-bearing nude mice and reduced the toxicity of the free drug, improving the safety of CHE. CONCLUSIONS: CHE is a candidate drug for NSCLC, and liposomes are effective in alleviating the toxicity of CHE.

Biological functions of NLRP3 inflammasome: A therapeutic target in inflammatory bowel disease.

Cases of inflammatory bowel disease (IBD), a debilitating intestinal disorder with complex pathological mechanisms, have been increasing in recent years, straining the capacity of healthcare systems. Thus, novel therapeutic targets and innovative agents must be developed. Notably, the NLRP3 inflammasome is upregulated in patients with IBD and/or in animal experimental models. As an innate immune supramolecular assembly, the NLRP3 inflammasome is persistently activated during the pathogenesis of IBD by multiple stimuli. Moreover, this protein complex regulates pro-inflammatory cytokines. Thus, targeting this multiprotein oligomer may offer a feasible way to relieve IBD symptoms and improve clinical outcomes. The mechanisms by which the NLRP3 inflammasome is activated, its role in IBD pathogenesis, and the drugs administered to target this protein complex are reviewed herein. This review establishes that the use of inflammasome-targeting drugs are effective for IBD treatment. Moreover, this review suggests that the value and potential of naturally sourced or derived medicines for IBD treatment must be recognized and appreciated.

Applications of Fourier transform infrared spectroscopy to pharmaceutical preparations.

Introduction: Various pharmaceutical preparations are widely used for clinical treatment. Elucidation of the mechanisms of drug release and evaluation of drug efficacy in biological samples are important in drug design and drug quality control.Areas covered: This review classifies recent applications of Fourier transform infrared (FTIR) spectroscopy in the field of medicine to comprehend drug release and diffusion. Drug release is affected by many factors of preparations, such as drug delivery system and microstructure polymorphism. The applications of FTIR imaging and nano-FTIR technique in biological samples lay a foundation for studying drug mechanism in vivo.Expert opinion: FTIR spectroscopy meets the research needs on preparations to understand the processes and mechanisms underlying drug release. The combination of attenuated total reflectance-FTIR imaging and nano-FTIR accompanied by chemometrics is a potent tool to overcome the deficiency of conventional infrared detection. FTIR shows an enormous potential in drug characterization, drug quality control, and bio-sample detection.

Relationship of spread through air spaces and specific clinicopathological features or poor prognosis of lung adenocarcinoma: A systemic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To assess the specific clinicopathological characteristics as well as prognostic value of prognostic significance of spread through air spaces (STAS) in lung adenocarcinoma. Methods    We systematically searched the databases of PubMed, EMbase and Web of Science databases from their date of inception to March 2019. The quality of the included literature was assessed by the Newcastle-Ottawa scale (NOS). The NOS of the study higher than 6 points was considered as high quality. Software of Stata 12.0 was used for meta-analysis. Results    Twenty retrospective cohort studies involved with totally 6 225 patients were included. Quality of included studies was high with NOS score equal or higher than 6 points. STAS was associated with male sex, ever smoking history, abnormal carcino-embryonic antigen (CEA) level, air bronchogram negative, anaplasticlymphoma kinase (ALK) arrangement positive, epidermal growth factor receptor (EGFR) mutation positive, advanced pathological tumor stage and more invasive pathological adenocarcinoma subtypes. The presence of STAS indicated significantly poor recurrence free survival (RFS) (HR=1.960, 95%CI 1.718-2.237, P<0.001) as well as poor overall survival (OS) (HR=1.891, 95%CI 1.389-2.574, P<0.001). Further subgroup analyses showed that exhibiting tumor size including diameter less than 2 cm (HR=2.344, 95%CI 1.703-3.225,  P<0.001) and diameter over 2 cm (HR=2.571, 95%CI 1.559-4.238, P<0.001), resection type including lobectomy (HR=1.636, 95%CI 1.258-2.127, P<0.001) and sublobar resection (HR=3.549, 95%CI 2.092-6.021, P<0.001) in stageⅠ adenocarcinoma suggested that STAS had a bad effect on RFS. Conclusion    Presence of STAS is associated with more aggressive clinicopathological features and independently associated with worse RFS and OS in lung adenocarcinoma. STAS positive has a negative effect on RFS whatever the tumor size (including the diameter<2 cm or >2 cm) and resection types in stageⅠ adenocarcinoma.

Effect of light with different wavelengths on Nostoc flagelliforme cells in liquid culture.

The effects of lights with different wavelengths on the growth and the yield of extracellular polysaccharides of Nostoc flagelliforme cells were investigated in a liquid cultivation. N. flagelliforme cells were cultured for 16 days in 500 ml conical flasks containing BG11 culture medium under 27 micromol·m-2·s-1 of light intensity and 25 degrees C on a rotary shaker (140 rpm). The chlorophyll a, phycocyanin, allophycocyanin, and phycoerythrin contents in N. flagelliforme cells under the lights of different wavelengths were also measured. It was found that the cell biomass and the yield of polysaccharide changed with different wavelengths of light. The biomass and the yield of extracellular polysaccharides under the red or violet light were higher than those under other light colors. Chlorophyll a, phycocyanin, and allophycocyanin are the main pigments in N. flagelliforme cells. The results showed that N. flagelliforme, like other cyanobacteria, has the ability of adjusting the contents and relative ratio of its pigments with the light quality. As a conclusion, N. flagelliforme cells favor red and violet lights and perform the complementary chromatic adaptation ability to acclimate to the changes of the light quality in the environment.