PuRenDan alleviates type 2 diabetes mellitus symptoms by modulating the gut microbiota and its metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: PuRenDan (PRD) is a traditional Chinese medicine formula comprising five herbs that have been traditionally used to treat type 2 diabetes mellitus (T2DM). While PRD has been shown to be effective in treating T2DM in clinical and animal studies, the mechanisms by which it works on the gut microbiome and metabolites related to T2DM are not well understood. AIM OF THE STUDY: The objective of this study was to partially elucidate the mechanism of PRD in treating T2DM through analyses of the gut microbiota metagenome and metabolome. MATERIALS AND METHODS: Sprague-Dawley rats were fed high-fat diets (HFDs) and injected with low-dose streptozotocin (STZ) to replicate T2DM models. Then the therapeutic effects of PRD were evaluated by measuring clinical markers such as blood glucose, insulin resistance (IR), lipid metabolism biomarkers (total cholesterol, low-density lipoprotein, non-esterified fatty acids, and triglycerides), and inflammatory factors (tumor necrosis factor alpha, interleukin-6 [IL-6], interferon gamma, and IL-1ß). Colon contents were collected, and metagenomics, combined with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry metabolic profiling, was performed to evaluate the effects of T2DM and PRD on gut microbiota and its metabolites in rats. Spearman analysis was used to calculate the correlation coefficient among different microbiota, clinical indices, and metabolites. RESULTS: PRD exhibited significant improvement in blood glucose and IR, and reduced serum levels of lipid metabolism biomarkers and inflammatory factors. Moreover, the diversity and abundance of gut microbiota undergo significant changes in rats with T2DM that PRD was able to reverse. The gut microbiota associated with T2DM including Rickettsiaceae bacterium 4572_127, Psychrobacter pasteurii, Parabacteroides sp. CAG409, and Paludibacter propionicigenes were identified. The gut microbiota most closely related to PRD were Prevotella sp. 10(H), Parabacteroides sp. SN4, Flavobacteriales bacterium, Bacteroides massiliensis, Alistipes indistinctus, and Ruminococcus flavefaciens. Additionally, PRD regulated the levels of gut microbiota metabolites including pantothenic acid, 1-Methylhistamine, and 1-Methylhistidine; these affected metabolites were involved in pantothenate and coenzyme A biosynthesis, histidine metabolism, and secondary bile acid biosynthesis. Correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. CONCLUSION: Our study provides insights into the gut microbiota and its metabolites of PRD therapy for T2DM. It clarifies the role of gut microbiota and the metabolites in the pathogenesis of T2DM, highlighting the potential of PRD for the treatment of this disease.

Biodegradable FePS3 nanoplatform for efficient treatment of osteosarcoma by combination of gene and NIR-II photothermal therapy.

As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.

A retrospective study of Pupingqinghua prescription versus Lianhuaqingwen in Chinese participants infected with SARS-CoV-2 Omicron variants.

Background: Coronavirus disease (COVID-19) seriously endangers global public health. Pupingqinghua prescription (PPQH) is an herbal formula from traditional Chinese medicine used for treatment of SARS-CoV-2 infection. This study aims to evaluate the clinical efficacy and safety of PPQH in Chinese participants infected with the SARS-CoV-2 Omicron variant. Methods: A total of 873 SARS-CoV-2 (Omicron)-infected patients were included. Among them, the patients were divided into the PPQH group (653 cases) and LHQW group (220 cases) according to different medications. The effectiveness indicators (hematological indicators, Ct values of novel Coronavirus nucleic acid tests, and viral load-shedding time) and safety indicators (liver and kidney function and adverse events) were analyzed. Results: There was no significant difference in baseline characteristics between the PPQH group and the LHQW group, except the gender; After the treatment, the levels of IL-5, IL-6, IL-10, NK cells, and INF-α of the patients in the PPQH group showed a downward trend (p < 0.05); The viral load shedding time was 5.0 (5.0, 7.0) in the PPQH group and 5.0 (4.0, 7.0) in the LHQW group; both PPQH and LHQW can shorten the duration of symptoms of fever, cough, and sore throat. The re-positive rate of COVID-19 test was 1.5 % in the PPQH group and 2.3 % in the LHQW group. In terms of safety, the levels of γ-GTT decreased significantly (p < 0.01); gastrointestinal reaction was the primary adverse reaction, and the reaction rate was 4.7 % in the PPQH group and 9.5 % in the LHQW group. Conclusion: PPQH can shorten the length of hospital stay and improve clinical symptoms of patients with SARS-COV-2 (Omicron), and it also has a good safety profile.

[Mechanism of Potentilla discolor in treating UC by regulating mitochondrial autophagy].

To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.

Impact of microsatellite status on negative lymph node count and prognostic relevance after curative gastrectomy.

BACKGROUND AND OBJECTIVES: The impact of microsatellite instability-high (MSI-H) phenotype on lymph node yield after lymphadenectomy has never been discussed in gastric cancer (GC). In this study, we aimed to assess the association of microsatellite status with negative lymph node count (NLNC) as well as its prognostic value. METHODS: We retrospectively analyzed 1491 GC patients and divided them into two groups: MSI-HGC (n = 141 [9.5%]) and microsatellite stability (MSSGC ) (n = 1350 [90.5%]). The NLNC and survival data were compared between the two groups. The log odds of positive lymph nodes (LNs) to negative LNs and the target lymph node examined threshold (TLNT) were calculated in both groups. RESULTS: A statistically significant difference was found in median NLNC (26 vs. 23, p < .001) between MSI-HGC and MSSGC patients. MSI status was an independent factor for NLNC (p < .001). NLNC showed positive prognostic value for cases with metastatic lymph node (LN+ ) in both MSI-HGC and MSSGC groups. The TLNT(90%) for MSI-HGC and MSSGC were 33 and 26, respectively. CONCLUSIONS: MSI-HGC was associated with higher NLNC in GC patients and this was independent of the presence of LN+ . However, more LNs are needed during pathological examination to capture LN+ cases in MSI-HGC.

Traditional Chinese Medicine Regulating Lymphangiogenesis: A Literature Review.

Lymphatic vessels, as an important part of the lymphatic system, form a fine vascular system in humans and play an important role in regulating fluid homeostasis, assisting immune surveillance and transporting dietary lipids. Dysfunction of lymphatic vessels can cause many diseases, including cancer, cardiovascular diseases, lymphedema, inflammation, rheumatoid arthritis. Research on lymphangiogenesis has become increasingly important over the last few decades. Nevertheless, the explicit role of regulating lymphangiogenesis in preventing and treating diseases remains unclear owing to the lack of a deeper understanding of the cellular and molecular pathways of the specific and tissue-specific changes in lymphangiopathy. TCM, consisting of compound extracted from TCM, Injections of single TCM and formula, is an important complementary strategy for treating disease in China. Lots of valuable traditional Chinese medicines are used as substitutes or supplements in western countries. As one of the main natural resources, these TCM are widely used in new drug research and development in Asia. Moreover, as a historical and cultural heritage, TCM has been widely applied to clinical research on lymphangiogenesis leveraging new technologies recently. Available studies show that TCM has an explicit effect on the regulation of lymphatic regeneration. This review aims to clarify the function and mechanisms, especially the inhibitory effect of TCM in facilitating and inhibiting lymphatic regeneration.

Regulatory effect of Garidisan on dysbiosis of the gut microbiota in the mouse model of ulcerative colitis induced by dextran sulfate sodium.

BACKGROUND: Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. METHODS: The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. RESULTS: The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. CONCLUSION: Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.

Garidisan: Improving the Quality of Ulcer Healing in Rats with Ulcerative Colitis.

Garidisan, commonly used in Mongolia to treat ulcerative colitis (UC), contains wild poppy and Artemisia frigida Willd. Clinical evidence shows that Garidisan can effectively treat UC and that recurrence is low. Thus, we evaluated the effects of Garidisan on ulcer healing quality and the regulation of immune balance in rats with experimental UC. UC was induced by immunization with TNBS and Garidisan significantly reduced DAI, CMDI, and HS. H&E staining, SEM, and VG staining showed that Garidisan repaired damaged intestinal mucosa and significantly reduced expression of ICAM-1 and CD105 in regenerated tissues of UC rats. Collagen fibers were significantly fewer as well after treatment. Garidisan elevated EGF, VEGF, bFGF, VEGFR2, and FGFR1 of UC rats, reduced CD3+CD4+/CD3+CD8+ T cell ratios, and increased CD4+Th1/CD4+Th2 cell ratios and IFN-r/IL-4 ratios in peripheral blood of UC rats. In conclusion, Garidisan promoted tissue maturation of regenerated tissues by regulating the immune balance and improved functional maturity of regenerated tissues by reducing collagen formation, promoting maturation of new blood vessels, and increasing expression of growth factors and their receptors.