The adjuvant treatment role of ω-3 fatty acids by regulating gut microbiota positively in the acne vulgaris.

Objectives:We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.Materials and Methods:We randomly divided the untreated acne patients into two groups with or without ω-3 fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.Results:ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.Conclusion:Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.

How the National Health Insurance Coverage policy changed the use of lenvatinib for adult patients with advanced hepatocellular carcinoma: a retrospective cohort analysis with real world big data.

BACKGROUND: To establish a long-term mechanism to control the cost burden of drugs, the Chinese government organized seven rounds of price negotiations for the national reimbursement drug list (NRDL) from 2016 to the end of 2022. The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the use of lenvatinib as the first-line treatment for advanced hepatocellular carcinoma (HCC) within a specific medical insurance region from the micro perspective of individual patient characteristics. METHODS: The data of HCC patients that received lenvatinib from September 2019 to August 2022 was retrieved from the Medical and Health Big Data Center and longitudinally analyzed. Contingency table chi-square statistics and binary logistic regression analysis were used to compare the differences in the categorical variables. Interrupted time-series (ITS) regression analysis was performed to evaluate the changes in the utilization of lenvatinib over 36 months. Multiple linear regression was used to analyze the impact of receiving lenvatinib on the total hospitalization expenses of hospitalized patients with advanced HCC. RESULTS: A total of 12,659 patients with advanced HCC were included in this study. The usage rate of lenvatinib increased from 6.19% to 15.28% over 36 months (P < 0.001). By controlling the other factors, consistent with this, the probability of patients with advanced HCC receiving lenvatinib increased by 2.72-fold after the implementation of the NHIC policy (OR = 2.720, 95% CI:2.396-3.088, P < 0.001). Older, residency in rural areas, lack of fixed income, treatment at hospitals below the tertiary level, and coverage by urban-rural residents' basic medical insurance (URRBMI) were the factors affecting the use of lenvatinib among patients with advanced HCC (P < 0.05). After the implementation of the NHIC policy, the total hospitalization expenses increased (Beta=-0.040, P < 0.001). However, compared to patients who received lenvatinib, the total hospitalization expenses were higher for those who did not receive the drug (US$5022.07 ± US$5488.70 vs. US$3701.63 ± US$4330.70, Beta = 0.062, P < 0.001). CONCLUSIONS: The NHIC policy has significantly increased the utilization of lenvatinib. In addition, we speculate that establishing multi-level medical insurance systems for economically disadvantaged patients would be beneficial in improving the effectiveness of the NHIC policy in the real world.

Koumine regulates macrophage M1/M2 polarization via TSPO, alleviating sepsis-associated liver injury in mice.

BACKGROUND: Translocator protein (TSPO) is an 18-kDa transmembrane protein found primarily in the mitochondrial outer membrane, and it is implicated in inflammatory responses, such as cytokine release. Koumine (KM) is an indole alkaloid extracted from Gelsemium elegans Benth. It has been reported to be a high-affinity ligand of TSPO and to exert anti-inflammatory and immunomodulatory effects in our recent studies. However, the protective effect of KM on sepsis-associated liver injury (SALI) and its mechanisms are unknown. PURPOSE: To explore the role of TSPO in SALI and then further explore the protective effect and mechanism of KM on SALI. METHODS: The effect of KM on the survival rate of septic mice was confirmed in mouse models of caecal ligation and puncture (CLP)-induced and lipopolysaccharide (LPS)-induced sepsis. The protective effect of KM on CLP-induced SALI was comprehensively evaluated by observing the morphology of the mouse liver and measuring liver injury markers. The serum cytokine content was detected in mice by flow cytometry. Macrophage polarization in the liver was examined using western blotting. TSPO knockout mice were used to explore the role of TSPO in sepsis liver injury and verify the protective effect of KM on sepsis liver injury through TSPO. RESULTS: KM significantly improved the survival rate of both LPS- and CLP-induced sepsis in mice. KM has a significant liver protective effect on CLP-induced sepsis in mice. KM treatment ameliorated liver ischaemia, improved liver pathological injuries, and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and proinflammatory cytokines in serum. Western blotting results showed that KM inhibited M1 polarization of macrophages and promoted M2 polarization. In TSPO knockout mice, we found that TSPO knockout can improve the survival rate of septic mice, ameliorate liver ischaemia, improve liver pathological injuries, and decrease the levels of ALT, AST, and LDH. In addition, TSPO knockout inhibits the M1 polarization of macrophages in the liver of septic mice and promotes M2 polarization and the serum levels of proinflammatory cytokines. Interestingly, in TSPO knockout septic mice, these protective effects of KM were no longer effective. CONCLUSIONS: We report for the first time that TSPO plays a critical role in sepsis-associated liver injury by regulating the polarization of liver macrophages and reducing the inflammatory response. KM, a TSPO ligand, is a potentially desirable candidate for the treatment of SALI that may regulate macrophage M1/M2 polarization through TSPO in the liver.

Sempervirine Inhibits Proliferation and Promotes Apoptosis by Regulating Wnt/ß-Catenin Pathway in Human Hepatocellular Carcinoma.

Gelsemium elegans (G. elegans) Benth., recognized as a toxic plant, has been used as traditional Chinese medicine for the treatment of neuropathic pain and cancer for many years. In the present study, we aim to obtain the anti-tumor effects of alkaloids of G. elegans and their active components in hepatocellular carcinoma (HCC) and the potential mechanism was also further investigated. We demonstrated that sempervirine induced HCC cells apoptosis and the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and down-regulation of cyclin D1, cyclin B1 and CDK2. Furthermore, sempervirine inhibited HCC tumor growth and enhances the anti-tumor effect of sorafenib in vivo. In addition, inactivation of Wnt/ß-catenin pathway was found to be involved in sempervirine-induced HCC proliferation. The present study demonstrated that alkaloids of G. elegans were a valuable source of active compounds with anti-tumor activity. Our findings justified that the active compound sempervirine inhibited proliferation and induced apoptosis in HCC by regulating Wnt/ß-catenin pathway.

Bacterial community dynamics and functional variation during the long-term decomposition of cyanobacterial blooms in-vitro.

Cyanobacterial blooms drastically influence carbon and nutrient cycling in eutrophic freshwater lakes. To understand the mineralization process of cyanobacteria-derived particulate organic matter (CyanPOM), the aerobic degradation of cyanobacterial blooms dominated by Microcystis sp. was investigated over a 95-day microcosm experiment. Approximately 91%, 95% and 83% of the initial particulate organic carbon (POC), particulate organic nitrogen (PON), and particulate organic phosphorus (POP) were decomposed, respectively. The POC:PON ratio gradually increased from 5.9 to 13.5, whereas the POC:POP ratio gradually decreased from 230.3 to 120. These results indicated that the coupling of POC, PON, and POP changed during the decomposition of CyanPOM. Moreover, approximately 29%, 51% and 46% of POC, PON, and POP were mineralized to dissolved organic carbon, NO3-, and PO43-, respectively. Rhodospirillales (10.9%), Burkholderiales (16.5%), and Verrucomicrobiales (14.3%) dominated during the rapid phase (days 0-21), whereas Sphingomonadales (12.8%), Rhizobiales (11.8%), and Xanthomonadales (36.5%) dominated during the slow phase (days 21-50) of CyanPOM decomposition. Nitrospira (16.6%-32.9%) dominated and NO3- increased during the refractory phase (days 50-95), thus suggesting the occurrence of nitrification. Redundancy analysis revealed that bacterial communities during rapid decomposition were distinct from those during the slow and refractory periods. POC:POP, NH4+, and NO3- were the major driving factors for the patterns of bacterial communities. Furthermore, increase in nitrogen metabolism, methane metabolism, amino acid related enzymes and pyruvate metabolism characterized the functional variation of bacterial communities during degradation. Therefore, CyanPOM is an important nutrient source, and its decomposition level shapes bacterial communities.