Actinomycetes in extreme alpine habitat have attracted much attention due to their unique physiological activities and functions. However, little is known about their ecological distribution and diversity. Here, we explored the phylogenetic relationship and physiological heterogeneity of cultivable actinomycetes from near-root soils of different plant communities in the Laohu Ditch (2200 – 4200 m) and Gaize County area (5018 – 5130 m) on the Qinghai-Tibetan Plateau. A total of 128 actinomycete isolates were obtained, 16S rDNA-sequenced and examined for antimicrobial activities and organic acid, H 2 S, diffusible pigments, various extracellular enzymes production. Seventy three isolates of the total seventy eight isolates from the Laohu Ditch, frequently isolated from 2200 to 4200 m, were closely related to Streptomyces spp. according to the 16S rDNA sequencing, while four isolates within the genus Nocardia spp. were found at 2200, 2800, and 3800 m. In addition, one potential novel isolate with 92% sequence similarity to its nearest match Micromonospora saelicesensis from the GenBank database, was obtained at 2200 m. From the Gaize County area, fifty Streptomyces isolates varied in diversity at different sites from 5018 to 5130 m. The investigation of phenotypic properties of 128 isolates showed that 94.5, 78.9, 68, 64.8, 53, 51.6, 50, 36.7, 31.2, and 22.7% of the total isolates produced catalase, lipase 2, urease, protease, H 2 S, lipase 3, amylase, lipase 1, diffusible pigment and organic acid, respectively. The antimicrobial assays of the total isolates revealed that 5, 28, 19, and 2 isolates from Streptomyces spp. exhibited antimicrobial activity against Escherichia coli , Staphylococcus aureus , Candida albicans , and Pseudomonas aeruginosa , respectively. This study intends to bring helpful insights in the exploitation and utilization of alpine actinomycetes for novel bioactive compounds discovery.
Background Peripheral blood cell count ratios, including the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR), have been reported to be prognostic factors in many malignancies as markers of inflammation and immune status. The aim of this study was to determine whether NLR, PLR, or LMR can be clinical response and prognostic biomarkers of non‐surgical esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy. Methods 193 non‐surgical ESCC patients who underwent radiotherapy were retrospectively analyzed. The peripheral blood cell count ratios were obtained before, during (weekly) and at the end of the treatment. Then, we compared the subsequent results with the corresponding pretreatment values and computed the rates of change, which were defined as cNLR, cPLR, and cLMR. Univariate and multivariate Cox regression analyses were used for overall survival (OS). Ordinal logistic regression was used to analyze the clinical response. Results In multivariate analysis, cNLR at week 4(P = .026) and week 5(P = .025) during radiotherapy were significantly associated with OS, along with BMI, tumor stage, tumor length, tumor location, and grade of adverse events. Besides, BMI, tumor stage, tumor length, adverse event grade, cNLR at week 4(P = .044) and week 5(P = .013), and cPLR at week 4(P = .034) and week 5(P = .015) were significantly associated with the clinical response in the multivariate logistic regression analysis. Conclusions The cNLR at weeks 4 and 5 was negatively correlated with the OS and clinical response of non‐surgical ESCC patients treated with radiotherapy. The elevated cPLR at weeks 4 and 5 was only related to poor clinical response.
Background Endophytic actinomycetes, as emerging sources of bioactive metabolites, have been paid great attention over the years. Recent reports demonstrated that endophytic streptomycetes could yield compounds with potent anticancer properties that may be developed as chemotherapeutic drugs. Results Here, a total of 15 actinomycete-like isolates were obtained from the root tissues of Lilium davidii var. unicolor (Hoog) Cotton based on their morphological appearance, mycelia coloration and diffusible pigments. The preliminary screening of antagonistic capabilities of the 15 isolates showed that isolate LRE541 displayed antimicrobial activities against all of the seven tested pathogenic microorganisms. Further in vitro cytotoxicity test of the LRE541 extract revealed that this isolate possesses potent anticancer activities with IC50 values of 0.021, 0.2904, 1.484, 4.861, 6.986, 8.106, 10.87, 12.98, and 16.94 μg/mL against cancer cell lines RKO, 7901, HepG2, CAL-27, MCF-7, K562, Hela, SW1990, and A549, respectively. LRE541 was characterized and identified as belonging to the genus Streptomyces based on the 16S rRNA gene sequence analysis. It produced extensively branched red substrate and vivid pink aerial hyphae that changed into amaranth, with elliptic spores sessile to the aerial mycelia. To further explore the mechanism underlying the decrease of cancer cell viability following the LRE541 extract treatment, cell apoptosis and cell cycle arrest assays were conducted in two cancer cell lines, RKO and 7901. The result demonstrated that LRE541 extract inhibited cell proliferation of RKO and 7901 by causing cell cycle arrest both at the S phase and inducing apoptosis in a dose-dependent manner. The chemical profile of LRE541 extract performed by the UHPLC-MS/MS analysis revealed the presence of thirty-nine antitumor compounds in the extract. Further chemical investigation of the LRE541 extract led to the discovery of one prenylated indole diketopiperazine (DKP) alkaloid, elucidated as neoechinulin A, a known antitumor agent firstly detected in Streptomyces; two anthraquinones 4-deoxy-ε-pyrromycinone (1) and epsilon-pyrromycinone (2) both displaying anticancer activities against RKO, SW1990, A549, and HepG2 with IC50 values of 14.96 ± 2.6 − 20.42 ± 4.24 μg/mL for (1); 12.9 ± 2.13, 19.3 ± 4.32, 16.8 ± 0.75, and 18.6 ± 3.03 μg/mL for (2), respectively. Conclusion Our work evaluated the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 and obtained one prenylated indole diketopiperazine alkaloid and two anthraquinones. Neoechinulin A, as a known antitumor agent, was identified for the first time in Streptomyces. Though previously found in Streptomyces, epsilon-pyrromycinone and 4-deoxy-ε-pyrromycinone were firstly shown to possess anticancer activities. Graphical Abstract
Purpose The relationship between examined lymph nodes (ELN) and survival has been confirmed in several single early-stage malignancies. We studied the association between the ELN count and the long-term survival of T1-2N0M0 double primary non-small cell lung cancer (DP-NSCLC) patients after surgery, based on the Surveillance, Epidemiology and End Results (SEER) database. Methods A total of 948 patients were identified and their independent prognostic factors were analyzed. These factors included the ELN count, which related to overall survival (OS) and the cancer-specific survival (CSS) of synchronous (n = 426) and metachronous (n = 522) T1-2N0M0 DP-NSCLC patients after surgery. Results X-tile analysis indicated that the cutoff value for the sum of ELNs was 22 for both OS and CSS in the synchronous DP-NSCLC group. Patients with a sum of ELNs >22 were statistically more likely to survive than those with ≤22 ELNs. X-tile analysis revealed that the ELN count of the second lesion was related to both OS and CSS in the metachronous DP-NSCLC group. The optimal cutoff value was nine. These results were confirmed using univariate and multivariate Cox regression analyses. Conclusion Our findings indicate that ELN count was highly correlated with the long-term survival of T1-2N0M0 double primary NSCLC patients after surgery.
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