Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages.

The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.

[Identification of key enzyme genes involved in biosynthesis pathways of lignan and lignin in Eucommia ulmoides based on transcriptome assembly].

Lignan is the main medicinal component of Eucommia ulmoides, and lignin is involved in the defense of plants against diseases and insect pests.They are synthesized from coniferyl alcohol with the help of dirigent(DIR) and peroxidase(POD), respectively.In this study, transcriptome assembly of stems and leaves of E.ulmoides was performed, yielding 112 578 unigenes.Among them, 70 459 were annotated in seven databases.A total of 59 unigenes encodes 11 key enzymes in the biosynthesis pathways of lignin and lignin, of which 11 encode POD and 8 encode DIR.A total of 13 unigenes encoding transcription factors are involved in phenylpropanoid metabolism. Compared with leaves of E.ulmoides, 7 575 unigenes were more highly expressed in stems, of which 462 were involved in phenylpropanoid biosynthesis.Our results extend the public transcriptome dataset of E.ulmoides, which provide valuable information for the analysis of biosynthesis pathways of lignan and lignin in E.ulmoides and lay a foundation for further study on the functions and regulation mechanism of key enzymes in lignan and lignin biosynthesis pathways.

Comparative transcriptomic analysis reveals the regulatory mechanisms of catechins synthesis in different cultivars of Camellia sinensis.

Camellia sinensis (L.) O. Kuntze is used to produce tea, a beverage consumed worldwide. Catechins are major medically active components of C. sinensis and can be used clinically to treat hyperglycaemia, hypertension, and cancer. In this study, we aimed to identify the genes involved in catechins biosynthesis. To this end, we analysed transcriptome data from two different cultivars of C. sinensis using DNBSEQ technology. In total,47,717 unigenes were obtained from two cultivars of C. sinensis, of which 9429 were predicted as new unigenes. In our analyses of the Kyoto Encyclopedia of Genes and Genomes database, 212 unigenes encoding 13 key enzymes involved in catechins biosynthesis were identified; the structures of leucoanthocyanidin reductase and anthocyanidin reductase were spatially modelled. Some of these key enzymes were verified by real-time quantitative polymerase chain reaction, and multiple genes encoding plant resistance proteins or transcription factors were identified and analysed. Furthermore, two microRNAs involved in the regulation of catechins biosynthesis were explored. Differentially expressed genes involved in the flavonoid biosynthesis pathway were identified from pairwise comparisons of genes from different cultivars of tea plants. Overall, our findings expanded the number of publicly available transcript datasets for this valuable plant species and identified candidate genes related to the biosynthesis of C. sinensis catechins, thereby establishing a foundation for further in-depth studies of catechins biosynthesis in varieties or cultivars of C. sinensis.

[Identification of key enzyme genes involved in biosynthesis of steroidal saponins and analysis of biosynthesis pathway in Polygonatum cyrtonema].

Steroidal saponins, which are the characteristic and main active constituents of Polygonatum, exhibit a broad range of pharmacological functions, such as regulating blood sugar, preventing cardiovascular and cerebrovascular diseases and anti-tumor. In this study, we performed RNA sequencing(RNA-Seq) analysis for the flowers, leaves, roots, and rhizomes of Polygonatum cyrtonema using the BGISEQ-500 platform to understand the biosynthesis pathway of steroidal saponins and study their key enzyme genes. The assembly of transcripts for four tissues generated 129 989 unigenes, of which 88 958 were mapped to several public databases for functional annotation, 22 813 unigenes were assigned to 53 subcategories and 64 877 unigenes were annotated to 136 pathways in KEGG database. Furthermore, 502 unigenes involved in the biosynthesis pathway of steroidal saponins were identified, of which 97 unigenes encoding 12 key enzymes. Cycloartenol synthase, the first key enzyme in the pathway of phytosterol biosynthesis, showed conserved catalytic domain and substrate binding domain based on sequence analysis and homology modeling. Differentially expressed genes(DEGs) were identified in rhizomes as compared to other tissues(flowers, leaves or roots).The 2 437 unigenes annotated by KEGG showed rhizome-specific expression, of which 35 unigenes involved in the biosynthesis of steroidal saponins. Our results greatly extend the public transcriptome dataset of Polygonatum and provide valuable information for the identification of candidate genes involved in the biosynthesis of steroidal saponins and other important secondary metabolites.

Coumarin-pi, a new antioxidant coumarin derivative from Paxillus involutus.

Chemical investigation of Paxillus involutus lead to the isolation of a new coumarin derivative coumarin-pi (1), and three known compounds (2-4). The structure of the new compound was elucidated by interpretation of 1D and 2D NMR data. Compound 1 possesses a rare benzofuranylcoumarin skeleton. The isolated compounds were evaluated for antioxidant activities and coumarin-pi (1) exhibited significant activity with IC50 value of 16.3 µg/mL.

[Genetic Screening of Thalassemia among the Couples of Childbearing Age in Ding'an County of Hainan Province and Its Analysis].

OBJECTIVE: To investigate the gene-carrying rate and genetic types of thalassemia among the couples of child-bearing age in Ding'an, Hainan province. METHODS: A total of 1742 couples at child bearing age in the region were screened for thalassemia by detecting the mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). If the sample data of either spouse of couples was tested as MCV＜82 fl and /or MCH＜27 pg, both samples of the couple would be further assayed by hemoglobin electrophoresis. Those samples of HbA2 2.5 % or HbA2＞3.5 % were judged as positive in the preliminary screening, then subjected to genetic diagnosis of thalassemia. RESULTS: 478 cases out of 1 742 couples of child bearing age were diagnosed as thalassemia gene mutation, and the gene-carrying rate was 13.72 %. In those carriers, 42 couples were diagnosed with the same type of thalassemia, accounting for 3.67 %. The gene-carrying rate of α-thalassemia, ß-thalassemia and αß-thalassemia was 9.56%, 3.10% and 1.06 % respectively. CONCLUSION: The Ding'an area in Hainan Province is an area with high incidence of thalassemia, and the main genotype is α-thalassemia, showing a distribution of local characteristics. The government should make efferts to popularise the screening for thalassemia, so as to effectively prevent the birth of children with thalassemia major.

[Analysis of Genetic Screening in Couples of Reproductive Age for Thalassemia in Lingshui Li Autonomous County of Hainan Province].

OBJECTIVE: To investigate the genetic carrier rate of thalassemia and its gene mutation types as well as the distribution characteristics among the people in Lingshui Li autonomous county of Hainan province, so as to provide the basis for making the prevention programs of thalassemia in administrative departments. METHODS: Samples were collected from couples undergoing premarital and pregestational screenings, in which the positive ones in preliminary screening were further tested by genetic diagnoses and the genotypes were analyzed. RESULTS: The rate of thalassemia gene carriers was 19.41% （274/1412） of the couples of childbearing age in Lingshui Li autonomous County of Hainan Province. In these carriers,α-thalassemia accounted for 83.21%（228/274）, ß-thalassemia for 8.03%（22/274）, and both α-and ß-thalassemia gene accounted for 8.76% （28/274）. CONCLUSION: The carrying rate of thalassemia gene in population Lingshui Li autonomous county of Hainan province is high, and its distribution has geographical characteristics,the major type is α-thalassemia. Blood screening and genetic diagnosis of thalassemia should be strengthened, and corresponding measures should be taken to reduce its gene frequency.

A Primary Study of the Antioxidant, Hypoglycemic, Hypolipidemic, and Antitumor Activities of Ethanol Extract of Brown Slimecap Mushroom, Chroogomphus rutilus (Agaricomycetes).

In vivo and in vitro treatments were carried out to investigate the effects of a 95% ethanol extract of Chroogomphus rutilus (CRE) on antioxidant, hypoglycemic, hypolipidemic, and antitumor properties. CRE showed potent radical scavenging activity against DPPH in vitro. It could increase antioxidant enzymatic activities (superoxide dismutase and glutathione peroxidase) and could reduce malondialdehyde content in vivo in mice in which aging was induced by D-galactose. CRE had hypoglycemic activity and could significantly inhibit α-glucosidase activity in vitro and decrease blood glucose concentration in vivo. CRE could decrease the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and increase the high-density lipoprotein cholesterol level in diabetic mice. The MTT assay showed that CRE also had a certain inhibitory effect on the tumor cells. These results suggest that CRE may be beneficial for human health and could be useful for applications in medicine, the food industry, and agriculture.

[Change from inflammation to carcinoma in ulcerative colitis: the role of PTEN/PI3K/AKT].

OBJECTIVE: To detect the changes of expression of PTEN protein and AKT protein in patients with Ulcerative Colitis (UC) in the pathway from inflammation to carcinoma. METHODS: A total of 110 paraffin colorectal sections were examined, which included 65 cases with UC, 25 cases with colorectal cancer and 25 cases with normal tissues. The expression of PTEN protein and AKT protein was detected with immunohistochemistry. RESULTS: (1) The patients with UC had lower expression of PTEN protein and higher expression of AKT than those with normal tissues (P < 0.01). (2) The patients with UC had higher expression of PTEN protein and lower expression of AKT protein than those with colorectal cancer (P < 0.01). (3) With the progress of UC, the expression of PTEN protein decreased while the expression of AKT protein increased (P < 0.01). (4) The expression of PTEN protein was negatively correlated with the expression with AKT protein in patients with UC and colorectal cancer (r = -0. 542 and -0. 674, respectively P < 0.01). CONCLUSION: The change of expressions of PTEN protein and AKT protein might play an important role in the development of UC and colorectal cancer. Decreased PTEN protein and increased AKT protein might be a marker for the early detection of the occurrence of colorectal cancer in patients with UC.

Progress in molecular-genetic studies on congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

BACKGROUND: 11beta-hydroxylase deficiency is one of the main causes of congenital adrenal hyperplasia (CAH). It is caused by the mutation of the CYP11B1 gene that encodes the enzyme. Researches have shown that mutations of the CYP11B1 gene would result in activity decrease or inactivation of the enzyme in classical 11beta-hydroxylase deficiency. DATA SOURCES: Articles on CAH and CYP11B1 gene mutation were retrieved from PubMed and MEDLINE published after 1991. RESULTS: The prevalence, pathophysiology, and molecular-genetic mechanisms were summarized. CONCLUSIONS: The disease is caused by genetic mutations of CYP11B1, and types of the mutations are varied. In classical 11beta-hydroxylase deficiency, genetic mutations of CYP11B1 lead to activity decrease or loss; mutations in unclassical 11beta-hydroxylase deficiency are not definite. And the relationship between genotype and phenotype is not established.

[Screen of early indicators for renal damage in mercury workers].

OBJECTIVE: To study the early indicators for renal damages in mercury workers and the clinical significance. METHODS: Eighty-five mercury workers were divided into 2 experimental groups: the normal & subject-under-surveillance group and the mercury-poisoning group. Sixty-five healthy adults with no mercury exposure history were assigned as the control group. Any subjects with history of renal diseases or concurrent renal diseases were excluded. The results from physical examinations and measurements of HgU, B-Cr, U-Cr, BUN, N-acetyl-beta-D-glucosaminidase (NAG), beta2-microglobulin (beta2-MG), urinary alpha1-microglobulin (alpha1-MG), and retinol-binding protein (RBP) in all the groups were analyzed. RESULTS: The levels of HgU, NAG, alpha1-MG, beta2-MG, and RBP were significantly higher in the experimental groups than in the control group. The levels of NAG, beta2-MG and RBP were significantly higher in the nomal & subject-under-surveillance group than in the control group. However, there was no statistically significant difference between the levels of B-Cr and BUN in the experimental groups and those of the control group. CONCLUSIONS: Long-term exposure to mercury can cause renal damages. The level of NAG, alpha1-MG, beta2-MG, and RBP can be used as sensitive indicators for detecting early renal damages caused by mercury.

[Combined therapy for stage IIIa non-small cell lung cancer].

OBJECTIVE: To evaluate the long-term outcome of combined therapy for stage IIIa non-small cell lung cancer (NSCLC). METHODS: Eight and twelve patients with stage IIIa NSCLC, 662 males and 150 females, aged 58.6 (24-79), underwent surgical resection, 326 of which received pre- and postoperative chemotherapy and/or radiotherapy, and 486 of which received surgery alone. The patients were classified according to the TNM staging, and the specimens of resected cancer were examined pathologically. The clinical data of these patients were analyzed. RESULTS: The overall 5-year survival rate was 16.4%. The 5-year survival rate of the combined therapy group was 23.5%, significantly higher than that of the surgical resection alone group (P < 0.01). The 5-year survival rate was 27.6% for the squamous cell carcinoma (SCC), and 23.5% for adenocarcinoma (AC) in the combined therapy group; and was 115.2% for SCC and 9.9% for AC in the surgical resection alone group (all P < 0.01). CONCLUSION: The curative effectiveness of combined therapy is significantly better than surgical resection alone for stage IIIa NSCLC. However, The combination should be based on the TNM staging and pathological type.

[Second-line Hycamtin in the treatment of lung cancer].

OBJECTIVE: To discuss the therapeutic effect and toxicity of second line Hycamtin for lung cancer patients. METHODS: Ten of these 21 patients had been treated with operation. All these 21 patients received second line Hycamtin treatment; given at the dose of 1.2 mg/m(2) per day, four consecutive days as one cycle and 21 days as one course. A total of 1 - 4 courses were given according to the patient's tolerance. Four of these 21 patients also received combination of cisplatin. RESULTS: Among the 13 un-operated patients, two patients showed CR, six showed PR, three SD and two PD, giving an effective rate of 62%. Among the 8 operated patients, seven showed SD but one developed distant metastasis. The 1-year survival rate was 88%. TOXICITY: leukopenia I-II degree 14 (66.7%), leukopenia III-IV degree 5 (23.8%), thrombocytopenia III-IV degree 1 (4.8%) and one patient died of high fever and neutocytopenia. Nausea 8 (38.1%), vomiting 3 (14.3%) and diarrhea 2 (9.5%) alopecia 4 (19.1%). Were the other side-effects. CONCLUSION: Hycamtin is indicated for second line therapy for lung cancer giving tolerable toxicity.

[Application of vascular surgery in the treatment of thoracic neoplasm].

OBJECTIVE: To investigate superior vena cava (SVC) and anonymous vein resection with prosthesis replacement for lung carcinoma and mediastinal tumor, and to assess the surgical procedure and prognosis. METHODS: Experimental research: Eighteen adult dogs were divided randomly into two groups. Group A (n = 9) underwent blocking of the SVC system, and Group B (n = 9) underwent SVC resection with prosthesis replacement. The SVC pressure and histological changes of brain tissue were measured and evaluated for group A. The histological changes of prosthesis were studied in group B. Clinical research: Fifty-six patients with thoracic neoplasm were studied, of which 42 were lung carcinoma and 14 were mediastinal tumor. Resection of primary lesions and metastatic lymph nodes with replacement of SVC system were performed for all patients. Long-term follow-up was performed. RESULTS: Experimental research: In Group A, the pressure of SVC was higher when both SVC and the azygous vein were blocked as compared to SVC blocking only (P < 0.05); hyperemia and edema of brain tissue were not observed in two-hour obstruction. The inner face of vascular prosthesis was covered with fibrin two months after operation in group B. Vascular endothelial cells were found to grow in it, and there was no thrombosis without anticoagulation. Clinical research revealed that there was no death associated with the operation and there was no early or late obstruction of SVC. The survival rates of the patients with lung carcinoma in 1, 3 and 5 years were 84.2% 40.9% and 38.9% respectively. The patients with mediastinal tumor were all alive except 1 patient who died of metastasis. CONCLUSIONS: Radical resection combined with prosthesis replacement of SVC system extends the indications of thoracic neoplasm resection and improve the long-term survival rate and living qualities of the patients. It may be recommended in the surgical treatment of thoracic tumor.