Landscape genetics reveals that adaptive genetic divergence in Pinus bungeana (Pinaceae) is driven by environmental variables relating to ecological habitats.

BACKGROUND: Understanding the genetic basis of local adaptation has long been the concern of biologists. Identifying these adaptive genetic variabilities is crucial not only to improve our knowledge of the genetic mechanism of local adaptation but also to explore the adaptation potential of species. RESULTS: Using 10 natural populations and 12 start codon targeted (SCoT) markers, a total of 430 unambiguous loci were yielded. The Bayesian analysis of population structure clearly demonstrated that the 10 populations of P. bungeana could be subdivided into three groups. Redundancy analysis showed that this genetic divergence was caused by divergence selection from environmental variables related to the ecological habitats of "avoidance of flooding" and "avoidance of high temperature and humidity." LFMM results indicated that Bio1, Bio5, Bio8, Bio12, Bio14, and Bio16, which are related to the ecological habitat of P. bungeana, were correlated with the highest numbers of environment-associated loci (EAL). CONCLUSIONS: The results of EAL characterization in P. bungeana clearly supported the hypothesis that environmental variations related to the ecological habitat of species are the key drivers of species adaptive divergence. Moreover, a method to calculate the species landscape adaptation index and quantify the adaptation potential of species was proposed and verified using ecological niche modeling. This model could estimate climatically suitable areas of species spatial distribution. Taking the results together, this study improves the current understanding on the genetic basis of local adaptation.

Pin1-based diagnostic and therapeutic strategies for breast cancer.

Pin1 is the only known cis-to-trans isomerase that recognizes the phosphorylated pThr/pSer-Pro motifs in many signaling molecules, playing unique roles in the pathogenesis of breast cancer. First, Pin1 is prevalently over-expressed in kinds of breast cancer cell lines and tissues, such as MDA-MB-231 cell, MCF-7 cell, Her2+, ERα+, and basal-like breast cancer subtypes. Second, Pin1 amplifies many oncogenic signaling pathways, inhibits multiple tumor suppressors, promotes the angiogenesis and metastasis of breast cancer cells, and enhances the resistance of breast cancer cells to anti-tumor medicines. Third, inhibiting Pin1 blocks most of these detrimental effects in a great number of breast cancer cell lines. These findings suggest Pin1 as a promising diagnostic biomarker as well as an efficient therapeutic target for breast cancer. It is strongly expected that a Pin1-positive subtype of breast cancers should be extremely concerned and that the therapeutic efficacy of Pin1 inhibitors on breast cancer patients should be evaluated as soon as possible. Nonetheless, Pin1-based therapeutic strategies for breast cancer still deserve some debates. Hence, we give the predictions of several important issues, such as application precondition, side effects, and personalized medication, when Pin1 inhibitors are used in the breast cancer therapy. These proposals are meaningful for the further development of Pin1-based diagnostic and therapeutic strategies in order to conquer breast cancer.

[Minimally invasive low-collar incision in near total thyroidectomy].

OBJECTIVE: To explore the clinical feasibility and features of adopting a low-collar arc-shaped incision for minimally invasive near total thyroidectomy. METHODS: From April 1998 to March 2007, the procedure was accepted by 53 patients with thyroidal nodules, including nodular goiter (n = 34), thyroid adenoma (n = 12) and thyroid carcinoma (n = 7). Near total thyroidectomy was performed through a 2 - 4 cm low-collar horizontal skin incision by conventional instrumentation. RESULTS: The incision yielded excellent cosmetic results because the small and lower incisions were completely hidden by clothing collar. The recurrent laryngeal nerve and parathyroid glands were easily identified and preserved. The mean operation time was 62.2 minutes (range: 58 - 112). No complication occurred. The mean bleeding amount was 25 ml (min: 10, max: 100). The drainage was extracted at Day 2 or 3 postoperatively. The mean postoperative stay was 7.6 days (range: 7 - 12) while the post-operative follow-up 2 months to 9 years. CONCLUSION: Such technique is feasible, safe, minimally invasive, less time-consuming and cosmetically ideal. It is suitable for young and middle-aged women.

Red blood cell distribution width is associated with neuronal damage in acute ischemic stroke.

Elevated red blood cell distribution width (RDW) has been found to be associated with the occurrence of ischemic stroke. However, there is no defined relationship between RDW and neuronal damage in acute ischemic stroke (AIS). This study was designed to determine the relationship between RDW and neuronal damage in AIS patients. A total of 442 consecutive AIS patients from January 2018 to June 2019 were evaluated for neuronal damage, which was estimated by serum neuron-specific enolase (NSE) levels. Red blood cell distribution width-standard deviation (RDW-SD), a parameter that reflects the heterogeneity of red blood cell volume, was also assessed. We evaluated the association between the RDW-SD and serum NSE level through multivariate-adjusted linear regression analysis. Both the serum NSE level and the incidence of high NSE increased according to the increased RDW-SD tertile in AIS patients (p<0.01). There was a positive correlation between RDW-SD and serum NSE levels (r=0.275, 95% CI: 0.187-0.359, p<0.001). The beta coefficients (95% CI) between RDW-SD and serum NSE levels were 0.32 (0.21-0.42, p<0.001) and 0.26 (0.15-0.38, p<0.001), respectively, in AIS patients before and after adjusting for potential confounders. In conclusion, we found a significant positive association between RDW-SD and neuronal damage in AIS patients.

Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression through sponging miR-1271.

Circular RNA (circRNA) is a key regulator in the development and progression of human cancers, however its role in breast cancer tumorigenesis is not well understood. The present study aims to investigate the expression profiles and potential modulation of circRNA on breast cancer carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in breast cancer tissue. Results found circ-ABCB10, was significantly up-regulated in breast cancer tissue. And results were replicated in a larger sample size. In vitro, loss-of-function experiments showed circ-ABCB10 knockdown suppressed the proliferation and increased apoptosis of breast cancer cells. Bioinformatics prediction program predicted the complementary sequence within circ-ABCB10 and miR-1271, which was validated by luciferase reporter assay. Finally, miR-1271 rescued the function of circ-ABCB10 on breast cancer cells, confirming the sponge effect of circ-ABCB10 on miR-1271. Overall, results identified a new functional circ-ABCB10 in breast cancer tumorigenesis, and reveal the important regulatory role of circ-ABCB10 through sponging miR-1271, providing a novel insight for breast cancer pathogenesis.

Mechanisms of CXCR7 induction in malignant melanoma development.

Malignant melanoma (MM) is a highly malignant skin tumor. The mechanism of MM pathogenesis and its signaling pathways are not well characterized. C-X-C chemokine receptor type 7 (CXCR7) has been reported to regulate cancer cell invasion. The present study sought to investigate the effects of CXCR7 on MM development. First, CXCR7 expression levels were assessed in the skin tumor tissue of patients with MM. Then, CXCR7 small hairpin RNA was used in M14 melanoma cells in a Transwell culture model and in a transplanted mouse model to test the effects of CXCR7. In addition, immunohistochemistry staining, reverse transcription-quantitative polymerase chain reaction and western blotting were used. The results revealed that CXCR7 expression levels were significantly higher in MM tissue compared with squamous cell carcinoma or basal cell carcinoma tissue. Knocking down CXCR7 in M14 cells significantly inhibited cell migration and invasion in the Transwell culture model. Furthermore, CXCR7 knockdown also significantly reduced the transplanted tumor size, weight and vascular number in the mouse model. It was concluded that CXCR7 interacts with C-X-C motif chemokine ligand 12 to activate the chemokine receptor signaling pathway, and to increase melanoma cell migration, invasion and development.

Effects of microRNA-374 on proliferation, migration, invasion, and apoptosis of human SCC cells by targeting Gadd45a through P53 signaling pathway.

The present study investigated the effects of microRNA-374 (miR-374) on human squamous cell carcinoma (SCC) cell proliferation, migration, invasion, and apoptosis through P53 signaling pathway by targeting growth arrest and DNA-damage-inducible protein 45 α (Gadd45a). Skin samples were collected from patients with skin SCC and normal skin samples. Expression of miR-374, Gadd45a, P53, P73, P16, c-myc, bcl-2, Bax, caspase-3, and caspase-9 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. A431 and SCL-1 cells were divided into blank, negative control (NC), miR-374 mimics, miR374 inhibitors, siRNA-Gadd45a, and miR-374 inhibitors + siRNA-Gadd45a groups. Their proliferation, migration, invasion, cell cycle, and apoptosis were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. SCC skin tissues exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased levels of Gadd45a, P53, c-myc, and Bcl-2 compared with the normal skin tissues. The miR-374 inhibitors group exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased expression of Gadd45a, P53, c-myc, and Bcl-2, enhanced cell proliferation, migration, and invasion, and reduced apoptosis compared with the blank and NC groups; the miR-374 mimics group followed opposite trends. Compared with the blank and NC groups, the miR-374 inhibitors + siRNA-Gadd45a group showed decreased miR-374 level; the siRNA-Gadd45a group showed elevated levels of P73, P16, Bax, caspase-3 and caspase-9, decreased levels of Gadd45a, P53, c-myc, and Bcl-2, reduced cell proliferation, migration, and invasion, and accelerated apoptosis. miR-374 induces apoptosis and inhibits proliferation, migration, and invasion of SCC cells through P53 signaling pathway by down-regulating Gadd45a.

[Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients].

OBJECTIVE: To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients. METHODS: Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01). CONCLUSION: JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid.

Pin1 liberates the human immunodeficiency virus type-1 (HIV-1): Must we stop it?

Acquired immune deficiency syndrome (AIDS) is mainly caused by the human immunodeficiency virus type-1 (HIV-1). To our knowledge, this is the first review focusing on the vital role of Pin1 in the infection of HIV-1 and the development of AIDS. We and others have demonstrated that Pin1, the only known cis-to-trans isomerase recognizing the pThr/pSer-Pro motifs in proteins, plays striking roles in several human diseases. Interestingly, recent evidence gradually indicates that Pin1 regulates several key steps of the life cycle of HIV-1, including the uncoating of the HIV-1 core, the reverse transcription of the RNA genome of HIV-1, and the integration of the HIV-1 cDNA into human chromosomes. Whereas inhibiting Pin1 suppresses all of these key steps and attenuates the replication of HIV-1, at the same time different PIN1 gene variants are correlated with the susceptibility to HIV-1 infection. Furthermore, Pin1 potentially promotes HIV-1 infection by activating multiple oncogenes and inactivating multiple tumor suppressors, extending the life span of HIV-infected cells. These descriptions suggest Pin1 as a promising therapeutic target for the prevention of HIV-1 and highlight the possibility of blocking the development of AIDS by Pin1 inhibitors.

Correlation between the expression of S100A4 and the efficacy of TAC neoadjuvant chemotherapy in breast cancer.

The aim of this study was to investigate the correlation between the expression of S100A4 and the efficacy of neoadjuvant chemotherapy in breast cancer. A total of 65 patients with invasive breast cancer were treated with neoadjuvant chemotherapy using the TAC regimen. The expression of S100A4 was detected by an immunohistochemical two-step method prior to treatment, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy. Pathological evaluations of the chemotherapy were performed using the Miller and Payne (MP) grading system and their correlation with the changes of S100A4 expression during and after the treatment were explored. Between pre-neoadjuvant chemotherapy and 4 cycles post-chemotherapy, there was a significant difference in the expression of S100A4 (P<0.05); S100A4 expression was associated with neoadjuvant chemotherapy. However, between pre-neoadjuvant chemotherapy and 2 cycles post-chemotherapy, there was no significant difference in the expression of S100A4 (P>0.05). The intensity and changes of S100A4 expression were positively correlated with the efficacy of neoadjuvant chemotherapy (r=0.259, P<0.05). When patients with an MP grade of I or II following the second cycle of neoadjuvant chemotherapy were continually treated with the original chemotherapy for another 2 cycles, the desired effect was generally not achieved. S100A4 may be used as a predictor of the efficacy of neoadjuvant chemotherapy in breast cancer, guiding the formulation of individualized programs to improve the effectiveness of the treatment. For patients with an MP grade level of I or II after 2 cycles of neoadjuvant chemotherapy, the use of alternative chemotherapy regimens should be considered.

[Analysis of the factors contributing to diabetes insipidus after surgeries for craniopharyngiomas].

OBJECTIVE: To analyze the factors contributing to the occurrence of diabetes insipidus after operations for craniopharyngiomas. METHODS: A total of 121 cases of diabetes insipidus following surgeries for craniopharyngiomas were retrospectively analyzed and the factors associated with postoperative diabetes insipidus were analyzed. RESULTS: The incidence of diabetes insipidus was 27.3% (33/121 cases) before the operation, 89.9% (107/1119) early after the operation and 39.8%(37/93) in later stages after the operation. The occurrence of early postoperative diabetes insipidus showed a significant relation to the classification and calcification of the craniopharyngioma. Patients with supradiaphragmatic and extraventricular tumors had the lowest incidence of postoperative diabetes insipidus. Late postoperative diabetes insipidus was closely correlated to such factors as age, classification of craniopharyngioma, and intraoperative treatment of the pituitary stalk, but not to the scope of tumor resection or tumor calcification. Late diabetes insipidus was more frequent in children and patients with severed pituitary stalk. The incidence of late postoperative diabetes insipidus was significantly higher in patients with supradiaphragmatic and extra-intraventricular tumors than in those with tumors beneath the diaphragma sellae and extraventricular tumors. CONCLUSIONS: Postoperative diabetes insipidus following surgeries for craniopharyngiomas is closely related to the tumor classification, calcification and pituitary stalk protection.

[Growth of craniopharyngioma involving the third ventricular floor in relation to the hypothalamus].

OBJECTIVE: To investigate the growth of craniopharyngioma involving the third ventricular floor with regard to the hypothalamus by detecting expressions of leukocyte common antigen (CD45) and intercellular adhesion molecule (ICAM-1) in the tumor tissue. METHODS: The expressions of CD45 and ICAM-1 proteins in 30 craniopharyngioma samples with third ventricular floor involvement were detected by SP immunohistochemistry. RESULTS: The inflammations labeled by CD45 were identified commonly in the craniopharyngioma tissues involving the third ventricular floor. The expression of ICAM-1 was mainly in the inner tumor cells and interstitial cells, but not detected in the basilar tumor cells growing toward the third ventricular floor. Adamantinomatous craniopharyngiomas showed markedly higher CD45 and ICAM-1 expressions than squamous papillary tumors (P<0.05). CONCLUSION: Inflammatory adhesion largely characterizes the growth of the craniopharyngioma tissues involving the third ventricular floor toward the hypothalamus without the tendency of invasion. The difference in the inflammation between the two types of craniopharyngioma may affect the prognosis of the patients.

Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol.

AIM: To study whether urotensin II (UII), a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol (ISO). METHODS: Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO group, and group 3 was the ISO+UII group. In groups 2 and 3, ISO (5 mg x kg(-1) x d(-1)) was given (sc) once daily for 7 d. Group 3 was also given UII in the first day [3 nmol/kg (5 microg/kg), iv], followed by sc (1.5 microg/kg) twice daily. Group 1 received 0.9% saline. UII receptor (UT) mRNA expression was determined by RT-PCR. The contents of UII and angiotensin II (Ang II) were determined by radioimmunoassay. In vitro, the effects of UII on DNA/collagen synthesis of cardiac fibroblasts were determined by [3H]thymidine/[3H]proline incorporation. RESULTS: The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UII and ventricular Ang II, compared with the control group (P< 0.01). ISO induced significant myocardial fibrogenesis. Moreover, UII+ISO co-treatment significantly increased the changes of biochemical markers of injury and the degree of cardiac hypertrophy and fibrosis. In vitro, 5 x 10(-9 )-5 x 10(-7 ) mol/L UII stimulated [3H]thymidine/[3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner (P< 0.01). CONCLUSION: These results suggest that UII was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.