Poor Glycemic Control Affecting Screening of Prostate Carcinoma.

Introduction Diabetes and cancer are commonly linked together. The possible links include insulin resistance, hyperinsulinemia, hyperglycemia, oxidative stress, and chronic inflammation. These are factors that have potential promoting effects on the progression of cancer in many ways. Measurement of prostate-specific antigen (PSA) is widely applied for early detection of prostate cancer. However, several factors influence serum PSA levels in men including age, benign prostatic hyperplasia, prostatitis, and body mass index (BMI). The risk of several malignancies is increased in diabetes but the risk of prostate carcinoma in diabetic patients is reduced secondary to lowering of testosterone levels during the state of hyperinsulinemia. A negative association between serum PSA levels and metformin use is also an explanation of low cancer prostate incidence with diabetes. Objective The study aims to evaluate the PSA levels in diabetic patients with poor glycemic control i.e., glycated hemoglobin (HbA1c) ≥ 7%) vs good glycemic control (HbA1c < 7%). Materials and methods Samples of PSA in diabetic patients collected in the Department of Biochemistry at Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, were included. The observational study was carried out on clinically diagnosed 318 cases of diabetes attending both the outpatient and inpatient Department, IGIMS, Patna. Six ml venous blood samples were collected from patients after obtaining informed consent and ethical clearance. Patient details regarding age, complete clinical details, and general physical examinations were recorded. Serum levels of PSA, fasting plasma glucose (FPG) and HbA1c were analyzed and values were compared. The serum level of PSA was estimated by the chemiluminescent immunoassay (CLIA) method on an automated immunoassay analyzer in the Department of Biochemistry, maintaining all the quality control precautions using a control, calibrator, and reagent kit. HbA1c estimation was by chromatography technique. Fasting plasma glucose was estimated using the hexokinase method on an automated chemistry analyzer. Statistical analyses were performed using SPSS software, version 16.0 (SPSS Inc., Chicago). The median and interquartile range were calculated for numerical variables. Covariance analysis was used in the comparisons among groups. The Mann-Whitney U test was applied to detect the comparison between the two groups. Significance was determined by the P value. P value<0.05 was considered significant. Result Serum PSA value was found to be higher in (the good glycemic control group) with a median of 0.99 with an interquartile range of 3.14, than in (the bad glycemic control group) with a median of 0.49 with an interquartile range of 3.9, and the difference is statistically significant. The difference is also statistically significant in the subgroup (i) with PSA value <4 ng/ml. In subgroups (ii) and (iii), PSA values 4 ng/ml-8 ng/ml and PSA values >8 ng/ml respectively, no significant differences were found. Conclusion It was found that serum prostate-specific antigen levels have been lower in diabetic patients with poor glycemic control than in good glycemic control. Future studies with a larger sample size and detailed information on diabetes duration and management are recommended.

Three in-one fenestrated approaches of yolk-shell, silver-silica nanoparticles: A comparative study of antibacterial, antifungal and anti-cancerous applications.

Yolk-shell-based silica-coated silver nanoparticles are prominently used in the biomedical field aas well as bare silver nanoparticles for various biological applications. The present work narrates the synthesis and silica coating of metallic silver nanoparticles and investigates their antibacterial, antifungal, and anticancerous activity. Both synthesized nanoparticles were characterized by TEM, and SEM-EDX. The average size of silver nanoparticles was 50 nm, while after coating with silica, the average size of silica-coated silver nanoparticles was 80 nm. The nanoparticles' antibacterial, antifungal, and anticancer properties were comparatively examined in vitro. Agar well diffusion method was employed to explore the antibacterial activity against gram-positive bacteria (Bacillus cereus) and gram-negative bacteria (Escherichia coli) at different concentrations and antifungal activity against Candida Albicans. To understand the minimum concentration of both nanoparticles, we employed the minimum inhibitory concentration (MIC) test, against bacterial and fungal strains, which was dose dependent. We learned that bare silver nanoparticles showed high antibacterial activity, whereas silica-coated silver nanoparticles surpassed their antifungal capability over bare silver nanoparticles against Candida albicans. The anticancer activity of the as-prepared nanoparticles was executed in opposition to the prostate cancer cell (PC-3) line by MTT assay, which showed meaningful activity. Following this, flow cytometry was also effectuated to learn about the number of apoptotic and necrotic cells. The results of this study demonstrate the dynamic anti-cancerous, antibacterial, and antifungal activities of bare silver nanoparticles and silica-coated silver nanoparticles for a long-lasting period.

Synthesis of novel DOTA-/AAZTA-based bifunctional chelators: Solution thermodynamics, peptidomimetic conjugation, and radiopharmaceutical evaluation.

Bifunctional chelators (BFCs), which link metallic radionuclide and a targeting vector, are some of the most crucial components of metallic radionuclide-based radiopharmaceuticals for positron-emission computed tomography (PET) imaging. In this study, we designed and synthesized two versatile BFCs, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA, and we conjugated them with a prostate-specific membrane antigen (PSMA) inhibitor. These two chelators showed high affinity for Ga (III) according to a study of the thermodynamics and kinetics and DFT calculations. The labeled PSMA targeted probes, [68Ga]Ga-p-NCS-Ph-DE4TA-PSMA and [68Ga]Ga-p-NCS-Ph-AAZ4TA-PSMA, maintained excellent stability in vitro, and they exhibited high specific activity when binding to PSMA. A PET/CT imaging study in mice bearing SMMC-7721 hepatocellular carcinoma xenografts demonstrated clear visualization of tumors with a high tumor uptake and low background level, indicating the excellent performance in vivo and specific activity when targeting hepatocellular carcinomas. In summary, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA are leading developmental candidates for PET imaging for tumor diagnosis.

Diplopia and Ptosis: An Unusual Case of Prostate Cancer Metastasis to the Sphenoid Bone Treated With Palliative Radiotherapy.

We report a case of a 72-year-old male who presented to the hospital with a chief complaint of diplopia in the setting of a recent onset of urinary incontinence and right-sided back pain. He was subsequently diagnosed with prostate cancer, notably metastasizing to the right sphenoid bone, causing impingement of the oculomotor nerve. Our case is unique in that the patient's initial presentation of prostate cancer was oculomotor nerve palsy with subsequent histologic analysis of the primary tumor showing both small cell neuroendocrine carcinoma along with adenocarcinoma. Also, the initial routine stroke protocol MRI and computed tomography angiography (CTA) missed the lesion, while gadolinium-enhanced targeted MRI revealed lesions in both the spine and the orbit. This case emphasizes the need for enhanced contrast as well as focused imaging in patients presenting with diplopia with a negative initial workup for stroke. Ptosis can be a sign of metastasis from other cancers and it is important to have a broad differential including metastatic disease in patients' presenting with similar symptoms and negative initial workup who may otherwise be at risk of cancer.

Early prostate-specific antigen response among Black and non-Black patients with advanced prostate cancer treated with apalutamide.

Aim: To assess reduction in prostate-specific antigen (PSA) levels among Black and non-Black patients treated with apalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC) or metastatic castration-sensitive prostate cancer (mCSPC). Patients & methods: Patients were identified from electronic medical data. PSA reduction (≥50%, ≥90% or below 0.2 ng/ml) after apalutamide initiation was assessed. Results: A total of 313 patients with nmCRPC and 260 patients with mCSPC were identified. The majority of patients treated with apalutamide achieved a 90% reduction in PSA regardless of indication or race. The proportion of patients achieving a PSA reduction at any level was similar among Black and non-Black patients and was consistent with apalutamide phase III trials. Conclusion: In routine clinical practice, apalutamide consistently produced reduction in PSA levels in Black and non-Black men with nmCRPC or mCSPC.

Blocking Rice Shoot Gravitropism by Altering One Amino Acid in LAZY1.

Tiller angle is an important trait that determines plant architecture and yield in cereal crops. Tiller angle is partially controlled during gravistimulation by the dynamic re-allocation of LAZY1 (LA1) protein between the nucleus and plasma membrane, but the underlying mechanism remains unclear. In this study, we identified and characterized a new allele of LA1 based on analysis of a rice (Oryza sativa L.) spreading-tiller mutant la1G74V, which harbors a non-synonymous mutation in the predicted transmembrane (TM) domain-encoding region of this gene. The mutation causes complete loss of shoot gravitropism, leading to prostrate growth of plants. Our results showed that LA1 localizes not only to the nucleus and plasma membrane but also to the endoplasmic reticulum. Removal of the TM domain in LA1 showed spreading-tiller phenotype of plants similar to la1G74V but did not affect the plasma membrane localization; thus, making it distinct from its ortholog ZmLA1 in Zea mays. Therefore, we propose that the TM domain is indispensable for the biological function of LA1, but this domain does not determine the localization of the protein to the plasma membrane. Our study provides new insights into the LA1-mediated regulation of shoot gravitropism.

Villous adenoma of the prostatic urethra.

Primary villous adenoma originating from the urinary tract is an infrequent entity. We present a rare case of villous adenoma arising from a prostatic urethra with no sign of malignant transformation. Villous adenoma should be considered as one of the differential diagnoses of urethral lesions, especially if it has similar magnetic resonance imaging features as its colonic counterpart. Due to its potential for malignant transformation, its complete resection is mandatory.

Indigoferavallicola (Fabaceae), a new species from Yunnan, southwest China.

Indigoferavallicola (Fabaceae), a new species is described and illustrated. This plant is only found from two localities in the central Yunnan Province, southwest China. It is characterized by having the prostrate habit, usually 13-17-foliolate leaves and the relatively small (3-5 mm long) flowers. Morphological comparisons with its closest relatives, I.rigioclada, I.franchetii, I.chaetodonta, and I.henryi are also presented.

The Relationships between Plant Developmental Traits and Winter Field Survival in Rye (Secale cereale L.).

Overwintering cereals accumulate low temperature tolerance (LTT) during cold acclimation in the autumn. Simultaneously, the plants adjust to the colder season by making developmental changes at the shoot apical meristem. These processes lead to higher winter hardiness in winter rye varieties (Secale cereale L.) adapted to Northern latitudes as compared to other cereal crops. To dissect the winter-hardiness trait in rye, a panel of 96 genotypes of different origins and growth habits was assessed for winter field survival (WFS), LTT, and six developmental traits. Best Linear Unbiased Estimates for WFS determined from five field trials correlated strongly with LTT (r = 0.90, p < 0.001); thus, cold acclimation efficiency was the major contributor to WFS. WFS also correlated strongly (p < 0.001) with final leaf number (r = 0.80), prostrate growth habit (r = 0.61), plant height (r = 0.34), but showed weaker associations with top internode length (r = 0.30, p < 0.01) and days to anthesis (r = 0.25, p < 0.05). The heritability estimates (h2) for WFS-associated traits ranged from 0.45 (prostrate growth habit) to 0.81 (final leaf number) and were overall higher than for WFS (h2 = 0.48). All developmental traits associated with WFS and LTT are postulated to be regulated by phytohormone levels at shoot apical meristem.

Metastatic Castrate-Resistant Prostate Cancer: A Rare Cause of Bowel Obstruction.

Prostate cancer most commonly metastasizes to bone, lymph nodes, lungs, or liver, but rarely spreads to the large intestine. This case highlights a rare case of castrate-resistant prostate cancer (CRPC) that spread locally to the large intestine and rectum, significant enough to cause bowel obstruction. Metastatic prostate carcinomas are considered an infrequent cause of bowel obstruction.

Synthesis and characterization of reduced graphene oxide using the aqueous extract of Eclipta prostrata.

In this study, biological deoxygenation of graphene oxide (GO) using an Eclipta prostrata phytoextract was performed via the infusion method. The presence of oxide groups on the surface of graphene and removal of oxides groups by reduction were characterized through morphological and structural analyses. Field emission scanning electron microscopy images revealed that the synthesized GO and rGO were smooth and morphologically sound. Transmission electron microscopy images showed rGO developing lattice fringes with smooth edges and transparent sheets. Atomic force microscopy images showed an increase in the surface roughness of graphite oxide (14.29 nm) compared with that of graphite (1.784 nm) due to the presence of oxide groups after oxidation, and the restoration of surface roughness to 2.051 nm upon reduction. Energy dispersive X-ray analysis indicated a difference in the carbon/oxygen ratio between GO (1.90) and rGO (2.70). Fourier-transform infrared spectroscopy spectrum revealed peak stretches at 1029, 1388, 1578, and 1630 cm-1 for GO, and a decrease in the peak intensity after reduction that confirmed the removal of oxide groups. X-ray photoelectron microscopy also showed a decrease in the intensity of oxygen peak after reduction. In addition, thermogravimetric analysis suggested that rGO was less thermally stable than graphite, graphite oxide, and GO, with rGO decomposing after heating at temperatures ranging from room temperature to 600 °C.

Genetic authentication of Eclipta prostrate (Asteraceae) from Penthorum chinense (Penthoraceae) by Sequence Characterized Amplified Region (SCAR) markers

Introduction: For the rapid and accurate genetic identification and authentication of living organisms, improved random amplified polymorphic DNA (RAPD) fragment based development of sequence-characterized amplified region (SCAR) markers is an important genetic technique. Objective: This study aimed to develop SCAR markers for perennial herb Eclipta prostrate (E. prostrate). Methods: Here the RAPD fragments by improved RAPD amplification with primers A11 and N-7 for E. prostrate were cloned into pGEX-T vector, and PCR amplification identified the positive clones. After the enzymatic digestion, they were sequenced with Sanger sequencing. Results: Two SCAR markers were developed, which were very specific to E. prostrate, not found in Penthorum chinense Pursh(P. chinense). The nucleotide sequence search by BLAST GenBank database showed that they are novel in E. prostrate, therefore they were deposited in Genbank with accession number KX671034, KX671035. The markers did not show any identity to other species. Conclusions: Thus, in this study two specific SCAR markers were developed for genetically distinguishing and identifying the plant species E. prostrate from herb P. chinense and others.

Introducción: Verificación genética del arbusto Eclipta prostrate (Asteraceae) (Para la identificación y verificación genética rápida y precisa de organismos vivos, el uso de fragmentos de ADN polimórfico amplificado aleatoriamente (RAPD) mejorado de marcadores de región amplificada caracterizada por secuencia (SCAR) es una técnica genética importante. Objetivo: Este estudio tuvo como objetivo desarrollar marcadores SCAR para la hierba perenne Eclipta postrate (E. postrate). Métodos: En este estudio os fragmentos RAPD mediante amplificación RAPD mejorada con los cebadores A11 y N-7 para E. postrate se clonaron en el vector pGEX-T, y la amplificación por PCR identificó los clones positivos. Después de la digestión enzimática, se realizó una secuenciación Sanger. Resultados: Se desarrollaron dos marcadores SCAR, muy específicos para E. postrate, que no se encuentran en Penthorum chinense Pursh (P. chinense). La búsqueda de las secuencias de nucleótidos con BLAST en GenBank mostró que son nuevos en E. postrate, por lo que fueron depositados en Genbank con los números de acceso: KX671034 y KX671035. Los marcadores no mostraron ninguna identidad a otras especies. Conclusiones: En este estudio se desarrollaron dos marcadores SCAR específicos para distinguir e identificar genéticamente la especie de planta E. postrate de la hierba P. chinense y otras.

Physiological responses and transcriptome analysis of the Kochia prostrata (L.) Schrad. to seedling drought stress.

Kochia prostrata is a good forage plant, which has important economic and ecological value in arid and semi-arid regions of China. Drought is one of the main factors affecting its productivity. At present, there are few studies on the mechanism of drought resistance. In order to reveal the changes of physiological and biochemical indexes, stomatal structure and gene expression profiles of Kochia prostrata under drought treatment, the classical determination method and high-throughput Illumina Hiseq sequencing platform were applied to the control group (CK) and drought treatment group of Kochia prostrata. The results showed that under the condition of moderate to mild drought stress, the SOD activity reached the maximum value of 350.68 U/g min on the 5th day of stress, and under the condition of severe drought stress, the SOD activity reached the maximum on the 2nd day of stress. The accumulation of Proline remained at a high level on the 5th day of stress, and there was at least one epidermal cell interval between the two adult stomatal of the leaf epidermis, so that the evaporation shell of each stomatal did not overlap, it ensures the efficient gas exchange of the stomatal, indicating that the Kochia prostrata has strong drought resistance. A total of 1,177.46 M reads were obtained by sequencing, with a total of 352.25 Gbp data and Q30 of 85%. In the differential gene annotation to the biological process (BP), a total of 261 GO terms were enriched in the up-regulated genes, and a total of 231 GO terms were enriched in the down-regulated genes. The differentially expressed genes (DEGs) were obtained in 27 KEGG metabolic pathways, which laid a foundation for revealing the molecular mechanism of drought tolerance.

In vitro design of mesenchymal to epithelial transition of prostate cancer metastasis using 3D nanoclay bone-mimetic scaffolds.

Nanocomposite scaffolds show extensive applications in regenerative medicine and have shown promise as in vitro analogues of human tissue that can be used for the study of diseases. The complex nature of cancer metastasis is recently investigated using several 3D scaffold models. Herein, we report a polymer-nanoclay-based in vitro tumour model that recapitulates early stage of prostate cancer (PCa) colonization during skeletal metastasis on bone mimetic scaffolds. A unique cell culture system termed as "sequential culture (SC)" has been applied to create a bone-mimetic niche for colonization of PCa cells. Human mesenchymal stem cells (MSCs) were seeded on the bone-mimetic scaffolds, where they differentiated into bone cells and then formed mineralized bone matrix without osteogenic supplements. Further, PCa was seeded on MSCs-seeded scaffolds. Sequentially cultured PCa cells with MSCs formed self-organized multicellular tumoroids with distinct tight cellular junctions and hypoxic core regions. Extensive quantitative reverse transcription-polymerase chain reaction experiments were performed to evaluate the expressions of genes related to osteotropic bone metastasis of PCa. On the nanoclay scaffolds, the MSCs differentiated to mature osteoblasts and epithelial to mesenchymal transition was inhibited whereas mesenchymal to epithelial transition was enhanced, as also the hypoxia increased angiogenesis, and finally, PCa cells initiated osteoblastic lesion. Further, the SC technique has significant effects on expression of key metastasis-related genes. Therefore, the SC-based tumour model can be applied to recapitulate more consistent osteotropic cancer cell behavior in understanding tumour biology. This model also can be implemented for drug screening to target colonization stage of PCa cells in the bone microenvironment.

Decreased HoxD10 Expression Promotes a Proliferative and Aggressive Phenotype in Prostate Cancer.

HoxD10 gene plays a critical role in cell proliferation in the process of tumor development. However, the protein expression level and the function of HoxD10 in prostate cancer remain unknown. Using tissue microarray, we demonstrate that the protein expression of HoxD10 is commonly decreased in prostate cancer tissues (n = 92) compared to adjacent benign prostate tissues (n = 77). Functionally, knockdown of HoxD10 resulted in significant promotion of prostate cancer cell proliferation. Moreover, knockdown of HoxD10 strikingly stimulated prostate tumor growth in a mouse xenograft model. We also found a significant association between decreased immunohistochemical staining of HoxD10 expression and higher Gleason score (P = 0.031) and advanced clinical pathological stage (P = 0.011). An analysis of the Taylor database revealed that decreased HoxD10 expression predicted worse biochemical recurrence (BCR)-free survival of PCa patients (P = 0.005) and the multivariate analyses further supported that HoxD10 might be an independent predictor for BCR-free survival (P = 0.027). Collectively, our data suggest that the loss of HoxD10 function is common and may thus result in a progressive phenotype in PCa. HoxD10 may function as a biomarker that differentiates patients with BCR disease from the ones that are not after radical prostatectomy, implicating its potential as a therapeutic target.

A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses. AIMS OF THE STUDY: To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma. MATERIALS AND METHODS: Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500mgkg-1 concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed. RESULTS: The concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250mgkg-1 of extract, which provided 0.745, 4.22 and 4.30mgkg-1day-1 of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced (P<0.05) respiratory resistance and elastance. Such effects were comparable with those produced by dexamethasone. The total number of inflammatory cells and eosinophils in the bronchoalveolar lavage and the concentrations of interleukin (IL)-4, IL-5 and IL-13 in lung homogenate were significantly reduced (P<0.05) by the methanol extract of E. prostrata. CONCLUSION: The results presented herein demonstrate for the first time the anti-inflammatory activity of E. prostrata in a murine model of asthma, thereby supporting the ethnopharmacological uses of the plant.

Lung, Breast, and Prostate Cancer Patients with Unknown Ethnicity in US Department of Defense Cancer Registry Data: Comparisons to Patients with Known Ethnicity.

INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer death for both men and women in the United States. Several factors can increase one's risk of CRC, including a personal or family history of CRC, a diagnosis or family history of a hereditary colon cancer syndrome, or a diagnosis of chronic inflammatory bowel disease. The purpose of this project was to create a colorectal cancer registry (Co-Care) for individuals with a personal or family history of CRC, and those with disorders of the colon or rectum that are associated with an increased risk for developing CRC. METHODS: To be eligible for the registry, patients either had a personal or family history of CRC, a diagnosis or family history of Lynch syndrome, familial adenomatous polyposis, or a diagnosis of Crohn's colitis or ulcerative colitis with dysplasia. Participants were recruited after seeing their gastroenterologist or genetic counselor, or after undergoing a full or partial colectomy at Mount Sinai Hospital in New York City. Eligible patients who agreed to participate were interviewed by a member of the research staff and asked a wide range of questions pertaining to CRC risk. RESULTS: A total of 224 patients were enrolled in the registry. Participants are mostly white, born in the United States, and married, with a bachelor's or graduate degree, reporting an annual household income of $100,000 or more. The largest portion have a family history of CRC (27.2%), and almost half of participants are of Jewish descent (46.2%) and have undergone full or partial colectomy (48.2%). More than half of participants have neither received genetic counseling (54.5%) nor undergone genetic testing (59.7%). Only 3.6% report that they currently smoke cigarettes, and 41.1% consume alcohol at least once per week. Lastly, 18.3%, 10.3%, and 27.7% of participants report that they currently take aspirin, folic acid/folate pills or tablets, or calcium pills/tablets, respectively. CONCLUSIONS: This registry can improve our understanding of CRC and related diseases, and be used to design future interventions related to disease risk, prognosis, and prevention of CRC.

Molecular Mechanism of Inducing GLC-82 Cells Apoptosis by Ethanol Extract from Wedelia prostrate (Hook.et Arn.) Hemsl / 中国生物工程杂志

Objective:To study the antitumor mechanism of W40,a monomer purified from Wedelia prostrate (Hook.et Arn.) Hemsl.Methods:The effects of W40 on the cell proliferative of GLC-82 cells were detected by MTT assay and colony formation assay.The migratory abilities of GLC-82 cells were observed by wound healing assay.Cell apoptosis was evaluated by Annexin V-FITC/PI staining analysis.The levels of apoptosis-relative proteins and cell proliferation-related proteins,such as Caspase-3,PARP,Stat3 and ERK,were detected by Western blotting.Results:MTF assay showed that W40 had a significant cytotoxic effect on non-small cell lung cancer GLC-82 cells.Colony formation assays showed that W40 significantly inhibited GLC-82 cells proliferation.The migration of GLC-82 cells was inhibited by W40 in a dose-dependent manner.Flow cytometry showed that the apoptotic rate increased gradually in a concentration-dependent manner.W40 down-regulated Stat3 as decreasing p-Stat3 and downstream proteins of Bcl-2 and Mcl-1.At the same time,W40 up-regulated the expression of pro-apoptotic protein Bax,and increased the cleavaged Caspase-9,Caspase-3 and PARP.W40 also down-regulated BRAF / MAPK / ERK signal pathway as decreasing p-BRAF,p-MEK and p-ERK.Conclusions:W40 induced apoptosis by inhibiting BRAF / MAPK / ERK and Stat3 signaling pathways.

The association of diabetes and obesity with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study.

PURPOSE: Few studies have investigated the role of race in the association of diabetes and obesity with prostate cancer aggressiveness. Here we evaluate the independent association between diabetes and obesity with prostate cancer aggressiveness in White Americans and Black Americans. METHODS: Our cross-sectional, case-only study consisted of 1,058 White Americans and 991 Black Americans from the North Carolina-Louisiana Prostate Cancer (PCaP) project. Diabetes status was determined by self-report. Obesity was determined using body mass index and calculated based on anthropometric measurements. High aggressive prostate cancer was defined as Gleason sum ≥8, or prostate-specific antigen >20 ng/ml, or Gleason sum = 7 and clinical stage cT3-cT4. The association between diabetes and obesity with high aggressive prostate cancer at diagnosis was evaluated using multivariable logistic regression and adjusted for potential confounders. RESULTS: Diabetes was not associated with high aggressive prostate cancer in the overall sample (OR 1.04; 95% CI 0.79, 1.37), White Americans (OR 1.00; 95% CI 0.65, 1.57) or Black Americans (OR 1.07; 95% CI 0.75, 1.53). Obesity, independent of diabetes, was positively associated with high aggressive prostate cancer in White Americans (OR 1.98; 95% CI 1.14, 3.43), but not in the overall sample (OR 1.37; 95% CI 0.99, 1.92) or Black Americans (OR 1.09; 95% CI 0.71, 1.67). CONCLUSIONS: Diabetes was not associated with prostate cancer aggressiveness, overall, or in either race group. Obesity, independent of diabetes, was associated with high aggressive prostate cancer only in White Americans.

New Visual Prostate Symptom Score versus International Prostate Symptom Score in Men with Lower Urinary Tract Symptoms: A Prospective Comparision in Indian Rural Population.

INTRODUCTION: Benign prostrate hyperplasia (BPH) is a leading source of healthcare problem in aging men around the world including India. Both International Prostate Symptom Score (IPSS) and New Visual Prostate Symptom Score (VPSS) are used to assess the lower urinary tracts symptoms (LUTSs) in men. The present study was planned to compare these two scores, IPSS and VPSS in Indian rural men prospectively and their efficacy was compared with urodynamic evaluation of the patients. MATERIALS AND METHODS: With Institutional Ethical Committee approval, this study was conducted on 100 patients having LUTS and BPH after obtaining written informed consent. Patients' educational status was noted. All the patients were requested to complete the IPSS and VPSS questionnaire, and they were correlated. The urodynamic study was performed on all the patients with uroflowmeter. Two parameters of uroflowmetry, Qmax (maximum urine flow rate expressed in ml/s) and Qavrg (average urine flow rate expressed in ml/s) were measured and correlated. RESULTS: Most of the patients (55%) in this study were uneducated. Out of 100 patients, 83% were able to fill the VPSS questionnaire without assistance as compared to only 40% patients in IPSS questionnaire (Z = 6.557, P < 0.001). There was a positive correlation between IPSS and VPSS total score in this study (r = 0.453 and P ≤ 0.001). It was noticed that IPSS Question 2 for frequency of urination had a positive correlation with VPSS Question 1 (day time frequency of urination) r = 0.645 (P = 0.000). Similarly, IPSS Question 7 for night frequency when compared with VPSS Question 2 (nocturia); the value for r was found to be 0.536 (P = 0.000). The IPSS Question 5 for straining when compared to the VPSS Question 3, i.e., the question for the strength of stream during micturition; the positive correlation was found to be 0.266 (P = 0.007). There was a negative correlation between IPSS total score and Qavrg with value - 0.368 (P = 0.000) and between IPSS total score and Qmax of - 0.433 (P = 0.000). A negative correlation is also noted between VPSS total score and Qavrg of value 0.497 (P = 0.000) and VPSS total score and Qmax of value - 0.719 (P = 0.000). CONCLUSION: VPSS correlates significantly with the IPSS to quantify the LUTS due to BPH. The VPSS can be used instead of the IPSS for the assessment of symptom severity in men with LUTS, who are illiterate or have limited education.