Assessing diaphragm function status is vital for diagnosing and treating acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Diaphrag-matic ultrasound has become increasingly important due to its non-i...Assessing diaphragm function status is vital for diagnosing and treating acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Diaphrag-matic ultrasound has become increasingly important due to its non-invasive nature,absence of radiation exposure,widespread availability,prompt results,high accuracy,and repeatability at the bedside.The diaphragm is a crucial respiratory muscle.Decline or dysfunction of the diaphragm can lead to dyspnea and even respiratory failure in AECOPD patients.In this editorial,we comment on an article,retrospectively analyzed ninety-four acute exacerbations of chronic obstructive pulmonary disease patients who received mechanical ventilation from January 2022 to December 2023.The study found that the diaphragm thickening fraction,an index from diaphragm ultrasound,can better predict the outcome of non-invasive ventilation in patients with AECOPD.The value of non-invasive ventilation in treating respiratory failure caused by AECOPD has been widely acknowledged.Diaphragmatic dysfunction diagnosed with ultrasound is asso-ciated with prolonged mechanical ventilation and weaning times and higher mortality.展开更多
A two-compartment model of the universe is proposed to further refine Albert Einstein’s insight into curvature of space and the energy tensor. The two compartments are energy contained by a shell prism. The model all...A two-compartment model of the universe is proposed to further refine Albert Einstein’s insight into curvature of space and the energy tensor. The two compartments are energy contained by a shell prism. The model allows for a non-unification of fundamental forces with gravity resulting from the curvature of a space-time prism. Carrier forces travel within the prism and particles emerge from the prism. Giving a thickness to the manifold negates infinity and will allow solutions at both microscopic and cosmic levels. Geometry is the link between quantum mechanics and general relativity. Negative entropy, as proposed by Erwin Schrödinger, gives order to particles and the cosmic. The source of this energy is in the shell of the containment vessel. The acceleration of the expansion of the universe occurred when energy within the container transformed into mass, warping the space-time container and causing an explosion of the container. Star movement is explained by the surface tension of the prism of space-time.展开更多
BACKGROUND Hip dysplasia(HD)is characterized by insufficient acetabular coverage of the femoral head,leading to a predisposition for osteoarthritis.While radiographic measurements such as the lateral center edge angle...BACKGROUND Hip dysplasia(HD)is characterized by insufficient acetabular coverage of the femoral head,leading to a predisposition for osteoarthritis.While radiographic measurements such as the lateral center edge angle(LCEA)and Tönnis angle are essential in evaluating HD severity,patient-reported outcome measures(PROMs)offer insights into the subjective health impact on patients.AIM To investigate the correlations between machine-learning automated and manual radiographic measurements of HD and PROMs with the hypothesis that artificial intelligence(AI)-generated HD measurements indicating less severe dysplasia correlate with better PROMs.METHODS Retrospective study evaluating 256 hips from 130 HD patients from a hip preservation clinic database.Manual and AI-derived radiographic measurements were collected and PROMs such as the Harris hip score(HHS),international hip outcome tool(iHOT-12),short form(SF)12(SF-12),and Visual Analogue Scale of the European Quality of Life Group survey were correlated using Spearman's rank-order correlation.RESULTS The median patient age was 28.6 years(range 15.7-62.3 years)with 82.3%of patients being women and 17.7%being men.The median interpretation time for manual readers and AI ranged between 4-12 minutes per patient and 31 seconds,respectively.Manual measurements exhibited weak correlations with HHS,including LCEA(r=0.18)and Tönnis angle(r=-0.24).AI-derived metrics showed similar weak correlations,with the most significant being Caput-Collum-Diaphyseal(CCD)with iHOT-12 at r=-0.25(P=0.042)and CCD with SF-12 at r=0.25(P=0.048).Other measured correlations were not significant(P>0.05).CONCLUSION This study suggests AI can aid in HD assessment,but weak PROM correlations highlight their continued importance in predicting subjective health and outcomes,complementing AI-derived measurements in HD management.展开更多
Cholangiocarcinoma is a rare malignancy of the biliary tract. Key factors in determining therapeutic options include knowledge of tumor extent, anatomy and obtaining tissue diagnosis. Endoscopically, there are three m...Cholangiocarcinoma is a rare malignancy of the biliary tract. Key factors in determining therapeutic options include knowledge of tumor extent, anatomy and obtaining tissue diagnosis. Endoscopically, there are three modalities available to make the diagnosis of cholangiocarcinoma. These include endoscopic retrograde cholangiopancreatography, endoscopic ultrasound with fine needle aspiration and cholangioscopy. Management of cholangiocarcinoma endoscopically is typically confined to stent placement for palliative purposes or as a bridge to surgery. In this article, we will review the endoscopic techniques available for the diagnosis and management of cholangiocarcinoma.展开更多
Cholangiocarcinoma continues to be a challenging disease to treat. Systemic therapy is used in unresectable disease, disease progression after surgery, and in the palliative setting. Unfortunately, results of multiple...Cholangiocarcinoma continues to be a challenging disease to treat. Systemic therapy is used in unresectable disease, disease progression after surgery, and in the palliative setting. Unfortunately, results of multiple phase Ⅱ trials have rarely yielded positive results. As data on the molecular carcinogenesis of cholangiocarcinoma is developing, we are more able to understand the disease process and can use this understanding to create unique targeted therapies. We reviewed the role of c-Met/ hepatocyte growth factor (HGF) in the development of cholangiocarcinoma. Furthermore, we explored the use of the c-Met guided cascade as a target to treat cholangiocarcinoma. We reviewed the current use and options for future development of c-Met agents to treat this disease.展开更多
Normal and neoplastic growth of the prostate gland are dependent on androgen receptor (AR) expression and function. Androgenic activation of the AR, in association with its coregulatory factors, is the classical pat...Normal and neoplastic growth of the prostate gland are dependent on androgen receptor (AR) expression and function. Androgenic activation of the AR, in association with its coregulatory factors, is the classical pathway that leads to transcriptional activity of AR target genes. Alternatively, cytoplasmic signaling crosstalk of AR by growth factors, neurotrophic peptides, cytokines or nonandrogenic hormones may have important roles in prostate carcinogenesis and in metastatic or androgen-independent (AI) progression of the disease. In addition, cross-modulation by various nuclear transcription factors acting through basal transcriptional machinery could positively or negatively affect the AR or AR target genes expression and activity. Androgen ablation leads to an initial favorable response in a significant number of patients; however, almost invariably patients relapse with an aggressive form of the disease known as castration-resistant or hormone-refractory prostate cancer (PCa). Understanding critical molecular events that lead PCa cells to resist androgen-deprivation therapy is essential in developing successful treatments for hormone-refractory disease. In a significant number of hormone-refractory patients, the AR is overexpressed, mutated or genomically amplified. These genetic alterations maintain an active presence for a highly sensitive AR, which is responsive to androgens, antiandrogens or nonandrogenic hormones and collectively confer a selective growth advantage to PCa cells. This review provides a brief synopsis of the AR structure, AR coregulators, posttranslational modifications of AR, duality of AR function in prostate epithelial and stromal cells, AR-dependent signaling, genetic changes in the form of somatic and germline mutations and their known functional significance in PCa cells and tissues.展开更多
Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage,...Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts(ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts(TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems(DDS), co-administration of platelet-rich plasma(PRP), and pretreatment with chondroitinase ABC(Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix(ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia(DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.展开更多
Aim:To determine the effect of saposin C (a known trophic domain of prosaposin) on proliferation,migration and invasion,as well as its effect on the expression of urokinase plasmonogen activator (uPA),its receptor (uP...Aim:To determine the effect of saposin C (a known trophic domain of prosaposin) on proliferation,migration and invasion,as well as its effect on the expression of urokinase plasmonogen activator (uPA),its receptor (uPAR) and matrix metalloproteinases (MMP)-2 and -9 in normal and malignant prostate cells.In addition,we tested whether saposin C can activate p42/44 and stress-activated protein kinase/c-Jun NH_2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) superfamily.Methods:We employed West- ern blot analysis,phospho-specific antibodies,cell proliferation assay,reverse transcriptase-polymerase chain reaction, in vitro kinase assays and migration and invasion to determine the effect of saposin C on various biological behaviors of prostate stromal and cancer cells.Results:Saposin C,in a cell type-specific manner,upregulates uPA/uPAR and immediate early gene c-Jun expression,stimulates cell proliferation,migration and invasion and activates p42/44 and SAPK/JNK MAPK pathways in prostate stromal and cancer cells.Normal prostate epithelial cells were not responsive to saposin C treatment in the above studies.Conclusion:Saposin C functions as a multipotential modulator of diverse biological activities in prostate cancer and stromal cells.These results strongly suggest that saposin C functions as a potent growth factor for prostatic cells and may contribute to prostate carcinogenesis and/or the development of hormone-refractory prostate cancer.展开更多
Cholangiocytes are the epithelial cells that line the biliary tree.In the adult liver,they are a mitotically dormant cell population,unless ductular reaction is triggered by injury.The ability of cholangiocytes to pro...Cholangiocytes are the epithelial cells that line the biliary tree.In the adult liver,they are a mitotically dormant cell population,unless ductular reaction is triggered by injury.The ability of cholangiocytes to proliferate is important in many different human pathological liver conditions that target this cell type,which are termed cholangiopathies(i.e.primary biliary cirrhosis,primary sclerosing cholangitis and biliary atresia).In our article,we provide background information on the morphological and functional heterogeneity of cholangiocytes,summarize what is currently known about their proliferative processes,and briefly describe the diseases that target these cells.In addition,we address recent findings that suggest cholangiocyte involvement in epithelial-to-mesenchymal transformation and liver fibrosis,and propose directions for future studies.展开更多
Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thir...Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life.展开更多
Benign prostatic hyperplasia is a nonmalignant adenomatous enlargement of the pefiurethral prostate gland. It is a common disease in older men. In addition to man,spontaneous benign prostatic hyperplasia occurs in chi...Benign prostatic hyperplasia is a nonmalignant adenomatous enlargement of the pefiurethral prostate gland. It is a common disease in older men. In addition to man,spontaneous benign prostatic hyperplasia occurs in chimpanzee and the dog. Alternatives to these spontaneous models are induced benign prostatic hyperplasia,xenografts and in vitro models. Xenografts may be induced by cells cultured in vitro or by the heterotransplantation of primary surgical specimens into immunosuppressed mice. The purpose of this review is to integrate data from more than 30 years of heterotransplantation research in the study of benign hyperplasia of the prostate. Heterotransplantation has provided data regarding the histopathology,morphology,tissue markers,androgen receptor expression,tissue kinetics,take rate and tissue vasculature for this prostate disease.There are advantages,as well as limitations,that have been identified for human prostate disease heterotransplants versus xenotransplantation of cultured cells.Overall,heterotransplanted tissue is better at retaining tissue morphology,pathology,secretory activity,expression of tissue markers and human vasculature of the patient's original specimen. Furthermore,heterotransplanted tissue preserves the three-dimensional tissular architecture of the prostate to maintain critical stromal-epithelial cell interactions.展开更多
Sperm function testing, once commonly performed for the infertile couple before employing assisted reproductive technology (ART), has fallen out of favour in many reproductive medicine centers throughout the world. ...Sperm function testing, once commonly performed for the infertile couple before employing assisted reproductive technology (ART), has fallen out of favour in many reproductive medicine centers throughout the world. Indeed, the most recent addition of the 'World Health Organisation (WHO) Laboratory Manual for the Examination and Processing of Hu- man Semen' now groups many of these procedures into a section termed Research Procedures. In large part, this reflects the current clinical practice of bypassing the in-depth evaluation of the male partner, while assuming that if a spermatozoon can be found for intracytoplasmic sperm injection (ICSI), it must be a healthy cell capable of achieving fertilization. Never- theless, sperm function testing can provide valuable clinical insights into defects causing male infertility. Admittedly, in some cases, functional sperm deficiencies can be overcome using an ART. In other cases, couples will be empowered by the knowledge of the cause of their infertility, and for some couples, perhaps even the likelihood of ICSI success (relative to the spermatozoa). The knowledge allows them to make truly informed reproductive decisions, including (perhaps) the de- cision to seek donor insemination, to adopt or to remain childless. Knowledge of the cause of their infertility may provide closure for couples and a sense of confidence regarding their choice of reproductive treatment.展开更多
Cholangiocarcinomas are malignant epithelial liver tumors arising from the intra- and extra-hepatic bile ducts. Little is known about the molecular development of this disease, and very few effective treatment options...Cholangiocarcinomas are malignant epithelial liver tumors arising from the intra- and extra-hepatic bile ducts. Little is known about the molecular development of this disease, and very few effective treatment options are available. Thus, prognosis is poor. Genetic and epigenetic changes play an integral role in the neoplastic transformation of human cells to their malignant counterparts. This review summarizes some of the more prevalent genetic alterations (by microRNA expression) and epigenetic changes (hypermethylation of specific gene promoters) that are thought to contribute to the carcinogenic process in cholancliocarcinoma.展开更多
For more than 70 years, it has been believed that a severe reduction of serum androgen levels caused regression of prostate cancer (PCa) and that increasing androgen levels enhanced growth of PCa. However, numerous ...For more than 70 years, it has been believed that a severe reduction of serum androgen levels caused regression of prostate cancer (PCa) and that increasing androgen levels enhanced growth of PCa. However, numerous recent studies have questioned this traditional belief. In our study, LNCaP and MDA PCa 2b PCa cells were treated with various levels of androgens for 10 or 20 days, and the cell growth was measured with crystal violet mitogenic assay. The results indicated that the effect of androgens on the proliferation of PCa cells occurs in a biphasic pattern, with the androgen levels promoting optimal cell growth at approximately 0.23 ng m1-1 for LNCaP cells and between I and 2 ng m1-1 for MDA PCa 2b cells. Both of the optimal androgen levels are within the adult men's physiological low range (〈2.4 ng ml-1). At lower concentrations than the optimal androgen level, increasing androgen concentration promoted the proliferation of PCa cells. However, at the higher concentrations, increasing androgen concentration resulted in a dose-dependent proliferative inhibition. We conclude that physiologically normal levels of androgen inhibit the proliferation of PCa cells in vitro. However, at very low levels androgens are essential for initial growth of PCa cells.展开更多
Cholangiocarcinoma is a rare cancer originating from the neoplastic transformation of the epithelial cells (i.e. cholangiocytes) that line the biliary tract. The prognosis for patients with cholangiocarcinoma is grim ...Cholangiocarcinoma is a rare cancer originating from the neoplastic transformation of the epithelial cells (i.e. cholangiocytes) that line the biliary tract. The prognosis for patients with cholangiocarcinoma is grim due to lack of viable treatment options. The increase in world-wide incidence and mortality from cholangiocarcinoma highlights the importance of understanding the intracellular mechanisms that trigger the neoplastic transformation of cholangiocytes and the growth of biliary cancers. The purpose of the following review is to address what has been learned over the past decade concerning the molecular basis of cholangiocarcinogenesis. The material presented is divided into two sections:(1) mechanisms regulating neoplastic transformation of cholangiocytes; and (2) factors regulating cholangiocarcinoma growth. An understanding of the growth regulatory mechanisms of cholangiocarcinoma will lead to the identification of therapeutic targets for this devastating cancer.展开更多
AIM:To investigate stapled transanal rectal resection (STARR) procedures as surgical techniques for obstructed defecation syndrome (ODS) by analyzing specimen evaluation,anorectal manometry,endoanal ultrasonography an...AIM:To investigate stapled transanal rectal resection (STARR) procedures as surgical techniques for obstructed defecation syndrome (ODS) by analyzing specimen evaluation,anorectal manometry,endoanal ultrasonography and clinical follow-up.METHODS:From January to December 2007,we have treated 30 patients.Fifteen treated with double PPH-01 staplers and 15 treated using new CCS 30 contour.Resected specimen were measured with respect to average surface and volume.All patients have been evaluated at 24 mo with clinical examination,anorectal manometry and endoanal ultrasonography.RESULTS:Average surface in the CCS 30 group was 54.5 cm2 statistically different when compared to the STARR group (36.92 cm2).The average volume in the CCS 30 group was 29.8 cc,while in the PPH-01 it was23.8 cc and difference was statistically significant.The mean hospital stay in the CCS 30 group was 3.1 d,while in the PPH-01 group the median hospital stay was 3.4 d.As regards the long-term follow-up,an overall satisfactory rate of 83.3% (25/30) was achieved.Endoanal ultrasonography performed 1 year following surgery was considered normal in both of the studied groups.Mean resting pressure was higher than the preoperative value (67.2 mmHg in the STARR group and 65.7 mmHg in the CCS30 group vs 54.7 mmHg and 55.3 mmHg,respectively).Resting and squeezing pressures were lower in those patients not satisfied,but data are not statistically significant.CONCLUSION:The STARR procedure with two PPH-01 is a safe surgical procedure to correct ODS.The new Contour CCS 30 could help to increase the amount of the resected tissue without differences in early complications,post-operative pain and in hospital stay compared to the STARR with two PPH-01 technique.展开更多
文摘Assessing diaphragm function status is vital for diagnosing and treating acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Diaphrag-matic ultrasound has become increasingly important due to its non-invasive nature,absence of radiation exposure,widespread availability,prompt results,high accuracy,and repeatability at the bedside.The diaphragm is a crucial respiratory muscle.Decline or dysfunction of the diaphragm can lead to dyspnea and even respiratory failure in AECOPD patients.In this editorial,we comment on an article,retrospectively analyzed ninety-four acute exacerbations of chronic obstructive pulmonary disease patients who received mechanical ventilation from January 2022 to December 2023.The study found that the diaphragm thickening fraction,an index from diaphragm ultrasound,can better predict the outcome of non-invasive ventilation in patients with AECOPD.The value of non-invasive ventilation in treating respiratory failure caused by AECOPD has been widely acknowledged.Diaphragmatic dysfunction diagnosed with ultrasound is asso-ciated with prolonged mechanical ventilation and weaning times and higher mortality.
文摘A two-compartment model of the universe is proposed to further refine Albert Einstein’s insight into curvature of space and the energy tensor. The two compartments are energy contained by a shell prism. The model allows for a non-unification of fundamental forces with gravity resulting from the curvature of a space-time prism. Carrier forces travel within the prism and particles emerge from the prism. Giving a thickness to the manifold negates infinity and will allow solutions at both microscopic and cosmic levels. Geometry is the link between quantum mechanics and general relativity. Negative entropy, as proposed by Erwin Schrödinger, gives order to particles and the cosmic. The source of this energy is in the shell of the containment vessel. The acceleration of the expansion of the universe occurred when energy within the container transformed into mass, warping the space-time container and causing an explosion of the container. Star movement is explained by the surface tension of the prism of space-time.
基金the University of Texas Southwestern Institutional Review Board(approval No.Stu-2022-1014).
文摘BACKGROUND Hip dysplasia(HD)is characterized by insufficient acetabular coverage of the femoral head,leading to a predisposition for osteoarthritis.While radiographic measurements such as the lateral center edge angle(LCEA)and Tönnis angle are essential in evaluating HD severity,patient-reported outcome measures(PROMs)offer insights into the subjective health impact on patients.AIM To investigate the correlations between machine-learning automated and manual radiographic measurements of HD and PROMs with the hypothesis that artificial intelligence(AI)-generated HD measurements indicating less severe dysplasia correlate with better PROMs.METHODS Retrospective study evaluating 256 hips from 130 HD patients from a hip preservation clinic database.Manual and AI-derived radiographic measurements were collected and PROMs such as the Harris hip score(HHS),international hip outcome tool(iHOT-12),short form(SF)12(SF-12),and Visual Analogue Scale of the European Quality of Life Group survey were correlated using Spearman's rank-order correlation.RESULTS The median patient age was 28.6 years(range 15.7-62.3 years)with 82.3%of patients being women and 17.7%being men.The median interpretation time for manual readers and AI ranged between 4-12 minutes per patient and 31 seconds,respectively.Manual measurements exhibited weak correlations with HHS,including LCEA(r=0.18)and Tönnis angle(r=-0.24).AI-derived metrics showed similar weak correlations,with the most significant being Caput-Collum-Diaphyseal(CCD)with iHOT-12 at r=-0.25(P=0.042)and CCD with SF-12 at r=0.25(P=0.048).Other measured correlations were not significant(P>0.05).CONCLUSION This study suggests AI can aid in HD assessment,but weak PROM correlations highlight their continued importance in predicting subjective health and outcomes,complementing AI-derived measurements in HD management.
文摘Cholangiocarcinoma is a rare malignancy of the biliary tract. Key factors in determining therapeutic options include knowledge of tumor extent, anatomy and obtaining tissue diagnosis. Endoscopically, there are three modalities available to make the diagnosis of cholangiocarcinoma. These include endoscopic retrograde cholangiopancreatography, endoscopic ultrasound with fine needle aspiration and cholangioscopy. Management of cholangiocarcinoma endoscopically is typically confined to stent placement for palliative purposes or as a bridge to surgery. In this article, we will review the endoscopic techniques available for the diagnosis and management of cholangiocarcinoma.
文摘Cholangiocarcinoma continues to be a challenging disease to treat. Systemic therapy is used in unresectable disease, disease progression after surgery, and in the palliative setting. Unfortunately, results of multiple phase Ⅱ trials have rarely yielded positive results. As data on the molecular carcinogenesis of cholangiocarcinoma is developing, we are more able to understand the disease process and can use this understanding to create unique targeted therapies. We reviewed the role of c-Met/ hepatocyte growth factor (HGF) in the development of cholangiocarcinoma. Furthermore, we explored the use of the c-Met guided cascade as a target to treat cholangiocarcinoma. We reviewed the current use and options for future development of c-Met agents to treat this disease.
文摘Normal and neoplastic growth of the prostate gland are dependent on androgen receptor (AR) expression and function. Androgenic activation of the AR, in association with its coregulatory factors, is the classical pathway that leads to transcriptional activity of AR target genes. Alternatively, cytoplasmic signaling crosstalk of AR by growth factors, neurotrophic peptides, cytokines or nonandrogenic hormones may have important roles in prostate carcinogenesis and in metastatic or androgen-independent (AI) progression of the disease. In addition, cross-modulation by various nuclear transcription factors acting through basal transcriptional machinery could positively or negatively affect the AR or AR target genes expression and activity. Androgen ablation leads to an initial favorable response in a significant number of patients; however, almost invariably patients relapse with an aggressive form of the disease known as castration-resistant or hormone-refractory prostate cancer (PCa). Understanding critical molecular events that lead PCa cells to resist androgen-deprivation therapy is essential in developing successful treatments for hormone-refractory disease. In a significant number of hormone-refractory patients, the AR is overexpressed, mutated or genomically amplified. These genetic alterations maintain an active presence for a highly sensitive AR, which is responsive to androgens, antiandrogens or nonandrogenic hormones and collectively confer a selective growth advantage to PCa cells. This review provides a brief synopsis of the AR structure, AR coregulators, posttranslational modifications of AR, duality of AR function in prostate epithelial and stromal cells, AR-dependent signaling, genetic changes in the form of somatic and germline mutations and their known functional significance in PCa cells and tissues.
基金supported,in part,by a research grant from Baylor Scott&White Health Central Texas Foundation and NIH grant R01-NS067435(JHH)
文摘Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts(ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts(TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems(DDS), co-administration of platelet-rich plasma(PRP), and pretreatment with chondroitinase ABC(Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix(ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia(DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.
文摘Aim:To determine the effect of saposin C (a known trophic domain of prosaposin) on proliferation,migration and invasion,as well as its effect on the expression of urokinase plasmonogen activator (uPA),its receptor (uPAR) and matrix metalloproteinases (MMP)-2 and -9 in normal and malignant prostate cells.In addition,we tested whether saposin C can activate p42/44 and stress-activated protein kinase/c-Jun NH_2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) superfamily.Methods:We employed West- ern blot analysis,phospho-specific antibodies,cell proliferation assay,reverse transcriptase-polymerase chain reaction, in vitro kinase assays and migration and invasion to determine the effect of saposin C on various biological behaviors of prostate stromal and cancer cells.Results:Saposin C,in a cell type-specific manner,upregulates uPA/uPAR and immediate early gene c-Jun expression,stimulates cell proliferation,migration and invasion and activates p42/44 and SAPK/JNK MAPK pathways in prostate stromal and cancer cells.Normal prostate epithelial cells were not responsive to saposin C treatment in the above studies.Conclusion:Saposin C functions as a multipotential modulator of diverse biological activities in prostate cancer and stromal cells.These results strongly suggest that saposin C functions as a potent growth factor for prostatic cells and may contribute to prostate carcinogenesis and/or the development of hormone-refractory prostate cancer.
基金Supported by the Grant Awarded to Dr.Glaser from Scott and White Hospitalby a NIH RO1 Grant,No.DK081442
文摘Cholangiocytes are the epithelial cells that line the biliary tree.In the adult liver,they are a mitotically dormant cell population,unless ductular reaction is triggered by injury.The ability of cholangiocytes to proliferate is important in many different human pathological liver conditions that target this cell type,which are termed cholangiopathies(i.e.primary biliary cirrhosis,primary sclerosing cholangitis and biliary atresia).In our article,we provide background information on the morphological and functional heterogeneity of cholangiocytes,summarize what is currently known about their proliferative processes,and briefly describe the diseases that target these cells.In addition,we address recent findings that suggest cholangiocyte involvement in epithelial-to-mesenchymal transformation and liver fibrosis,and propose directions for future studies.
文摘Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life.
文摘Benign prostatic hyperplasia is a nonmalignant adenomatous enlargement of the pefiurethral prostate gland. It is a common disease in older men. In addition to man,spontaneous benign prostatic hyperplasia occurs in chimpanzee and the dog. Alternatives to these spontaneous models are induced benign prostatic hyperplasia,xenografts and in vitro models. Xenografts may be induced by cells cultured in vitro or by the heterotransplantation of primary surgical specimens into immunosuppressed mice. The purpose of this review is to integrate data from more than 30 years of heterotransplantation research in the study of benign hyperplasia of the prostate. Heterotransplantation has provided data regarding the histopathology,morphology,tissue markers,androgen receptor expression,tissue kinetics,take rate and tissue vasculature for this prostate disease.There are advantages,as well as limitations,that have been identified for human prostate disease heterotransplants versus xenotransplantation of cultured cells.Overall,heterotransplanted tissue is better at retaining tissue morphology,pathology,secretory activity,expression of tissue markers and human vasculature of the patient's original specimen. Furthermore,heterotransplanted tissue preserves the three-dimensional tissular architecture of the prostate to maintain critical stromal-epithelial cell interactions.
文摘Sperm function testing, once commonly performed for the infertile couple before employing assisted reproductive technology (ART), has fallen out of favour in many reproductive medicine centers throughout the world. Indeed, the most recent addition of the 'World Health Organisation (WHO) Laboratory Manual for the Examination and Processing of Hu- man Semen' now groups many of these procedures into a section termed Research Procedures. In large part, this reflects the current clinical practice of bypassing the in-depth evaluation of the male partner, while assuming that if a spermatozoon can be found for intracytoplasmic sperm injection (ICSI), it must be a healthy cell capable of achieving fertilization. Never- theless, sperm function testing can provide valuable clinical insights into defects causing male infertility. Admittedly, in some cases, functional sperm deficiencies can be overcome using an ART. In other cases, couples will be empowered by the knowledge of the cause of their infertility, and for some couples, perhaps even the likelihood of ICSI success (relative to the spermatozoa). The knowledge allows them to make truly informed reproductive decisions, including (perhaps) the de- cision to seek donor insemination, to adopt or to remain childless. Knowledge of the cause of their infertility may provide closure for couples and a sense of confidence regarding their choice of reproductive treatment.
基金Supported by a NIH mentored award (KO1 DK078532) as well as a grant award from Scott & White Hospital
文摘Cholangiocarcinomas are malignant epithelial liver tumors arising from the intra- and extra-hepatic bile ducts. Little is known about the molecular development of this disease, and very few effective treatment options are available. Thus, prognosis is poor. Genetic and epigenetic changes play an integral role in the neoplastic transformation of human cells to their malignant counterparts. This review summarizes some of the more prevalent genetic alterations (by microRNA expression) and epigenetic changes (hypermethylation of specific gene promoters) that are thought to contribute to the carcinogenic process in cholancliocarcinoma.
文摘For more than 70 years, it has been believed that a severe reduction of serum androgen levels caused regression of prostate cancer (PCa) and that increasing androgen levels enhanced growth of PCa. However, numerous recent studies have questioned this traditional belief. In our study, LNCaP and MDA PCa 2b PCa cells were treated with various levels of androgens for 10 or 20 days, and the cell growth was measured with crystal violet mitogenic assay. The results indicated that the effect of androgens on the proliferation of PCa cells occurs in a biphasic pattern, with the androgen levels promoting optimal cell growth at approximately 0.23 ng m1-1 for LNCaP cells and between I and 2 ng m1-1 for MDA PCa 2b cells. Both of the optimal androgen levels are within the adult men's physiological low range (〈2.4 ng ml-1). At lower concentrations than the optimal androgen level, increasing androgen concentration promoted the proliferation of PCa cells. However, at the higher concentrations, increasing androgen concentration resulted in a dose-dependent proliferative inhibition. We conclude that physiologically normal levels of androgen inhibit the proliferation of PCa cells in vitro. However, at very low levels androgens are essential for initial growth of PCa cells.
基金a grant award (#060483) to Dr. Glaser from Scotand White Hospital
文摘Cholangiocarcinoma is a rare cancer originating from the neoplastic transformation of the epithelial cells (i.e. cholangiocytes) that line the biliary tract. The prognosis for patients with cholangiocarcinoma is grim due to lack of viable treatment options. The increase in world-wide incidence and mortality from cholangiocarcinoma highlights the importance of understanding the intracellular mechanisms that trigger the neoplastic transformation of cholangiocytes and the growth of biliary cancers. The purpose of the following review is to address what has been learned over the past decade concerning the molecular basis of cholangiocarcinogenesis. The material presented is divided into two sections:(1) mechanisms regulating neoplastic transformation of cholangiocytes; and (2) factors regulating cholangiocarcinoma growth. An understanding of the growth regulatory mechanisms of cholangiocarcinoma will lead to the identification of therapeutic targets for this devastating cancer.
文摘AIM:To investigate stapled transanal rectal resection (STARR) procedures as surgical techniques for obstructed defecation syndrome (ODS) by analyzing specimen evaluation,anorectal manometry,endoanal ultrasonography and clinical follow-up.METHODS:From January to December 2007,we have treated 30 patients.Fifteen treated with double PPH-01 staplers and 15 treated using new CCS 30 contour.Resected specimen were measured with respect to average surface and volume.All patients have been evaluated at 24 mo with clinical examination,anorectal manometry and endoanal ultrasonography.RESULTS:Average surface in the CCS 30 group was 54.5 cm2 statistically different when compared to the STARR group (36.92 cm2).The average volume in the CCS 30 group was 29.8 cc,while in the PPH-01 it was23.8 cc and difference was statistically significant.The mean hospital stay in the CCS 30 group was 3.1 d,while in the PPH-01 group the median hospital stay was 3.4 d.As regards the long-term follow-up,an overall satisfactory rate of 83.3% (25/30) was achieved.Endoanal ultrasonography performed 1 year following surgery was considered normal in both of the studied groups.Mean resting pressure was higher than the preoperative value (67.2 mmHg in the STARR group and 65.7 mmHg in the CCS30 group vs 54.7 mmHg and 55.3 mmHg,respectively).Resting and squeezing pressures were lower in those patients not satisfied,but data are not statistically significant.CONCLUSION:The STARR procedure with two PPH-01 is a safe surgical procedure to correct ODS.The new Contour CCS 30 could help to increase the amount of the resected tissue without differences in early complications,post-operative pain and in hospital stay compared to the STARR with two PPH-01 technique.