There is significant controversy on how aggressively to treat older men with prostate cancer. We identified 1082 patients diagnosed with prostate cancer from 1998-2008 with Gleason score ≥ 7 on biopsy or prostatectom...There is significant controversy on how aggressively to treat older men with prostate cancer. We identified 1082 patients diagnosed with prostate cancer from 1998-2008 with Gleason score ≥ 7 on biopsy or prostatectomy pathology in the South Texas Veteran’s Healthcare System. Prostate specific antigen (PSA) values, pathology, treatment and response to treatment were analyzed. Mean follow up was 4.99 years. Patients > 74 years had significantly higher pretreatment PSA, higher grade disease, and were received hormone therapy more often. Unadjusted hazard ratios for metastasis and cancer related death were 2.15 (95% CI 1.02, 4.52;p = 0.04) and 2.66 (95% CI 1.18, 6;p = 0.02), respectively. However, after controlling for treatment, Gleason score and pre-treatment PSA, there was no significant difference in cancer specific survival (CSS) by age group. In the patients > 74 years, there was also no significant difference in overall survival (OS) or CSS among patients treated with surgery, radiation or hormones after controlling for Gleason score and pre-treatment PSA. Our oldest patients have worse cancer presumably to later diagnosis, but they do just as well as younger patients with any given treatment modality. Most importantly, they have similar cancer specific survival with hormone therapy as they do with radiation or surgery.展开更多
Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryoni...Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.展开更多
The range and distribution of sources of lower gastrointestinal bleeding (LGIB) seem to be evolving over time. Ischemic colitis (IC) has long been recognized as a common cause of LGIB. Due to a variety of contributing...The range and distribution of sources of lower gastrointestinal bleeding (LGIB) seem to be evolving over time. Ischemic colitis (IC) has long been recognized as a common cause of LGIB. Due to a variety of contributing factors, we suspect that IC may be implicated in an increasing proportion of inpatient cases of lower GI bleeding compared to previously published rates. We examined the medical records of 464 patients admitted to the Methodist Hospital from 2005 to 2013. Patients with LGIB admitted to the hospital with a diagnostic colonoscopy were eligible for the study. Demographics and diagnoses were grouped and categorized for ease of comparison and compatibility with prior studies. Statistical analysis was used to summarize disease distribution and calculate probability outcomes based on pooled mean values obtained from 6 previously published epidemiological studies of LGIB. Anorectal bleeding including hemorrhoids, fissures, and stercoral ulcers was the most frequent diagnosis overall (20%) followed by ischemic colitis (16%) and diverticulosis (14%). There were a significantly higher proportion of IC cases observed in our population compared to the expected proportion of cases (p < 0.01, 95%). When stratified by sex, IC was the leading overall cause in females.展开更多
Purpose: This study investigated the anatomical and histological characteristics of the rat Eustachian tube(E-tube)and the feasibility of Eustachian tubography in a rat model.Materials and methods: Fifteen male Wistar...Purpose: This study investigated the anatomical and histological characteristics of the rat Eustachian tube(E-tube)and the feasibility of Eustachian tubography in a rat model.Materials and methods: Fifteen male Wistar rats were used in this study, and the bilateral E-tubes of each rat were examined. Ten E-tubes were used for anatomical studies, another ten for histological analysis, and the other ten for Eustachian tubography. Five rats were euthanized and decapitated, and ten E-tubes were dissected to describe the anatomy of the E-tube. Ten E-tube specimens obtained from five other rats were sectioned to investigate Etube histology. Eustachian tubography was performed on the bilateral E-tubes of the other five rats using the trans-tympanic approach.Results: The rat E-tubes consisted of bony and membranous parts. Cartilage and bone tissue covered only the bony part. The E-tubes’ mean diameter and overall length were 2.97 mm and 4.96 mm, respectively. The tympanic orifices’ mean diameter was 1.21 mm. The epithelium of E-tubes was mainly composed of pseudostratified ciliated and goblet cells. Eustachian tubography was successfully performed on both sides of the E-tube for each rat.The technical success rate was 100%, the average running time was 4.9 min, and no procedure-related complications occurred. On tubography images, the E-tube, tympanic cavity, and nasopharynx could be identified because of the visualization of bony landmarks.Conclusion: In this study, we described the anatomical and histological features of rat E-tubes. With the aid of these findings, E-tube angiography was successfully performed using a transtympanic approach. These results will facilitate further investigation of E-tube dysfunction.展开更多
Objectives:Oxidative stress(OS)plays a pivotal role in chronic and neurodegenerative diseases,which has sparked interest in molecules that modulate redox-regulating enzymes.Melatonin and its metabolites exhibit antiox...Objectives:Oxidative stress(OS)plays a pivotal role in chronic and neurodegenerative diseases,which has sparked interest in molecules that modulate redox-regulating enzymes.Melatonin and its metabolites exhibit antioxidant properties;however,their molecular mechanisms of enzymatic and transcriptional modulation remain unclear.This study aimed to investigate,through an exploratory in silico approach,the interactions of melatonin and related compounds with OS-related enzymes to generate hypotheses about their role in cellular redox control.Methods:A rational selection of antioxidant,pro-oxidant,and transcriptional targets was performed.Ligands were optimized at the DFT level(M05-2X/6-311+G(d,p))and docked to OS related enzymes.Docking results were analyzed using polygenic antioxidant indices(PAOX)and a similarity interaction index(SSI).Molecular dynamics simulations of selected complexes provided additional insight into potential ligand-protein interaction mechanisms.Results:In silico analyses revealed that N1-acetyl-5-methoxykynuramine(AMK),N1-acetyl-N2-formyl-5-methoxykynuramine(AFMK),and 3-hydroxymelatonin(3OH-M)could partially inhibit pro-oxidant enzymes such as neuronal nitric oxide synthase(nNOS),5-lipoxygenase(5-LOX),thioredoxin reductase(TrxR),and nicotinamide adenine dinucleotide phosphate oxidase(NOX5).The N-(2-(2-acetyl-6,7-dihydroxy-1H-indol-3-yl)ethyl)acetamide(IIcD)and N-(2-(6-hydroxy-7-mercapto-5-methoxy-1H-indol)ethyl)acetamide(dM38)derivatives could potentially stabilize superoxide dismutase(SOD1)and catalase(CAT)enzymes,respectively.Finally,AFMK and dM38 showed consistent interactions with transcriptional regulators,particularly peroxisome proliferator-activated receptor alpha(PPARα)and Kelchlike ECH-associated protein 1(KEAP1).Conclusion:These studies about melatonin-related compounds support a multifactorial profile of redox modulation and provide mechanistic hypotheses for future experimental validation.Among these approaches,the interaction-similarity index is introduced as a novel tool to facilitate the identification of promising redox-active candidates.展开更多
Melanoma is the most aggressive form of skin cancer,characterized by a poor prognosis,and its incidence has risen rapidly over the past 30 years.Recent therapies,notably immunotherapy and targeted therapy,have signifi...Melanoma is the most aggressive form of skin cancer,characterized by a poor prognosis,and its incidence has risen rapidly over the past 30 years.Recent therapies,notably immunotherapy and targeted therapy,have significantly improved the outcome of patients with metastatic melanoma.Previously dismal five-year survival rates of below 5%have shifted to over 50%of patients surviving the five-year mark,marking a significant shift in the landscape of melanoma treatment and survival.Unfortunately,about 50%of patients either do not respond to therapy or experience early or late relapses following an initial response.The underlying mechanisms for primary and secondary resistance to targeted therapies or immunotherapy and relapse patterns remain not fully identified.However,several molecular pathways and genetic factors have been associated with melanoma resistance to these treatments.Understanding these mechanisms paves the way for creating novel treatments that can address resistance and ultimately enhance patient outcomes in melanoma.This review explores the mechanisms behind immunotherapy and targeted therapy resistance in melanoma patients.Additionally,it describes the treatment strategies to overcome resistance,which have improved patients’outcomes in clinical trials and practice.展开更多
文摘There is significant controversy on how aggressively to treat older men with prostate cancer. We identified 1082 patients diagnosed with prostate cancer from 1998-2008 with Gleason score ≥ 7 on biopsy or prostatectomy pathology in the South Texas Veteran’s Healthcare System. Prostate specific antigen (PSA) values, pathology, treatment and response to treatment were analyzed. Mean follow up was 4.99 years. Patients > 74 years had significantly higher pretreatment PSA, higher grade disease, and were received hormone therapy more often. Unadjusted hazard ratios for metastasis and cancer related death were 2.15 (95% CI 1.02, 4.52;p = 0.04) and 2.66 (95% CI 1.18, 6;p = 0.02), respectively. However, after controlling for treatment, Gleason score and pre-treatment PSA, there was no significant difference in cancer specific survival (CSS) by age group. In the patients > 74 years, there was also no significant difference in overall survival (OS) or CSS among patients treated with surgery, radiation or hormones after controlling for Gleason score and pre-treatment PSA. Our oldest patients have worse cancer presumably to later diagnosis, but they do just as well as younger patients with any given treatment modality. Most importantly, they have similar cancer specific survival with hormone therapy as they do with radiation or surgery.
基金National Institute of Dental&Craniofacial Research,No.1R21DE028265-01A1.
文摘Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.
文摘The range and distribution of sources of lower gastrointestinal bleeding (LGIB) seem to be evolving over time. Ischemic colitis (IC) has long been recognized as a common cause of LGIB. Due to a variety of contributing factors, we suspect that IC may be implicated in an increasing proportion of inpatient cases of lower GI bleeding compared to previously published rates. We examined the medical records of 464 patients admitted to the Methodist Hospital from 2005 to 2013. Patients with LGIB admitted to the hospital with a diagnostic colonoscopy were eligible for the study. Demographics and diagnoses were grouped and categorized for ease of comparison and compatibility with prior studies. Statistical analysis was used to summarize disease distribution and calculate probability outcomes based on pooled mean values obtained from 6 previously published epidemiological studies of LGIB. Anorectal bleeding including hemorrhoids, fissures, and stercoral ulcers was the most frequent diagnosis overall (20%) followed by ischemic colitis (16%) and diverticulosis (14%). There were a significantly higher proportion of IC cases observed in our population compared to the expected proportion of cases (p < 0.01, 95%). When stratified by sex, IC was the leading overall cause in females.
基金funding from the Korea Health Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (HI17C0881)。
文摘Purpose: This study investigated the anatomical and histological characteristics of the rat Eustachian tube(E-tube)and the feasibility of Eustachian tubography in a rat model.Materials and methods: Fifteen male Wistar rats were used in this study, and the bilateral E-tubes of each rat were examined. Ten E-tubes were used for anatomical studies, another ten for histological analysis, and the other ten for Eustachian tubography. Five rats were euthanized and decapitated, and ten E-tubes were dissected to describe the anatomy of the E-tube. Ten E-tube specimens obtained from five other rats were sectioned to investigate Etube histology. Eustachian tubography was performed on the bilateral E-tubes of the other five rats using the trans-tympanic approach.Results: The rat E-tubes consisted of bony and membranous parts. Cartilage and bone tissue covered only the bony part. The E-tubes’ mean diameter and overall length were 2.97 mm and 4.96 mm, respectively. The tympanic orifices’ mean diameter was 1.21 mm. The epithelium of E-tubes was mainly composed of pseudostratified ciliated and goblet cells. Eustachian tubography was successfully performed on both sides of the E-tube for each rat.The technical success rate was 100%, the average running time was 4.9 min, and no procedure-related complications occurred. On tubography images, the E-tube, tympanic cavity, and nasopharynx could be identified because of the visualization of bony landmarks.Conclusion: In this study, we described the anatomical and histological features of rat E-tubes. With the aid of these findings, E-tube angiography was successfully performed using a transtympanic approach. These results will facilitate further investigation of E-tube dysfunction.
基金supported by the SECIHTI project Ciencia Basica y de Frontera(No.CBF2023-2024-1141)https://secihti.mx/(accessed on 01 August 2025).
文摘Objectives:Oxidative stress(OS)plays a pivotal role in chronic and neurodegenerative diseases,which has sparked interest in molecules that modulate redox-regulating enzymes.Melatonin and its metabolites exhibit antioxidant properties;however,their molecular mechanisms of enzymatic and transcriptional modulation remain unclear.This study aimed to investigate,through an exploratory in silico approach,the interactions of melatonin and related compounds with OS-related enzymes to generate hypotheses about their role in cellular redox control.Methods:A rational selection of antioxidant,pro-oxidant,and transcriptional targets was performed.Ligands were optimized at the DFT level(M05-2X/6-311+G(d,p))and docked to OS related enzymes.Docking results were analyzed using polygenic antioxidant indices(PAOX)and a similarity interaction index(SSI).Molecular dynamics simulations of selected complexes provided additional insight into potential ligand-protein interaction mechanisms.Results:In silico analyses revealed that N1-acetyl-5-methoxykynuramine(AMK),N1-acetyl-N2-formyl-5-methoxykynuramine(AFMK),and 3-hydroxymelatonin(3OH-M)could partially inhibit pro-oxidant enzymes such as neuronal nitric oxide synthase(nNOS),5-lipoxygenase(5-LOX),thioredoxin reductase(TrxR),and nicotinamide adenine dinucleotide phosphate oxidase(NOX5).The N-(2-(2-acetyl-6,7-dihydroxy-1H-indol-3-yl)ethyl)acetamide(IIcD)and N-(2-(6-hydroxy-7-mercapto-5-methoxy-1H-indol)ethyl)acetamide(dM38)derivatives could potentially stabilize superoxide dismutase(SOD1)and catalase(CAT)enzymes,respectively.Finally,AFMK and dM38 showed consistent interactions with transcriptional regulators,particularly peroxisome proliferator-activated receptor alpha(PPARα)and Kelchlike ECH-associated protein 1(KEAP1).Conclusion:These studies about melatonin-related compounds support a multifactorial profile of redox modulation and provide mechanistic hypotheses for future experimental validation.Among these approaches,the interaction-similarity index is introduced as a novel tool to facilitate the identification of promising redox-active candidates.
文摘Melanoma is the most aggressive form of skin cancer,characterized by a poor prognosis,and its incidence has risen rapidly over the past 30 years.Recent therapies,notably immunotherapy and targeted therapy,have significantly improved the outcome of patients with metastatic melanoma.Previously dismal five-year survival rates of below 5%have shifted to over 50%of patients surviving the five-year mark,marking a significant shift in the landscape of melanoma treatment and survival.Unfortunately,about 50%of patients either do not respond to therapy or experience early or late relapses following an initial response.The underlying mechanisms for primary and secondary resistance to targeted therapies or immunotherapy and relapse patterns remain not fully identified.However,several molecular pathways and genetic factors have been associated with melanoma resistance to these treatments.Understanding these mechanisms paves the way for creating novel treatments that can address resistance and ultimately enhance patient outcomes in melanoma.This review explores the mechanisms behind immunotherapy and targeted therapy resistance in melanoma patients.Additionally,it describes the treatment strategies to overcome resistance,which have improved patients’outcomes in clinical trials and practice.
