Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical ...Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.展开更多
Time series analysis is a valuable tool in epidemiology that complements the classical epidemiological models in two different ways:Prediction and forecast.Prediction is related to explaining past and current data bas...Time series analysis is a valuable tool in epidemiology that complements the classical epidemiological models in two different ways:Prediction and forecast.Prediction is related to explaining past and current data based on various internal and external influences that may or may not have a causative role.Forecasting is an exploration of the possible future values based on the predictive ability of the model and hypothesized future values of the external and/or internal influences.The time series analysis approach has the advantage of being easier to use(in the cases of more straightforward and linear models such as Auto-Regressive Integrated Moving Average).Still,it is limited in forecasting time,unlike the classical models such as Susceptible-Exposed-Infectious-Removed.Its applicability in forecasting comes from its better accuracy for short-term prediction.In its basic form,it does not assume much theoretical knowledge of the mechanisms of spreading and mutating pathogens or the reaction of people and regulatory structures(governments,companies,etc.).Instead,it estimates from the data directly.Its predictive ability allows testing hypotheses for different factors that positively or negatively contribute to the pandemic spread;be it school closures,emerging variants,etc.It can be used in mortality or hospital risk estimation from new cases,seroprevalence studies,assessing properties of emerging variants,and estimating excess mortality and its relationship with a pandemic.展开更多
Objective Scorpion （Hemiscorpius lepturus） stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom th...Objective Scorpion （Hemiscorpius lepturus） stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock （which can sometimes even lead to death）. The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus （H. lepturus） venom in mice. Methods Eight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues （liver, kidney, heart, brain, and spinal cord） using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species （ROS） production, mitochondrial membrane potential （MMP）, ATP level, and the release of cytochrome c from the mitochondria was performed. Results Our results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling. Conclusion In general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.展开更多
Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intric...Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation.展开更多
Prostate cancer(Pca;adenocarcinoma)is one of the most common cancers in adult males and one of the leading causes of death in both men and women.The diagnosis of Pca requires substantial experience,and even then the l...Prostate cancer(Pca;adenocarcinoma)is one of the most common cancers in adult males and one of the leading causes of death in both men and women.The diagnosis of Pca requires substantial experience,and even then the lesions can be difficult to detect.Moreover,although the diagnostic approach for this disease has improved significantly with the advent of multiparametric magnetic resonance,that technology has certain unresolved limitations.In recent years artificial intelligence(AI)has been introduced to the field of radiology,providing new software solutions for prostate diagnostics.Precise mapping of the prostate has become possible through AI and this has greatly improved the accuracy of biopsy.AI has also allowed for certain suspicious lesions to be attributed to a given group according to the Prostate Imaging-Reporting&Data System classification.Finally,AI has facilitated the combination of data obtained from clinical,laboratory(prostate-specific antigen),imaging(magnetic resonance),and biopsy examinations,and in this way new regularities can be found which at the moment remain hidden.Further evolution of AI in this field is inevitable and it is almost certain to significantly expand the efficacy,accuracy and efficiency of diagnosis and treatment of Pca.展开更多
Meniscus injuries are widespread and the available treatments do not offer enough healing potential.Here,we provide critical support for using pigs as a biological model for meniscal degeneration and the development o...Meniscus injuries are widespread and the available treatments do not offer enough healing potential.Here,we provide critical support for using pigs as a biological model for meniscal degeneration and the development of cutting-edge therapies in orthopedics.We present a single-cell transcriptome atlas of the meniscus,consisting of cell clusters corresponding to four major cell types:chondrocytes,endothelial cells,smooth muscle cells,and immune cells.Five distinct chondrocyte subclusters(CH0–CH4)were annotated,of which only one was widespread in both the red and white zones,indicating a major difference in the cellular makeup of the zones.Subclusters distinct to the white zone appear responsible for cartilage-specific matrix deposition and protection against adverse microenvironmental factors,while those in the red zone exhibit characteristics of mesenchymal stem cells and are more likely to proliferate and migrate.Additionally,they induce remodeling actions in other chondrocyte subclusters and promote the proliferation and maturation of endothelial cells,inducing healing and vascularization processes.Considering that they have substantial remodeling capabilities,these subclusters should be of great interest for tissue engineering studies.We also show that the cellular makeup of the pig meniscus is comparable to that of humans,which supports the use of pigs as a model in orthopedic therapy development.展开更多
BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal g...BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.展开更多
BACKGROUND Breast cancer morbidity has been increasing worldwide,but treatments are improving.The therapeutic response depends on the stage at which the disease is diagnosed.Therefore,early diagnosis has never been mo...BACKGROUND Breast cancer morbidity has been increasing worldwide,but treatments are improving.The therapeutic response depends on the stage at which the disease is diagnosed.Therefore,early diagnosis has never been more essential for successful treatment and a reduction in mortality rates.Radiology plays a pivotal role in cancer detection,and advances in ultrasound(US)palpation have shown promising results for breast cancer imaging.The addition of two-dimensional-shear wave elastography(2D-SWE)US in the routine breast imaging exam can increase early cancer detection and promote better surveillance.AIM To evaluate the clinical applications of 2D-SWE US in breast cancer detection and its combination with other imaging modalities.METHODS The 200 consecutive female patients aged 50-80 were examined to evaluate palpable breast lesions.All patients underwent mammography,bright mode(B-mode)US,and 2D-SWE followed by US-guided biopsy in two consecutive sessions.RESULTS Combining B-mode and shear wave US imaging with X-ray mammography revealed 100%of the suspicious lesions,resulting in greater sensitivity,specificity,and negative predictive value.The result improves compared to either B-mode or 2D-SWE alone(P=0.02).CONCLUSION Combining 2D-SWE with conventional US and X-ray techniques improves the chance of early cancer detection.Including 2D-SWE in regular breast imaging routines can reduce the need for biopsies and improve the chance of early cancer detection and survivability with the proper line of therapy.展开更多
Multiple primary cancers （MPC） are specific .malignant tumors type, manifesting as more than one primary tumor diagnosed in the same patient, either simultaneously or sequentially. The diagnostic criteria include： ...Multiple primary cancers （MPC） are specific .malignant tumors type, manifesting as more than one primary tumor diagnosed in the same patient, either simultaneously or sequentially. The diagnostic criteria include： the cancer must be clearly malignant as determined by histological evaluation; each cancer must be geographically separate and distinct;展开更多
基金Supported by The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.
基金Supported by European Union-NextGenerationEU,Through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008-C01.
文摘Time series analysis is a valuable tool in epidemiology that complements the classical epidemiological models in two different ways:Prediction and forecast.Prediction is related to explaining past and current data based on various internal and external influences that may or may not have a causative role.Forecasting is an exploration of the possible future values based on the predictive ability of the model and hypothesized future values of the external and/or internal influences.The time series analysis approach has the advantage of being easier to use(in the cases of more straightforward and linear models such as Auto-Regressive Integrated Moving Average).Still,it is limited in forecasting time,unlike the classical models such as Susceptible-Exposed-Infectious-Removed.Its applicability in forecasting comes from its better accuracy for short-term prediction.In its basic form,it does not assume much theoretical knowledge of the mechanisms of spreading and mutating pathogens or the reaction of people and regulatory structures(governments,companies,etc.).Instead,it estimates from the data directly.Its predictive ability allows testing hypotheses for different factors that positively or negatively contribute to the pandemic spread;be it school closures,emerging variants,etc.It can be used in mortality or hospital risk estimation from new cases,seroprevalence studies,assessing properties of emerging variants,and estimating excess mortality and its relationship with a pandemic.
基金supported by Molecular Biology Research Center,Baqiyatallah University of Medical Sciences(NO.340-5-5771.Sin)
文摘Objective Scorpion （Hemiscorpius lepturus） stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock （which can sometimes even lead to death）. The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus （H. lepturus） venom in mice. Methods Eight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues （liver, kidney, heart, brain, and spinal cord） using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species （ROS） production, mitochondrial membrane potential （MMP）, ATP level, and the release of cytochrome c from the mitochondria was performed. Results Our results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling. Conclusion In general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.
基金Supported by The National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008-C01.
文摘Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation.
基金Supported by the European Union’s NextGenerationEU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,Project No.BG-RRP-2.004-0008-C01.
文摘Prostate cancer(Pca;adenocarcinoma)is one of the most common cancers in adult males and one of the leading causes of death in both men and women.The diagnosis of Pca requires substantial experience,and even then the lesions can be difficult to detect.Moreover,although the diagnostic approach for this disease has improved significantly with the advent of multiparametric magnetic resonance,that technology has certain unresolved limitations.In recent years artificial intelligence(AI)has been introduced to the field of radiology,providing new software solutions for prostate diagnostics.Precise mapping of the prostate has become possible through AI and this has greatly improved the accuracy of biopsy.AI has also allowed for certain suspicious lesions to be attributed to a given group according to the Prostate Imaging-Reporting&Data System classification.Finally,AI has facilitated the combination of data obtained from clinical,laboratory(prostate-specific antigen),imaging(magnetic resonance),and biopsy examinations,and in this way new regularities can be found which at the moment remain hidden.Further evolution of AI in this field is inevitable and it is almost certain to significantly expand the efficacy,accuracy and efficiency of diagnosis and treatment of Pca.
基金supported by the National Centre for Research and Development TECHMATSTRATEG-Ⅲ/0027/2019,POWR.03.02.00-00-I006/17the IDUB UAM。
文摘Meniscus injuries are widespread and the available treatments do not offer enough healing potential.Here,we provide critical support for using pigs as a biological model for meniscal degeneration and the development of cutting-edge therapies in orthopedics.We present a single-cell transcriptome atlas of the meniscus,consisting of cell clusters corresponding to four major cell types:chondrocytes,endothelial cells,smooth muscle cells,and immune cells.Five distinct chondrocyte subclusters(CH0–CH4)were annotated,of which only one was widespread in both the red and white zones,indicating a major difference in the cellular makeup of the zones.Subclusters distinct to the white zone appear responsible for cartilage-specific matrix deposition and protection against adverse microenvironmental factors,while those in the red zone exhibit characteristics of mesenchymal stem cells and are more likely to proliferate and migrate.Additionally,they induce remodeling actions in other chondrocyte subclusters and promote the proliferation and maturation of endothelial cells,inducing healing and vascularization processes.Considering that they have substantial remodeling capabilities,these subclusters should be of great interest for tissue engineering studies.We also show that the cellular makeup of the pig meniscus is comparable to that of humans,which supports the use of pigs as a model in orthopedic therapy development.
基金Supported by National Natural Science Foundation of China,No. 81502556Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province,No. 2X2019-01-02
文摘BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.
基金Supported by The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘BACKGROUND Breast cancer morbidity has been increasing worldwide,but treatments are improving.The therapeutic response depends on the stage at which the disease is diagnosed.Therefore,early diagnosis has never been more essential for successful treatment and a reduction in mortality rates.Radiology plays a pivotal role in cancer detection,and advances in ultrasound(US)palpation have shown promising results for breast cancer imaging.The addition of two-dimensional-shear wave elastography(2D-SWE)US in the routine breast imaging exam can increase early cancer detection and promote better surveillance.AIM To evaluate the clinical applications of 2D-SWE US in breast cancer detection and its combination with other imaging modalities.METHODS The 200 consecutive female patients aged 50-80 were examined to evaluate palpable breast lesions.All patients underwent mammography,bright mode(B-mode)US,and 2D-SWE followed by US-guided biopsy in two consecutive sessions.RESULTS Combining B-mode and shear wave US imaging with X-ray mammography revealed 100%of the suspicious lesions,resulting in greater sensitivity,specificity,and negative predictive value.The result improves compared to either B-mode or 2D-SWE alone(P=0.02).CONCLUSION Combining 2D-SWE with conventional US and X-ray techniques improves the chance of early cancer detection.Including 2D-SWE in regular breast imaging routines can reduce the need for biopsies and improve the chance of early cancer detection and survivability with the proper line of therapy.
文摘Multiple primary cancers （MPC） are specific .malignant tumors type, manifesting as more than one primary tumor diagnosed in the same patient, either simultaneously or sequentially. The diagnostic criteria include： the cancer must be clearly malignant as determined by histological evaluation; each cancer must be geographically separate and distinct;
