Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081930
Matthew I Hiskens, Anthony G Schneiders, Andrew S Fenning
Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 and COX-2 isoforms providing differing responses. Selective COX-2 inhibitors have shown potential as neuroprotective agents. Results from animal models of TBI suggest potential treatment through the alleviation of secondary injury mechanisms involving neuroinflammation and neuronal cell death. Additionally, early clinical trials have shown that the use of celecoxib improves patient mortality and outcomes. This review aims to summarize the therapeutic effects of COX-2 inhibitors observed in TBI animal models, highlighting pertinent studies elucidating molecular pathways and expounding upon their mechanistic actions. We then investigated the current state of evidence for the utilization of COX-2 inhibitors for TBI patients.
{"title":"Selective COX-2 Inhibitors as Neuroprotective Agents in Traumatic Brain Injury.","authors":"Matthew I Hiskens, Anthony G Schneiders, Andrew S Fenning","doi":"10.3390/biomedicines12081930","DOIUrl":"https://doi.org/10.3390/biomedicines12081930","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 and COX-2 isoforms providing differing responses. Selective COX-2 inhibitors have shown potential as neuroprotective agents. Results from animal models of TBI suggest potential treatment through the alleviation of secondary injury mechanisms involving neuroinflammation and neuronal cell death. Additionally, early clinical trials have shown that the use of celecoxib improves patient mortality and outcomes. This review aims to summarize the therapeutic effects of COX-2 inhibitors observed in TBI animal models, highlighting pertinent studies elucidating molecular pathways and expounding upon their mechanistic actions. We then investigated the current state of evidence for the utilization of COX-2 inhibitors for TBI patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081918
Pasquale Ferorelli, Manfred Doepp, Stefano Lenzi, Roberto Rovelli, Gennaro Gisonna, Giuseppe Maierà, Francesco Antonelli, Massimo Radaelli, Anna Shevchenko, Giordana Feriotto, Carlo Mischiati, Ilaria Borromeo, Simone Beninati
Pressure ulcers (PUs) are a debilitating and often painful condition. They are localized lesions on the skin and/or underlying tissues and are common in the elderly, people with mobility difficulties, diabetics, and vascular disease or malnutrition, as well as in those requiring intensive or palliative care. The prevention and treatment of PUs involve strategies to optimize hydration, circulation, and nutrition. Nutrition plays a key role in pressure ulcer care because wounds require macronutrients and micronutrients to heal. Reports relating to the effectiveness of "Complementary Enzyme Therapy" also in the vulnological field led us to this study, the aim of which was to test the activity of a biodynamic food supplement (Citozym®) rich in carbohydrates, vitamins, and amylase and lactase and characterized by marked antioxidant activity. Citozym® administered topically and/or systemically, and in particular in both administrations, in patients suffering from Pus, has shown a marked reduction in bedsores and, in many cases, complete healing. Furthermore, it was possible to observe a lower incidence of side effects compared to conventional therapies. The results obtained, confirmed by various tests and recognized by the scientific community, allow us to conclude that treatment with Citozym® could represent a new and effective strategy for the treatment of PUs.
{"title":"Therapeutic Potential of a Biodynamic Supplement on Skin Pressure Ulcers: A Randomized Clinical Study.","authors":"Pasquale Ferorelli, Manfred Doepp, Stefano Lenzi, Roberto Rovelli, Gennaro Gisonna, Giuseppe Maierà, Francesco Antonelli, Massimo Radaelli, Anna Shevchenko, Giordana Feriotto, Carlo Mischiati, Ilaria Borromeo, Simone Beninati","doi":"10.3390/biomedicines12081918","DOIUrl":"https://doi.org/10.3390/biomedicines12081918","url":null,"abstract":"<p><p>Pressure ulcers (PUs) are a debilitating and often painful condition. They are localized lesions on the skin and/or underlying tissues and are common in the elderly, people with mobility difficulties, diabetics, and vascular disease or malnutrition, as well as in those requiring intensive or palliative care. The prevention and treatment of PUs involve strategies to optimize hydration, circulation, and nutrition. Nutrition plays a key role in pressure ulcer care because wounds require macronutrients and micronutrients to heal. Reports relating to the effectiveness of \"Complementary Enzyme Therapy\" also in the vulnological field led us to this study, the aim of which was to test the activity of a biodynamic food supplement (Citozym<sup>®</sup>) rich in carbohydrates, vitamins, and amylase and lactase and characterized by marked antioxidant activity. Citozym<sup>®</sup> administered topically and/or systemically, and in particular in both administrations, in patients suffering from Pus, has shown a marked reduction in bedsores and, in many cases, complete healing. Furthermore, it was possible to observe a lower incidence of side effects compared to conventional therapies. The results obtained, confirmed by various tests and recognized by the scientific community, allow us to conclude that treatment with Citozym<sup>®</sup> could represent a new and effective strategy for the treatment of PUs.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adenomyosis is characterized by ectopic proliferation of endometrial tissue within the myometrium. Histologically, this condition is marked by the presence of islands of benign endometrial glands surrounded by stromal cells. The myometrium appears thinner, and cross-sectional analysis often reveals signs of recent or chronic hemorrhage. The ectopic endometrial tissue may respond to ovarian hormonal stimulation, exhibiting proliferative or secretory changes during the menstrual cycle, potentially leading to bleeding, uterine swelling, and pain. Adenomyosis can appear as either a diffuse or focal condition. It is crucial to understand that adenomyosis involves the infiltration of the endometrium into the myometrium, rather than its displacement. The surgical management of adenomyosis is contingent upon its anatomical extent. The high incidence of the disease and the myths that develop around it increase the need to study its characteristics and its association with pregnancy and potential obstetric complications. These complications often require quick decisions, appropriate diagnosis, and proper counseling. Therefore, knowing the possible risks associated with adenomyosis is key to decision making. Pregnancy has a positive effect on adenomyosis and its painful symptoms. This improvement is not only due to the inhibition of ovulation, which inhibits the bleeding of adenomyotic tissue, but also to the metabolic, hormonal, immunological, and angiogenic changes associated with pregnancy. Adenomyosis affects pregnancy through disturbances of the endocrine system and the body's immune response at both local and systemic levels. It leads to bleeding from the adenomyotic tissue, molecular and functional abnormalities of the ectopic endometrium, abnormal placentation, and destruction of the adenomyotic tissue due to changes in the hormonal environment that characterizes pregnancy. Some of the obstetric complications that occur in women with adenomyosis in pregnancy include miscarriage, preterm delivery, placenta previa, low birth weight for gestational age, obstetric hemorrhage, and the need for cesarean section. These complications are an understudied field and remain unknown to the majority of obstetricians. These pathological conditions pose challenges to both the typical progression of pregnancy and the smooth conduct of labor in affected women. Further multicenter studies are imperative to validate the most suitable method for concluding labor following surgical intervention for adenomyosis.
{"title":"The Impact of Adenomyosis on Pregnancy.","authors":"Panagiotis Tsikouras, Nektaria Kritsotaki, Konstantinos Nikolettos, Sonia Kotanidou, Efthymios Oikonomou, Anastasia Bothou, Sotiris Andreou, Theopi Nalmpanti, Kyriaki Chalkia, Vlasios Spanakis, Nikolaos Tsikouras, Melda Chalil, Nikolaos Machairiotis, George Iatrakis, Nikolaos Nikolettos","doi":"10.3390/biomedicines12081925","DOIUrl":"https://doi.org/10.3390/biomedicines12081925","url":null,"abstract":"<p><p>Adenomyosis is characterized by ectopic proliferation of endometrial tissue within the myometrium. Histologically, this condition is marked by the presence of islands of benign endometrial glands surrounded by stromal cells. The myometrium appears thinner, and cross-sectional analysis often reveals signs of recent or chronic hemorrhage. The ectopic endometrial tissue may respond to ovarian hormonal stimulation, exhibiting proliferative or secretory changes during the menstrual cycle, potentially leading to bleeding, uterine swelling, and pain. Adenomyosis can appear as either a diffuse or focal condition. It is crucial to understand that adenomyosis involves the infiltration of the endometrium into the myometrium, rather than its displacement. The surgical management of adenomyosis is contingent upon its anatomical extent. The high incidence of the disease and the myths that develop around it increase the need to study its characteristics and its association with pregnancy and potential obstetric complications. These complications often require quick decisions, appropriate diagnosis, and proper counseling. Therefore, knowing the possible risks associated with adenomyosis is key to decision making. Pregnancy has a positive effect on adenomyosis and its painful symptoms. This improvement is not only due to the inhibition of ovulation, which inhibits the bleeding of adenomyotic tissue, but also to the metabolic, hormonal, immunological, and angiogenic changes associated with pregnancy. Adenomyosis affects pregnancy through disturbances of the endocrine system and the body's immune response at both local and systemic levels. It leads to bleeding from the adenomyotic tissue, molecular and functional abnormalities of the ectopic endometrium, abnormal placentation, and destruction of the adenomyotic tissue due to changes in the hormonal environment that characterizes pregnancy. Some of the obstetric complications that occur in women with adenomyosis in pregnancy include miscarriage, preterm delivery, placenta previa, low birth weight for gestational age, obstetric hemorrhage, and the need for cesarean section. These complications are an understudied field and remain unknown to the majority of obstetricians. These pathological conditions pose challenges to both the typical progression of pregnancy and the smooth conduct of labor in affected women. Further multicenter studies are imperative to validate the most suitable method for concluding labor following surgical intervention for adenomyosis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081931
Fabrice Demoniere, Rim Abdelli, Léna Rivard
Atrial fibrillation (AF) and dementia are major global public health issues and share common risk factors, especially after the age of 65 and regardless of the presence of stroke. Despite accounting for potential confounders, AF appears to be an independent risk factor for cognitive decline and dementia. The mechanisms are likely to be multifactorial and may include AF-related ischemic stroke, cerebral hypoperfusion, microbleeds, systemic inflammation, genetic factors, and small vessel disease, leading to brain atrophy and white matter damage. The early aggressive management of AF and comorbidities may reduce the risk of dementia. Indeed, the early detection of AF-related cognitive impairment should allow for the early implementation of measures to prevent the development of dementia, mainly through integrative approaches involving the correction of risk factors and maintenance of rhythm control. Well-designed prospective studies are needed to determine whether early detection and AF treatment can prevent dementia and identify whether optimal integrative measures are effective in preventing cognitive impairment and dementia.
{"title":"Could the Early Detection of Atrial Fibrillation Reduce the Risk of Developing Dementia?","authors":"Fabrice Demoniere, Rim Abdelli, Léna Rivard","doi":"10.3390/biomedicines12081931","DOIUrl":"https://doi.org/10.3390/biomedicines12081931","url":null,"abstract":"<p><p>Atrial fibrillation (AF) and dementia are major global public health issues and share common risk factors, especially after the age of 65 and regardless of the presence of stroke. Despite accounting for potential confounders, AF appears to be an independent risk factor for cognitive decline and dementia. The mechanisms are likely to be multifactorial and may include AF-related ischemic stroke, cerebral hypoperfusion, microbleeds, systemic inflammation, genetic factors, and small vessel disease, leading to brain atrophy and white matter damage. The early aggressive management of AF and comorbidities may reduce the risk of dementia. Indeed, the early detection of AF-related cognitive impairment should allow for the early implementation of measures to prevent the development of dementia, mainly through integrative approaches involving the correction of risk factors and maintenance of rhythm control. Well-designed prospective studies are needed to determine whether early detection and AF treatment can prevent dementia and identify whether optimal integrative measures are effective in preventing cognitive impairment and dementia.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081929
Silvia Salvi, Stefano Fruci, Valentina Lacconi, Federica Totaro Aprile, Roberta Rullo, Heidi Stuhlmann, Antonio Lanzone, Luisa Campagnolo, Micol Massimiani
The primary intervention for pre-eclampsia (PE) remains iatrogenic delivery, which can be very preterm and not optimal for the fetus. Although many efforts have been made to prevent and manage PE, there is still a dearth of drugs to treat its pathophysiological progression. Pravastatin (PRA), a hydrophilic statin, has gained interest for the prevention and treatment of PE. The aim of the present study was to evaluate the ability of PRA to modulate factors involved in placentation, such as Epidermal Growth Factor-Like Domain 7 (EGFL7), in human chorionic villous culture from healthy controls and women with PE. A total of 18 women were enrolled: 10 controls and 8 cases. Chorionic villous explants were maintained in culture for 24 h with or without 10 μM Pravastatin, and the expression of EGFL7 and NOTCH1 pathway members was evaluated by qRT-PCR and Western blot analysis. The rationale of the present study was to establish an ex vivo model to identify potential different responses to PRA treatment of chorionic villous explants in order to clarify the molecular mechanism of PRA in the prevention and treatment of PE and to predict whether there are specific clinical conditions that modulate the response to the drug treatment. Within PE patients, two different groups were identified: the high responders, whose villous cultures exhibit significantly increased expressions of the EGFL7 and Notch pathways after PRA incubation; and the low responders, who are high-risk PE patients in which prophylaxis failed to prevent PE and PRA was not able to modulate EGFL7 expression. In conclusion, we identified EGFL7 as a new factor regulated by PRA, placing interest in early discrimination between low- and high- risk women, in which the well-known pharmacological prophylaxis seems to be ineffective, and to explore new potential prevention strategies.
先兆子痫(PE)的主要干预措施仍然是先兆流产,这可能会导致早产,对胎儿不利。尽管人们为预防和控制子痫前期做出了许多努力,但治疗其病理生理进展的药物仍然匮乏。普伐他汀(PRA)是一种亲水性他汀类药物,在预防和治疗 PE 方面已引起人们的关注。本研究旨在评估 PRA 在健康对照组和 PE 妇女的人绒毛膜培养中调节参与胎盘形成的因子(如表皮生长因子样域 7 (EGFL7))的能力。共有 18 名妇女参加了研究:其中对照组 10 人,病例 8 人。绒毛外植体在添加或不添加 10 μM 普拉伐他汀的情况下培养 24 小时,并通过 qRT-PCR 和 Western 印迹分析评估 EGFL7 和 NOTCH1 通路成员的表达。本研究的目的是建立一个体外模型,以确定绒毛膜外植体对 PRA 治疗的潜在不同反应,从而阐明 PRA 在预防和治疗 PE 中的分子机制,并预测是否有特定的临床条件会调节对药物治疗的反应。在 PE 患者中,我们发现了两个不同的群体:高反应者,他们的绒毛培养物在经过 PRA 培养后,EGFL7 和 Notch 通路的表达明显增加;低反应者,他们是高危 PE 患者,预防性治疗未能预防 PE,PRA 也无法调节 EGFL7 的表达。总之,我们发现 EGFL7 是受 PRA 调控的一个新因子,这使我们有兴趣及早区分低风险和高风险妇女(众所周知的药物预防似乎对这些妇女无效),并探索新的潜在预防策略。
{"title":"Effect of Pravastatin on Placental Expression of Epidermal Growth Factor-like Domain 7 in Early-Onset Pre-Eclampsia: A New Potential Mechanism of Action.","authors":"Silvia Salvi, Stefano Fruci, Valentina Lacconi, Federica Totaro Aprile, Roberta Rullo, Heidi Stuhlmann, Antonio Lanzone, Luisa Campagnolo, Micol Massimiani","doi":"10.3390/biomedicines12081929","DOIUrl":"https://doi.org/10.3390/biomedicines12081929","url":null,"abstract":"<p><p>The primary intervention for pre-eclampsia (PE) remains iatrogenic delivery, which can be very preterm and not optimal for the fetus. Although many efforts have been made to prevent and manage PE, there is still a dearth of drugs to treat its pathophysiological progression. Pravastatin (PRA), a hydrophilic statin, has gained interest for the prevention and treatment of PE. The aim of the present study was to evaluate the ability of PRA to modulate factors involved in placentation, such as Epidermal Growth Factor-Like Domain 7 (EGFL7), in human chorionic villous culture from healthy controls and women with PE. A total of 18 women were enrolled: 10 controls and 8 cases. Chorionic villous explants were maintained in culture for 24 h with or without 10 μM Pravastatin, and the expression of EGFL7 and NOTCH1 pathway members was evaluated by qRT-PCR and Western blot analysis. The rationale of the present study was to establish an ex vivo model to identify potential different responses to PRA treatment of chorionic villous explants in order to clarify the molecular mechanism of PRA in the prevention and treatment of PE and to predict whether there are specific clinical conditions that modulate the response to the drug treatment. Within PE patients, two different groups were identified: the high responders, whose villous cultures exhibit significantly increased expressions of the EGFL7 and Notch pathways after PRA incubation; and the low responders, who are high-risk PE patients in which prophylaxis failed to prevent PE and PRA was not able to modulate EGFL7 expression. In conclusion, we identified EGFL7 as a new factor regulated by PRA, placing interest in early discrimination between low- and high- risk women, in which the well-known pharmacological prophylaxis seems to be ineffective, and to explore new potential prevention strategies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081926
Anca Otilia Farcas, Mihai Ciprian Stoica, Ioana Maria Maier, Adrian Cornel Maier, Anca Ileana Sin
Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the sampling of a fragment of myocardial tissue from the right ventricular septum using fluoroscopic guidance. This tissue can later be subjected to histopathological, immunohistochemical or molecular analysis, providing valuable information for cardiac allograft rejection, but this procedure is not without complications. To increase the accuracy of the rejection diagnosis, EMB requires a systematic evaluation of endocardium, myocardium, interstitium and intramural vessels. There are three types of rejection: hyperacute, acute or chronic, diagnosed by the histopathological evaluation of EMB as well as by new diagnostic methods such as DSA, ddcfDNA and gene expression profiling, the last having a high negative predictive value. More than 50 years after the introduction of EMB in medical practice, it still remains the "gold standard" in monitoring rejection in HT recipients but other new, less invasive diagnostic methods reduce the number of EMBs required.
{"title":"Heart Transplant Rejection: From the Endomyocardial Biopsy to Gene Expression Profiling.","authors":"Anca Otilia Farcas, Mihai Ciprian Stoica, Ioana Maria Maier, Adrian Cornel Maier, Anca Ileana Sin","doi":"10.3390/biomedicines12081926","DOIUrl":"https://doi.org/10.3390/biomedicines12081926","url":null,"abstract":"<p><p>Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the sampling of a fragment of myocardial tissue from the right ventricular septum using fluoroscopic guidance. This tissue can later be subjected to histopathological, immunohistochemical or molecular analysis, providing valuable information for cardiac allograft rejection, but this procedure is not without complications. To increase the accuracy of the rejection diagnosis, EMB requires a systematic evaluation of endocardium, myocardium, interstitium and intramural vessels. There are three types of rejection: hyperacute, acute or chronic, diagnosed by the histopathological evaluation of EMB as well as by new diagnostic methods such as DSA, ddcfDNA and gene expression profiling, the last having a high negative predictive value. More than 50 years after the introduction of EMB in medical practice, it still remains the \"gold standard\" in monitoring rejection in HT recipients but other new, less invasive diagnostic methods reduce the number of EMBs required.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081922
George Ciulei, Olga Hilda Orășan, Angela Cozma, Vasile Negrean, Teodora Gabriela Alexescu, Simina Țărmure, Florin Eugen Casoinic, Roxana Liana Lucaciu, Adriana Corina Hangan, Lucia Maria Procopciuc
(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case-control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development.
(1)结直肠癌是癌症相关死亡的主要原因,结直肠腺瘤(CRA)是其前兆。确定维生素 D 缺乏和胰岛素样生长因子(IGF)轴等风险因素对于预防至关重要。(2)这项病例对照研究包括 85 名接受结肠镜检查的参与者(53 名 CRA 患者和 32 名对照组)。我们测量了血清维生素 D3(胆钙化醇)、降钙素醇(维生素 D 代谢物)、降钙素三醇(活性维生素 D 代谢物)、胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3),以探讨它们与 CRA 风险的关系。(3)结果:我们发现,较低的胆钙化醇水平是导致 CRA 的重要风险因素(OR = 4.63,P = 0.004)。虽然在 CRA 患者和对照组之间没有观察到降钙二醇和降钙素三醇水平的明显差异,但在研究人群中,降钙二醇缺乏症很常见。在 CRA 患者中,IGF-1 水平与年龄、降钙素三醇和 IGFBP-3 成反比。(4)本研究强调了较低的胆钙化醇水平有可能检测出有CRA风险的患者,而降钙素三醇水平则不能,这表明在癌症预防研究中评估不同维生素D代谢物的重要性。我们的发现强调了进一步研究降钙三醇(维生素 D 的活性形式)与 IGF 轴在结直肠癌发展中的相互作用的必要性。
{"title":"Exploring Vitamin D Deficiency and IGF Axis Dynamics in Colorectal Adenomas.","authors":"George Ciulei, Olga Hilda Orășan, Angela Cozma, Vasile Negrean, Teodora Gabriela Alexescu, Simina Țărmure, Florin Eugen Casoinic, Roxana Liana Lucaciu, Adriana Corina Hangan, Lucia Maria Procopciuc","doi":"10.3390/biomedicines12081922","DOIUrl":"https://doi.org/10.3390/biomedicines12081922","url":null,"abstract":"<p><p>(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case-control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, <i>p</i> = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081928
Antonio Arnaiz-Villena, Ignacio Juarez, Christian Vaquero-Yuste, Tomás Lledo, José Manuel Martin-Villa, Fabio Suarez-Trujillo
The relationship between microbiota and the immune system is complex and characterized by the ways in which microbiota directs immune function interactions, both innate and acquired and also keeps activating the immune system throughout an individual's life. In this respect, the human Major Histocompatibility Complex (MHC, referred to as HLA in humans) plays a crucial role and is also established in self-defense against microbes by presenting microbial-derived peptides to the immune cells. However, this assumption has some unclear aspects that should be investigated. For example, how is the microbiota shaped by microbe species diversity, quantity and functions of the immune system, as well as the role and molecular mechanisms of the HLA complex during this process. There are autoimmune diseases related to both HLA and specific microbiota changes or alterations, many of which are mentioned in the present review. In addition, the HLA peptide presenting function should be put in a framework together with its linkage to diseases and also with HLA compatibility necessary for transplants to be successful. These are still quite an enigmatically statistical and phenomenological approach, but no firm pathogenic mechanisms have been described; thus, HLA's real functioning is still to be fully unveiled. After many years of HLA single-genes studies, firm pathogenesis mechanisms underlying disease linkage have been discovered. Finally, microbiota has been defined as conformed by bacteria, protozoa, archaea, fungi, and viruses; notwithstanding, endogenous viral sequences integrated into the human genome and other viral particles (obelisks) recently found in the digestive mucosa should be taken into account because they may influence both the microbiome and the immune system and their interactions. In this context, we propose to integrate these microbial-genetic particle components into the microbiome concept and designate it as "microgenobiota".
{"title":"Complex Interactions between the Human Major Histocompatibility Complex (MHC) and Microbiota: Their Roles in Disease Pathogenesis and Immune System Regulation.","authors":"Antonio Arnaiz-Villena, Ignacio Juarez, Christian Vaquero-Yuste, Tomás Lledo, José Manuel Martin-Villa, Fabio Suarez-Trujillo","doi":"10.3390/biomedicines12081928","DOIUrl":"https://doi.org/10.3390/biomedicines12081928","url":null,"abstract":"<p><p>The relationship between microbiota and the immune system is complex and characterized by the ways in which microbiota directs immune function interactions, both innate and acquired and also keeps activating the immune system throughout an individual's life. In this respect, the human Major Histocompatibility Complex (MHC, referred to as HLA in humans) plays a crucial role and is also established in self-defense against microbes by presenting microbial-derived peptides to the immune cells. However, this assumption has some unclear aspects that should be investigated. For example, how is the microbiota shaped by microbe species diversity, quantity and functions of the immune system, as well as the role and molecular mechanisms of the HLA complex during this process. There are autoimmune diseases related to both HLA and specific microbiota changes or alterations, many of which are mentioned in the present review. In addition, the HLA peptide presenting function should be put in a framework together with its linkage to diseases and also with HLA compatibility necessary for transplants to be successful. These are still quite an enigmatically statistical and phenomenological approach, but no firm pathogenic mechanisms have been described; thus, HLA's real functioning is still to be fully unveiled. After many years of HLA single-genes studies, firm pathogenesis mechanisms underlying disease linkage have been discovered. Finally, microbiota has been defined as conformed by bacteria, protozoa, archaea, fungi, and viruses; notwithstanding, endogenous viral sequences integrated into the human genome and other viral particles (obelisks) recently found in the digestive mucosa should be taken into account because they may influence both the microbiome and the immune system and their interactions. In this context, we propose to integrate these microbial-genetic particle components into the microbiome concept and designate it as \"microgenobiota\".</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.3390/biomedicines12081923
Ahmed Farag, Sai Koung Ngeun, Masahiro Kaneda, Mohamed Aboubakr, Ryou Tanaka
Mesenchymal stem cells (MSCs) exhibit multipotency, self-renewal, and immune-modulatory properties, making them promising in regenerative medicine, particularly in cardiovascular treatments. However, optimizing the MSC source and induction method of cardiac differentiation is challenging. This study compares the cardiomyogenic potential of bone marrow (BM)-MSCs and adipose-derived (AD)-MSCs using 5-Azacytidine (5-Aza) alone or combined with low doses of Fibroblast Growth Factor (FGF) and Insulin-like Growth Factor (IGF). BM-MSCs and AD-MSCs were differentiated using two protocols: 10 μmol 5-Aza alone and 10 μmol 5-Aza with 1 ng/mL FGF and 10 ng/mL IGF. Morphological, transcriptional, and translational analyses, along with cell viability assessments, were performed. Both the MSC types exhibited similar morphological changes; however, AD-MSCs achieved 70-80% confluence faster than BM-MSCs. Surface marker profiling confirmed CD29 and CD90 positivity and CD45 negativity. The differentiation protocols led to cell flattening and myotube formation, with earlier differentiation in AD-MSCs. The combined protocol reduced cell mortality in BM-MSCs and enhanced the expression of cardiac markers (MEF2c, Troponin I, GSK-3β), particularly in BM-MSCs. Immunofluorescence confirmed cardiac-specific protein expression in all the treated groups. Both MSC types exhibited the expression of cardiac-specific markers indicative of cardiomyogenic differentiation, with the combined treatment showing superior efficiency for BM-MSCs.
{"title":"Optimizing Cardiomyocyte Differentiation: Comparative Analysis of Bone Marrow and Adipose-Derived Mesenchymal Stem Cells in Rats Using 5-Azacytidine and Low-Dose FGF and IGF Treatment.","authors":"Ahmed Farag, Sai Koung Ngeun, Masahiro Kaneda, Mohamed Aboubakr, Ryou Tanaka","doi":"10.3390/biomedicines12081923","DOIUrl":"https://doi.org/10.3390/biomedicines12081923","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) exhibit multipotency, self-renewal, and immune-modulatory properties, making them promising in regenerative medicine, particularly in cardiovascular treatments. However, optimizing the MSC source and induction method of cardiac differentiation is challenging. This study compares the cardiomyogenic potential of bone marrow (BM)-MSCs and adipose-derived (AD)-MSCs using 5-Azacytidine (5-Aza) alone or combined with low doses of Fibroblast Growth Factor (FGF) and Insulin-like Growth Factor (IGF). BM-MSCs and AD-MSCs were differentiated using two protocols: 10 μmol 5-Aza alone and 10 μmol 5-Aza with 1 ng/mL FGF and 10 ng/mL IGF. Morphological, transcriptional, and translational analyses, along with cell viability assessments, were performed. Both the MSC types exhibited similar morphological changes; however, AD-MSCs achieved 70-80% confluence faster than BM-MSCs. Surface marker profiling confirmed CD29 and CD90 positivity and CD45 negativity. The differentiation protocols led to cell flattening and myotube formation, with earlier differentiation in AD-MSCs. The combined protocol reduced cell mortality in BM-MSCs and enhanced the expression of cardiac markers (<i>MEF2c</i>, <i>Troponin I</i>, <i>GSK-3β</i>), particularly in BM-MSCs. Immunofluorescence confirmed cardiac-specific protein expression in all the treated groups. Both MSC types exhibited the expression of cardiac-specific markers indicative of cardiomyogenic differentiation, with the combined treatment showing superior efficiency for BM-MSCs.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The dysregulation of miRNA expression has been shown to impact cellular physiology and tumorigenesis. Studies have reported several miRNA regulatory elements and pathways that play a significant role in the diagnosis, prognosis, and treatment of hematological malignancies. This is the first study to test the differential expression of miRNAs at crucial stages of the disease, specifically newly diagnosed, resistant to treatment, and remission. Circulating miRNAs extracted from the blood samples of 18 patients diagnosed with leukemia or lymphoma at different stages and 2 healthy controls were quantified by qPCR using a panel of 96 tumorigenic miRNAs. An enrichment analysis was performed to understand the mechanisms through which differential miRNA expression affects cellular and molecular functions. Significant upregulation of hsa-miR-1, hsa-miR-20a-5p, hsa-miR-23a-3p, hsa-miR-92b3p, and hsa-miR-196a-5p was detected among the different stages of leukemia and lymphoma. mir-1 and mir-196a-5p were upregulated in the remission stage of leukemia, while mir-20a-5p, mir-23a-3p, and mir-92b-3p were upregulated during the resistant stage of lymphoma. The enrichment analysis revealed these miRNAs' involvement in the RAS signaling pathway, TGF-β signaling, and apoptotic pathways, among others. This study highlights new biomarkers that could be used as potential targets for disease diagnosis, prognosis, and treatment, therefore enhancing personalized treatments and survival outcomes for patients.
{"title":"miRNA Profiles in Patients with Hematological Malignancy at Different Stages of the Disease: A Preliminary Study.","authors":"Jood Hashem, Lujain Alkhalaileh, Hassan Abushukair, Mahmoud Ayesh","doi":"10.3390/biomedicines12081924","DOIUrl":"https://doi.org/10.3390/biomedicines12081924","url":null,"abstract":"<p><p>The dysregulation of miRNA expression has been shown to impact cellular physiology and tumorigenesis. Studies have reported several miRNA regulatory elements and pathways that play a significant role in the diagnosis, prognosis, and treatment of hematological malignancies. This is the first study to test the differential expression of miRNAs at crucial stages of the disease, specifically newly diagnosed, resistant to treatment, and remission. Circulating miRNAs extracted from the blood samples of 18 patients diagnosed with leukemia or lymphoma at different stages and 2 healthy controls were quantified by qPCR using a panel of 96 tumorigenic miRNAs. An enrichment analysis was performed to understand the mechanisms through which differential miRNA expression affects cellular and molecular functions. Significant upregulation of hsa-miR-1, hsa-miR-20a-5p, hsa-miR-23a-3p, hsa-miR-92b3p, and hsa-miR-196a-5p was detected among the different stages of leukemia and lymphoma. mir-1 and mir-196a-5p were upregulated in the remission stage of leukemia, while mir-20a-5p, mir-23a-3p, and mir-92b-3p were upregulated during the resistant stage of lymphoma. The enrichment analysis revealed these miRNAs' involvement in the RAS signaling pathway, TGF-β signaling, and apoptotic pathways, among others. This study highlights new biomarkers that could be used as potential targets for disease diagnosis, prognosis, and treatment, therefore enhancing personalized treatments and survival outcomes for patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}