Pub Date : 2024-10-17DOI: 10.3390/biomedicines12102371
Lu He, Rui Yin, Weijian Hang, Jinli Han, Juan Chen, Bin Wen, Ling Chen
Background: Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). Histone lactylation, a novel epigenetic modification where lactate is added to lysine residues, may play a role in HIE pathogenesis. This study investigates the role of histone lactylation in hypoxia-induced M1 microglial polarization and inflammation, aiming to provide insights for HIE treatment.
Methods: In this study, we assessed the effects of hypoxia on microglial polarization using both an HIE animal model and an oxygen-glucose deprivation cell model. Histone lactylation at various lysine residues was detected by Western blotting. Microglial polarization and inflammatory cytokines were analyzed by immunofluorescence, qPCR, and Western blotting. RNA sequencing, ChIP-qPCR, and siRNA were used to elucidate mechanisms of H3K9 lactylation.
Results: H3K9 lactylation increased due to cytoplasmic lactate during M1 polarization. Inhibiting P300 or reducing lactate dehydrogenase A expression decreased H3K9 lactylation, suppressing M1 polarization. Transcriptomic analysis indicated that H3K9 lactylation regulated M1 polarization via the TNF signaling pathway. ChIP-qPCR confirmed H3K9 lactylation enrichment at the TNFα locus, promoting OGD-induced M1 polarization and inflammation.
Conclusions: H3K9 lactylation promotes M1 polarization and inflammation via the TNF pathway, identifying it as a potential therapeutic target for neonatal HIE.
背景:缺氧诱导的小胶质细胞 M1 极化和由此产生的炎症参与了缺氧缺血性脑病(HIE)造成的损害。组蛋白乳酰化是一种新型表观遗传修饰,即在赖氨酸残基上添加乳酸,可能在 HIE 发病机制中发挥作用。本研究探讨了组蛋白乳酰化在缺氧诱导的M1小胶质细胞极化和炎症中的作用,旨在为HIE的治疗提供启示:在这项研究中,我们利用HIE动物模型和氧-葡萄糖剥夺细胞模型评估了缺氧对小胶质细胞极化的影响。通过 Western 印迹法检测了不同赖氨酸残基上的组蛋白乳酰化。通过免疫荧光、qPCR 和 Western 印迹分析了小胶质细胞极化和炎性细胞因子。利用 RNA 测序、ChIP-qPCR 和 siRNA 阐明了 H3K9 乳化的机制:结果:在M1极化过程中,细胞质乳酸导致H3K9乳酸化增加。抑制 P300 或减少乳酸脱氢酶 A 的表达可减少 H3K9 乳化,从而抑制 M1 极化。转录组分析表明,H3K9 乳酰化通过 TNF 信号通路调控 M1 极化。ChIP-qPCR证实H3K9乳酰化富集于TNFα位点,促进了OGD诱导的M1极化和炎症:结论:H3K9乳酰化通过TNF通路促进M1极化和炎症,是新生儿HIE的潜在治疗靶点。
{"title":"Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway.","authors":"Lu He, Rui Yin, Weijian Hang, Jinli Han, Juan Chen, Bin Wen, Ling Chen","doi":"10.3390/biomedicines12102371","DOIUrl":"10.3390/biomedicines12102371","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). Histone lactylation, a novel epigenetic modification where lactate is added to lysine residues, may play a role in HIE pathogenesis. This study investigates the role of histone lactylation in hypoxia-induced M1 microglial polarization and inflammation, aiming to provide insights for HIE treatment.</p><p><strong>Methods: </strong>In this study, we assessed the effects of hypoxia on microglial polarization using both an HIE animal model and an oxygen-glucose deprivation cell model. Histone lactylation at various lysine residues was detected by Western blotting. Microglial polarization and inflammatory cytokines were analyzed by immunofluorescence, qPCR, and Western blotting. RNA sequencing, ChIP-qPCR, and siRNA were used to elucidate mechanisms of H3K9 lactylation.</p><p><strong>Results: </strong>H3K9 lactylation increased due to cytoplasmic lactate during M1 polarization. Inhibiting P300 or reducing lactate dehydrogenase A expression decreased H3K9 lactylation, suppressing M1 polarization. Transcriptomic analysis indicated that H3K9 lactylation regulated M1 polarization via the TNF signaling pathway. ChIP-qPCR confirmed H3K9 lactylation enrichment at the TNFα locus, promoting OGD-induced M1 polarization and inflammation.</p><p><strong>Conclusions: </strong>H3K9 lactylation promotes M1 polarization and inflammation via the TNF pathway, identifying it as a potential therapeutic target for neonatal HIE.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494290","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 : 2024-10-17DOI: 10.3390/biomedicines12102372
Roberta Granata, Antonio Zanghì, Marianna Scribano, Giordana Riccioli, Francesca Privitera, Sandro La Vignera, Rosita Angela Condorelli, Francesco Leonforte, Antonio Mistretta, Aldo Eugenio Calogero, Massimiliano Veroux
Background: Hypoparathyroidism with hypocalcemia is the most frequent complication after thyroid surgery. Many risk factors have been involved in the development of this complication, with conflicting results. Incidental parathyroidectomy (IP) may be a frequent cause of postoperative hypocalcemia. In this study, we have evaluated the risk factors associated with the IP in a single-center cohort of patients undergoing thyroid surgery.
Patients and methods: The incidence and the risk factors for IP were evaluated in 799 patients scheduled for surgical treatment for thyroid disease between January 2018 and December 2023. Parathyroid hormone levels and serum calcium levels, together with the histological specimens, were evaluated in all patients.
Results: Post-operative temporary hypocalcemia was present in 239 (29.9%) patients. A total of 144 patients (21.9%) had an incidental parathyroidectomy. Younger patients (<40 years) had the highest risk of having an incidental parathyroidectomy (RR 1.53 (95% CI 1.084-2.161), OR 1.72 (95% CI 1.091-2.710), p = 0.014). Moreover, thyroid cancer (RR 1.4 (95 CI 1.114-1.882) OR 1.68 (95% CI 1.145-2.484), p < 0.05) and the neck dissection (RR 1.75 (95% CI 1.409-2.198) OR 2.38 (95% CI 1.644-3.460), p < 0.001) were strongly associated with the risk of incidental parathyroidectomy.
Conclusions: Younger female patients with thyroid cancer and neck dissection were at the highest risk of incidental parathyroidectomy. A meticulous surgical dissection, together with imaging methods for the detection of the parathyroid glands, may reduce the incidence of this complication.
背景:甲状旁腺功能减退伴低钙血症是甲状腺手术后最常见的并发症。许多风险因素都与这种并发症的发生有关,但结果却相互矛盾。偶然的甲状旁腺切除术(IP)可能是导致术后低钙血症的一个常见原因。在这项研究中,我们评估了单中心甲状腺手术患者队列中与IP相关的风险因素:对2018年1月至2023年12月期间计划接受甲状腺疾病手术治疗的799名患者进行了IP发生率和风险因素评估。对所有患者的甲状旁腺激素水平、血清钙水平以及组织学标本进行了评估:239名患者(29.9%)出现术后暂时性低钙血症。共有144名患者(21.9%)偶然进行了甲状旁腺切除术。患者年龄较小(P = 0.014)。此外,甲状腺癌(RR 1.4 (95 CI 1.114-1.882) OR 1.68 (95 CI 1.145-2.484),p <0.05)和颈部切除术(RR 1.75 (95 CI 1.409-2.198) OR 2.38 (95 CI 1.644-3.460),p <0.001)与偶然甲状旁腺切除术的风险密切相关:甲状腺癌和颈部切除术的年轻女性患者发生甲状旁腺切除术意外的风险最高。细致的手术切除,加上检测甲状旁腺的成像方法,可以降低这种并发症的发生率。
{"title":"Incidental Parathyroidectomy After Thyroid Surgery: A Single-Center Study.","authors":"Roberta Granata, Antonio Zanghì, Marianna Scribano, Giordana Riccioli, Francesca Privitera, Sandro La Vignera, Rosita Angela Condorelli, Francesco Leonforte, Antonio Mistretta, Aldo Eugenio Calogero, Massimiliano Veroux","doi":"10.3390/biomedicines12102372","DOIUrl":"10.3390/biomedicines12102372","url":null,"abstract":"<p><strong>Background: </strong>Hypoparathyroidism with hypocalcemia is the most frequent complication after thyroid surgery. Many risk factors have been involved in the development of this complication, with conflicting results. Incidental parathyroidectomy (IP) may be a frequent cause of postoperative hypocalcemia. In this study, we have evaluated the risk factors associated with the IP in a single-center cohort of patients undergoing thyroid surgery.</p><p><strong>Patients and methods: </strong>The incidence and the risk factors for IP were evaluated in 799 patients scheduled for surgical treatment for thyroid disease between January 2018 and December 2023. Parathyroid hormone levels and serum calcium levels, together with the histological specimens, were evaluated in all patients.</p><p><strong>Results: </strong>Post-operative temporary hypocalcemia was present in 239 (29.9%) patients. A total of 144 patients (21.9%) had an incidental parathyroidectomy. Younger patients (<40 years) had the highest risk of having an incidental parathyroidectomy (RR 1.53 (95% CI 1.084-2.161), OR 1.72 (95% CI 1.091-2.710), <i>p</i> = 0.014). Moreover, thyroid cancer (RR 1.4 (95 CI 1.114-1.882) OR 1.68 (95% CI 1.145-2.484), <i>p</i> < 0.05) and the neck dissection (RR 1.75 (95% CI 1.409-2.198) OR 2.38 (95% CI 1.644-3.460), <i>p</i> < 0.001) were strongly associated with the risk of incidental parathyroidectomy.</p><p><strong>Conclusions: </strong>Younger female patients with thyroid cancer and neck dissection were at the highest risk of incidental parathyroidectomy. A meticulous surgical dissection, together with imaging methods for the detection of the parathyroid glands, may reduce the incidence of this complication.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494298","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 : 2024-10-17DOI: 10.3390/biomedicines12102375
Yannick Teumer, Daniel Eckart, Lyuboslav Katov, Markus Graf, Carlo Bothner, Wolfgang Rottbauer, Karolina Weinmann-Emhardt
Background: In electrophysiological procedures, multiple punctures on the femoral vein can be necessary depending on the number of catheters required. The femoral vein is typically located indirectly by using its anatomical relationship to the artery as a reference. However, this conventional approach can lead to significant complications, including bleeding, peri-interventional transfusion, pseudoaneurysms, or arteriovenous fistulas. Despite these risks, there is limited evidence comparing the safety of ultrasound-guided venipuncture versus the conventional technique in electrophysiological procedures. Objective: This study aimed to evaluate the impact of ultrasound-guided venipuncture on vascular access complications in electrophysiological procedures and to identify associated risk factors. Methods: In this single-center trial, patients scheduled for electrophysiological procedures at Ulm University Heart Center, Germany, were enrolled between November 2021 and October 2023. Venipuncture in the groin was performed using either the conventional or an ultrasound-guided approach. The primary composite endpoint was defined as peri-interventional major vascular access complications (Bleeding Academic Research Consortium (BARC) ≥2 bleeding, pseudoaneurysms, arteriovenous fistulas, and peri-interventional transfusion) and minor complications (BARC 1). Results: A total of 1370 patients were included: 749 in the conventional group and 621 in the ultrasound group. The primary endpoint was achieved in 19.2% of the conventional group and 12.1% of the ultrasound group (p < 0.001). An increased sheath diameter and a higher number of venous accesses were identified as risk factors for the primary endpoint. Conclusions: Ultrasound guidance for venous groin puncture in electrophysiological procedures reduces access-related complications, supporting its use with careful attention to sheath size and number.
{"title":"Ultrasound-Guided Venous Puncture Reduces Groin Complications in Electrophysiological Procedures.","authors":"Yannick Teumer, Daniel Eckart, Lyuboslav Katov, Markus Graf, Carlo Bothner, Wolfgang Rottbauer, Karolina Weinmann-Emhardt","doi":"10.3390/biomedicines12102375","DOIUrl":"10.3390/biomedicines12102375","url":null,"abstract":"<p><p><b>Background</b>: In electrophysiological procedures, multiple punctures on the femoral vein can be necessary depending on the number of catheters required. The femoral vein is typically located indirectly by using its anatomical relationship to the artery as a reference. However, this conventional approach can lead to significant complications, including bleeding, peri-interventional transfusion, pseudoaneurysms, or arteriovenous fistulas. Despite these risks, there is limited evidence comparing the safety of ultrasound-guided venipuncture versus the conventional technique in electrophysiological procedures. <b>Objective</b>: This study aimed to evaluate the impact of ultrasound-guided venipuncture on vascular access complications in electrophysiological procedures and to identify associated risk factors. Methods: In this single-center trial, patients scheduled for electrophysiological procedures at Ulm University Heart Center, Germany, were enrolled between November 2021 and October 2023. Venipuncture in the groin was performed using either the conventional or an ultrasound-guided approach. The primary composite endpoint was defined as peri-interventional major vascular access complications (Bleeding Academic Research Consortium (BARC) ≥2 bleeding, pseudoaneurysms, arteriovenous fistulas, and peri-interventional transfusion) and minor complications (BARC 1). <b>Results</b>: A total of 1370 patients were included: 749 in the conventional group and 621 in the ultrasound group. The primary endpoint was achieved in 19.2% of the conventional group and 12.1% of the ultrasound group (<i>p</i> < 0.001). An increased sheath diameter and a higher number of venous accesses were identified as risk factors for the primary endpoint. <b>Conclusions</b>: Ultrasound guidance for venous groin puncture in electrophysiological procedures reduces access-related complications, supporting its use with careful attention to sheath size and number.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494443","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}
Background/objectives: Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. Methods: Patients fulfilling the ACR 1987- or ACR/EULAR 2010-criteriae for RA. performed radiographs (erosions evaluated by the modified Sharp/van der Heidje erosion score) and biology for anti-citrullinated peptide antibodies (ACPAs), rheumatoid factors (RFs) and anti-nuclear antibodies (ANAs) at intervals of less than 2 years from dual-energy X-ray absorptiometry (DXA) for BMD assessment. Results: A total of 149 patients were included, (75.8% women, mean age of 62 y.o (SD 9.61) and a median disease duration of 132 months [60; 240]). A total of 61.1% patients were ACPA positive, 79.9% were erosive and 10.7% had a hip or spine T-score ≤ -2.5. A higher erosion score was associated with a lower BMD (value: -0.222; p = 0.009) and T-score (value -0.397; p < 0.0001) in the hip. ACPA status was associated with a higher erosion score (63.0 (53.2) vs. 45.5 (44.1) for ACPA- (p = 0.04)). ACPA titers were associated with a lower BMD in the hip (value -0.216; p = 0.01). In linear regression, erosion and BMD were still associated, but this association is not driven by ACPA status or titer. Conclusions: In RA patients, erosions and BMD are inversely associated but this relationship does not seem to be driven by autoimmunity only. However, the presence of ACPA or erosion should lead to osteoporosis screening.
背景/目的:类风湿性关节炎(RA)的侵蚀和骨质疏松症具有共同的机制。本研究旨在评估类风湿性关节炎的侵蚀与骨矿物质密度(BMD)之间的关系,以及这种关系是否由自身免疫驱动。研究方法对符合 ACR 1987 年或 ACR/EULAR 2010 年标准的 RA 患者进行影像学检查(用改良的 Sharp/van der Heidje 侵蚀评分法评估侵蚀情况),并在双能 X 射线吸收测定法(DXA)进行 BMD 评估后,间隔不到 2 年进行抗瓜氨酸肽抗体 (ACPA)、类风湿因子 (RF) 和抗核抗体 (ANA) 的生物学检查。结果共纳入 149 名患者(75.8% 为女性,平均年龄为 62 岁(SD 9.61),中位病程为 132 个月 [60; 240])。61.1%的患者ACPA阳性,79.9%为侵蚀性,10.7%的患者髋关节或脊柱T评分≤-2.5。侵蚀评分越高,髋部的 BMD(值:-0.222;p = 0.009)和 T 评分(值:-0.397;p < 0.0001)越低。ACPA 状态与较高的侵蚀评分相关(63.0 (53.2) vs. 45.5 (44.1) for ACPA- (p = 0.04))。ACPA 滴度与髋部较低的 BMD 相关(值为 -0.216;p = 0.01)。在线性回归中,侵蚀与 BMD 仍有关联,但这种关联并非由 ACPA 状态或滴度驱动。结论:在 RA 患者中,侵蚀与 BMD 呈反比关系,但这种关系似乎并非仅由自身免疫驱动。不过,出现 ACPA 或侵蚀时应进行骨质疏松症筛查。
{"title":"A Clinical Evaluation of the Role of Autoimmunity in the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis.","authors":"Margaux Moret, Caroline Morizot, Marcelo de Carvalho Bittencourt, Edem Allado, Isabelle Chary-Valckenaere, Damien Loeuille","doi":"10.3390/biomedicines12102376","DOIUrl":"10.3390/biomedicines12102376","url":null,"abstract":"<p><p><b>Background/objectives:</b> Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. <b>Methods:</b> Patients fulfilling the ACR 1987- or ACR/EULAR 2010-criteriae for RA. performed radiographs (erosions evaluated by the modified Sharp/van der Heidje erosion score) and biology for anti-citrullinated peptide antibodies (ACPAs), rheumatoid factors (RFs) and anti-nuclear antibodies (ANAs) at intervals of less than 2 years from dual-energy X-ray absorptiometry (DXA) for BMD assessment. <b>Results:</b> A total of 149 patients were included, (75.8% women, mean age of 62 y.o (SD 9.61) and a median disease duration of 132 months [60; 240]). A total of 61.1% patients were ACPA positive, 79.9% were erosive and 10.7% had a hip or spine T-score ≤ -2.5. A higher erosion score was associated with a lower BMD (value: -0.222; <i>p</i> = 0.009) and T-score (value -0.397; <i>p</i> < 0.0001) in the hip. ACPA status was associated with a higher erosion score (63.0 (53.2) vs. 45.5 (44.1) for ACPA- (<i>p</i> = 0.04)). ACPA titers were associated with a lower BMD in the hip (value -0.216; <i>p</i> = 0.01). In linear regression, erosion and BMD were still associated, but this association is not driven by ACPA status or titer. <b>Conclusions</b>: In RA patients, erosions and BMD are inversely associated but this relationship does not seem to be driven by autoimmunity only. However, the presence of ACPA or erosion should lead to osteoporosis screening.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494189","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}
Objectives: We aimed to explore the correlation between thyroid function and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 7516 T2DM patients were enrolled and grouped according to DKD status. Clinical parameters, including blood glucose parameters, thyroid function, and indicators of renal impairment, were collected and compared between the DKD and Non-DKD groups. Correlation analysis and univariate/multivariate logistic regression analyses were performed. Results: Age, T2DM duration, the use of insulin and lipid-lowering drugs, systolic and diastolic blood pressure, body mass index, and fasting blood glucose levels were greater in the DKD group than in the Non-DKD group (p < 0.001). Notably, compared with those in the Non-DKD group, patients in the DKD group had lower triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) levels and higher thyrotropin levels (p < 0.001). Univariate logistic regression analysis revealed that T3, T4, FT3, and FT4 levels were negatively correlated with the risk of DKD. Spearman correlation analysis confirmed that T3, T4, FT3, and FT4 levels were negatively correlated with blood urea nitrogen levels, blood creatinine levels, and the urinary albumin-to-creatinine ratio (p < 0.05). Multivariate logistic regression analysis revealed that a greater FT4 level was a protective factor against DKD in T2DM patients, especially in males, with a cut-off value of 13.35 pmol/L (area under the curve = 0.604). Conclusions: Thyroid hormone levels, especially FT4 levels, were significantly negatively correlated with DKD in T2DM patients.
{"title":"Lower Free Thyroxine Levels Are Associated with Diabetic Kidney Disease in Males with Type 2 Diabetes Mellitus: An Observational Cross-Sectional Study.","authors":"Jianan Shang, Yixuan Zheng, Meng Zhang, Meng Li, Wei Qiang, Jing Sui, Hui Guo, Bingyin Shi, Mingqian He","doi":"10.3390/biomedicines12102370","DOIUrl":"10.3390/biomedicines12102370","url":null,"abstract":"<p><p><b>Objectives</b>: We aimed to explore the correlation between thyroid function and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). <b>Methods</b>: A total of 7516 T2DM patients were enrolled and grouped according to DKD status. Clinical parameters, including blood glucose parameters, thyroid function, and indicators of renal impairment, were collected and compared between the DKD and Non-DKD groups. Correlation analysis and univariate/multivariate logistic regression analyses were performed. <b>Results</b>: Age, T2DM duration, the use of insulin and lipid-lowering drugs, systolic and diastolic blood pressure, body mass index, and fasting blood glucose levels were greater in the DKD group than in the Non-DKD group (<i>p</i> < 0.001). Notably, compared with those in the Non-DKD group, patients in the DKD group had lower triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) levels and higher thyrotropin levels (<i>p</i> < 0.001). Univariate logistic regression analysis revealed that T3, T4, FT3, and FT4 levels were negatively correlated with the risk of DKD. Spearman correlation analysis confirmed that T3, T4, FT3, and FT4 levels were negatively correlated with blood urea nitrogen levels, blood creatinine levels, and the urinary albumin-to-creatinine ratio (<i>p</i> < 0.05). Multivariate logistic regression analysis revealed that a greater FT4 level was a protective factor against DKD in T2DM patients, especially in males, with a cut-off value of 13.35 pmol/L (area under the curve = 0.604). <b>Conclusions</b>: Thyroid hormone levels, especially FT4 levels, were significantly negatively correlated with DKD in T2DM patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494332","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 : 2024-10-17DOI: 10.3390/biomedicines12102377
Natalia Stepanova
Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily in terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy in dialysis patients due to insufficient evidence of its benefits on cardiovascular mortality. However, the impact of dyslipidemia in PD patients may extend beyond cardiovascular concerns, influencing PD-related outcomes such as the peritoneal ultrafiltration rate, residual kidney function, PD technique survival, and overall mortality. This review challenges the traditional perspective by discussing dyslipidemia's potential role in PD-related complications, which may account for the observed link between dyslipidemia and increased all-cause mortality in PD patients. It explores the pathophysiology of dyslipidemia in PD, the molecular mechanisms linking dyslipidemia to peritoneal membrane dysfunction, and summarizes clinical evidence supporting this hypothesis. In addition, this paper examines the potential for therapeutic strategies to manage dyslipidemia to improve peritoneal membrane function and patient outcomes. The review calls for future research to investigate dyslipidemia as a potential contributor to peritoneal membrane dysfunction and to develop targeted interventions for PD patients.
{"title":"Dyslipidemia in Peritoneal Dialysis: Implications for Peritoneal Membrane Function and Patient Outcomes.","authors":"Natalia Stepanova","doi":"10.3390/biomedicines12102377","DOIUrl":"10.3390/biomedicines12102377","url":null,"abstract":"<p><p>Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily in terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy in dialysis patients due to insufficient evidence of its benefits on cardiovascular mortality. However, the impact of dyslipidemia in PD patients may extend beyond cardiovascular concerns, influencing PD-related outcomes such as the peritoneal ultrafiltration rate, residual kidney function, PD technique survival, and overall mortality. This review challenges the traditional perspective by discussing dyslipidemia's potential role in PD-related complications, which may account for the observed link between dyslipidemia and increased all-cause mortality in PD patients. It explores the pathophysiology of dyslipidemia in PD, the molecular mechanisms linking dyslipidemia to peritoneal membrane dysfunction, and summarizes clinical evidence supporting this hypothesis. In addition, this paper examines the potential for therapeutic strategies to manage dyslipidemia to improve peritoneal membrane function and patient outcomes. The review calls for future research to investigate dyslipidemia as a potential contributor to peritoneal membrane dysfunction and to develop targeted interventions for PD patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494215","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 : 2024-10-17DOI: 10.3390/biomedicines12102374
Maria L Perepechaeva, Natalia A Stefanova, Alevtina Y Grishanova, Nataliya G Kolosova
Background: It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions.
Methods: The work was performed on senescence-accelerated OXYS rats featuring elevated blood pressure, OXYSb rats (an OXYS substrain with normal blood pressure), and Wistar rats as a "healthy" control. The mRNA level was determined in the right and left ventricles, the right and left atria, and the aorta of 1-, 3-, and 12-month-old rats.
Results: We showed that all heart regions express CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs and revealed significant differences between heart regions both in the mRNA level of genes CYP1B1, CYP2J3, and CYP1A1 and in the time course of expression changes with age.
Conclusions: We noticed that expression levels of these CYPs in the heart regions and aorta differ between hypertensive OXYS rats, normotensive OXYSb rats, and healthy Wistar rats but could not detect any clear-cut patterns associated with the hypertensive status of OXYS rats.
{"title":"The Expression of Genes <i>CYP1A1</i>, <i>CYP1B1</i>, and <i>CYP2J3</i> in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension.","authors":"Maria L Perepechaeva, Natalia A Stefanova, Alevtina Y Grishanova, Nataliya G Kolosova","doi":"10.3390/biomedicines12102374","DOIUrl":"10.3390/biomedicines12102374","url":null,"abstract":"<p><strong>Background: </strong>It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions.</p><p><strong>Methods: </strong>The work was performed on senescence-accelerated OXYS rats featuring elevated blood pressure, OXYSb rats (an OXYS substrain with normal blood pressure), and Wistar rats as a \"healthy\" control. The mRNA level was determined in the right and left ventricles, the right and left atria, and the aorta of 1-, 3-, and 12-month-old rats.</p><p><strong>Results: </strong>We showed that all heart regions express CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs and revealed significant differences between heart regions both in the mRNA level of genes <i>CYP1B1</i>, <i>CYP2J3</i>, and <i>CYP1A1</i> and in the time course of expression changes with age.</p><p><strong>Conclusions: </strong>We noticed that expression levels of these CYPs in the heart regions and aorta differ between hypertensive OXYS rats, normotensive OXYSb rats, and healthy Wistar rats but could not detect any clear-cut patterns associated with the hypertensive status of OXYS rats.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494392","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 : 2024-10-16DOI: 10.3390/biomedicines12102366
Susell Parra-Rojas, Juliana Cassol Spanemberg, Nerea Del Mar Díaz-Robayna, Mariela Peralta-Mamani, Rocío Trinidad Velázquez Cayón
Background: We report on the cost-effectiveness of photobiomodulation (PBM) for the prevention and treatment of oral mucositis (OM) derived from the cytotoxic effects of antineoplastic therapy.
Methods: This review followed the PRISMA 2020 guidelines. A search was conducted in PubMed, Scopus, Web of Science, Embase, and OpenGrey. Articles published before 23 July 2024, were included. Randomized controlled trials (RCTs) that included patients with head and neck cancer undergoing chemotherapy and/or radiotherapy and a placebo group compared to an intervention group (PBM) were selected. The risk of bias was evaluated using the Joanna Briggs Institute tools. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and was rated as moderate.
Results: A total of 3 RCTs and 229 patients were included. PBM may represent an additional cost in the short term, but the incremental expenses derived from the cytotoxic effects of antineoplastic therapy are greater in the medium-long term. The intervention group (PBM) showed a lower incidence of severe OM compared to the control group (placebo).
Conclusions: PBM is a cost-effective long-term treatment, effective in preventing severe OM and improving the quality of life of cancer patients. More RCTs following the same standardized protocols are needed (registration CDR42024498825).
{"title":"Assessing the Cost-Effectiveness of Photobiomodulation for Oral Mucositis Prevention and Treatment: A Systematic Review.","authors":"Susell Parra-Rojas, Juliana Cassol Spanemberg, Nerea Del Mar Díaz-Robayna, Mariela Peralta-Mamani, Rocío Trinidad Velázquez Cayón","doi":"10.3390/biomedicines12102366","DOIUrl":"10.3390/biomedicines12102366","url":null,"abstract":"<p><strong>Background: </strong>We report on the cost-effectiveness of photobiomodulation (PBM) for the prevention and treatment of oral mucositis (OM) derived from the cytotoxic effects of antineoplastic therapy.</p><p><strong>Methods: </strong>This review followed the PRISMA 2020 guidelines. A search was conducted in PubMed, Scopus, Web of Science, Embase, and OpenGrey. Articles published before 23 July 2024, were included. Randomized controlled trials (RCTs) that included patients with head and neck cancer undergoing chemotherapy and/or radiotherapy and a placebo group compared to an intervention group (PBM) were selected. The risk of bias was evaluated using the Joanna Briggs Institute tools. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and was rated as moderate.</p><p><strong>Results: </strong>A total of 3 RCTs and 229 patients were included. PBM may represent an additional cost in the short term, but the incremental expenses derived from the cytotoxic effects of antineoplastic therapy are greater in the medium-long term. The intervention group (PBM) showed a lower incidence of severe OM compared to the control group (placebo).</p><p><strong>Conclusions: </strong>PBM is a cost-effective long-term treatment, effective in preventing severe OM and improving the quality of life of cancer patients. More RCTs following the same standardized protocols are needed (registration CDR42024498825).</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494213","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 : 2024-10-16DOI: 10.3390/biomedicines12102368
Alexander Lang, Daniel Oehler, Marcel Benkhoff, Yvonne Reinders, Maike Barcik, Khatereh Shahrjerdi, Madlen Kaldirim, Albert Sickmann, Lisa Dannenberg, Amin Polzin, Susanne Pfeiler, Malte Kelm, Maria Grandoch, Christian Jung, Norbert Gerdes
Background/objectives: Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion.
Methods: Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins.
Results: We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage.
Conclusions: Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.
{"title":"Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction.","authors":"Alexander Lang, Daniel Oehler, Marcel Benkhoff, Yvonne Reinders, Maike Barcik, Khatereh Shahrjerdi, Madlen Kaldirim, Albert Sickmann, Lisa Dannenberg, Amin Polzin, Susanne Pfeiler, Malte Kelm, Maria Grandoch, Christian Jung, Norbert Gerdes","doi":"10.3390/biomedicines12102368","DOIUrl":"10.3390/biomedicines12102368","url":null,"abstract":"<p><strong>Background/objectives: </strong>Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion.</p><p><strong>Methods: </strong>Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins.</p><p><strong>Results: </strong>We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage.</p><p><strong>Conclusions: </strong>Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494355","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}
With the increasing prevalence of end-stage kidney disease, the number of patients requiring hemodialysis (HD) continues to rise. While life-sustaining, HD is often associated with adverse effects such as muscle loss, physical deconditioning, fatigue, and compromised health-related quality of life (HRQoL). Recent research suggests that intradialytic exercise (IDE) and home-based exercise (HBE) may mitigate these adverse effects and improve patient outcomes. However, the existing literature mainly focuses on the outcomes of both exercises, whereas the comparison of types is often omitted. Hence, this review consolidates findings from studies investigating the effectiveness, implementation, safety, feasibility, and adherence of different types of IDE and HBE in HD patients. Overall, the current literature bolsters the significance of IDE and HBE for improving health in HD patients. IDE and HBE enhance physical function, cardiopulmonary capacity, HRQoL, and cognitive well-being. Some research proposed an indirect link between IDE and survival rates. Despite these benefits, challenges remain in implementing these exercise modalities, including patient adherence and the feasibility of routine exercise during HD sessions. Integrating these exercises into routine care allows healthcare providers to enhance outcomes for HD patients. Further research is suggested to optimize exercise protocols and explore long-term effects and cost-effectiveness.
随着终末期肾病发病率的不断上升,需要进行血液透析(HD)的患者人数也持续增加。血液透析虽然可以维持生命,但往往会带来肌肉流失、体能下降、疲劳和健康相关生活质量(HRQoL)下降等不良影响。最新研究表明,肾内锻炼(IDE)和家庭锻炼(HBE)可减轻这些不良影响,改善患者预后。然而,现有文献主要关注这两种运动的效果,而往往忽略了对运动类型的比较。因此,本综述整合了对不同类型 IDE 和 HBE 在 HD 患者中的有效性、实施情况、安全性、可行性和依从性的研究结果。总体而言,目前的文献证明了 IDE 和 HBE 对改善 HD 患者健康的重要意义。IDE 和 HBE 可增强患者的身体功能、心肺功能、心身质量和认知能力。一些研究提出,IDE 与存活率之间存在间接联系。尽管有这些益处,但在实施这些锻炼方式时仍面临挑战,包括患者的依从性和在 HD 治疗期间进行常规锻炼的可行性。将这些运动纳入常规护理,可使医护人员提高 HD 患者的治疗效果。建议进一步开展研究,以优化运动方案,探索长期效果和成本效益。
{"title":"Comparisons of Intradialytic Exercise Versus Home-Based Exercise in Hemodialysis Patients: A Narrative Review.","authors":"Chao-Lin Lee, Ping-Chen Wang, Yi-Ling Chen, Zen-Yong Chen, Ching-Cherng Uen, Hsien-Yung Lai, Chih-Chung Shiao","doi":"10.3390/biomedicines12102364","DOIUrl":"10.3390/biomedicines12102364","url":null,"abstract":"<p><p>With the increasing prevalence of end-stage kidney disease, the number of patients requiring hemodialysis (HD) continues to rise. While life-sustaining, HD is often associated with adverse effects such as muscle loss, physical deconditioning, fatigue, and compromised health-related quality of life (HRQoL). Recent research suggests that intradialytic exercise (IDE) and home-based exercise (HBE) may mitigate these adverse effects and improve patient outcomes. However, the existing literature mainly focuses on the outcomes of both exercises, whereas the comparison of types is often omitted. Hence, this review consolidates findings from studies investigating the effectiveness, implementation, safety, feasibility, and adherence of different types of IDE and HBE in HD patients. Overall, the current literature bolsters the significance of IDE and HBE for improving health in HD patients. IDE and HBE enhance physical function, cardiopulmonary capacity, HRQoL, and cognitive well-being. Some research proposed an indirect link between IDE and survival rates. Despite these benefits, challenges remain in implementing these exercise modalities, including patient adherence and the feasibility of routine exercise during HD sessions. Integrating these exercises into routine care allows healthcare providers to enhance outcomes for HD patients. Further research is suggested to optimize exercise protocols and explore long-term effects and cost-effectiveness.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494185","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}