{"title":"Human umbilical cord mesenchymal stem cell-derived exosomes combined with mouse nerve growth factor can more effectively ameliorate the motor disorder and brain pathological injury in mice with cerebral palsy.","authors":"Xingxing Chen, Yipa Sai, Weijing Cui, Xiaoxia Hu, Jing Liu, Xiaofeng Cao, Shili Wu","doi":"10.17219/acem/192773","DOIUrl":"https://doi.org/10.17219/acem/192773","url":null,"abstract":"<p><strong>Background: </strong>Cerebral palsy (CP) is a neurodevelopmental disorder and motor disorder syndrome. It has been confirmed that mesenchymal stem cells (MSCs) and mouse nerve growth factor (mNGF) can repair brain tissue damage and nerve injury; however, exosomes derived from healthy cells may have a comparable therapeutic potential as the cells themselves.</p><p><strong>Objectives: </strong>The purpose of this study was to explore the improvement effect of human umbilical cord mesenchymal stem cell (hUC-MSCs)-derived exosomes on a CP model and determine whether there is a synergistic effect when combined with mNGF.</p><p><strong>Material and methods: </strong>Exosomes were isolated from hUC-MSCs and examined using transmission electron microscopy (TEM), particle size and western blot (WB). A total of 38 BALB/c mice (male, postnatal day 6 (PND6)) were randomly divided into 5 groups: sham group, CP group, CP-exo group, CP-mNGF group, and CP-exo-mNGF group. Hypoxic induction after unilateral common carotid artery ligation combined with lipopolysaccharide (LPS) infection was used to construct the CP model. Pathological damage to neuron tissue and synaptic structures in the hippocampus was confirmed using light microscopy after hematoxylin-eosin (H&E) staining and TEM, respectively. Survival of neurons was evaluated using Nissl staining. Western blot was applied to monitor PSD-95 and synaptophysin (SYN) protein levels.</p><p><strong>Results: </strong>This study indicated that exosomes released by hUC-MSCs ameliorated brain damage and synaptic structure destruction in CP mice induced by hypoxic ischemia and LPS infection. When combined with mNGF, there was more effective improvement. In the CP group, neuronal function was severely impaired; however, hUC-MSCs-derived exosomes and mNGF improved it. PSD-95 and SYN proteins were presynaptic and postsynaptic proteins, respectively. Interestingly, the PSD-95 and SYN protein levels were significantly lower in the CP mice, but with the addition of hUC-MSCs-exosomes or mNGF, they increased significantly, especially in the CP-exo-mNGF group.</p><p><strong>Conclusions: </strong>The nerve function injury in CP can be improved the most when hUC-MSCs-derived exosomes are combined with mNGF through intraperitoneal (ip.) administration.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Se-Kwon Kim, Venkatesan Jayachandran, Thanh Sang Vo, Isuru Wijesekara
{"title":"Safety assessment of turmeric-boswellia-sesame formulation in healthy adult volunteers: An open-label prospective study.","authors":"Se-Kwon Kim, Venkatesan Jayachandran, Thanh Sang Vo, Isuru Wijesekara","doi":"10.17219/acem/193023","DOIUrl":"https://doi.org/10.17219/acem/193023","url":null,"abstract":"<p><strong>Background: </strong>Turmeric and boswellia supplements have gained popularity for their anti-inflammatory and antioxidant properties. It is important to critically assess the safety of such supplements for prolonged use.</p><p><strong>Objectives: </strong>To assess the safety and tolerability of turmeric-boswellia-sesame oil formulation (TBSF) in healthy human volunteers.</p><p><strong>Material and methods: </strong>Forty participants were supplemented with TBSF at a dose of 2,000 mg daily for 90 days. Safety assessments were performed at baseline, as well as on day 30, 60 and 90. Adverse events were monitored throughout the study period. Any evidence of hepatotoxicity injury or drug induced liver injury (DILI) was assessed using R value (R ratio/R factor), which is a relative pattern of liver enzymes. Additionally, Hy's law criteria, based on liver enzymes and bilirubin levels, were employed, along with an evaluation of drug-induced serious hepatotoxicity (eDISH) plot. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated, as these values are relevant to the safety of the intervention.</p><p><strong>Results: </strong>The study found that TBSF supplementation did not cause any adverse effects or clinically significant variations in vital signs, hematological parameters, lipid profile, liver function enzymes, and renal function markers, and all were within the normal range after 90 days of TBSF supplementation. Platelet-to-lymphocyte ratio and NLR did not change significantly and were within the normal range. All the participants when plotted were in the normal range quadrant of the eDISH plot throughout the study period. No abnormal findings were observed in R value and Hy's law criteria, indicating that TBSF does not induce any hepatotoxicity. The present study showed a normal estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine (Cr), Cr clearance, and BUN/Cr ratio throughout the study period. There was no significant change between these values at 4 abovementioned time points.</p><p><strong>Conclusions: </strong>The study findings suggest that TBSF is a safe supplement for regular and long-term consumption.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effect of downregulation of ARL9 expression on the proliferation, metastasis and biological behavior of AGS gastric cancer cell lines.","authors":"Caihua Sun, Hongliang Yao, Jipan Liu, Shuai Wang","doi":"10.17219/acem/193399","DOIUrl":"https://doi.org/10.17219/acem/193399","url":null,"abstract":"<p><strong>Background: </strong>Some ADP ribosylation factors (ARF) and ADP ribosylation factor-like (ARL) family are involved in the regulation of certain cancers, but the role of ADP ribosylation factor-like 9 (ARL9) in gastric tumorigenesis remains elusive.</p><p><strong>Objectives: </strong>The main aim of this study was to evaluate the ARL9 expression within stomach cancer cells and elucidate its influence on the modulation of cancer cell behavior.</p><p><strong>Material and methods: </strong>Differential ARL9 protein expression in normal stomach and stomach cancer tissue was ascertained through data sourced from the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN). Quantitative analysis of ARL9 expression in gastric cancer tissue and its association with clinicopathological features was performed using quantitative polymerase chain reaction (qPCR) and western blot analysis (WB). Small interfering RNA (siRNA) was employed to suppress ARL9 protein expression in the human stomach gastric adenocarcinoma human gastric adenocarcinoma cells (AGS) cell line. Assessment of AGS gastric cancer (GC) cell proliferation, invasion and migration was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and transwell techniques.</p><p><strong>Results: </strong>The expression of ARL9 protein exhibited a significant upregulation in GC tissue, and showed a close association between tumor dimensions (p < 0.05) and the presence of distant metastases (p < 0.05) among individuals diagnosed with GC. However, no significant link was observed with sex, age and tumor-node-metastasis (TNM) staging in gastric malignancy patients. After the introduction of si-ARL9 in the experimental set, there was a noteworthy decrease in ARL9 protein levels in AGS cells (p < 0.01). In contrast to the control cohort, the restraint of ARL9 expression significantly hampered the growth, mobility and infiltration abilities of the AGS GC cell line (p < 0.01).</p><p><strong>Conclusions: </strong>The significant correlation of ARL9 with the biological behavior of GC indicates its potentially pivotal role in the pathophysiology of the malignancy.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Renal protection by acacetin in streptozotocin-induced diabetic nephropathy via TLR4/NF-κB pathway modulation in rats.","authors":"Hangying Yu, Min Guo","doi":"10.17219/acem/192225","DOIUrl":"https://doi.org/10.17219/acem/192225","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN), the most severe microvascular consequence of diabetes mellitus (DM), is the precursor to end-stage renal disease (ESRD). The development of problems linked to DN involves both oxidative damage and inflammation. Natural flavone acacetin (AC) has anti-inflammatory, antioxidant and anti-cancer properties. However, the effect of AC on DN is not clear.</p><p><strong>Objectives: </strong>To investigate potential nephroprotective effects of AC caused by reducing inflammation and oxidative stress via the TLR4/NF-κB pathway in rats with streptozotocin (STZ)-induced DN.</p><p><strong>Material and methods: </strong>In this study, we investigated the nephroprotective effect of AC compared to that of a positive control therapy of irbesartan (IRB) in DN induced with STZ. In this model, rats were given an intraperitoneal injection of STZ (180 mg/kg body weight (BW)), along with daily doses of AC (10 mg/kg BW) or IRB (180 mg/kg BW) to induce DN. Histopathology, albumin, blood glucose (Bg), BW, oxidative stress indicators, and western blot of inflammatory signaling pathways in the kidney were examined.</p><p><strong>Results: </strong>Reduction of blood glucose, proteinuria, serum malondialdehyde (MDA), serum creatinine, and blood urea nitrogen (BUN), as well as the inhibition of toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1) and nuclear factor kappa B (NF-κB) protein expression were observed. These data demonstrated that AC could improve BW, antioxidant enzyme and renal histopathology in rats with STZ-induced DN.</p><p><strong>Conclusions: </strong>Results from the rat model highlight how AC-suppressed inflammation and oxidative stress can attenuate STZ-induced DN by downregulating the TLR4/NF-κB pathway in rats.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Systematic review and meta-analysis of randomized controlled trials comparing the clinical outcomes of SARS-CoV-2 and influenza in pediatric patients.","authors":"Chiqiong Liu, Fengying He","doi":"10.17219/acem/192224","DOIUrl":"https://doi.org/10.17219/acem/192224","url":null,"abstract":"<p><p>Only a few studies have examined the effects of coronavirus disease 2019 (COVID-19) and influenza on clinical outcomes in pediatric patients. Furthermore, no meta-analysis has assessed the impact of these diseases on adverse outcomes. This study aims to compare the clinical outcomes of COVID-19 and influenza in pediatric patients. Searches were conducted from December 2019 to February 2022 in databases including Embase, Scopus, PubMed Central (PMC), MEDLINE, Google Scholar, Cochrane Library, and ScienceDirect. Our meta-analysis used a random-effects model, reporting pooled odds ratios (ORs) or standardized mean differences with 95% confidence intervals (95% CIs). Thirteen studies meeting the inclusion criteria were analyzed. Most studies had poor quality. The pooled OR was 0.13 for oxygen requirement (95% CI: 0.04-0.45; I2 = 74%) and 0.03 for steroid requirement (95% CI: 0.01-0.19; I2 = 60.8%). No significant differences were found in outcomes such as intensive care unit (ICU) admission, duration of inpatient stay, invasive/non-invasive ventilation, death, acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI). SARS-CoV-2 infection was comparable to influenza regarding mortality, pediatric intensive care unit (PICU) admissions, mechanical ventilation, and AKI incidence, but with notable differences in oxygen supplementation.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weiqi Song, Rongyue Yao, Annamalai Vijayalakshmi, Yuan An
{"title":"Eupatorin modulates BCPAP in thyroid cancer cell proliferation via suppressing the NF-κB/P13K/AKT signaling pathways.","authors":"Weiqi Song, Rongyue Yao, Annamalai Vijayalakshmi, Yuan An","doi":"10.17219/acem/191595","DOIUrl":"https://doi.org/10.17219/acem/191595","url":null,"abstract":"<p><strong>Background: </strong>Thyroid carcinoma (TC), the most prevalent endocrine cancer worldwide, has become progressively more common, especially in women. Most TCs are epithelial-derived differentiated TCs, specifically papillary thyroid cancer (PTC). Although there are many therapeutic drugs available, curing TC is a difficult task.</p><p><strong>Objectives: </strong>A flavone called eupatorin (EUP) obtained from herbs can prevent the growth of many types of cancerous cells. Nonetheless, the mechanisms of EUP's actions against PTC are still unknown.</p><p><strong>Material and methods: </strong>The goal of our work was to evaluate the mechanisms of EUP (20 and 30 μM/mL) and examine its antiproliferative and apoptotic effects on human PTC cells BCPAP. The MTT test; dual acridine orange/ethidium bromide (AO/EB), rhodamine-123 (Rh-123), and 4',6-diamidino-2-phenylindole (DAPI) staining; adherence assays; and western blot analyses were used to evaluate the antiproliferative and apoptotic properties of EUP on BCPAP cells.</p><p><strong>Results: </strong>Our research showed that the quantity-dependent administration of EUP inhibited the proliferation of BCPAP cells, which in turn caused apoptosis through the increase in caspase-9 and p53 protein expression and the reduction of proliferating cell nuclear antigen (PCNA) levels. Additionally, when P13K/AKT signaling is inhibited by nuclear factor kappa B (NF-κB), EUP reduces inflammation and BCPAP proliferation.</p><p><strong>Conclusions: </strong>By blocking the NF-κB and P13K/AKT pathways, EUP can reduce the growth of BCPAP cells and promote cell death.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arianna Giorgetti, Jennifer P Pascali, Guido Pelletti, Marco Garagnani, Raffaella Roffi, Marialuisa Grech, Paolo Fais
{"title":"Optimizing screening cutoffs for drugs of abuse in hair using immunoassay for forensic applications.","authors":"Arianna Giorgetti, Jennifer P Pascali, Guido Pelletti, Marco Garagnani, Raffaella Roffi, Marialuisa Grech, Paolo Fais","doi":"10.17219/acem/183124","DOIUrl":"10.17219/acem/183124","url":null,"abstract":"<p><strong>Background: </strong>In forensic toxicology, positive immunoassay (IA) test results do not hold forensic validity and need to be confirmed with mass spectrometry (MS). On the other hand, a negative result is a strong indication that the drug and/or the drug metabolites are not present in the sample and that confirmatory analyses are not necessary. Consequently, a negative IA result must have forensic validity since it can be admitted in court during a trial.</p><p><strong>Objectives: </strong>Screening cutoffs for the analysis of hair samples using immunoassays (IAs) were retrospectively optimized based on the Society of Hair Testing (SoHT) confirmation cutoffs and the utility of the test for forensic applications was discussed.</p><p><strong>Material and methods: </strong>Hair samples taken from 150 patients with a history of drug addiction were analyzed with ILab 650, Werfen (Milan, Italy) using DRI® reagents. Confirmatory analyses were subsequently performed using the ACQUITY UPLC® System, Waters Corporation (Milford, USA). Screening cutoffs were retrospectively optimized using receiver operating characteristic (ROC) analysis.</p><p><strong>Results: </strong>A total of 162 single positive results were obtained for confirmatory analysis (10 for amphetamines/methamphetamines, 11 for MDMA, 37 for cocaine, 40 for THC, 33 for methadone, and 31 for opiates). The optimized screening cutoffs were 0.27 IA ng/mg for amphetamines, 0.51 IA ng/mg for MDMA, 0.59 IA ng/mg for cocaine, 0.14 IA ng/mg for cannabinoids, 0.63 IA ng/mg for methadone, and 0.26 IA ng/mg for opiates. An area under the curve (AUC) greater than 0.95 was obtained with very high sensitivity and specificity for all drugs.</p><p><strong>Conclusions: </strong>The presented screening method proved to be a useful technique on hair samples for the classes of drugs most commonly found in Italy and Europe and can be applied to forensic analysis.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"75-82"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patryk Sobieralski, Maria Bieniaszewska, Łukasz Bołkun, Tomasz Sacha, Magdalena Muzalewska-Wolska, Wojciech Homenda, Łucja K Bartkowiak, Justyna Smith, Marcin Rymko, Anna Jachalska, Andrzej R Mital, Witold Prejzner, Jan Zaucha
{"title":"Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach.","authors":"Patryk Sobieralski, Maria Bieniaszewska, Łukasz Bołkun, Tomasz Sacha, Magdalena Muzalewska-Wolska, Wojciech Homenda, Łucja K Bartkowiak, Justyna Smith, Marcin Rymko, Anna Jachalska, Andrzej R Mital, Witold Prejzner, Jan Zaucha","doi":"10.17219/acem/182857","DOIUrl":"10.17219/acem/182857","url":null,"abstract":"<p><strong>Background: </strong>The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group).</p><p><strong>Objectives: </strong>To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis.</p><p><strong>Material and methods: </strong>The study group consisted of 308 PV and ET patients recruited from 6 Polish Adult Leukemia Group (PALG) Centers. Patients were analyzed with respect to disease phenotype, risk group, treatment approach, cardiovascular (CV) risk factors, and occurrence of bleeding or thrombosis.</p><p><strong>Results: </strong>Overall, 74% of patients in the study group were started on cytoreduction at diagnosis, including 70% of the low-risk PV patients and 85-89% of the non-high-risk ET patients. Factors influencing the decision to start the treatment included higher hemoglobin (Hb) concentration (in PV) as well as higher platelet (PLT) count, and the presence of CV risk factors (in ET). Introducing cytoreduction at diagnosis had no impact on thrombotic events. Patients harboring CV risk factors experienced a higher incidence of complications both at diagnosis and follow-up, independently of the treatment strategy.</p><p><strong>Conclusions: </strong>We underline the low adherence to recommendations in the treatment of intermediate-age PV and ET patients. Moreover, we emphasize the importance of CV risk factors and stress their impact on disease phenotype in this patient population.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"25-32"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ye Zhao, Shi Rong Huang, Yu Jie Zhang, Yong Qiang Chen, Wen Gang Liu, Fu Shun Gu, Hui Wen, Xi Lin Xu, Jiu Yi Chen, Da Xiang Jin, Hong Yin, Zhong Dong, Wei An Yuan, Hong Sheng Zhan
{"title":"Safety and efficacy of Yaobitong capsules for lumbar disc herniation: A multicenter, randomized, double-blinded, parallel, positive-controlled clinical trial.","authors":"Ye Zhao, Shi Rong Huang, Yu Jie Zhang, Yong Qiang Chen, Wen Gang Liu, Fu Shun Gu, Hui Wen, Xi Lin Xu, Jiu Yi Chen, Da Xiang Jin, Hong Yin, Zhong Dong, Wei An Yuan, Hong Sheng Zhan","doi":"10.17219/acem/185523","DOIUrl":"10.17219/acem/185523","url":null,"abstract":"<p><strong>Background: </strong>Lumbar disc herniation (LDH) is one of the most common diseases and is a global medical and socioeconomic problem characterized by leg or back pain, weakness in the lower extremities and paresthesia.</p><p><strong>Objectives: </strong>A multicenter, randomized, double-blinded, parallel, positive-controlled clinical trial was conducted to evaluate the efficacy and safety of Yaobitong capsules (YBT) for LDH.</p><p><strong>Material and methods: </strong>Patients (n = 479) were recruited and randomized into YBT and Jingyaokang capsule (JYK) groups (the positive control), and received YBT or JYK at a dose of 3 capsules 3 times per day after a meal for 30 days. The primary efficacy outcome was the Oswestry Disability Index (ODI), with the visual analogue scale (VAS) used as the secondary efficacy outcome. The adverse events and adverse reactions were also evaluated.</p><p><strong>Results: </strong>There was no significant difference in baseline characteristics between YBT (n = 358) and JYK groups (n = 120), and no difference was observed between groups for mean ODI score at day 0 (p = 0.064) or day 7 (p = 0.196), but there were differences at days 14, 21 and 30 (p < 0.001). The YBT showed more decline from baseline, and the decreased ODI score was substantially different from JYK (p < 0.001). The differences in decreased VAS scores between YBT and JYK were also significant at each time point (days 7, 14, 21, and 30), with better scores in the YBT group than in the JYK group (p < 0.001). In terms of safety, there was no obvious disparity in adverse events or adverse reactions between the 2 groups (p > 0.05).</p><p><strong>Conclusions: </strong>Yaobitong was better than JYK for LDH treatment, with no significant difference in safety. The study suggests that YBT is a promising and effective treatment for LDH.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"33-42"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Bo Li, Jia Li Liu, Shuang Zhao, Jing Li, Guang-Yan Zhang, Qing Tang, Wei Yong Chen
{"title":"Recombinant Klotho protein protects pulmonary alveolar epithelial cells against sepsis-induced apoptosis by inhibiting the Bcl-2/Bax/caspase-3 pathway.","authors":"Xiao Bo Li, Jia Li Liu, Shuang Zhao, Jing Li, Guang-Yan Zhang, Qing Tang, Wei Yong Chen","doi":"10.17219/acem/184639","DOIUrl":"10.17219/acem/184639","url":null,"abstract":"<p><strong>Background: </strong>Inflammation-induced apoptosis of alveolar type II epithelial cells is a primary contributor to sepsis-induced acute respiratory distress syndrome (ARDS). Klotho is a single-pass transmembrane protein with anti-inflammatory and anti-apoptotic effects. However, the role and mechanism of Klotho in the development of ARDS remains unknown.</p><p><strong>Objectives: </strong>This study aimed to investigate the effect of Klotho on sepsis-induced apoptosis in human pulmonary alveolar epithelial cells (HPAEpiCs) together with the potential mechanism.</p><p><strong>Material and methods: </strong>Cecal ligation and puncture (CLP) were performed to generate an in vivo sepsis model, and HPAEpiCs were treated with lipopolysaccharide (LPS) to mimic sepsis in vitro. Both models were administered recombinant Klotho protein. The morphology of the lung tissue was observed, and apoptotic cells and cell viability were detected. Interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA), while the expression of Bcl-2, Bax and cleaved caspase-3 was detected with western blotting.</p><p><strong>Results: </strong>Klotho reversed the CLP-induced decrease in mouse survival in vivo (p < 0.001) and increased inflammatory cell infiltration and inflammatory substance exudation in the lung tissue of mice with sepsis (both p < 0.001). Klotho also suppressed apoptosis (p < 0.001) as demonstrated by IL-1β, IL-6 and TNF-α expression (all p < 0.001), and Bcl-2/Bax/caspase-3 pathway activation (p < 0.001). Klotho pretreatment significantly prevented LPS-induced apoptosis in vitro (p < 0.001), as demonstrated by IL-1β, IL-6 and TNF-α upregulation (all p < 0.001); and Bcl-2/Bax/caspase-3 pathway activation in HPAEpiCs (p < 0.001).</p><p><strong>Conclusions: </strong>This study demonstrated that Klotho can ameliorate acute lung injury (ALI) induced by sepsis by inhibiting inflammatory responses and exerting anti-apoptotic effects by suppressing Bcl-2/Bax/caspase-3 pathway activation.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"123-134"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}