bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC10 inhibits non-small-cell lung cancer cell ferroptosis through the microRNA-223-5p-SLC7A11 axis
Authors: Shi Zhihua , Jiang Tao , Sun Xusheng , Peng Liangbiao , Cao Bingji , Wang Yi 
Published: October 2024

Abstract

Objective
Non-small-cell lung cancer (NSCLC) is a leading attributor to cancer deaths. High HDAC10 and low microRNA (miR)-223-5p levels have been observed in NSCLC. But their roles remain elusive. This study illustrated their roles in NSCLC cell ferroptosis and the mechanism.

Methods
HDAC10, miR-223-5p, and solute carrier family 7 member 11 (SLC7A11) levels in cells were determined by RT-qPCR. Iron ion content, reactive oxygen species (ROS), and glutathione (GSH) levels were tested using reagent kits, and levels of SLC7A11 and Acyl-CoA synthesis long chain family (ACSL4) were examined using Western blot. Chromatin immunoprecision was performed to analyze the enrichment of HDAC10 and acetylated lysine 9 of histone H3 (H3K9ac) on the miR-223-5p promoter. The targeted binding of miR-223-5p and SLC7A11 was analyzed by dual-luciferase assay. Joint experiments were designed to identify the role of miR-223-5p/SLC7A11 axis in HDAC10-regulated ferroptosis in NSCLC cells.

Results
HDAC10 was highly expressed in NSCLC cells. Silencing HDAC10 significantly reduced GSH and SLC7A11 levels, upregulated iron ion content, ROS levels, and ACSL4 expression, promoting cell ferroptosis. Mechanically, HDAC10 inhibited miR-223-5p expression through H3K9ac deacetylation of the miR-223-5p promoter, thereby targeting SLC7A11. The joint experimental results showed that overexpression of SLC7A11 or downregulation of miR-223-5p alleviated the promoting effect of silencing HDAC10 on ferroptosis in NSCLC cells.

Conclusion
HDAC10 inhibits miR-223-5p expression through H3K9ac deacetylation of the miR-223-5p promoter, thereby promoting SLC7A11 expression and inhibiting ferroptosis in NSCLC cells.
Design and computational analysis of a novel Leptulipin-p28 fusion protein as a multitarget anticancer therapy in breast cancer
Authors: Khalid Sania , Rehman Hafiz Muhammad , Al-Qassab Yasamin , Ahmad Irfan , Fatima Tehreem , Mubasher Mian Muhammad , Kalsoom Maria , Nadeem Tariq , Bashir Hamid 
Published: October 2024

Abstract
The search for novel therapeutic agents to treat breast cancer has compelled the development of fusion proteins that synergize the functional benefits of different bioactive peptides. Leptulipin, derived from scorpion venom, exhibits antitumor properties. On the other hand, p28, a peptide from the bacterial protein azurin, enhances cell penetration. The current study investigated the design and computational evaluation of a Leptulipin-p28 fusion protein for breast cancer treatment. The amino acid sequences of Leptulipin and p28 were joined via a rigid linker to maintain structural and functional integrity. Secondary and tertiary structure predictions were performed using online servers of GOR-IV and I-TASSER. Physicochemical properties and solubility were analyzed using ProtParam and Protein-Sol. Validation and quality assessment of the fusion protein were confirmed through Rampage and ERRAT2. Finally, the fusion protein was docked with 2 receptors (VEGFR and Cadherin) and docked complexes were simulated on GROMACS. The Leptulipin-p28 fusion protein exhibited a stable structure exhibiting a high quality score of 92 on ERRAT and Ramachandran plot analysis highlighting 76.3% of residues in the favorable region. Docking studies with VEGFR and Cadherin receptors followed by 100 ns simulations on GROMACS showed stable complex formation. Molecular dynamics simulations confirmed the stability and robust interaction of the fusion protein-receptor complexes over time. The computational analysis indicates that the Leptulipin-p28 fusion protein holds promise as a multitarget therapeutic agent in breast cancer. The current findings warrant further investigation through in vitro and in vivo studies to validate the current outcomes.
Assessment of uptake of sulphadoxine-pyrimethamine for intermittent preventive treatment among pregnant women in Osun State, Nigeria
Authors: Adegbola Adebanjo J , Ogboye Ruth M , Ijarotimi Omotade A , Ubom Akaninyene E , Adesoji Bukola A , Bolaji Oluseye O 
Published: October 2024

Abstract

Background
About 32 million pregnant women are at the risk of malaria infection yearly in malaria-endemic sub-Saharan Africa. To mitigate the risks associated with malaria in pregnancy, the WHO recommends ≥3 doses of intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP), covering from the second trimester of pregnancy until delivery.

Methods
This cross-sectional study assessed the uptake and extent of adherence with IPTp-SP among pregnant women in Osun State, Nigeria, from October 2020 to March 2021. Assessment of the uptake was done by extracting information from the validated case report forms. Venous blood samples were obtained to assess the levels of sulphadoxine in plasma through HPLC-UV.

Results
In total, 49.24%, 38.17% and 12.58% of the study participants obtained 1, 2 and ≥3 doses of IPTp-SP, respectively. In assessing the extent of adherence, 46.67% obtained their last dose within 28 d before sample collection. Uptake of IPTp-SP is not associated with gravidity (p=0.603), but is weakly associated with the age of the study participants (p=0.04). The median (IQR) plasma sulphadoxine concentration was 10.6248 (2.8124–27.1242) ug/mL.

Conclusions
Utilisation of the intervention is still very low and adherence appears to be inadequate among the study population, suggesting that more advocacy on the IPTp-SP strategy and the implementation of directly observed therapy is necessary.
TMEM182 inhibits myocardial differentiation of human iPS cells by maintaining the activated state of Wnt/β‐catenin signaling through an increase in ILK expression
Authors: Morihara Hirofumi , Yokoe Shunichi , Wakabayashi Shigeo , Takai Shinji 
Published: October 2024

AbstractTransmembrane protein 182 (TMEM182) is notably abundant in muscle and adipose tissue, but its role in the heart remains unknown. This study examined the contribution of TMEM182 in the differentiation of human induced pluripotent stem cells (hiPSCs) into cardiomyocytes. For this, we generated hiPSCs overexpressing TMEM182 in a doxycycline‐inducible manner and induced their differentiation into cardiomyocytes. On Day 12 of differentiation, expression of the cardiomyocyte markers, TNNT2 and MYH6, was significantly decreased in TMEM182‐overexpressing cells. Additionally, we found that phosphorylation of GSK‐3β (Ser9) and β‐catenin (Ser552) was increased during TMEM182 overexpression, suggesting activation of Wnt/β‐catenin signaling. We further focused on integrin‐linked kinase (ILK) as the mechanism by which TMEM182 activates Wnt/β‐catenin signaling. Evaluation showed that ILK expression was increased in cells overexpressing TMEM182. These results suggest that TMEM182 maintains Wnt/β‐catenin signaling in an activated state after mesoderm formation by increasing ILK expression, thereby suppressing hiPSCs differentiation into cardiomyocytes.
Plasma membrane repair defect in Alzheimer's disease neurons is driven by the reduced dysferlin expression
Authors: Bulgart Hannah R. , Lopez Perez Miguel A. , Tucker Alexis , Giarrano Gianni N. , Banford Kassidy , Miller Olivia , Bonser Sidney W. G. , Wold Loren E. , Scharre Douglas , Weisleder Noah 
Published: October 2024

AbstractAlzheimer's disease (AD) is the most common neurodegenerative disease, and a defect in neuronal plasma membrane repair could exacerbate neurotoxicity, neuronal death, and disease progression. In this study, application of AD patient cerebrospinal fluid (CSF) and recombinant human Aβ to otherwise healthy neurons induces defective neuronal plasma membrane repair in vitro and ex vivo. We identified Aβ as the biochemical component in patient CSF leading to compromised repair capacity and depleting Aβ rescued repair capacity. These elevated Aβ levels reduced expression of dysferlin, a protein that facilitates membrane repair, by altering autophagy and reducing dysferlin trafficking to sites of membrane injury. Overexpression of dysferlin and autophagy inhibition rescued membrane repair. Overall, these findings indicate an AD pathogenic mechanism where Aβ impairs neuronal membrane repair capacity and increases susceptibility to cell death. This suggests that membrane repair could be therapeutically targeted in AD to restore membrane integrity and reduce neurotoxicity and neuronal death.
Surgical Outcomes After Preoperative Embolization in Hypervascular Spinal Metastases
Authors: Pierik Robertus J.B. , Amelink Jantijn J.G.J. , Groot Olivier Q. , Som Avik , van Munster Bram T. , de Reus Daniël C. , Chua Theresa L. , Zijlstra Hester , Verlaan Jorrit-Jan , Shin John H. , Rabinov James D. , Tobert Daniel G. 
Published: October 2024

Study Design.
Retrospective propensity-score matched, case control study at 2 academic tertiary care centers.

Objective.
To assess the effect of PE on (1) intraoperative blood loss, defined as conventional estimates of blood loss (EBL) and hemoglobin mass loss, and (2) secondary outcomes in patients with spinal metastases from hypervascular histologies.

Background Context.
Preoperative embolization (PE) intends to reduce blood loss during surgery for spinal metastases of hypervascular tumors such as renal cell carcinoma. However, studies investigating the effect of PE in hypervascular tumors often consist of small cohorts, do not correct for confounding factors, and have conflicting results.

Methods.
After propensity score matching (PSM), 46 PE patients were matched to 46 non-PE patients without baseline differences. The constraints of PSM did not allow analysis of patients with tumor volumes>9 cm3. Multiple linear regression models were fitted for EBL and hemoglobin mass loss. Poisson regression models were fitted for both intraoperative and postoperative transfusions.

Results.
There was no difference in EBL (948 mL [IQR 500−1750] vs. 1100 mL [IQR 388−1925], P=0.68) and hemoglobin mass loss (201g [IQR 119–307] vs. 232g [IQR 173–373], P=0.18) between PE and non-PE patients. Other than higher 1-year survival rates (65% vs. 43%, P=0.05) in PE-patients, there were no differences in secondary outcomes. In multiple regression analyses, PE was not associated with decreased intraoperative blood loss, hemoglobin mass loss or perioperative blood transfusions.

Conclusions.
Our study demonstrated that, for tumors <9 cm3, PE did not reduce EBL, hemoglobin mass loss or perioperative blood transfusions in patients undergoing spine surgery for metastases from hypervascular histologies. These findings suggest that urgent spine surgeries indicated for hypervascular histologies should not be delayed based on the availability of PE and accurate detection of pre-operative hypervascularity, beyond histology, will likely be an important determination of future PE utilization for spinal metastases.

Level of Evidence.
Treatment Benefits, Level III
Accelerated Takedown of Melolabial Interpolation Flaps at 1 to 2 Weeks, Indications and Safety for Improved Patient Experience
Authors: Prasad Smriti , Neill Brett , Yu Wesley , Leitenberger Justin J. , Bar Anna 
Published: October 2024

BACKGROUND
The melolabial interpolation flap is an effective surgical technique for reconstructing defects in the nasal ala and tip regions. Traditionally, this technique involves waiting for the standard 3-week period before pedicle division.

OBJECTIVE
To evaluate whether accelerated takedown at 1- or 2-week postflap creation is possible while maintaining the flap's viability and functionality.

METHODS
Retrospective cohort study at Oregon Health and Science University from 2018 to 2023.

RESULTS
The authors examined 67 patients who underwent reconstruction with a melolabial interpolation flap surgery, of which 50 had their flap takedown at <21 days and 17 had their takedown at 21 or more days. This analysis revealed similar complication rates for both groups. There were no increased rates of infection, necrosis, or hematoma formation in the earlier takedown group. Those undergoing earlier takedown were more likely to have a history of hypertension but less likely to have a history of diabetes, immunosuppression, and smoking, though the differences were not statistically significant.

CONCLUSION
This study provides valuable insights into the safety and feasibility of early melolabial interpolation flap takedown. This approach has the potential to enhance the quality of life for patients undergoing this flap by decreasing the amount of time with a pedicle.
Long-term comparative outcomes in patients undergoing transcatheter aortic valve implantation with self-expanding valves versus balloon-expandable valves
Authors: Hoo Chee Eng , Chen Po-Lin , Chen Ying-Hwa , Chen I-Ming , Wu Nai-Yuan , Chang Hsiao-Huang 
Published: October 2024

ABSTRACT

Background
This study aimed to compare long-term clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) with self-expanding (SEV) valve versus balloon-expandable valve (BEV), with a minimum follow-up period of five years.

Materials and Methods
Utilizing a prospectively maintained database, this observational study identified patients who underwent TAVI using either SEV or BEV for severe aortic stenosis and were followed for at least five years. Clinical outcomes encompassed both 30-day post-TAVI outcomes and long-term outcomes, including all-cause mortality, cardiovascular mortality, structural valve deterioration (SVD), heart failure related hospitalization, bioprosthetic valve failure, and valve related hospitalization and complications.

Results
A total of 74 patients were included in this study, with 64 patients in the SEV group and 10 patients in the BEV group. The median follow-up duration was 6.8 years, ranging from 5.0 to 10.2 years. Throughout the post-TAVI period, the SEV group consistently demonstrated a lower mean pressure gradient than the BEV group. No significant differences were observed between the two groups in terms of short-term or long-term outcomes. Within the study, four patients encountered moderate or severe SVD and one experienced thrombosis, and no cases of bioprosthetic valve failure or endocarditis were observed.

Conclusions
This study revealed that SEV and BEV demonstrated comparable long-term outcomes in patients undergoing TAVI, including all-cause and cardiovascular mortality, as well as the risk of SVD.
Efficacy of Extranasal Neurostimulation for Patients With Neuropathic Corneal Pain: A Pilot Study
Authors: Olcucu Onur , de Leeuw Anya , Lamazales Luiz Luciano , Mallone Fabiana , Hamrah Pedram 
Published: October 2024

Purpose:
Neuropathic corneal pain (NCP) has been recognized as a distinct disease, yet treatment options remain limited. The aim of this pilot study was to explore the effectiveness of extranasal neurostimulation (EXNS) as a potential pain relief strategy for individuals with the peripheral component of NCP.

Methods:
A retrospective study was performed to identify patients who were diagnosed with refractory peripheral or mixed NCP and subsequently underwent a single session of EXNS. Visual analog scale (VAS) was used to evaluate pain intensities in the office before and after 60 seconds of EXNS. Demographic information, changes in pain scores, and comorbidities were recorded, and their correlations with pain score changes were analyzed.

Results:
Twenty-two patients with a mean age of 48.91 ± 3.32 years were included. The average VAS score before EXNS was 5.59 ± 0.41, which was reduced to 2.59 ± 0.43 after EXNS, indicating a 54.88% reduction (P < 0.001). EXNS reduced VAS scores from 4.90 ± 0.72 to 1.60 ± 0.42 (68.40%) for 10 patients with peripheral NCP and from 6.17 ± 0.42 to 3.42 ± 0.62 (43.61%) for 12 patients with mixed (peripheral and central) NCP (P = 0.005 for both groups). Fourteen patients (63.63%) experienced an improvement of at least 50% in their pain scores, 2 patients (9.09%) showed an improvement between 30% and 49.9%, while 6 patients (27.27%) experienced an improvement of less than 30%. No correlations between the change in pain scores and patient demographics, as well as comorbidities were detected.

Conclusions:
EXNS may be used as an adjuvant therapy to ameliorate pain among patients with NCP with the peripheral pain component.
Regenerative medicine for spinal cord injury using induced pluripotent stem cells: from animals to humans
Authors: Nagoshi Narihito , Hashimoto Shogo , Okano Hideyuki , Nakamura Masaya 
Published: October 2024

Abstract
Spinal cord injury (SCI) results in permanent neurological dysfunction and neuropathic pain. To address this pathology, we recently conducted a clinical study in which we transplanted neural precursor cells (NPCs) derived from human induced pluripotent stem cells into patients during the subacute phase of SCI. One of the therapeutic mechanisms of cell transplantation is the formation of synaptic connections with the host's neural tissues, which we demonstrated using a chemogenetic tool. In addition, we have developed innovative strategies to enhance the effectiveness of cell transplantation through gene therapy. Moreover, our current study is focused on developing cell therapy for chronic SCI, a more challenging pathology characterized by the formation of cavities and scar tissue. In such situations, transplanting NPCs with neurogenic properties could effectively penetrate scar tissue and form functional synapses with the host neurons. To improve the outcomes of cell transplantation alone, we have found that incorporating rehabilitation is beneficial. In animal models of SCI, we have established an effective rehabilitative training program in which NPCs were transplanted during the chronic phase. Robotic rehabilitation has demonstrated improvements in gait ability and trunk function in clinical situations. Therefore, regenerative medicine shows promise for chronic SCI, particularly when rehabilitation strategies are incorporated.
Evaluation of problem-based learning for pharmacology based on a comprehensive analysis in undergraduate students
Authors: Yang Xiding , Yang Zehua , Ma Sijia , Yan Miao , Yang Yongyu 
Published: October 2024

Background:
Problem-based learning (PBL) has been widely employed in pharmacology teaching. However, the benefits of PBL for undergraduate students have not been clearly demonstrated. We performed a meta-analysis to compare the effects of PBL and lecture-based learning (LBL) in undergraduate pharmacology education.

Methods:
We systematically searched literature databases for comparative studies related to PBL pedagogy in the undergraduate pharmacology curriculum from the inception of the databases to December 2023. The obtained literature was screened according to the selection criteria, and Review Manager 5.4 was used for the meta-analysis of the included studies.

Results:
A total of 33 comparative studies involving 4425 undergraduate students were enrolled. The standardized mean differences (95% confidence intervals) of the examination scores and students’ self-rated scores on learning interest, comprehension of knowledge and thinking ability between PBL and LBL were calculated to be 2.03 (1.53–2.53), 0.50 (0.26–0.74), 0.69 (0.46–0.92), and 1.65 (1.21–2.09), respectively. The risk ratios of the proportion of satisfaction on improving students’ learning interest, comprehension of knowledge, thinking ability, self-study ability, and communication skills were calculated to be 2.08 (1.17–3.71), 1.84 (1.26–2.67), 1.42 (1.19–1.69), 1.44 (1.16–1.79), and 1.66 (1.22–2.27), respectively.

Conclusions:
The current evidence indicates that PBL is more effective than LBL in improving examination scores and student satisfaction in undergraduate pharmacology education.
Effect of needle types and diameters using in spinal anesthesia on optic nerve sheath diameter: Prospective randomized study
Authors: Kumaş Solak Sezen , Demirgan Serdar , Karali Elif , Selcan Ayşin 
Published: October 2024

Background:
This prospective randomized study aimed to investigate the impact of needle types and diameters used in spinal anesthesia (SA) on optic nerve sheath diameter (ONSD) in patients undergoing lower extremity orthopedic surgery.

Methods:
Patients were randomly assigned to 3 groups based on the needle type and size used for SA: Group 25w (25 gauge Whitacre needle), Group 27q (27 gauge Quincke needle), and Group 25q (25 gauge Quincke needle). Initially, 165 patients (55 in each group) were enrolled, with 146 patients ultimately included in the analysis (Group 25w, n = 49; Group 27q, n = 48; Group 25q, n = 49). ONSD measurements were conducted using ultrasound guidance at 5 time points: T0 (pre-SA), T1 (5 minutes post-SA), T2 (5 minutes post-tourniquet inflation), T3 (5 minutes post-tourniquet deflation), and T4 (24 hours post-operation). Additionally, oxygen saturation, systolic arterial pressure, mean arterial pressure, diastolic arterial pressure, and heart rate were recorded at these time points.

Results:
Analysis of ONSD measurements revealed no significant differences among the groups at time points T0,T1,T2, and T4 (P = .7293, P = .4428, P = .3676, and P = .3667, respectively). However, at T3, ONSD values were significantly higher in Group 27q compared to Group 25q (P = .0325). Across all groups, the mean ONSD values measured post-tourniquet release (T3) were higher than those at T0,T2, and T4 (P < .001 for all). The incidence of nausea was similar among the groups, and no cases of headache or visual impairment were reported within the initial 24 hours post-surgery.

Conclusion:
In conclusion, our study suggests that while subarachnoid injection and tourniquet inflation do not impact intracranial pressure (ICP), tourniquet deflation leads to an increase in ICP during lower limb surgery under SA. Therefore, caution should be exercised when using a tourniquet in patients at risk of elevated ICP.