bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARID1A loss activates MAPK signaling via DUSP4 downregulation
Authors: Mandal Jayaprakash , Yu Zheng-Cheng , Shih Ie-Ming , Wang Tian-Li 
Published: December 2023

Abstract
Background
ARID1A, a tumor suppressor gene encoding BAF250, a protein participating in chromatin remodeling, is frequently mutated in endometrium-related malignancies, including ovarian or uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). However, how ARID1A mutations alter downstream signaling to promote tumor development is yet to be established.

Methods
We used RNA-sequencing (RNA-seq) to explore transcriptomic changes in isogenic human endometrial epithelial cells after deleting ARID1A. Chromatin immunoprecipitation sequencing (ChIP-seq) was employed to assess the active or repressive histone marks on DUSP4 promoter and regulatory regions. We validated our findings using genetically engineered murine endometroid carcinoma models, human endometroid carcinoma tissues, and in silico approaches.

Results
RNA-seq revealed the downregulation of the MAPK phosphatase dual-specificity phosphatase 4 (DUSP4) in ARID1A-deficient cells. ChIP-seq demonstrated decreased histone acetylation marks (H3K27Ac, H3K9Ac) on DUSP4 regulatory regions as one of the causes for DUSP4 downregulation in ARID1A-deficient cells. Ectopic DUSP4 expression decreased cell proliferation, and pharmacologically inhibiting the MAPK pathway significantly mitigated tumor formation in vivo.

Conclusions
Our findings suggest that ARID1A protein transcriptionally modulates DUSP4 expression by remodeling chromatin, subsequently inactivating the MAPK pathway, leading to tumor suppression. The ARID1A-DUSP4-MAPK axis may be further considered for developing targeted therapies against ARID1A-mutated cancers.
Evaluation of a new fusion antigen, cd loop and HAP2-GCS1 domain (cd-HAP) of Plasmodium falciparum Generative Cell Specific 1 antigen formulated with various adjuvants, as a transmission blocking vaccine
Authors: Pourhashem Zeinab , Nourani Leila , Sani Jafar J. , Yousefi Hemn , Pirahmadi Sakineh , Sabouri Mobina , Raz Abbasali , Djadid Navid Dinparast , Zakeri Sedigheh , Mehrizi Akram Abouie 
Published: December 2023

Abstract
Background
Malaria is a major global health challenge, and for the elimination and eradication of this disease, transmission-blocking vaccines (TBVs) are a priority. Plasmodium falciparum Generative Cell Specific 1 (PfGCS1), a promising TBV candidate, is essential for gamete fertilization. The HAP2-GCS1 domain of this antigen as well as its cd loop could induce antibodies that partially inhibit transmission of P. falciparum.

Methods
In the current study, a new synthetic fusion antigen containing cd loop and HAP2-GCS1 domain (cd-HAP) of PfGCS1 was evaluated as a transmission blocking vaccine candidate. Initially, the profile of naturally acquired IgG antibodies to the cd-HAP antigen was analysed in Iranian individuals infected with P. falciparum, to confirm that this new fusion protein has the appropriate structure containing common epitopes with the native form of PfGCS1. Then, the immunogenicity of cd-HAP was evaluated in BALB/c mice, using different adjuvant systems such as CpG, MPL, QS-21, and a combination of them (CMQ). Furthermore, the blocking efficacy of polyclonal antibodies induced against these formulations was also assessed by oocyst intensity and infection prevalence in the Standard Membrane Feeding Assay (SMFA).

Results
The naturally acquired antibodies (dominantly IgG1 and IgG3 subclasses) induced in P. falciparum-infected individuals could recognize the cd-HAP antigen which implies that the new fusion protein has a proper conformation that mimics the native structure of PfGCS1. Concerning the immunogenicity of cd-HAP antigen, the highest IgG levels and titers, by a Th1-type immune profile, and elevated antibody avidity were induced in mice immunized with the cd-HAP antigen formulated with a combination of adjuvants (P < 0.0001). Additionally, cytokine profiling of the immunized mice displayed that a high level of IFN-γ response, a Th1-type immune response, was produced by splenocytes from immunized mice that received cd-HAP antigen in combination with CMQ adjuvants (P < 0.0001). This formulation of cd-HAP antigen with CMQ adjuvants could reduce oocyst intensity and infection prevalence by 82%, evidenced by the SMFA and hold significant implications for future malaria vaccine development.

Conclusion
Altogether, the results showed that cd-HAP antigen formulated with a combination of the adjuvants (CMQ), could be a promising formulation to develop a PfGCS1-based transmission-blocking vaccine.
Advancements in engineered mesenchymal stem cell exosomes for chronic lung disease treatment
Authors: Zhai Zhengyao , Cui Tairong , Chen Jialiang , Mao Xulong , Zhang Ting 
Published: December 2023

AbstractChronic lung diseases include an array of conditions that impact airways and lung structures, leading to considerable societal burdens. Mesenchymal stem cells (MSCs) and their exosomes (MSC-exos) can be used for cell therapy and exhibit a diverse spectrum of anti-inflammatory, antifibrotic, and immunomodulatory properties. Engineered MSC-exos possesses enhanced capabilities for targeted drug delivery, resulting in more potent targeting effects. Through various engineering modifications, these exosomes can exert many biological effects, resulting in specific therapeutic outcomes for many diseases. Moreover, engineered stem cell exosomes may exhibit an increased capacity to traverse physiological barriers and infiltrate protected lesions, thereby exerting their therapeutic effects. These characteristics render them a promising therapeutic agent for chronic pulmonary diseases. This article discusses and reviews the strategies and mechanisms of engineered MSC-exos in the treatment of chronic respiratory diseases based on many studies to provide new solutions for these diseases.
Preliminary analysis of immune-related markers in thymic carcinoid
Authors: Zhang Jiaqi , Guo Chao , Liu Lei , Zhao Ke , Zhou Mengxin , Chen Yeye , Li Shanqing 
Published: December 2023

AbstractThe immune-related microenvironment of thymic carcinoid has rarely been reported. We analyzed the expression of PD-L1 and VISTA, and the distribution of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the thymic carcinoid by immunohistochemical staining, and showed the correlation between these markers and clinical survival, indicating the potential therapeutic prospects.
Cemented or uncemented fixation: Which allows a more acceptable prosthetic femoral version in total hip arthroplasty?
Authors: Moralidou Maria , Di Laura Anna , Hothi Harry , Henckel Johann , Hart Alister J. 
Published: December 2023

Abstract
Background
Three-dimensional computed-tomography (3D-CT) planning for primary Total Hip Arthroplasty (THA) typically uses the external femoral surface; as a result, it is difficult to predict the prosthetic femoral version (PFV) for uncemented femoral stems that press-fit to the internal surface of the bone. Cemented fixation allows the surgeon to adjust the version independent of the internal femoral anatomy. We aimed to better understand the effect of the fixation type on PFV.

Methods
This was a case series study including a total of 95 consecutive patients (106 hips), who underwent uncemented (n = 81 hips) and cemented (n = 25 hips) primary THA using the posterior approach. The surgeon aimed for a PFV of 20°. Our primary objective was to compare PFV in both groups; our secondary objective was to evaluate the clinical outcomes.

Results
The mean (± SD) PFV was 13° (± 9°) and 23° (± 8°) for the uncemented and cemented THA groups (P < 0.001), respectively. In the uncemented THA group, 36% of the patients had a PFV of < 10°. In the cemented THA group, this clinically important threshold dropped to 8%. Similarly, the Bland–Altman (BA) plots showed wider 95% limits of agreement for the uncemented group. Satisfactory clinical outcomes were recorded.

Conclusion
We found that the PFV was more clinically acceptable, for the posterior surgical approach, in the cemented group when compared to the uncemented group. Both THA groups reported high variability indicating the need to develop surgical tools to guide the PFV closer to the surgical target.
Danggui Buxue Decoction exerts its therapeutic effect on rheumatoid arthritis through the inhibition of Wnt/β-catenin signaling pathway
Authors: Jiang Xin , He Yanxin , Zhao Ying , Pan Zhi , Wang Yinghang 
Published: December 2023

Abstract
Background
Danggui Buxue Decoction (DBD) is a traditional Chinese medicine prescription, which has the functions of benefiting Qi, generating blood and regulating the immune system. At present, various clinical reports suggest that DBD has some efficacy in Rheumatoid arthritis (RA), but its mechanism of action is still unclear. Thus, the present study explored mechanism of this preparation on RA.

Methods
The effect of DBD was evaluated by tumor necrosis factor (TNF)-α-induced Human fibroblast-like synoviocyte of rheumatoid arthritis (HFLS-RA) cell model and collagen-induced arthritis (CIA) rat model, respectively. Inflammatory factors including TNF-ɑ, IL-1β, IL-6 and IL-10 in the culture supernatants or rat serum were measured using ELISA. The related indexes including fur luster, mental state and activity of rat and the symptoms including swelling and deformation of toes and ankles were also measured.

Results
In vitro results showed that DBD cannot only inhibit the proliferation of HFLS-RA cells but also reduce the levels of pro-inflammatory factors while increasing the level of anti-inflammatory factors. Similar results were obtained from in vivo experiments. Rats receiving DBD showed a decrease in the severity of rheumatoid arthritis in rat models. Moreover, the protein levels of c-myc and β-catenin decreased significantly, while the protein level of SFRP4 increased, which indicated that DBD might inhibit the inflammatory reaction by regulating Wnt/β-catenin signaling pathway, thus alleviating the symptoms of RA.

Conclusion
Our findings not only provide insights for understanding the molecular mechanism of DBD in treating RA, but also provide the theoretical basis for further clinical prevention and treatment.
Spinal apolipoprotein E is involved in inflammatory pain via regulating lipid metabolism and glial activation in the spinal dorsal horn
Authors: Liu Siyi , Yang Shuting , Zhu Xuan , Li Xiang , Zhang Xi , Zhou Xiaoqiong , Cheng Hong , Huo Fu-Quan , Mao Qingxiang , Liang Lingli 
Published: December 2023

Abstract
Introduction
Inflammation and nerve injury promote astrocyte activation, which regulates the development and resolution of pain, in the spinal dorsal horn. APOE regulates lipid metabolism and is predominantly expressed in the astrocytes. However, the effect of astrocytic APOE and lipid metabolism on spinal cellular function is unclear. This study aimed to investigate the effect of spinal Apoe on spinal cellular functions using the complete Freund's adjuvant (CFA)-induced inflammatory pain mouse model.

Methods
After intraplantar injection of CFA, we assessed pain behaviors in C57BL6 and Apoe knockout (Apoe−/−) mice using von Frey and Hargreaves’ tests and analyzed dorsal horn samples (L4-5) using western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and RNA sequencing.

Results
The Apoe levels were markedly upregulated at 2 h and on days 1 and 3 post-CFA treatment. Apoe was exclusively expressed in the astrocytes. Apoe−/− mice exhibited decreased pain on day 1, but not at 2 h, post-CFA treatment. Apoe−/− mice also showed decreased spinal neuron excitability and paw edema on day 1 post-CFA treatment. Global transcriptomic analysis of the dorsal horn on day 1 post-CFA treatment revealed that the differentially expressed mRNAs in Apoe−/− mice were associated with lipid metabolism and the immune system. Astrocyte activation was impaired in Apoe−/− mice on day 1 post-CFA treatment. The intrathecal injection of Apoe antisense oligonucleotide mitigated CFA-induced pain hypersensitivity.

Conclusions
Apoe deficiency altered lipid metabolism in astrocytes, exerting regulatory effects on immune response, astrocyte activation, and neuronal activity and consequently disrupting the maintenance of inflammatory pain after peripheral inflammation. Targeting APOE is a potential anti-nociception and anti-inflammatory strategy.
Loa loa and Mansonella perstans microfilaremia in the department of Lékoumou, Republic of Congo
Authors: Hemilembolo Marlhand C. , Campillo Jérémy T. , Niama Ange Clauvel , Pion Sébastien D. S. , Missamou François , Boussinesq Michel , Bileckot Richard R. , Chesnais Cédric B. 
Published: December 2023

Abstract
Background
Loiasis is endemic in the northern and western part of the Republic of Congo. Between 2004 and 2010, surveys were conducted, using the RAPLOA method, in all departments of the Republic of Congo to assess the distribution of loiasis. Prior to 2004, only two parasitological surveys on loiasis had been conducted in Congo and mainly in the Department of Lékoumou, in the southwestern of the country. In 2019, we conducted a parasitological survey in this same department, more than 30 years after the first surveys.

Methods
The study was conducted in 21 villages. Loa loa and Mansonella perstans microfilaremia levels were quantified using 50 µl calibrated blood smears.

Results
A total of 2444 individuals were examined. The median age of the screened individuals was 43 (interquartile range: 30–57, range: 18–91) years old. The overall prevalences of L. loa and M. perstans microfilaremia were 20.0% [95% confidence intervals (CI) 18.0–21.6%] and 1.0% (95% CI 0.6–1.4%) respectively. The proportion of individuals with a microfilarial density of L. loa > 8000 mf/ml and > 30,000 mf/ml were 5.1% (95% CI 4.3–6.1%) and 1.1% (95% CI 0.8–1.7%), respectively. The overall community microfilarial load was 3.4 mf/ml.

Conclusions
Prevalences and intensities of L. loa infection remained generally stable between the late 1980s and 2019 in the Lékoumou Department. In contrast, parasitological indicators for M. perstans have declined sharply in the intervening years for an unknown reason.

Graphical Abstract
Characterization of class 1 integrons in metallo-β-lactamase-producing Acinetobacter baumannii isolates from hospital environment
Authors: Firoozeh Farzaneh , Ghorbani Mohammad , Zibaei Mohammad , Badmasti Farzad , Farid Malihe , Omidinia Narges , Bakhshi Fatemeh 
Published: December 2023

Abstract
Background and Objective
The emergence and widespread dissemination of antibiotic resistance in A. baumannii, has become a globally challenge. The increasing hospital outbreaks by multi-drug resistant (MDR) A. baumannii strains, shows the necessity of continuous monitoring to find sources of resistant strains in hospitals. This study aimed to identify the presence of class 1 integrons and metallo-β-lactamase (MBL) related genes in A. baumannii isolates from hospital environment.

Methods
In order to identify A. baumannii isolates, a total of 297 environmental samples were collected from burn wards and intensive care units (ICUs) of two university hospitals. Resistance to common antibiotics was studied by disk diffusion method and microbroth dilution assay was used to determine the minimum inhibitory concentrations (MICs) of imipenem, colistin and tigecycline. The A. baumannii isolates were studied by polymerase chain reaction (PCR) for the presence of class 1 integrons (intI1, intl CS) and metallo-β-lactamases (MBLs) (blaIMP, blaVIM, blaNDM) genes.

Results
A. baumannii was identified in 68/297 (22.9%) of hospital environment. All A. baumannii strains were multidrug-resistant (MDR), but none of them were resistant to colistin, tigecycline and ampicillin-sulbactam. All (100%) and 38 (95.0%) of A. baumannii isolates from ICUs and burn wards were imipenem resistant respectively. Class 1 integrons was identified in 30/40 (75.0%) and 23/28 (82.1%) isolates from burn wards and ICUs respectively. Two different types of gene cassettes were identified, which included: arr-2, ereC, aadA1, cmlA5 and arr2, cmlA5. MBL genes including blaVIM and blaIMP were detected in 26/28 (92.8%), 27/28(96.4%) and 39/40 (97.5%) and 31/40 (77.5%) of the isolates from the ICUs and the burn wards respectively. None of the isolates contained the blaNDM−1 gene.

Conclusion
The findings of the present study showed that the isolation rate of MBL producing carbapenem-resistant A. baumannii (CRAB) was relatively high in the environmental surface of burn wards and ICUs, which can be considered as a potential source of outbreaks in hospitalized patients.
The effect of nanomaterials on embryonic stem cell neural differentiation: a systematic review
Authors: Rahimi Darehbagh Ramyar , Mahmoodi Mozaffar , Amini Nader , Babahajiani Media , Allavaisie Azra , Moradi Yousef 
Published: December 2023

Abstract
Background
Humans’ nervous system has a limited ability to repair nerve cells, which poses substantial challenges in treating injuries and diseases. Stem cells are identified by the potential to renew their selves and develop into several cell types, making them ideal candidates for cell replacement in injured neurons. Neuronal differentiation of embryonic stem cells in modern medicine is significant. Nanomaterials have distinct advantages in directing stem cell function and tissue regeneration in this field. We attempted in this systematic review to collect data, analyze them, and report results on the effect of nanomaterials on neuronal differentiation of embryonic stem cells.

Methods
International databases such as PubMed, Scopus, ISI Web of Science, and EMBASE were searched for available articles on the effect of nanomaterials on neuronal differentiation of embryonic stem cells (up to OCTOBER 2023). After that, screening (by title, abstract, and full text), selection, and data extraction were performed. Also, quality assessment was conducted based on the STROBE checklist.

Results
In total, 1507 articles were identified and assessed, and then only 29 articles were found eligible to be included. Nine studies used 0D nanomaterials, ten used 1D nanomaterials, two reported 2D nanomaterials, and eight demonstrated the application of 3D nanomaterials. The main biomaterial in studies was polymer-based composites. Three studies reported the negative effect of nanomaterials on neural differentiation.

Conclusion
Neural differentiation is crucial in neurological regenerative medicine. Nanomaterials with different characteristics, particularly those cellular regulating activities and stem cell fate, have much potential in neural tissue engineering. These findings indicate a new understanding of potential applications of physicochemical cues in nerve tissue engineering.

Graphical Abstract
Dysregulated cholesterol regulatory genes in hepatocellular carcinoma
Authors: Cao Dan , Liu Huan 
Published: December 2023

AbstractCholesterol is an indispensable component in mammalian cells, and cholesterol metabolism performs important roles in various biological activities. In addition to the Warburg effect, dysregulated cholesterol metabolism is one of the metabolic hallmarks of several cancers. It has reported that reprogrammed cholesterol metabolism facilitates carcinogenesis, metastasis, and drug-resistant in various tumors, including hepatocellular carcinoma (HCC). Some literatures have reported that increased cholesterol level leads to lipotoxicity, inflammation, and fibrosis, ultimately promoting the development and progression of HCC. Contrarily, other clinical investigations have demonstrated a link between higher cholesterol level and lower risk of HCC. These incongruent findings suggest that the connection between cholesterol and HCC is much complicated. In this report, we summarize the roles of key cholesterol regulatory genes including cholesterol biosynthesis, uptake, efflux, trafficking and esterification in HCC. In addition, we discuss promising related therapeutic targets for HCC.
Mesenchymal stem cells-derived exosomes: novel carriers for nanoparticle to combat cancer
Authors: Abbasi Reza , Mesgin Raziye Momen , Nazari-Khanamiri Fereshteh , Abdyazdani Nima , Imani Zeynab , Talatapeh Shabnam Pirnezhad , Nourmohammadi Aidin , Nejati Vahid , Rezaie Jafar 
Published: December 2023

Abstract
Background
The advancement in novel cancer therapeutics brought a platform combining the properties of exosomes with nanoparticles to precision medicine. The novel therapeutic approach aim is cancer-targeted therapy. Exosomes from mesenchymal stem cells (MSCs-Exo) exhibit unique properties in cancer therapies, which makes them an ideal tool for delivering therapeutic agents into tumor cells.

The main body of the abstract
The key role of natural MSCs-Exo is controversial in cancer therapy; however, they can be engineered at their surface or cargo to serve as a smart drug delivery system for cancer-targeted therapy. In the last few years, researchers harnessed nanotechnology to enforce MSCs-Exo for cancer management including, tumor cell tracking, imaging, and tumor cell killing. Different nanoparticles such as gold nanoparticles have particularly been incorporated into MSCs-Exo, which showed an efficient accumulation at the site of tumor with improved anticancer impact. These findings indicate that a hybrid of exosomes–nanoparticles may serve as combination therapy for the effective removal of cancers.

Short conclusion
Although exhibiting impressive potential, the use of nanoparticle-loaded MSCs-Exo as a drug-delivery tool has been troubled by some challenges, therefore, translation to clinic prerequisites further scrutiny. In this review, we focus on nanoparticle-loaded MSCs-Exo as a new cancer therapy and discuss engineered MSC-Exo for target therapy.