bluuebunny/crossref_metadata_2025_split huggingface dataset:
BM-MSCs overexpressing the Numb enhance the therapeutic effect on cholestatic liver fibrosis by inhibiting the ductular reaction
Authors: Xu Yan-nan , Xu Wen , Zhang Xu , Wang Dan-yang , Zheng Xin-rui , Liu Wei , Chen Jia-mei , Chen Gao-feng , Liu Cheng-hai , Liu Ping , Mu Yong-ping 
Published: March 2023

Abstract
Background
Cholestatic liver fibrosis (CLF) is caused by inflammatory destruction of the intrahepatic bile duct and abnormal proliferation of the small bile duct after cholestasis. Activation of the Notch signaling pathway is required for hepatic stem cells to differentiate into cholangiocytes during the pathogenesis of CLF. Our previous research found that the expression of the Numb protein, a negative regulator of Notch signaling, was significantly reduced in the livers of patients with primary biliary cholangitis and CLF rats. However, the relationship between the Numb gene and CLF is largely unclear. In this study, we investigated the role of the Numb gene in the treatment of bile duct ligation (BDL)-induced CLF.

Methods
In vivo, bone marrow-derived mesenchymal stem cells (BM-MSCs) with Numb gene overexpression or knockdown obtained using lentivirus transfection were transplanted into the livers of rats with BDL-induced CLF. The effects of the Numb gene on stem cell differentiation and CLF were evaluated by performing histology, tests of liver function, and measurements of liver hydroxyproline, cytokine gene and protein levels. In vitro, the Numb gene was overexpressed or knocked down in the WB-F344 cell line by lentivirus transfection, Then, cells were subjected immunofluorescence staining and the detection of mRNA levels of related factors, which provided further evidence supporting the results from in vivo experiments.

Results
BM-MSCs overexpressing the Numb gene differentiated into hepatocytes, thereby inhibiting CLF progression. Conversely, BM-MSCs with Numb knockdown differentiated into biliary epithelial cells (BECs), thereby promoting the ductular reaction (DR) and the progression of CLF. In addition, we confirmed that knockdown of Numb in sodium butyrate-treated WB-F344 cells aggravated WB-F344 cell differentiation into BECs, while overexpression of Numb inhibited this process.

Conclusions
The transplantation of BM-MSCs overexpressing Numb may be a useful new treatment strategy for CLF.
Semi-quantitative indices of 2-[18F]FDG PET/CT in assessing cardiovascular and non-cardiovascular manifestations of IgG4-related disease and treatment response
Authors: Chen Mingwei , Tang Charlene Yu Lin , Fong Warren Weng Seng , Lam Winnie Wing-Chuen 
Published: March 2023

Abstract
Background
IgG4-related disease (IgG4-RD) is a heterogeneous autoimmune disorder characterised by inflammatory lesions. Diagnostic imaging, such as 2-[18F]FDG PET/CT, is critical in evaluation of the disease, especially for potentially lethal cardiovascular manifestations. This retrospective study examines the usefulness of semi-quantitative parameters of 2-[18F]FDG PET/CT in monitoring IgG4-RD in patients with and without cardiovascular manifestations.

Methods
Patients diagnosed with IgG4-RD who underwent a 2-[18F]FDG PET/CT scan were identified and classified based on presence or absence of cardiovascular disease. Clinical and laboratory data were extracted and compared to three 2-[18F]FDG PET/CT semi-quantitative parameters: maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Tissue-to-background blood (TBR) values were also evaluated for cardiovascular manifestations. These data were also compared in patients before and after receiving immunosuppressive therapy.

Results
Forty-six patients identified were divided into an eight member subgroup of patients with cardiovascular manifestations, and a thirty-eight member subgroup of patients without. Patients with cardiovascular lesions were most frequently identified incidentally on imaging evaluation for other diseases (37.5%), with none presenting with chest pain or other cardiovascular symptoms. Ten patients with pre-treatment and post-treatment 2-[18F]FDG PET/CT scans demonstrated significant decreases in all semi-quantitative parameters, with no significant decrease in total IgG or ESR. The decrease in SUVmax, MTV, TLG following therapy was replicated in patients with and without cardiovascular manifestations.

Conclusion
2-[18F]FDG PET/CT is an important investigation to determine all sites of involvement in this multisystemic disease and to rule out life-threatening cardiovascular manifestations even in the absence of symptoms. Semi-quantitative parameters such as SUVmax, MTV, TLG, and TBR are useful in assessing treatment response in patients. There are no serological substitutes that can quantify the extent of disease involvement like 2-[18F]FDG PET/CT.
Economic evaluation of strategies against coronavirus: a systematic review
Authors: Izadi Reyhane , Hatam Nahid , Baberi Fatemeh , Yousefzadeh Setareh , Jafari Abdosaleh 
Published: March 2023

Abstract
Background
The COVID-19 outbreak was defined as a pandemic on 11 March 2020 by the World Health Organization. After that, COVID-19 has enormously influenced health systems around the world, and it has claimed more than 4.2 million deaths until July 2021. The pandemic has led to global health, social and economic costs. This situation has prompted a crucial search for beneficial interventions and treatments, but little is known about their monetary value. This study is aimed at systematically reviewing the articles conducted on the economic evaluation of preventive, control and treatment strategies against COVID-19.

Material and method
We searched PubMed, Web of Science, Scopus, and Google Scholar from December 2019 to October 2021 to find applicable literature to the economic evaluation of strategies against COVID-19. Two researchers screened potentially eligible titles and abstracts. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to quality assessment of studies.

Results
Thirty-six studies were included in this review, and the average CHEERS score was 72. Cost-effectiveness analysis was the most common type of economic evaluation, used in 21 studies. And the quality-adjusted life year (QALY) was the main outcome applied to measure the effectiveness of interventions, which was used in 19 studies. In addition, articles were reported a wide range of incremental cost-effectiveness ratio (ICER), and the lowest cost per QALY ($321.14) was related to the use of vaccines.

Conclusion
Based on the results of this systematic review, it seems that all strategies are likely to be more cost-effective against COVID-19 than no intervention and vaccination was the most cost-effective strategy. This research provides insight for decision makers in choosing optimal interventions against the next waves of the current pandemic and possible future pandemics.
Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
Authors: Piri-Gharaghie Tohid , Doosti Abbas , Mirzaei Seyed Abbas 
Published: March 2023

AbstractDeveloping adjuvant vaccines to combat rising multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections is a promising and cost-effective approach. The aim of this analysis was to construct a pDNA-CPG C274-adjuvant nano-vaccine and investigate its immunogenicity and protection in BALB/c mice. The CPG ODN C274 adjuvant was chemically synthesized and cloned into pcDNA3.1( +), and the cloning was verified using PCR and BamHI/EcoRV restriction enzyme digestion. Then, utilizing a complex coacervation approach, pDNA-CPG C274 was encapsulated by chitosan (CS) nanoparticles (NPs). TEM and DLS are used to explore the properties of the pDNA/CSNP complex. TLR-9 pathway activation was investigated in human HEK-293 and RAW 264.7 mouse cells. The vaccine's immunogenicity and immune-protective effectiveness were investigated in BALB/c mice. The pDNA-CPG C274/CSNPs were small (mean size 79.21 ± 0.23 nm), positively charged (+ 38.87 mV), and appeared to be spherical. A continuous slow release pattern was achieved. TLR-9 activation was greatest in the mouse model with CpG ODN (C274) at concentrations of 5 and 10 μg/ml with 56% and 55%, respectively (**P < 0.01). However, in HEK-293 human cells, by increasing the concentration of CpG ODN (C274) from 1 to 50 μg/ml, the activation rate of TLR-9 also increased, so that the highest activation rate (81%) was obtained at the concentration of 50 μg/ml (***P < 0.001). pDNA-CPG C274/CSNPs immunized BALB/c mice produced increased amounts of total-IgG, as well as IFN-γ and IL-1B in serum samples, compared to non-encapsulated pDNA-CPG C274. Furthermore, liver and lung injuries, as well as bacterial loads in the liver, lung, and blood, were reduced, and BALB/c mice immunized with pDNA-CPG C274/CSNPs showed potent protection (50–75%) against acute fatal Intraperitoneal A. baumannii challenge. pDNA-CPG C274/CSNPs evoked total-IgG antibodies, Th1 cellular immunity, and the TLR-9 pathway, as well as protection against an acute fatal A. baumannii challenge. Our findings suggest that this nano-vaccine is a promising approach for avoiding A. baumannii infection when used as a powerful adjuvant.
A fabricated hydrogel of hyaluronic acid/curcumin shows super-activity to heal the bacterial infected wound
Authors: Khaleghi Maryam , Haghi Fakhri , Gholami Mina , Hourfar Hamdam , Shahi Farshad , Mir Mousavi Zekoloujeh Ali , Aliakbari Farhang , Ahmadi Ebrahim , Morshedi Dina 
Published: March 2023

AbstractHigh risk of acute morbidities and even mortality from expanding the antibiotics resistant infectious wounds force indefinite efforts for development of high performance wound-healing materials. Herein, we design a procedure to fabricate a hyaluronic acid (HA)-based hydrogel to conjugate curcumin (Gel-H.P.Cur). The highlight of this work is to provide a favorite condition for capturing curcumin while protecting its structure and intensifying its activities because of the synchronization with HA. Accordingly, HA as a major component of dermis with a critical role in establishing skin health, could fortify the wound healing property as well as antibacterial activity of the hydrogel. Gel-H.P.Cur showed antibacterial properties against Pseudomonas aeruginosa (P. aeruginosa), which were examined by bactericidal efficiency, disk diffusion, anti-biofilm, and pyocyanin production assays. The effects of Gel-H.P.Cur on the inhibition of quorum sensing (QS) regulatory genes that contribute to expanding bacteria in the injured place was also significant. In addition, Gel-H.P.Cur showed high potential to heal the cutaneous wounds on the mouse excisional wound model with repairing histopathological damages rapidly and without scar. Taken together, the results strongly support Gel-H.P.Cur as a multipotent biomaterial for medical applications regarding the treatment of chronic, infected, and dehiscent wounds.
Identification of the feed supplements commonly utilised by communal beef cattle farmers during the dry season at Ga-Matlala, Limpopo province
Authors: Monkwe T. R. , Gxasheka M. , Gunya B. 
Published: March 2023

AbstractA survey was carried out to identify the feed supplements commonly utilised by communal beef cattle farmers and investigate knowledge and perception of farmers on the feed supplement during the dry season in Ga-Matlala, whether they assess the feed supplements before feeding to cattle and their perception on how they affect cattle. A structured questionnaire was used to collect data from a total of 59 cattle farmers from three rural villages (Phofu, Phetole and Madietane) in the Ga-Matlala area using a snowball sampling technique. In the studied area, males outnumbered females, with the majority aged 55 and older. The majority of respondents were cattle owners with 16 years or more of farming experience. Secondary school was the most frequently reported educational background, followed by primary school whereas 20.3% of respondents never attended school. The most common cattle breed owned was Nguni, while Afrikaner was the second most common breed. More than 50% of respondents reported releasing cattle in the morning and returning late to provide them with feed supplements and water. The majority of respondents were using feed supplements during the dry season, and the most feed supplements that were identified in the study areas are lucerne hay and maize stover. Lucerne hay and maize stover were the most commonly used and acceptable supplementary feeds during the dry season. The major reasons for feeding cattle with lucerne hay and maize stover were reported to be weight gain and average weight gain of cattle, respectively. The majority of farmers reported that they do not assess the quality of supplementary feeds especially those who supplement with lucerne hay. However, the remaining percentage of farmers assesses the quality of lucerne hay by checking the moisture content and moulds in the feed supplements. It is thus concluded that there is a need for more knowledge and information on the overall quality of the locally available dry season supplementary feeds for enhancing productivity in communal areas.
SEPT2 crotonylation promotes metastasis and recurrence in hepatocellular carcinoma and is associated with poor survival
Authors: Zhang Xin-yue , Liu Ze-xian , Zhang Yi-fan , Xu Li-xia , Chen Meng-ke , Zhou Yu-feng , Yu Jun , Li Xiao-xing , Zhang Ning 
Published: March 2023

AbstractBackgroundHepatocellular carcinoma (HCC) metastasis and recurrence lead to therapy failure, which are closely associated with the proteome. However, the role of post-translational modification (PTM) in HCC, especially for the recently discovered lysine crotonylation (Kcr), is elusive.ResultsWe investigated the correlation between crotonylation and HCC in 100 tumor tissues and performed stable isotope labeling by amino acids and liquid chromatography tandem mass spectrometry in HCC cells, and we found that crotonylation was positively correlated with HCC metastasis, and higher crotonylation in HCC cells facilitated cell invasiveness. Through bioinformatic analysis, we found that the crotonylated protein SEPT2 was significantly hypercrotonylated in highly invasive cells, while the decrotonylated mutation of SEPT2-K74 impaired SEPT2 GTPase activity and inhibited HCC metastasis in vitro and in vivo. Mechanistically, SIRT2 decrotonylated SEPT2, and P85α was found to be the downstream effector of SEPT2. Moreover, we identified that SEPT2-K74cr was correlated with poor prognosis and recurrence in HCC patients, thus indicating its clinical potential as an independent prognostic factor.ConclusionsWe revealed the role of nonhistone protein crotonylation in regulating HCC metastasis and invasion. Crotonylation facilitated cell invasion through the crotonylated SEPT2-K74-P85α-AKT pathway. High SEPT2-K74 crotonylation predicted poor prognosis and a high recurrence rate in HCC patients. Our study revealed a novel role of crotonylation in promoting HCC metastasis.
ISL1 controls pancreatic alpha cell fate and beta cell maturation
Authors: Bohuslavova Romana , Fabriciova Valeria , Lebrón-Mora Laura , Malfatti Jessica , Smolik Ondrej , Valihrach Lukas , Benesova Sarka , Zucha Daniel , Berkova Zuzana , Saudek Frantisek , Evans Sylvia M , Pavlinkova Gabriela 
Published: March 2023

Abstract
Background
Glucose homeostasis is dependent on functional pancreatic α and ß cells. The mechanisms underlying the generation and maturation of these endocrine cells remain unclear.

Results
We unravel the molecular mode of action of ISL1 in controlling α cell fate and the formation of functional ß cells in the pancreas. By combining transgenic mouse models, transcriptomic and epigenomic profiling, we uncover that elimination of Isl1 results in a diabetic phenotype with a complete loss of α cells, disrupted pancreatic islet architecture, downregulation of key ß-cell regulators and maturation markers of ß cells, and an enrichment in an intermediate endocrine progenitor transcriptomic profile.

Conclusions
Mechanistically, apart from the altered transcriptome of pancreatic endocrine cells, Isl1 elimination results in altered silencing H3K27me3 histone modifications in the promoter regions of genes that are essential for endocrine cell differentiation. Our results thus show that ISL1 transcriptionally and epigenetically controls α cell fate competence, and ß cell maturation, suggesting that ISL1 is a critical component for generating functional α and ß cells.
Loss of TTC17 promotes breast cancer metastasis through RAP1/CDC42 signaling and sensitizes it to rapamycin and paclitaxel
Authors: Zhang Jingyao , Guo Fengzhu , Li Chunxiao , Wang Yang , Wang Jinsong , Sun Fangzhou , Zhou Yantong , Ma Fei , Zhang Bailin , Qian Haili 
Published: March 2023

Abstract
Background
Breast cancer (BC) metastasis is the leading cause of poor prognosis and therapeutic failure. However, the mechanisms underlying cancer metastasis are far from clear.

Methods
We screened candidate genes related to metastasis through genome-wide CRISPR screening and high-throughput sequencing of patients with metastatic BC, followed by a panel of metastatic model assays. The effects of tetratricopeptide repeat domain 17 (TTC17) on migration, invasion, and colony formation ability together with the responses to anticancer drugs were investigated in vitro and in vivo. The mechanism mediated by TTC17 was determined by RNA sequencing, Western blotting, immunohistochemistry, and immunofluorescence. The clinical significance of TTC17 was evaluated using BC tissue samples combined with clinicopathological data.

Results
We identified the loss of TTC17 as a metastasis driver in BC, and its expression was negatively correlated with malignancy and positively correlated with patient prognosis. TTC17 loss in BC cells promoted their migration, invasion, and colony formation capacity in vitro and lung metastasis in vivo. Conversely, overexpressing TTC17 suppressed these aggressive phenotypes. Mechanistically, TTC17 knockdown in BC cells resulted in the activation of the RAP1/CDC42 pathway along with a disordered cytoskeleton in BC cells, and pharmacological blockade of CDC42 abolished the potentiation of motility and invasiveness caused by TTC17 silencing. Research on BC specimens demonstrated reduced TTC17 and increased CDC42 in metastatic tumors and lymph nodes, and low TTC17 expression was linked to more aggressive clinicopathologic characteristics. Through screening the anticancer drug library, the CDC42 inhibitor rapamycin and the microtubule-stabilizing drug paclitaxel showed stronger inhibition of TTC17-silenced BC cells, which was confirmed by more favorable efficacy in BC patients and tumor-bearing mice receiving rapamycin or paclitaxel in the TTC17Low arm.

Conclusions
TTC17 loss is a novel factor promoting BC metastasis, that enhances migration and invasion by activating RAP1/CDC42 signaling and sensitizes BC to rapamycin and paclitaxel, which may improve stratified treatment strategies under the concept of molecular phenotyping-based precision therapy of BC.
Stem cell therapy combined with controlled release of growth factors for the treatment of sphincter dysfunction
Authors: Shan Shengzhou , Li Qingfeng , Criswell Tracy , Atala Anthony , Zhang Yuanyuan 
Published: March 2023

AbstractSphincter dysfunction often occurs at the end of tubule organs such as the urethra, anus, or gastroesophageal sphincters. It is the primary consequence of neuromuscular impairment caused by trauma, inflammation, and aging. Despite intensive efforts to recover sphincter function, pharmacological treatments have not achieved significant improvement. Cell- or growth factor-based therapy is a promising approach for neuromuscular regeneration and the recovery of sphincter function. However, a decrease in cell retention and viability, or the short half-life and rapid degradation of growth factors after implantation, remain obstacles to the translation of these therapies to the clinic. Natural biomaterials provide unique tools for controlled growth factor delivery, which leads to better outcomes for sphincter function recovery in vivo when stem cells and growth factors are co-administrated, in comparison to the delivery of single therapies. In this review, we discuss the role of stem cells combined with the controlled release of growth factors, the methods used for delivery, their potential therapeutic role in neuromuscular repair, and the outcomes of preclinical studies using combination therapy, with the hope of providing new therapeutic strategies to treat incontinence or sphincter dysfunction of the urethra, anus, or gastroesophageal tissues, respectively.
Clinical significance of human metapneumovirus detection in critically ill adults with lower respiratory tract infections
Authors: Kapandji Natacha , Darmon Michael , Valade Sandrine , Salmona Maud , Legoff Jérôme , Zafrani Lara , Azoulay Elie , Lemiale Virginie 
Published: March 2023

Abstract
Background
Unlike other viruses, the pathogenicity of human metapneumovirus (hMPV) in adults remains uncertain. To address this question, a retrospective monocentric cohort including all patients admitted to ICU with hMPV infection between January 1, 2010, and June 30, 2018 was performed. The characteristics of hMPV infected patients were studied and compared to matched influenza infected patients. Consecutively, a systematic review and meta-analyses investigating PUBMED, EMBASE and COCHRANE databases was conducted to explore the hMPV infections in adult patients (PROSPERO number: CRD42018106617). Trials, case series, and cohorts published between January 1, 2008 and August 31, 2019 compiling adults presenting hMPV infections were included. Pediatric studies were excluded. Data were extracted from published reports. Primary endpoint was the rate of low respiratory tract infections (LRTIs) among all hMPV infected patients.

Results
During the study period, 402 patients were tested positive for hMPV. Among them 26 (6.5%) patients were admitted to the ICU, 19 (4.7%) for acute respiratory failure. Twenty-four (92%) were immunocompromised. Bacterial coinfections were frequent 53.8%. Hospital mortality rate was 30.8%. In the case–control analysis, the clinical and imaging characteristics were not different between hMPV and influenza infected patients. The systematic review identified 156 studies and 69 of them (1849 patients) were eligible for analysis. Although there was heterogeneity between the studies, the rate of hMPV LRTIs was 45% (95% CI 31–60%; I2 = 98%). Intensive care unit (ICU) admission was required for 33% (95% CI 21–45%; I2 = 99%). Hospital mortality rate was 10% (95% CI 7–13%; I2 = 83%) and ICU mortality rate was 23% (95% CI 12–34%; I2 = 65%). Underlying malignancy was independently associated with increased mortality rate.

Conclusions
This preliminary work suggested that hMPV may be associated with severe infection and high mortality in patients with underlying malignancies. However, regarding the small size of the cohort and the heterogeneity of the review, more cohort studies are warranted.