bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanobiotechnology augmented cancer stem cell guided management of cancer: liquid-biopsy, imaging, and treatment
Authors: Sun Si , Yang Qiang , Jiang Dawei , Zhang Yuan 
Published: April 2024

AbstractCancer stem cells (CSCs) represent both a key driving force and therapeutic target of tumoral carcinogenesis, tumor evolution, progression, and recurrence. CSC-guided tumor diagnosis, treatment, and surveillance are strategically significant in improving cancer patients’ overall survival. Due to the heterogeneity and plasticity of CSCs, high sensitivity, specificity, and outstanding targeting are demanded for CSC detection and targeting. Nanobiotechnologies, including biosensors, nano-probes, contrast enhancers, and drug delivery systems, share identical features required. Implementing these techniques may facilitate the overall performance of CSC detection and targeting. In this review, we focus on some of the most recent advances in how nanobiotechnologies leverage the characteristics of CSC to optimize cancer diagnosis and treatment in liquid biopsy, clinical imaging, and CSC-guided nano-treatment. Specifically, how nanobiotechnologies leverage the attributes of CSC to maximize the detection of circulating tumor DNA, circulating tumor cells, and exosomes, to improve positron emission computed tomography and magnetic resonance imaging, and to enhance the therapeutic effects of cytotoxic therapy, photodynamic therapy, immunotherapy therapy, and radioimmunotherapy are reviewed.
Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma
Authors: Yang Lin , Li Hongjiao , Luo Aihua , Zhang Yao , Chen Hong , Zhu Li , Yang Deqin 
Published: April 2024

Abstract
Background
Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX.

Results
The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility.

Conclusions
Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.
Attenuation of inflammatory bowel disease by oral administration of mucoadhesive polydopamine-coated yeast β-glucan via ROS scavenging and gut microbiota regulation
Authors: Yang Fan , Su Yuting , Yan Chi , Chen Tianfeng , Cheung Peter Chi Keung 
Published: April 2024

AbstractTreatment for inflammatory bowel disease (IBD) is challenging since current anti-inflammatory and immunosuppressive therapies do not address the underlying causes of the illness, which include increased levels of reactive oxygen species (ROS) and dysbiosis of the gut commensal microbiota. Additionally, these treatments often have systemic off-target effects and adverse side effects. In this study, we have developed a prebiotic yeast β-glucan nanocomplex coated with bio-adhesive polydopamine (YBNs@PDA) to effectively prolong their retention time in the gastrointestinal (GI) tract. The oral administration of YBNs@PDA restored the epithelium barriers, reduced ROS levels, and minimized systemic drug exposure while improved therapeutic efficacy in an acute colitis mouse model. Furthermore, 16S ribosomal RNA genes sequencing demonstrated a higher richness and diversity in gut microflora composition following the treatments. In particular, YBNs@PDA markedly augmented the abundance of Lachnospiraceae NK4A136 and Bifidobacterium, both of which are probiotics with crucial roles in relieving colitis via retaining gut homeostasis. Cumulatively, these results demonstrate that the potential of YBNs@PDA as a novel drug-free, ROS-scavenging and gut microbiota regulation nanoplatform for the treatment of GI disorders.
Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19
Authors: Fang Jia-You , Huang Kuo-Yen , Wang Tong-Hong , Lin Zih-Chan , Chen Chin-Chuan , Chang Sui-Yuan , Chen En-Li , Chao Tai-Ling , Yang Shuenn-Chen , Yang Pan-Chyr , Chen Chi-Yuan 
Published: April 2024

AbstractIntroductionAngiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression.Materials and methodsIn this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection.ResultsOur data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection.ConclusionsWe have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.
HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
Authors: Chen Zhian , Zhou Tianhua , Luo Huan , Wang Zhen , Wang Qiang , Shi Rongmao , Li Zian , Pang Rongqing , Tan Hongbo 
Published: April 2024

AbstractThe current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton’s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-β/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-β, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery.
Graphical abstract
Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson’s disease
Authors: Guo Qinglong , Wang Yi , Yu Liangchen , Guan Liao , Ji Xuefei , Li Xiaohui , Pang Gang , Ren Zhenhua , Ye Lei , Cheng Hongwei 
Published: April 2024

Abstract
Background
Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice.

Methods
MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines.

Results
Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis.

Conclusions
This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.
Lactation duration and development of type 2 diabetes and metabolic syndrome in postpartum women with recent gestational diabetes mellitus
Authors: Suthasmalee Sasiwan , Phaloprakarn Chadakarn 
Published: April 2024

Abstract
Background
The World Health Organization and United Nations Children’s Fund recommend exclusive breastfeeding (EBF) for the first six months of an infant’s life. Although evidence suggests that maintaining breastfeeding has positive impacts on glucose and lipid metabolism in postpartum women with a history of gestational diabetes mellitus (GDM), no study has investigated whether such effects differ between breastfeeding intensities. This study aimed to evaluate the impact of maintaining breastfeeding on prediabetes, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) six months postpartum in women with GDM. This study also examined the potential variations in glucometabolic outcomes between EBF at six months and partial breastfeeding at six months.

Methods
This prospective cohort study included 130 women with recent GDM who experienced live births between 7 September 2020 and 31 January 2023 at a university hospital in Bangkok, Thailand. All the women were free of T2DM and MetS at baseline (six weeks postpartum). We followed up these women six months postpartum to assess their breastfeeding practices (EBF at six months, partial breastfeeding at six months, or not maintaining breastfeeding) and evaluate their progression to prediabetes, T2DM, and MetS. Maintaining breastfeeding was defined as breastfeeding for six months. EBF was determined using the “recall since birth” method.

Results
Of the 130 participants included, the rates of prediabetes, T2DM, and MetS six months postpartum were 33% (n = 43), 2% (n = 3), and 17% (n = 22), respectively. In the unadjusted model, maintaining breastfeeding was associated with a reduction in the risks of prediabetes and MetS but not T2DM. After adjusting for potential confounders, maintaining breastfeeding was a significant protective factor only for prediabetes. The adjusted risk ratios and 95% confidence intervals were 0.54 (0.29, 0.99) for prediabetes and 0.47 (0.19, 1.06) for MetS. When EBF at six months and partial breastfeeding at six months were separately analyzed, the risks of prediabetes and MetS differed between the two groups. In the EBF at six months-to-partial breastfeeding at six months comparison, the adjusted risk ratios (95% confidence intervals) of prediabetes and MetS were 0.46 (0.22, 0.97) vs. 0.79 (0.25, 2.49) and 0.34 (0.11, 0.99) vs. 0.69 (0.22, 2.07), respectively.

Conclusions
Maintaining breastfeeding reduced the risk of prediabetes and MetS, but not of T2DM, six months postpartum; these effects were significant only with EBF. These findings indicate that supporting maternal efforts to practice EBF for six months may improve women’s health after GDM.

Trial registration
Thai Clinical Trials Registry Registration No. TCTR20200902003. Date of registration: September 2, 2020. Date of initial participant enrollment: September 7, 2020.
Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles
Authors: Zheng Qing-Yuan , Tao Ye , Geng Lei , Ren Peng , Ni Ming , Zhang Guo-Qiang 
Published: April 2024

Abstract
Objective
Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives.

Methods
Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites.

Results
High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites.

Conclusions
Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.
Impact of delayed mobile medical team dispatch for respiratory distress calls: a propensity score matched study from a French emergency communication center
Authors: Charrin Léo , Romain-Scelle Nicolas , Di-Filippo Christian , Mercier Eric , Balen Frederic , Tazarourte Karim , Benhamed Axel 
Published: April 2024

Abstract
Background
Shortness of breath is a common complaint among individuals contacting emergency communication center (EMCCs). In some prehospital system, emergency medical services include an advanced life support (ALS)-capable team. Whether such team should be dispatched during the phone call or delayed until the BLS-capable paramedic team reports from the scene is unclear. We aimed to evaluate the impact of delayed MMT dispatch until receiving the paramedic review compared to immediate dispatch at the time of the call on patient outcomes.

Methods
A cross-sectional study conducted in Lyon, France, using data obtained from the departmental EMCC during the period from January to December 2019. We included consecutive calls related to adult patients experiencing acute respiratory distress. Patients from the two groups (immediate mobile medical team (MMT) dispatch or delayed MMT dispatch) were matched on a propensity score, and a conditional weighted logistic regression assessed the adjusted odds ratios (ORs) for each outcome (mortality on days 0, 7 and 30).

Results
A total of 870 calls (median age 72 [57–84], male 466 53.6%) were sought for analysis [614 (70.6%) “immediate MMT dispatch” and 256 (29.4%) “delayed MMT” groups]. The median time before MMT dispatch was 25.1 min longer in the delayed MMT group (30.7 [26.4–36.1] vs. 5.6 [3.9–8.8] min, p < 0.001). Patients subjected to a delayed MMT intervention were older (median age 78 [66–87] vs. 69 [53–83], p < 0.001) and more frequently highly dependent (16.3% vs. 8.6%, p < 0.001). A higher proportion of patients in the delayed MMT group required bag valve mask ventilation (47.3% vs. 39.1%, p = 0.03), noninvasive ventilation (24.6% vs. 20.0%, p = 0.13), endotracheal intubation (7.0% vs. 4.1%, p = 0.07) and catecholamine infusion (3.9% vs. 1.3%, p = 0.01). After propensity score matching, mortality at day 0 was higher in the delayed MMT group (9.8% vs. 4.2%, p = 0.002). Immediate MMT dispatch at the call was associated with a lower risk of mortality on day 0 (0.60 [0.38;0.82], p < 0.001) day 7 (0.50 [0.27;0.72], p < 0.001) and day 30 (0.56 [0.35;0.78], p < 0.001)

Conclusions
This study suggests that the deployment of an MMT at call in patients in acute respiratory distress may result in decreased short to medium-term mortality compared to a delayed MMT following initial first aid assessment.
Risk of conversion to mild cognitive impairment or dementia among subjects with amyloid and tau pathology: a systematic review and meta-analysis
Authors: Huszár Zsolt , Engh Marie Anne , Pavlekovics Márk , Sato Tomoya , Steenkamp Yalea , Hanseeuw Bernard , Terebessy Tamás , Molnár Zsolt , Hegyi Péter , Csukly Gábor 
Published: April 2024

Abstract
Background
Measurement of beta-amyloid (Aβ) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of developing a clinical syndrome in the presence of these protein changes (A+ and T+) remains unclear. By performing a systematic review and meta-analysis, we investigated the risk of mild cognitive impairment (MCI) or dementia in the non-demented population with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal fluid examination.

Methods
A systematic search of prospective and retrospective studies investigating the association of Aβ and p-tau with cognitive decline was performed in three databases (MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were pooled using a random-effects model. The effect of neurodegeneration was not studied due to its non-specific nature.

Results
A total of 18,162 records were found, and at the end of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aβ42 or Aβ42/40 analysis and amyloid PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects (11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73 [95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95% CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion (13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression showed that the ORs for Aβ exposure decreased with age in MCI. (beta = -0.04 [95% CI -0.03 to -0.083]).

Conclusions
Identifying Aβ-positive individuals, irrespective of the measurement technique employed (CSF or PET), enables the detection of the most at-risk population before disease onset, or at least at a mild stage. The inclusion of tau status in addition to Aβ, especially in A+T+ cases, further refines the risk assessment. Notably, the higher odds ratio associated with Aβ decreases with age.

Trial registration
The study was registered in PROSPERO (ID: CRD42021288100).