bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of Xiaozheng decoction for anti-bladder cancer effects via affecting the GSK3β/β-catenin signaling pathways: a network pharmacology-directed experimental investigation
Authors: Zhuang Jingming , Mo Jiahang , Huang Zhengnan , Yan Yilin , Wang Zeyi , Cao Xiangqian , Yang Chenkai , Shen Bing , Zhang Fang 
Published: August 2023

Abstract
Purpose
The combination of Xiaozheng decoction with postoperative intravesical instillation has been shown to improve the prognosis of bladder cancer patients and prevent recurrence. However, the mechanisms underlying the efficacy of this herbal formula remain largely unclear. This research aims to identify the important components of Xiaozheng decoction and explore their anti-bladder cancer effect and mechanism using network pharmacology-based experiments.

Methods
The chemical ingredients of each herb in the Xiaozheng decoction were collected from the Traditional Chinese Medicine (TCM) database. Network pharmacology was employed to predict the target proteins and pathways of action. Disease databases were utilized to identify target genes associated with bladder cancer. A Protein–Protein Interaction (PPI) network was constructed to illustrate the interaction with intersected target proteins. Key targets were identified using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. A compound-target-pathway network was established after molecular docking predictions. In vitro experiments with bladder cancer cell lines were conducted using core chemical components confirmed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to verify the conclusions of network pharmacology.

Results
45 active compounds were extracted, and their relationships with Traditional Chinese Medicines (TCMs) and protein targets were presented, comprising 7 herbs, 45 active compounds, and 557 protein targets. The intersection between potential TCM target genes and bladder cancer-related genes yielded 322 genes. GO and KEGG analyses indicated that these targets may be involved in numerous cancer-related pathways. Molecular docking results showed that candidate compounds except mandenol could form stable conformations with the receptor. In vitro experiments on three bladder cancer cell lines demonstrated that quercetin and two other impressive new compounds, bisdemethoxycurcumin (BDMC) and kumatakenin, significantly promoted cancer cell apoptosis through the B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/BAX) pathway and inhibited proliferation and migration through the glycogen synthase kinase 3 beta (GSK3β)/β-catenin pathway.

Conclusion
By employing network pharmacology and conducting in vitro experiments, the mechanism of Xiaozheng decoction’s effect against bladder cancer was tentatively elucidated, and its main active ingredients and targets were identified, providing a scientific basis for future research.
m6A eraser FTO impairs gemcitabine resistance in pancreatic cancer through influencing NEDD4 mRNA stability by regulating the PTEN/PI3K/AKT pathway
Authors: Lin Kai , Zhou Endi , Shi Ting , Zhang Siqing , Zhang Jinfan , Zheng Ziruo , Pan Yuetian , Gao Wentao , Yu Yabin 
Published: August 2023

Abstract
Background
Gemcitabine resistance has brought great challenges to the treatment of pancreatic cancer. The N6-methyladenosine (m6A) mutation has been shown to have a significant regulatory role in chemosensitivity; however, it is not apparent whether gemcitabine resistance can be regulated by fat mass and obesity-associated protein (FTO).

Methods
Cells with established gemcitabine resistance and tissues from pancreatic cancer patients were used to evaluate FTO expression. The biological mechanisms of the effects of FTO on gemcitabine resistant cells were investigated using CCK-8, colony formation assay, flow cytometry, and inhibitory concentration 50. Immunoprecipitation/mass spectrometry, MeRIP-seq, RNA sequencing and RIP assays, RNA stability, luciferase reporter, and RNA pull down assays were employed to examine the mechanism of FTO affecting gemcitabine resistant pancreatic cancer cells.

Results
The results revealed that FTO was substantially expressed in cells and tissues that were resistant to gemcitabine. Functionally, the gemcitabine resistance of pancreatic cancer could be enhanced by FTO, while its depletion inhibited the growth of gemcitabine resistant tumor cells in vivo. Immunoprecipitation/mass spectrometry showed that the FTO protein can be bound to USP7 and deubiquitinated by USP7, leading to the upregulation of FTO. At the same time, FTO knockdown significantly decreased the expression level of NEDD4 in an m6A-dependent manner. RNA pull down and RNA immunoprecipitation verified YTHDF2 as the reader of NEDD4, which promoted the chemoresistance of gemcitabine resistant cells. FTO knockdown markedly increased the PTEN expression level in an NEDD4-dependent manner and influenced the chemosensitivity to gemcitabine through the PI3K/AKT pathway in pancreatic cancer cells.

Conclusion
In conclusion, we found that gemcitabine resistance in pancreatic cancer can be influenced by FTO that demethylates NEDD4 RNA in a m6A-dependent manner, which then influences the PTEN expression level and thereby affects the PI3K/AKT pathway. We also identified that the FTO level can be upregulated by USP7.
Evidence for a personalized early start of norepinephrine in septic shock
Authors: Monnet Xavier , Lai Christopher , Ospina-Tascon Gustavo , De Backer Daniel 
Published: August 2023

AbstractDuring septic shock, vasopressor infusion is usually started only after having corrected the hypovolaemic component of circulatory failure, even in the most severe patients. However, earlier administration of norepinephrine, simultaneously with fluid resuscitation, should be considered in some cases. Duration and depth of hypotension strongly worsen outcomes in septic shock patients. However, the response of arterial pressure to volume expansion is inconstant, delayed, and transitory. In the case of profound, life-threatening hypotension, relying only on fluids to restore blood pressure may unduly prolong hypotension and organ hypoperfusion. Conversely, norepinephrine rapidly increases and better stabilizes arterial pressure. By binding venous adrenergic receptors, it transforms part of the unstressed blood volume into stressed blood volume. It increases the mean systemic filling pressure and increases the fluid-induced increase in mean systemic filling pressure, as observed in septic shock patients. This may improve end-organ perfusion, as shown by some animal studies. Two observational studies comparing early vs. later administration of norepinephrine in septic shock patients using a propensity score showed that early administration reduced the administered fluid volume and day-28 mortality. Conversely, in another propensity score-based study, norepinephrine administration within the first hour following shock diagnosis increased day-28 mortality. The only randomized controlled study that compared the early administration of norepinephrine alone to a placebo showed that the early continuous administration of norepinephrine at a fixed dose of 0.05 µg/kg/min, with norepinephrine added in open label, showed that shock control was achieved more often than in the placebo group. The choice of starting norepinephrine administration early should be adapted to the patient’s condition. Logically, it should first be addressed to patients with profound hypotension, when the arterial tone is very low, as suggested by a low diastolic blood pressure (e.g. ≤ 40 mmHg), or by a high diastolic shock index (heart rate/diastolic blood pressure) (e.g. ≥ 3). Early administration of norepinephrine should also be considered in patients in whom fluid accumulation is likely to occur or in whom fluid accumulation would be particularly deleterious (in case of acute respiratory distress syndrome or intra-abdominal hypertension for example).
Complex physical therapy employing self-adjusting garment (ReadyWrap®) in breast cancer-related lymphedema cases in Brazilian women: a protocol for a randomized controlled trial
Authors: da Silva Jéssica Malena Pedro , Araújo Raul Denner Duarte , da Silva Santos Francisca Cristina , Fabro Erica Alves Nogueira , de Mello Pinto Marcus Vinicius , de Aguiar Suzana Sales , Thuler Luiz Claudio Santos , Bergmann Anke 
Published: August 2023

Abstract
Background
Lymphedema is a common complication following breast cancer treatment. The aim of this study is to evaluate the effectiveness of a self-adjusting compression garment (ReadyWrap®) in reducing (phase 1) and maintaining (phase 2) upper limb volume in women presenting breast cancer-related lymphedema.

Methods
This study will comprise a randomized, controlled, single-blind clinical trial concerning women with breast cancer-related lymphedema undergoing treatment at a public cancer treatment reference hospital in the city of Rio de Janeiro, Brazil. The intervention will be carried out by adapting self-dressing versus the standard treatment of compressive bandaging (phase 1) and compressive mesh (phase 2). Both groups will be assessed at the beginning and end of intensive treatment and followed up for up to 12 months to evaluate immediate and late outcomes. Assessments will be carried out by physical upper limb examination (inspection, palpation, volume, dynamometry, and thermography) and questionnaires application to assess patient’s quality of life pertaining to the health, functionality, and symptoms of the affected upper limb, as well adverse effects and adherence to treatment. Data will be analyzed descriptively and analytically through univariate and multiple linear regressions. P values < 0.05 will be considered statistically significant.

Discussion
This study will evaluate the effectiveness of a self-adjustable garment (ReadyWrap®) in the treatment of lymphedema secondary to breast cancer in Brazilian women compared to the gold standard treatment for limb volume reduction (phase 1) and maintenance (phase 2) phases comprising, respectively, a compressive bandaging and a compressive mesh. The outcome results will provide data based on both quantitative responses and self-reported participant outcomes. The study will also assess the cost-effectiveness of the ReadyWrap® treatment versus standard care. Finally, we expect to reaffirm one more product/therapy as a treatment for this extremely complex and impactful condition following the data analysis.

Trial registration
NCT04934098 [Clinical trials phase 1]. Registered on June 22, 2021. NCT04881604 [Clinical trials phase 2]. Registered on May 11, 2021.
Molecular characterization of Carbapenem-resistant Escherichia coli isolates from sewage at Mulago National Referral Hospital, Kampala: a cross-sectional study
Authors: Bagaya Jamidah , Ssekatawa Kenneth , Nakabiri Gloria , Nsubuga Julius , Kitibwa Anna , Kato Charles Drago , Sembajwe Lawrence Fred 
Published: August 2023

Abstract
Background
Escherichia coli (E. coli) is one of the most frequent causes of fatal bacterial infections affecting both humans and animals. The resistance to Carbapenems is mainly associated with enzyme-mediated resistance mechanism, through the acquisition of Carbapenemase genes. In Uganda, no studies have been done to detect presence of Carbapenem-resistant E. coli in sewage. We therefore carried out a study to characterize Carbapenem-resistant E. coli from sewage from Mulago National Referral Hospital.

Methods and results
In this cross-sectional study, a total of 104, sewage samples were aseptically collected, cultured on MacConkey agar supplemented with Meropenem 1 µg/ml with other standard microbiology methods to screen for Carbapenem-resistant E. coli (CREC). Antimicrobial susceptibility testing was performed on the CREC, using Imipenem (10 mg/disc) and Meropenem (10 mg/disc), Carbapenem drugs readily available on market. Multiplex PCR was performed on selected Carbapenem-resistant and susceptible isolates to detect Carbapenemase genes. Later the isolates were pathotyped for virulence genes that included pathogenicity islands (PAIs) and phylogenetic markers. The results showed that the Carbapenem-resistant E. coli isolates were more resistant to Meropenem (64%) than Imipenem (60%). KPC gene was the most predominant (75%), followed by NDM gene (30%) while no OXA-48, IMP-1, and IMP-2 genes were detected. Pathotyping of virulence genes showed presence of eae gene, as the most predominant (40%), followed by elt gene (25%) and negative for stx and aggR genes. For PAI markers, only the PAI IV536 gene was detected at 10%. Then, pathotyping of the phylogenetic markers was present in 85% of the typed isolates with yjaA gene the most abundant (60%) while both chuA and TSPE4.C2 were detected in 5% of the isolates.

Conclusion
Both pathogenic and non-pathogenic Carbapenem-resistant E. coli strains are present in the sewage of Mulago National Referral Hospital in Uganda.
Bioenergetic profile and redox tone modulate in vitro osteogenesis of human dental pulp stem cells: new perspectives for bone regeneration and repair
Authors: Agriesti Francesca , Landini Francesca , Tamma Mirko , Pacelli Consiglia , Mazzoccoli Carmela , Calice Giovanni , Ruggieri Vitalba , Capitanio Giuseppe , Mori Giorgio , Piccoli Claudia , Capitanio Nazzareno 
Published: August 2023

Abstract
Background
Redox signaling and energy metabolism are known to be involved in controlling the balance between self-renewal and proliferation/differentiation of stem cells. In this study we investigated metabolic and redox changes occurring during in vitro human dental pulp stem cells (hDPSCs) osteoblastic (OB) differentiation and tested on them the impact of the reactive oxygen species (ROS) signaling.

Methods
hDPSCs were isolated from dental pulp and subjected to alkaline phosphatase and alizarin red staining, q-RT-PCR, and western blotting analysis of differentiation markers to assess achievement of osteogenic/odontogenic differentiation. Moreover, a combination of metabolic flux analysis and confocal cyto-imaging was used to profile the metabolic phenotype and to evaluate the redox tone of hDPSCs.

Results
In differentiating hDPSCs we observed the down-regulation of the mitochondrial respiratory chain complexes expression since the early phase of the process, confirmed by metabolic flux analysis, and a reduction of the basal intracellular peroxide level in its later phase. In addition, dampened glycolysis was observed, thereby indicating a lower energy-generating phenotype in differentiating hDPSCs. Treatment with the ROS scavenger Trolox, applied in the early-middle phases of the process, markedly delayed OB differentiation of hDPSCs assessed as ALP activity, Runx2 expression, mineralization capacity, expression of stemness and osteoblast marker genes (Nanog, Lin28, Dspp, Ocn) and activation of ERK1/2. In addition, the antioxidant partly prevented the inhibitory effect on cell metabolism observed following osteogenic induction.

Conclusions
Altogether these results provided evidence that redox signaling, likely mediated by peroxide species, influenced the stepwise osteogenic expansion/differentiation of hDPSCs and contributed to shape its accompanying metabolic phenotype changes thus improving their efficiency in bone regeneration and repair.
Comparative efficacy of oral drugs for chronic radiation proctitis — a systematic review
Authors: Liu Liangzhe , Xiao Nana , Liang Jinjun 
Published: August 2023

Abstract
Background
Chronic radiation proctitis (CRP) is a long-term complication of pelvic radiotherapy that manifests as rectal bleeding, diarrhoea, fistula formation and obstruction. Treatments such as endoscopic argon plasma coagulation, hyperbaric oxygen therapy and rectal topical formalin have imposed a significant medical burden on CRP patients. In contrast, oral therapies offer a more accessible and acceptable option for managing CRP. Here, we conducted a systematic review of the efficacy of oral treatments for CRP to assess their potential as an effective and convenient treatment option for this condition.

Methods
We searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, China National Knowledge Infrastructure and Chinese VIP in February 2021. We included post-radiotherapy participants with CRP that compared oral medicine alone or in combination with other treatments versus control treatments. The primary outcomes were bleeding, diarrhoea and symptom score. Heterogeneity between studies was checked using Cochrane Q test statistics and I2 test statistics. The Cochrane risk-of-bias tool was used to assess the quality of the included studies.

Results
We included 10 randomised controlled trials (RCTs) and 1 retrospective study with 898 participants. Three placebo-controlled trials evaluated the effects of oral sucralfate on CRP, with meta-analysis showing no significant different with placebo arm. Four trials on TCM demonstrated significant improvement of symptoms, especially for the 3 trials on oral TCM drinks. Retinyl palmitate and high-fibre diet were found to reduce rectal bleeding. The combination of oral pentoxifylline and tocopherol did not significantly change the process of CRP.

Conclusions
Our study implies that oral TCM drinks, retinyl palmitate and a high-fiber diet showed significant improvement in CRP symptoms, but not with the combination of oral pentoxifylline and tocopherol. Further multicentre, larger-scale RCTs are needed to confirm the efficacy and safety of these treatments and optimize treatment strategies, ultimately improving the quality of life for patients with CRP.
Effect of an integrated maternal and neonatal health intervention on maternal healthcare utilisation addressing inequity in Rural Bangladesh
Authors: Ahmed Anisuddin , Rahman Fariya , Sayeed Abu , Tanwi Tania Sultana , Siddique Abu Bakkar , Hossain Aniqa Tasnim , Ether Saraban Tahura , Akter Ema , Tahsina Tazeen , Rahman Syed Moshfiqur , Arifeen Shams El , Rahman Ahmed Ehsanur 
Published: August 2023

Abstract
Background
Although Bangladesh has made significant improvements in maternal, neonatal, and child health, the disparity between rich and poor remains a matter of concern.

Objective
The study aimed to increase coverage of skilled maternal healthcare services while minimising the inequity gap among mothers in different socioeconomic groups.

Methods
We implemented an integrated maternal and neonatal health (MNH) intervention between 2009 and 2012, in Shahjadpur sub-district of Sirajganj district, Bangladesh. The study was quasi-experimental in design for the evaluation. Socioeconomic status was derived from household assets using principal component analysis. Inequity in maternal healthcare utilisation was calculated using rich-poor ratio and concentration index to determine the changes in inequity between the baseline and the endline time period.

Result
The baseline and endline surveys included 3,158 (mean age 23.5 years) and 3,540 (mean age 24.3 years) recently delivered mothers respectively. Reduction in the rich-poor ratio was observed in the utilisation of skilled 4+ antenatal care (ANC) (2.4:1 to 1.1:1) and related concentration index decreased from 0.220 to 0.013 (p < 0.001). The rich-poor ratio for skilled childbirth reduced from 1.7:1 to 1.0:1 and the related concentration index declined from 0.161 to -0.021 (p < 0.001). A similar reduction was also observed in the utilisation of skilled postnatal care (PNC); where the rich-poor gap decreased from 2.5:1 to 1.0:1 and the related concentration index declined from 0.197 to -0.004 (p < 0.001).

Conclusion
The MNH intervention was successful in reducing inequity in receiving skilled 4+ ANC, delivery, and PNC in rural Bangladesh.
Prevalence of oral complications in the course of severe SARS-CoV-2 infection under mechanical non-invasive ventilation
Authors: Paszynska Elzbieta , Gawriolek Maria , Hernik Amadeusz , Otulakowska-Skrzynska Justyna , Winiarska Hanna , Springer Daria , Roszak Magdalena , Slebioda Zuzanna , Krahel Anna , Cofta Szczepan 
Published: August 2023

Abstract
Background
The management of oral health during severe symptoms of Covid-19 is still a challenge, especially in intensive care units under invasive/noninvasive ventilation in hospital. Understanding the cause-and-effect relationships may allow for individual adjustment of oral care recommendations during Covid-19 disease. The study’s objective was to assess Covid-19 patients’ oral health status under hospital treatment due to pulmonary adverse Covid-19 outcomes.

Material and methods
Covid-19 patients (mean age 74.4 ± 15.4; n = 120, male n = 50/female n = 70) were admitted to hospital in the acute phase of Covid-19 between January and March 2022 who required oxygen therapy due to pneumonia, rapid respiratory failure, low saturation. Blood and radiological tests were taken according to National Health Fund guidelines. The condition of teeth (Decayed, Missing, Filled teeth as DMFT index), dental hygiene (Plaque Control Record as PCR index), periodontal status (probing depth PD, clinical attachment CAL, bleeding on probing BOP) and oral mucosa (BRUSHED and Beck scores) were examined.

Results
Charateristics of the teeth (dental caries 35.2%, DMFT Median 22), plaque retention (83.4%), advanced periodontitis (48.3%), xerostomia (74.2%), oral mucosa inflammation (80.8%), angular cheilitis (53.3%), hemorrhagic (21.7%) showed a high incidence of harmful oral conditions. BRUSHED model and Beck score indicated moderate oral dysfunction and need for oral care every 8 h. Spearman’s analysis revealed a significant positive correlation between pneumonia and neutrophile, interleukin-6 IL-6, C-reactive protein CRP (p = 0.01, p < 0.001, p < 0.001), negative to lymphocyte count (p < 0.001). Multiple and logistic regressions selected the following risk predictors for pneumonia as IL-6, CRP, obesity and for severe COVID-19 symptoms D-dimer level and a lack of targeted vaccination (p < 0.001). Among oral predictors, the PCR index and Beck score were significant for both outcomes (respectively p < 0.001, p < 0.012). Patients who received oxygen therapy with face masks had more often angular heilitis and debris (p = 0.025, p = 0.035).

Conclusions
COVID-19 hospitalised patients with severe symptoms crossing with poor oral health-related conditions. This may exacerbate a response for COVID infection, and play a role in cytokine storm. For Covid-19 management, to inhibit extraoral/intraoral complications, it is recommended to adjust oral hygiene procedures, including antibacterial, protective, moisturising agents after individual oral health assessment.