bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of miR-506-3p reversed doxorubicin resistance in drug-resistant osteosarcoma cells
Authors: Wang Xinru , Ding Rumeng , Fu Zhe , Yang Meng , Li Duolu , Zhou Yubing , Qin Chongzhen , Zhang Wenda , Si Liuzhe , Zhang Jingmin , Chai Yuna 
Published: February 2024

Background and objective: Osteosarcoma is a common primary malignant tumor of bone, and doxorubicin is one of the most widely used therapeutic drugs. While the problem of doxorubicin resistance limits the long-term treatment benefits in osteosarcoma patients. The role of miRNAs and their target genes in osteosarcoma have become increasingly prominent. Currently, there is no report on miR-506-3p reversing doxorubicin resistance by targeting STAT3 in osteosarcoma. The purpose of this study was to investigate the molecular mechanism that overexpression of miR-506-3p reverses doxorubicin resistance in drug-resistant osteosarcoma cells.Methods: Doxorubicin-resistant osteosarcoma cells (U-2OS/Dox) were constructed by intermittent stepwise increasing stoichiometry. The target genes of miR-506-3p were predicted by bioinformatics approach and the targeting relationship between miR-506-3p and STAT3 was detected using dual luciferase reporter assay. U-2OS/Dox cells were treated with miR-506-3p overexpression and STAT3 silencing respectively. Then Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of JAK2/STAT3 signaling pathway, drug-resistant and apoptotic associated molecules. The migration and invasion were assessed by cell scratch assay and transwell assay. The cell proliferative viability and apoptosis were investigated by CCK8 assay and flow cytometry assay.Results: U-2OS/Dox cells were successfully constructed with a 14.4-fold resistance. MiR-506-3p is directly bound to the 3′-UTR of STAT3 mRNA. Compared with U-2OS cells, the mRNA expression of miR-506-3p was reduced in U-2OS/Dox cells. Overexpression of miR-506-3p decreased the mRNA expression levels of JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and decreased the protein expression levels of p-JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and conversely increased Bax expression. It also inhibited the proliferation, migration and invasion of U-2OS/Dox cells and promoted cells apoptosis. The results of STAT3 silencing experiments in the above indicators were consistent with that of miR-506-3p overexpression.Conclusion: Overexpression of miR-506-3p could inhibit the JAK2/STAT3 pathway and the malignant biological behaviors, then further reverse doxorubicin resistance in drug-resistant osteosarcoma cells. The study reported a new molecular mechanism for reversing the resistance of osteosarcoma to doxorubicin chemotherapy and provided theoretical support for solving the clinical problems of doxorubicin resistance in osteosarcoma.
Oxygen-supplying ROS-responsive prodrug for synergistic chemotherapy and photodynamic therapy of colon cancer
Authors: Hao Ying , Liu Tailuo , Zhou Hao , Xu Runhao , Li Ka , Chen Mao , Chen Yuwen 
Published: February 2024

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors.Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine–polyethylene glycol (DSPE–PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP).Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.
Polyphenols and extracts from Zingiber roseum (Roxb.) Roscoe leaf mitigate pain, inflammation and pyrexia by inhibiting cyclooxygenase-2: an in vivo and in silico studies
Authors: Ahmed Shakhawat , Ahmed Khondoker Shahin , Rahman Md. Naiemur , Hossain Hemayet , Han Aixia , Geng Peiwu , Daula A. F. M. Shahid Ud , Mamun Abdullah Al 
Published: February 2024

Zingiber roseum (Roxb.) Roscoe, a perennial herb from the Zingiberaceae family, has a long history of traditional use in the treatment of several ailments including pain, inflammation, fever, cough, arthritis, skin diseases, and liver infections. This study sought to confirm the efficacy of Zingiber roseum (Roxb.) Roscoe leaves methanol extract (ZrlME) as reported in traditional usage by evaluating its analgesic, anti-inflammatory, and antipyretic capabilities. In addition, in silico molecular docking of the metabolites identified in ZrlME was studied to verify the experimental outcomes. ZrlME demonstrated strong dose-dependent analgesic efficacy against all analgesic tests. ZrlME (400 mg/kg) showed higher anti-inflammatory activity than the standard in the carrageenan-induced paw edema test model. A significant reduction of rectal temperature (3.97°F↓) was also recorded at the same dose of ZrLME after 24 h of treatment. Seven polyphenolic metabolites were identified and quantified by HPLC-DAD analysis, including 3, 4- dihydroxy benzoic acid, (-) epicatechin, rutin hydrate, p-coumaric acid, trans-ferulic acid, rosmarinic acid, and myricetin. Strong binding affinities (ranges from −5.8 to −8.5 Kcal/mol) between the aforesaid polyphenols and cyclooxygenase-2 were discovered. Moreover, molecular dynamics simulations (MDS) demonstrated that these polyphenols exhibit significant COX-2 inhibitory activity due to their high stability in the COX-2 active site. In computational prediction, the polyphenols were also found to be nontoxic, and a variety of biological activities, such as antioxidant, analgesic, anti-inflammatory, antipyretic, and hepatoprotective, were observed. The results of this study revealed that ZrlME possesses notable analgesic, anti-inflammatory, and antipyretic properties.
Network pharmacology and gut microbiota insights: unraveling Shenling Baizhu powder’s role in psoriasis treatment
Authors: Tang Bin , Zheng Xuwei , Luo Qianqian , Li Xiong , Yang Yujie , Bi Yang , Chen Yonggen , Han Ling , Chen Haiming , Lu Chuanjian 
Published: February 2024

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood.Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models.Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing.Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement.Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP’s modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.
Targeting ferroptosis unveils a new era for traditional Chinese medicine: a scientific metrology study
Authors: Cao Siyang , Wei Yihao , Yue Yaohang , Chen Yingqi , Liao Shuai , Li Aikang , Liu Peng , Xiong Ao , Zeng Hui 
Published: February 2024

In the past 11 years, there has been a surge in studies exploring the regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, a significant gap persists in comprehensive scientometric analysis and scientific mapping research, especially in tracking the evolution, primary contributors, and emerging research focal points. This study aims to comprehensively update the advancements in targeting ferroptosis with various TCMs during the previous 11 years. The data, covering the period from 1 January 2012, to 30 November 2023, were retrieved from the Web of Science database. For in-depth scientometric and visualized analyses, a series of advanced analytical instruments were employed. The findings highlight China’s predominant role, accounting for 71.99% of total publications and significantly shaping research in this domain. Noteworthy productivity was observed at various institutions, including Guangzhou University of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, and Zhejiang University. Thomas Efferth emerged as the foremost author within this field, while Frontiers in Pharmacology boasted the highest publication count. This study pinpointed hepatocellular carcinoma, chemical and drug-induced liver injury, mitochondrial diseases, acute kidney injury, and liver failure as the most critical disorders addressed in this research realm. The research offers a comprehensive bibliometric evaluation, enhancing our understanding of the present status of TCM therapy in managing ferroptosis-related diseases. Consequently, it aids both seasoned researchers and newcomers by accelerating access to vital information and fostering innovative concept extraction within this specialized field.
Selection of M5 mutant lines of wheat (Triticum aestivum L.) for agronomic traits and biomass allocation under drought stress and non-stressed conditions
Authors: Makebe Athenkosi , Shimelis Hussein , Mashilo Jacob 
Published: February 2024

IntroductionIn the face of climate changes and limited water availability for irrigated crop production, enhanced drought tolerance and adaptation is vital to improve wheat productivity. The objective of this study was to determine the responses of newly bred and advanced mutant lines of wheat based on agronomic traits and biomass allocation under drought-stressed and non-stressed environments for production and breeding.MethodsFifty-three mutant lines, including the parental check and six check varieties, were evaluated under non-stressed (NS) and drought stressed (DS) conditions in the field and controlled environments using a 20 x 3 alpha lattice design with two replicates. The following agronomic data were collected: days to 50% heading (DTH), days to maturity (DTM), plant height (PH), number of productive tillers (PTN), shoot biomass (SB), root biomass (RB), total biomass (TB), root: shoot ratio (RSR), spike length (SL), thousand seeds weight (TSW) and grain yield (GY). Data were analyzed and summarized using various statistical procedures and drought tolerance indices were computed based on grain yield under NS and DS conditions.ResultsSignificant (P &lt; 0.05) differences were recorded among the mutant lines for most assessed traits under NS and DS conditions. Grain yield positively and significantly (p &lt; 0.001) correlated with PTN (r = 0.85), RB (r = 0.75), SB (r = 0.80), SL (r =0.73), TB (r = 0.65), and TSW (r = 0.67) under DS condition. Principal component analysis revealed three components contributing to 78.55% and 77.21% of the total variability for the assessed agronomic traits under DS and NS conditions, respectively. The following traits: GY, RB, SB, and PTN explained most of the variation with high loading scores under DS condition. Geometric mean productivity (GMP), mean productivity (MP), harmonic mean (HM), and stress tolerance index (STI) were identified as the best drought tolerance indices for the identification of tolerant lines with positive correlations with GY under NS and DS conditions.DiscussionAmong the advanced lines tested, LMA16, LMA37, LMA47, LMA2, and LMA42 were selected as the superior lines with high performance and drought tolerance. The selected lines are recommended for multi-environment trails and release for production in water-limited environments in South Africa.
Neurophysiological correlates of interpersonal discrepancy and social adjustment in an interactive decision-making task in dyads
Authors: Vicente Unai , Ara Alberto , Palacín-Lois María , Marco-Pallarés Josep 
Published: February 2024

IntroductionThe pursuit of convergence and the social behavioral adjustment of conformity are fundamental cooperative behaviors that help people adjust their mental frameworks to reach a common goal. However, while social psychology has extensively studied conformity by its influence context, there is still plenty to investigate about the neural cognitive mechanisms involved in this behavior.MethodsWe proposed a paradigm with two phases, a pre-activation phase to enhance cooperative tendencies and, later, a social decision-making phase in which dyads had to make a perceptual estimation in three consecutive trials and could converge in their decisions without an explicit request or reward to do so. In Study 1, 80 participants were divided in two conditions. In one condition participants did the pre-activation phase alone, while in the other condition the two participants did it with their partners and could interact freely. In Study 2, we registered the electroencephalographical (EEG) activity of 36 participants in the social decision-making phase.ResultsStudy 1 showed behavioral evidence of higher spontaneous convergence in participants who interacted in the pre-activation phase. Event related Potentials (ERP) recorded in Study 2 revealed signal differences in response divergence in different time intervals. Time-frequency analysis showed theta, alpha, and beta evidence related to cognitive control, attention, and reward processing associated with social convergence.DiscussionCurrent results support the spontaneous convergence of behavior in dyads, with increased behavioral adjustment in those participants who have previously cooperated. In addition, neurophysiological components were associated with discrepancy levels between participants, and supported the validity of the experimental paradigm to study spontaneous social behavioral adaptation in experimental settings.
Can a PERMA model-based positive psychological intervention affect the SIA and SWB of vocational college students majoring in nursing in China?
Authors: Yang Jie , Tan Yingchun , Yao Chunlin 
Published: February 2024

AimsThe study was conducted to investigate the effects of a PERMA model-based positive psychological intervention on vocational college students’ social interaction anxiety and subjective well-being.MethodsThis is an experimental study in which data were collected through self-administered questionnaire. A total of 261 students from four classes at Caofeidian College of Technology without differences in the levels of social interaction anxiety and subjective well-being were selected as the control group and intervention group randomly. Students in the control group received a traditional psychological intervention, while students in the invention group received a PERMA model-based positive psychological intervention. Thereafter, the research team collected data regarding students’ social interaction anxiety and subjective well-being.ResultsBased on the result obtained, the mean score for social interaction anxiety in the invention group was significantly lower than those in the control group (42.95 vs. 53.07, p &lt; 0.001) and the mean score for subjective well-being was significantly higher than those in the control group (92.58 vs. 87.26, p &lt; 0.001).ConclusionA PERMA model-based positive psychological intervention can effectively relieve the social interaction anxiety of nursing students in vocational colleges, and improve their subjective well-being levels.
Internalized stigma related to COVID-19 and its psychosocial and mental health correlates: a multicentric health facility based observational study from Nepal
Authors: Shah Bigya , Mahapatra Ananya , Singh Uday Narayan , Mishra Vilok , Daha Sunil Kumar , Pande Rajan , Neupane Madan Ratna , Banjade Anita , Khatik Chandra Bhal , K. C. Tej Bahadur , Mandal Rajesh Kumar , Pokharel Samjhana , Gupta Rishi , G. C. Krishna Bahadur 
Published: February 2024

IntroductionThe COVID-19 pandemic has led to physical and psychological complications and social consequences in the form of illness-related stigma. This study aimed (1) to assess the sociodemographic and clinical variable, as well as COVID-19 related knowledge and perception of persons admitted for COVID-19/Suspected COVID-19 in Nepal, (2) to determine their levels of COVID-19- related internalized stigma, depression, and anxiety symptoms, and (3) to evaluate the correlates of COVID-19- related internalized stigma.Materials and methodsIt was a cross-sectional exploratory study with a convenience sample of 395 participants (306 confirmed cases, 89 suspected cases) conducted between July–October 2020 in four health facilities in Madhesh and Lumbini provinces of Nepal. We used a semi-structured questionnaire to assess sociodemographic details, clinical information, COVID-19-related knowledge, perception, COVID-19-related internalized stigma, and the Hamilton Anxiety Depression Scale (HADS) in Nepali language. Descriptive statistics, correlation analyses, and linear regression analyses were performed. The level of statistical significance was considered at p &lt; 0.05.ResultsAround 23.3% of the patients had anxiety symptoms, 32.9% had depressive symptoms, and 20.3% had high COVID-19-related internalized stigma (mean ISMI score: 2.51–4.00). Linear regression analyses showed a significant positive association of COVID-19-related internalized stigma total score, with the following eight factors, i.e., no income in the past one month (p = 0.013), below average socioeconomic status (p = 0.004), anxiety symptoms (p = &lt;0.001), depressive symptoms (p = &lt;0.001), recent testing positive for COVID-19 (p = &lt;0.001), involuntary admission (p = &lt;0.001), prior experience of being in isolation and quarantine (p = 0.045), and those who blame others for COVID-19 (p = 0.025).ConclusionCOVID-19 survivors and suspects are vulnerable to symptoms of depression, anxiety, and COVID-19-related internalized stigma. For the first time from Nepal, our data suggests that COVID-19-related internalized stigma is associated with anxiety and depression symptoms, perceived below-average socioeconomic status, involuntary admission, prior experience of being in isolation and quarantine, recent COVID-19 positive report, self-blame, below-average socioeconomic status and no income in the past one month. Mitigating and preventing internalized stigma associated with a public health crisis such as COVID-19 is imperative by diagnosing and treating such mental health issues early and designing interventions and policies especially targeting vulnerable populations focusing on their economic background and socio-cultural beliefs.
Virtual reality-assisted cognitive behavioral therapy for patients with alcohol use disorder: a randomized feasibility study
Authors: Thaysen-Petersen Daniel , Hammerum Sigurd Krogh , Vissing Anne-Cathrine , Oestrich Irene Henriette , Nordentoft Merete , Düring Signe Wegmann , Fink-Jensen Anders 
Published: February 2024

IntroductionCognitive behavioral therapy (CBT) is an evidence-based treatment for alcohol use disorder (AUD). Exposure to high-risk situations in virtual reality (VR) has been suggested to have a potential therapeutical benefit, but no previous study has combined VR and CBT for AUD. We aimed to investigate the feasibility of using VR-simulated high-risk environments in CBT-based treatment of AUD.MethodsWe randomized ten treatment-seeking AUD-diagnosed individuals to three sessions of conventional CBT or VR-assisted CBT performed at two outpatient clinics in Denmark. In each session, patients randomized to VR-CBT were exposed to VR-simulations from a restaurant to induce authentic thoughts, emotions, physiological reactions, and craving for CBT purposes. The primary outcome measure was feasibility: Drop-out rate, psychological reactions, and simulator sickness. Secondary outcomes were assessment of preliminary short-term changes in alcohol consumption and craving from baseline to one-week and one-month follow-up. In addition, the study was conducted for training in operationalization of VR equipment, treatment manuals, and research questionnaires.ResultsThe majority of patients completed all study visits (90%). VR induced authentic high-risk related thoughts, emotions, and physiological reactions that were considered relevant for CBT by patients and therapists. Four of five patients randomized to VR-CBT experienced cravings during VR simulations, and most of these patients (3/5) experienced mild simulator sickness during VR exposure. The preliminary data showed that patients receiving VR-CBT had more reduction in alcohol consumption than patients receiving conventional CBT at one week- (median 94% vs. 72%) and one-month follow-up (median 98% vs. 55%). Similar results were found regarding changes in cravings.ConclusionWe demonstrated VR-CBT to be a feasible intervention for patients with AUD which supports continued investigations in a larger randomized clinical trial evaluating the efficacy of VR-CBT.Clinical trial registrationhttps://www.clinicaltrials.gov/study/NCT04990765?cond=addiction%20CRAVR&amp;rank=2, identifier NCT05042180.