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1.
Expert Opin Drug Metab Toxicol ; : 1-16, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225462

ABSTRACT

INTRODUCTION: Hepatocellular carcinoma (HCC) accounts for 85% of liver cancer cases and is the third leading cause of cancer death. Regorafenib is a multi-target inhibitor that dramatically prolongs progression-free survival in HCC patients who have failed sorafenib therapy. However, one of the primary factors limiting regorafenib's clinical utilization is toxicity. Using Clinical Trials.gov and PubMed, we gathered clinical data on regorafenib and conducted a extensive analysis of the medication's adverse reactions and mechanisms. Next, we suggested suitable management techniques to improve regorafenib's effectiveness. AREAS COVERED: We have reviewed the mechanisms by which regorafenib-induced toxicity occurs and general management strategies through clinical trials of regorafenib. Furthermore, by examining the literature on regorafenib and other tyrosine kinase inhibition, we summarized the mechanics of the onset of regorafenib toxicity and mechanism-based intervention strategies by reviewing the literature related to regorafenib and other tyrosine kinase inhibition. EXPERT OPINION: One of the primary factors restricting regorafenib's clinical utilization and combination therapy is its toxicity reactions. To optimize regorafenib treatment regimens, it is especially important to further understand the specific toxicity mechanisms of regorafenib as a multi-kinase inhibitor.

2.
Sci Rep ; 14(1): 20418, 2024 09 03.
Article in English | MEDLINE | ID: mdl-39223292

ABSTRACT

The epidemic and outbreaks of influenza B Victoria lineage (Bv) during 2019-2022 led to an analysis of genetic, epitopes, charged amino acids and Bv outbreaks. Based on the National Influenza Surveillance Network (NISN), the Bv 72 strains isolated during 2019-2022 were selected by spatio-temporal sampling, then were sequenced. Using the Compare Means, Correlate and Cluster, the outbreak data were analyzed, including the single nucleotide variant (SNV), amino acid (AA), epitope, evolutionary rate (ER), Shannon entropy value (SV), charged amino acid and outbreak. With the emergence of COVID-19, the non-pharmaceutical interventions (NPIs) made Less distant transmission and only Bv outbreak. The 2021-2022 strains in the HA genes were located in the same subset, but were distinct from the 2019-2020 strains (P < 0.001). The codon G → A transition in nucleotide was in the highest ratio but the transversion of C → A and T → A made the most significant contribution to the outbreaks, while the increase in amino acid mutations characterized by polar, acidic and basic signatures played a key role in the Bv epidemic in 2021-2022. Both ER and SV were positively correlated in HA genes (R = 0.690) and NA genes (R = 0.711), respectively, however, the number of mutations in the HA genes was 1.59 times higher than that of the NA gene (2.15/1.36) from the beginning of 2020 to 2022. The positively selective sites 174, 199, 214 and 563 in HA genes and the sites 73 and 384 in NA genes were evolutionarily selected in the 2021-2022 influenza outbreaks. Overall, the prevalent factors related to 2021-2022 influenza outbreaks included epidemic timing, Tv, Ts, Tv/Ts, P137 (B → P), P148 (B → P), P199 (P → A), P212 (P → A), P214 (H → P) and P563 (B → P). The preference of amino acid mutations for charge/pH could influence the epidemic/outbreak trends of infectious diseases. Here was a good model of the evolution of infectious disease pathogens. This study, on account of further exploration of virology, genetics, bioinformatics and outbreak information, might facilitate further understanding of their deep interaction mechanisms in the spread of infectious diseases.


Subject(s)
Disease Outbreaks , Evolution, Molecular , Influenza, Human , Mutation , Polymorphism, Single Nucleotide , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Influenza, Human/genetics , Influenza B virus/genetics , Amino Acids/genetics , Epitopes/genetics , Phylogeny , Amino Acid Substitution , Hemagglutinin Glycoproteins, Influenza Virus/genetics
3.
Theranostics ; 14(11): 4411-4437, 2024.
Article in English | MEDLINE | ID: mdl-39113804

ABSTRACT

In recent years, gene therapy has been made possible with the success of nucleic acid drugs against sepsis and its related organ dysfunction. Therapeutics based on nucleic acids such as small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs), and plasmid DNAs (pDNAs) guarantee to treat previously undruggable diseases. The advantage of nucleic acid-based therapy against sepsis lies in the development of nanocarriers, achieving targeted and controlled gene delivery for improved efficacy with minimal adverse effects. Entrapment into nanocarriers also ameliorates the poor cellular uptake of naked nucleic acids. In this study, we discuss the current state of the art in nanoparticles for nucleic acid delivery to treat hyperinflammation and apoptosis associated with sepsis. The optimized design of the nanoparticles through physicochemical property modification and ligand conjugation can target specific organs-such as lung, heart, kidney, and liver-to mitigate multiple sepsis-associated organ injuries. This review highlights the nanomaterials designed for fabricating the anti-sepsis nanosystems, their physicochemical characterization, the mechanisms of nucleic acid-based therapy in working against sepsis, and the potential for promoting the therapeutic efficiency of the nucleic acids. The current investigations associated with nanoparticulate nucleic acid application in sepsis management are summarized in this paper. Noteworthily, the potential application of nanotherapeutic nucleic acids allows for a novel strategy to treat sepsis. Further clinical studies are required to confirm the findings in cell- and animal-based experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for commercialization. It is expected that numerous anti-sepsis possibilities will be investigated for nucleic acid-based nanotherapeutics in the future.


Subject(s)
Nanoparticles , Nucleic Acids , Sepsis , Sepsis/drug therapy , Sepsis/therapy , Humans , Nucleic Acids/therapeutic use , Nucleic Acids/administration & dosage , Animals , Nanoparticles/chemistry , Genetic Therapy/methods , Multiple Organ Failure/therapy , Multiple Organ Failure/drug therapy , Gene Transfer Techniques
4.
Nat Commun ; 15(1): 6735, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112446

ABSTRACT

Improvements in the polarization of environmentally-friendly perovskite ferroelectrics have proved to be a challenging task in order to replace the toxic Pb-based counterparts. In contrast to common methods by complex chemical composition designs, we have formed Mn-inlaid antiphase boundaries in Mn-doped (K,Na)NbO3 thin films using pulsed laser deposition method. Here, we observed that mono- or bi-atomic layer of Mn has been identified to inlay along the antiphase boundaries to balance the charges originated from the deficiency of alkali ions and to induce the strain in the KNN films. Thus, rectangular saturated polarization-electric field hysteresis loops have been achieved, with a significantly improved twice remanent polarization of 114 µC/cm2 with an applied electric field of 606 kV/cm, which can be comparable to that of the typical Pb-based thin films. Moreover, we directly see the Mn occupation at the A-site of KNN perovskite structure using atomic-scale microstructure and composition analysis. The Mn-inlaid antiphase boundary can further enrich the understanding of perovskite crystal structure and give more possibilities for the design and optimization of perovskite materials.

5.
Nat Commun ; 15(1): 6765, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39117646

ABSTRACT

As a new class of organic photocatalysts, polymer dots show a potential application in photocatalytic hydrogen peroxide production coupled with chemical oxidation such as methanol oxidation. However, the poor methanol oxidation ability by polymer dots still inhibits the overall photocatalytic reaction occurring in the neutral condition. In this work, an organic molecular catalyst 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl radical is covalently linked to a fluorene unit in a polymer skeleton, eventually enabling photocatalytic hydrogen peroxide production coupled with methanol oxidation in the neutral condition. By conducting various spectroscopic measurements, charge transfer between components in this molecular catalyst-immobilized polymer dots system is studied and found to be very efficient for hydrogen peroxide production coupled with alcohol oxidation. This work proves a strategy for designing polymer dots photocatalysts with molecular catalysts, facilitating their future development and potential applications in other fields such as water splitting, CO2 reduction, photoredox catalysis and photodynamic therapy.

6.
Int J Food Microbiol ; 425: 110877, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39173287

ABSTRACT

Paocai is a traditional Chinese fermented vegetable product popular in Asian countries. Recently, functional starters were used to control the fermentation process and improve the quality of paocai. In this study, three autochthonous lactic acid bacteria including Lactiplantibacillus plantarum LB6, Lactiplantibacillus pentosus LB3, and Weissella cibaria W51 were selected as starters and the effect of the starters on the fermentation of paocai was investigated. The results suggested that the inoculated fermentation led to a lower nitrite peak and more pronounced changes in pH and total titratable acid in the early stage of fermentation, compared with natural fermentation. Analysis of the flavor compounds indicated that the total content of volatile organic compounds of paocai through natural fermentation was significantly lower than that in inoculated fermentation. As for free amino acids, in the early stage of fermentation, the types and contents of free amino acids in the inoculated fermentation paocai were higher than those in the blank group. In the later stage of fermentation, the contents of amino acids representing umami and sweet tastes were also higher than those in the blank group. The bacterial community analysis showed that Lactobacillus and Lactococcus were the dominant bacteria in both inoculated fermentation and natural fermentation. Then, the correlations among physicochemical properties, microbial community and flavor compounds were revealed, and it was found that the dominant bacteria such as Lactococcus, Leuconostoc, Lactobacillus and Weissella displayed a considerable impact on the physical and chemical properties and flavor of paocai. In addition, the metabolic pathways involved in flavor formation and the abundance of related enzymes were elucidated. The abundance of enzymes involved in generating prephenic acid, 2-methylbutanoic acid, L-lactic acid, D-lactic acid, butanoic acid, etc., and in the pathway of producing flavor substances (His, Met, ethyl hexanoate, etc.) was up-regulated in the inoculated fermentation. Results presented in this study may provide a reference for the development of paocai starters and further guidance for the flavor improvement of Sichuan paocai.

7.
Front Pharmacol ; 15: 1421635, 2024.
Article in English | MEDLINE | ID: mdl-39148543

ABSTRACT

Introduction: Angong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemia‒reperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms. Methods: A cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed. Results: AGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1. Conclusion: AGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of AQP4 expression on the astrocyte membrane, following LPS injection.

8.
Adv Mater ; : e2408777, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39101296

ABSTRACT

Organic-inorganic hybrid manganese(II) halides (OIMnHs) have garnered tremendous interest across a wide array of research fields owing to their outstanding optical properties, abundant structural diversity, low-cost solution processibility, and low toxicity, which make them extremely suitable for use as a new class of luminescent materials for various optoelectronic applications. Over the past years, a plethora of OIMnHs with different structural dimensionalities and multifunctionalities such as efficient photoluminescence (PL), radioluminescence, circularly polarized luminescence, and mechanoluminescence have been newly created by judicious screening of the organic cations and inorganic Mn(II) polyhedra. Specifically, through precise molecular and structural engineering, a series of OIMnHs with near-unity PL quantum yields, high anti-thermal quenching properties, and excellent stability in harsh conditions have been devised and explored for applications in light-emitting diodes (LEDs), X-ray scintillators, multimodal anti-counterfeiting, and fluorescent sensing. In this review, the latest advancements in the development of OIMnHs as efficient light-emitting materials are summarized, which covers from their fundamental physicochemical properties to advanced optoelectronic applications, with an emphasis on the structural and functionality design especially for LEDs and X-ray detection and imaging. Current challenges and future efforts to unlock the potentials of these promising materials are also envisioned.

9.
Article in English | MEDLINE | ID: mdl-39180652

ABSTRACT

Vibrational spectroscopy is a powerful analytical domain, within which Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy stand as exemplars, offering high chemical specificity and sensitivity. These methodologies have been instrumental in the characterization of chemical compounds for an extensive period. They are particularly adept at the identification and analysis of minute sample quantities. Both FTIR and Raman spectroscopy are proficient in elucidating small liquid samples and detecting nuanced molecular alterations. The application of chemometrics further augments their analytical prowess. Currently, these techniques are in the research phase within forensic medicine and have yet to be broadly implemented in examination and identification processes. Nonetheless, studies have indicated that a combined classification model utilizing FTIR and Raman spectroscopy yields exceptional results for the identification of biological fluid-related information and the determination of causes of death. The objective of this review is to delineate the current research trajectory and potential applications of these two vibrational spectroscopic techniques in the detection of body fluids and the ascertainment of causes of death within the context of forensic medicine.

10.
Plant Sci ; 348: 112230, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39154894

ABSTRACT

Plant vegetative organs present great potential for lipid storage, with tubers of Cyperus esculentus as a unique example. To investigate the genome and transcriptomic features of C. esculentus and related species, we sequenced and assembled the C. esculentus genome at the contig level. Through a comparative study of high-quality transcriptomes across 36 tissues from high-oil and intermediate-oil C. esculentus and low-oil Cyperus rotundus, we identified potential genes and regulatory networks related to tuber oil accumulation. First, we identified tuber-specific genes in two C. esculentus cultivars. Second, genes involved in fatty acid (FA) biosynthesis, triacylglycerol synthesis, and TAG packaging presented increased activity in the later stages of tuber development. Notably, tubers with high oil contents presented higher levels of these genes than those with intermediate oil contents did, whereas tubers with low oil contents presented minimal gene expression. Notably, a large fragment of the FA biosynthesis rate-limiting enzyme-encoding gene BCCP1 was missing from the C. rotundus transcript, which might be responsible for blocking FA biosynthesis in its tubers. WGCNA pinpointed a gene module linked to tuber oil accumulation, with a coexpression network involving the transcription factors WRI1, MYB4, and bHLH68. The ethylene-related genes in this module suggest a role for ethylene signaling in oil accumulation, which is supported by the finding that ethylene (ETH) treatment increases the oil content in C. esculentus tubers. This study identified potential genes and networks associated with tuber oil accumulation in C. esculentus, highlighting the role of specific genes, transcription factors, and ethylene signaling in this process.

11.
Front Psychiatry ; 15: 1404229, 2024.
Article in English | MEDLINE | ID: mdl-39086730

ABSTRACT

Objective: The purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults. Method: Participants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents' depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment. Result: A total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P<0.05). Depressive symptom had a mediating effect in the number of chronic diseases and cognitive impairment, and the mediating effect (1.109) accounted for 44.13% of the total effect (0.247). Conclusion: The mental health of the older adult needs to be taken seriously, and improving depressive symptom can reduce the occurrence of cognitive impairment in older patients with MCC to a certain extent.

12.
Medicine (Baltimore) ; 103(32): e37832, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39121304

ABSTRACT

INTRODUCTION: Ankle braces can effectively decrease the incidence of recurrent ankle sprain; however, whether the brace can decrease the severity of sprain and its related mechanism during sprain remain unknown. METHODS: Twenty-two patients with functional ankle instability (FAI) (12 males and 10 females) and 16 healthy subjects (8 males and 8 females) were enrolled in this study. All of the subjects walked on a custom-built tilting platform that offered a 30° inversion (IV) to mimic the IV of ankle sprain. We collected the kinematic and surface electromyography data of patients with FAI with or without ankle brace and normal controls 6 times. RESULTS: The FAI without brace group showed significantly higher maximum IV angles and average IV velocities than the control group (P < .001). The FAI with brace group revealed significantly lower maximum IV angles and average IV velocities than the FAI without brace group (P < .001); this group also showed significantly higher maximum external rotation (ER) angle and average ER velocities than the FAI with brace (P < .001) and control (P < .001) groups. The FAI with brace group indicated significantly lower average EMGPrep (P = .047), EMGTilt (P = .037), and EMGafterTilt (P = .004) of the peroneus longus than the FAI without brace group. CONCLUSIONS: The ankle brace could effectively decrease IV angles and their velocities and increase ER angles and their corresponding velocities during ankle sprain in patients with FAI. It could also decrease the activity of the peroneus longus muscle during ankle sprain.


Subject(s)
Ankle Injuries , Braces , Electromyography , Joint Instability , Humans , Male , Female , Ankle Injuries/physiopathology , Ankle Injuries/therapy , Biomechanical Phenomena , Joint Instability/physiopathology , Joint Instability/therapy , Adult , Young Adult , Muscle, Skeletal/physiopathology , Ankle Joint/physiopathology , Sprains and Strains/physiopathology , Case-Control Studies
13.
Turk J Gastroenterol ; 35(5): 366-373, 2024 May.
Article in English | MEDLINE | ID: mdl-39128112

ABSTRACT

BACKGROUND/AIMS:  Gastrointestinal stromal tumors are common gastric mesenchymal tumors that are potentially malignant. However, endoscopic ultrasonography is poor in diagnosing gastrointestinal stromal tumors. The study investigated the efficacy of texture features extracted from endoscopic ultrasonography images to differentiate gastrointestinal stromal tumors from gastric mesenchymal tumors. MATERIALS AND METHODS:  The endoscopic ultrasonography examinations of 120 patients with confirmed gastric gastrointestinal stromal tumors, leiomyoma, or schwannoma were evaluated. Histology was considered the gold standard. Three feature combinations were extracted from endoscopic ultrasonography images of each lesion: 48 gray-level co-occurrence matrix-based features, 48 gray-level co-occurrence matrix-based features plus 3 global gray features, and 15 gray-gradient co-occurrence matrix-based features. Support vector machine classifiers were constructed by using feature combinations to diagnose gastric gastrointestinal stromal tumors. The area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were used to evaluate the diagnostic performance. The support vector machine model's diagnostic performance was compared with the endoscopists. RESULTS:  The 3 feature combinations had better performance in differentiating gastrointestinal stromal tumors: gray-gradient cooccurrence matrix-based features yielded an area under the receiver operating characteristic curve of 0.90, which was significantly greater than an area under the receiver operating characteristic curve of 0.83 in gray-level co-occurrence matrix-based features and an area under the receiver operating characteristic curve of 0.84 in the texture features plus 3 global features. The support vector machine model (81.67% accuracy, 81.36% sensitivity, and 81.97% specificity) was also better than endoscopists (an average of 69.31% accuracy, 65.54% sensitivity, and 72.95% specificity) Conclusion: Texture features in computer-assisted endoscopic ultrasonography diagnosis are useful to differentiate gastrointestinal stromal tumors from benign gastric mesenchymal tumors and compare favorably with endoscopists. Support vector machine model using gray-gradient co-occurrence matrix-based texture features revealed the best diagnostic performance in diagnosing gastric gastrointestinal stromal tumors.


Subject(s)
Endosonography , Gastrointestinal Stromal Tumors , Sensitivity and Specificity , Stomach Neoplasms , Support Vector Machine , Humans , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Diagnosis, Differential , Female , Male , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Endosonography/methods , Middle Aged , Adult , Aged , ROC Curve , Leiomyoma/diagnostic imaging , Leiomyoma/pathology , Neurilemmoma/diagnostic imaging , Neurilemmoma/pathology
14.
Cancer Biomark ; 40(3-4): 241-250, 2024.
Article in English | MEDLINE | ID: mdl-39213051

ABSTRACT

Transforming growth factor-ß (TGF-ß) is a multifunctional cytokine that plays a vital role in regulating cell growth, differentiation and survival in various tissues. It participates in a variety of cellular processes, including cell apoptosis, cell migration and evasion, and plays a paradoxical role in tumor genesis and development. In the early stage of tumor, TGF-ß inhibits the occurrence of tumor by inhibiting cell proliferation and regulating cell apoptosis. In the advanced stage of tumor, TGF-ß promotes tumor development and affects prognosis by promoting cell survival and proliferation, cell migration and invasion, participates in immune escape, etc. In this article, we will review the paradoxical role of TGF-ß on the occurrence and development of oral squamous cell carcinoma.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Transforming Growth Factor beta , Humans , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Transforming Growth Factor beta/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Signal Transduction , Cell Proliferation , Apoptosis , Animals , Prognosis
15.
J Cell Mol Med ; 28(16): e70003, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39153207

ABSTRACT

Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD-associated drug targets for PH.


Subject(s)
Apoptosis , Hypertension, Pulmonary , Vascular Remodeling , Humans , Hypertension, Pulmonary/pathology , Hypertension, Pulmonary/physiopathology , Animals , Necroptosis , Signal Transduction , Autophagy , Ferroptosis , Pulmonary Artery/pathology , Pulmonary Artery/metabolism , Pyroptosis
16.
J Cell Mol Med ; 28(16): e70014, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39153211

ABSTRACT

Anaplastic thyroid cancer (ATC), an aggressive malignancy with virtually 100% disease-specific mortality, has long posed a formidable challenge in oncology due to its resistance to conventional treatments and the severe side effects associated with current regimens such as doxorubicin chemotherapy. Consequently, there was urgent need to identify novel candidate compounds that could provide innovative therapeutic strategies for ATC. Ophiopogonin D' (OPD'), a triterpenoid saponin extracted, yet its roles in ATC has not been reported. Our data demonstrated that OPD' potently inhibited proliferation and metastasis of ATC cells, promoting cell cycle arrest and apoptosis. Remarkably, OPD' impeded growth and metastasis of ATC in vitro and in vivo, displaying an encouraging safety profile. Regulator of G-protein signalling 4 (RGS4) expression was significantly up-regulated in ATC compared to normal tissues, and this upregulation was suppressed by OPD' treatment. Mechanistically, we elucidated that the transcription factor JUN bound to the RGS4 promoter, driving its transactivation. However, OPD' interacted with JUN, attenuating its transcriptional activity and thereby disrupting RGS4 overexpression. In summary, our research revealed that OPD' bound with JUN, which in turn resulted in the suppression of transcriptional activation of RGS4, thereby eliciting cell cycle arrest and apoptosis in ATC cells. These findings could offer promise in the development of high-quality candidate compounds for treatment in ATC.


Subject(s)
Apoptosis , Cell Proliferation , RGS Proteins , Saponins , Signal Transduction , Spirostans , Thyroid Carcinoma, Anaplastic , Humans , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Carcinoma, Anaplastic/pathology , Saponins/pharmacology , RGS Proteins/metabolism , RGS Proteins/genetics , Cell Proliferation/drug effects , Animals , Cell Line, Tumor , Signal Transduction/drug effects , Apoptosis/drug effects , Spirostans/pharmacology , Mice , Gene Expression Regulation, Neoplastic/drug effects , Cell Cycle Checkpoints/drug effects , Proto-Oncogene Proteins c-jun/metabolism , Mice, Nude , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/genetics , Xenograft Model Antitumor Assays , Neoplasm Metastasis
17.
Fa Yi Xue Za Zhi ; 40(3): 245-253, 2024 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-39166305

ABSTRACT

OBJECTIVES: To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification research. METHODS: The data retrieved and extracted from the Web of Science Core Collection (WoSCC), the core database of the Web of Science information service platform (hereinafter referred to as "WoS"), was used to analyze the trends and topic changes in research on forensic identification of human remains from 1991 to 2022. Network visualisation of publication trends, countries (regions), institutions, authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10. RESULTS: A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained. The journal with the largest number of publications was Forensic Science International (164 articles). The country (region) with the largest number of published papers was China (90 articles). Katholieke Univ Leuven (Netherlands, 21 articles) was the institution with the largest number of publications. Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation, and the most commonly studied remains were teeth. CONCLUSIONS: The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing. However, the scope of both international and domestic collaborations remains limited. Traditionally, human remains identification has primarily relied on key areas such as the pelvis, skull, and teeth. Looking ahead, future research will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.


Subject(s)
Bibliometrics , Body Remains , Forensic Anthropology , Humans , Forensic Anthropology/methods , Publications/statistics & numerical data
18.
Clin Transl Oncol ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162977

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, characterized by high incidence and mortality rates. Due to its insidious onset, most patients are diagnosed at an advanced stage, often missing the opportunity for surgical resection. Consequently, systemic treatments play a pivotal role. In recent years, an increasing number of drugs have been approved for first-line systemic treatment of HCC. However, their efficacy is limited, and some patients develop drug resistance after a period of treatment. For such patients, there is currently a lack of standard second-line systemic treatment options. This review summarizes the latest advancements in second-line systemic treatment research for HCC patients who have developed resistance to various first-line systemic treatments, aiming to provide more rational and personalized second-line treatment strategies.

19.
Medicine (Baltimore) ; 103(33): e39286, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39151536

ABSTRACT

RATIONALE: As one of the drugs used to treat Helicobacter pylori, furazolidone has been reported to cause gastrointestinal reactions, allergies, dizziness, and more. However, its related drug-induced lung injury has been rarely reported. Furthermore, there have been no reports of the timing for initiating hormone therapy when a pulmonary adverse reaction occurs. PATIENT CONCERNS: We report 2 cases, both of them showed interlobular septal thickening and nodules on the chest computed tomography. One had more discomfort symptoms and had a higher eosinophil count than the normal range, while the other only had fever symptoms and had an eosinophil count within the normal range. DIAGNOSES: Pulmonary adverse reaction caused by furazolidone was diagnosed. INTERVENTIONS: Furazolidone was discontinued, and the person with increased eosinophils received hormone therapy, while the other person did not. OUTCOMES: After discontinuation of medication and treatment, the symptoms of the 2 patients gradually improved. LESSONS: This report suggests that furazolidone may cause pulmonary adverse reactions to raise clinical awareness, and for the first time indicates that hormone therapy is needed for patients whose eosinophils continue to increase after discontinuation.


Subject(s)
Furazolidone , Humans , Furazolidone/adverse effects , Female , Male , Middle Aged , Anti-Bacterial Agents/adverse effects , Aged , Tomography, X-Ray Computed
20.
Vis Comput Ind Biomed Art ; 7(1): 22, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39190235

ABSTRACT

Fetal macrosomia is associated with maternal and newborn complications due to incorrect fetal weight estimation or inappropriate choice of delivery models. The early screening and evaluation of macrosomia in the third trimester can improve delivery outcomes and reduce complications. However, traditional clinical and ultrasound examinations face difficulties in obtaining accurate fetal measurements during the third trimester of pregnancy. This study aims to develop a comprehensive predictive model for detecting macrosomia using machine learning (ML) algorithms. The accuracy of macrosomia prediction using logistic regression, k-nearest neighbors, support vector machine, random forest (RF), XGBoost, and LightGBM algorithms was explored. Each approach was trained and validated using data from 3244 pregnant women at a hospital in southern China. The information gain method was employed to identify deterministic features associated with the occurrence of macrosomia. The performance of six ML algorithms based on the recall and area under the curve evaluation metrics were compared. To develop an efficient prediction model, two sets of experiments based on ultrasound examination records within 1-7 days and 8-14 days prior to delivery were conducted. The ensemble model, comprising the RF, XGBoost, and LightGBM algorithms, showed encouraging results. For each experimental group, the proposed ensemble model outperformed other ML approaches and the traditional Hadlock formula. The experimental results indicate that, with the most risk-relevant features, the ML algorithms presented in this study can predict macrosomia and assist obstetricians in selecting more appropriate delivery models.

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