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1.
Sensors (Basel) ; 24(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38894133

ABSTRACT

A light and displacement-compensation-based iPPG algorithm is proposed in this paper for heart-rate measurement in complex detection conditions. Two compensation sub-algorithms, including light compensation and displacement compensation, are designed and integrated into the iPPG algorithm for more accurate heart-rate measurement. In the light-compensation sub-algorithm, the measurement deviation caused by the ambient light change is compensated by the mean filter-based light adjustment strategy. In the displacement-compensation sub-algorithm, the measurement deviation caused by the subject motion is compensated by the optical flow-based displacement calculation strategy. A series of heart-rate measurement experiments are conducted to verify the effectiveness of the proposed method. Compared with conventional iPPG, the average measurement accuracy increases by 3.8% under different detection distances and 5.0% under different light intensities.

2.
Clin Cancer Res ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900040

ABSTRACT

PURPOSE: In multiple myeloma (MM), therapy-induced clonal evolution is associated with treatment resistance and is one of the most important hindrances toward a cure for MM. To further understand the molecular mechanisms controlling the clonal evolution of MM, we applied single-cell RNA-sequencing (scRNA-seq) to paired diagnostic and post-treatment bone marrow (BM) samples. EXPERIMENTAL DESIGN: scRNA-seq was performed on 38 BM samples from patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 1), MM patients at diagnosis (n = 19), MM post-treatment (n = 17), and one healthy donor. The single-cell transcriptome data of malignant plasma cells and the surrounding immune microenvironment were analyzed. RESULTS: Profiling by scRNA-seq data revealed three primary trajectories of transcriptional evolution after treatment: clonal elimination in patients with undetectable minimal residual disease (MRD-), as well as clonal stabilization and clonal selection in detectable MRD (MRD+) patients. We noted a metabolic shift towards fatty acid oxidation in cycling-resistant plasma cells (PCs), while selective PCs favored the NF-κB pathway. Intriguingly, when comparing the genetic and transcriptional dynamics, we found a significant correlation between genetic and non-genetic factors in driving the clonal evolution. Furthermore, we identified variations in cellular interactions between malignant plasma cells and the tumor microenvironment (TME). Selective PCs showed the most robust cellular interactions with the TME. CONCLUSIONS: These data suggest that MM cells could rapidly adapt to induction treatment through transcriptional adaptation, metabolic adaptation, and specialized immune evasion. Targeting therapy-induced resistance mechanisms may help to avert refractory disease in multiple myeloma.

3.
Foods ; 13(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38890934

ABSTRACT

To achieve a krill meal of high quality, a two-stage drying involving hot-air drying and vacuum drying was investigated. Five experimental groups were established according to the different drying conditions in the second stage, including 95 °C and 101 kPa, 95 °C and 60 kPa, 75 °C and 101 kPa, 75 °C and 60 kPa, and 75 °C and 20 kPa. The results showed that reducing the drying temperature and vacuum pressure in the second stage had a significant impact on the drying characteristics, sensory quality, and bioactive compounds of krill meal. Among all five groups, the drying condition of 75 °C and 60 kPa maintained a high drying rate while preserving a phospholipid content of 30.01 mg/kg and an astaxanthin content of 37.41 mg/kg. It also effectively reduced the isomerization of astaxanthin and the oxidation of unsaturated fatty acids. These results suggested that the two-stage drying method may contribute to the production of high-quality krill meal.

4.
Elife ; 122024 May 30.
Article in English | MEDLINE | ID: mdl-38814697

ABSTRACT

Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. Helicoverpa armigera as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100-1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the Xenopus expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.


Subject(s)
Larva , Moths , Sensilla , Sucrose , Animals , Sucrose/metabolism , Sucrose/pharmacology , Larva/physiology , Moths/physiology , Moths/drug effects , Sensilla/physiology , Sensilla/metabolism , Taste/physiology , Taste Perception/physiology , Helicoverpa armigera
5.
Leukemia ; 38(6): 1299-1306, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38609496

ABSTRACT

Growing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a "two-step" process in the clonal size changes of gain/amp(1q) in MM.


Subject(s)
In Situ Hybridization, Fluorescence , Multiple Myeloma , Humans , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Multiple Myeloma/mortality , In Situ Hybridization, Fluorescence/methods , Male , Female , Middle Aged , Aged , Prognosis , Chromosomes, Human, Pair 1/genetics , Adult , Clonal Evolution/genetics , Aged, 80 and over , Chromosomal Instability , Chromosome Aberrations , Disease Progression
6.
Braz J Med Biol Res ; 57: e12951, 2024.
Article in English | MEDLINE | ID: mdl-38511766

ABSTRACT

The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.


Subject(s)
Osteoporosis , Periodontitis , Humans , Mendelian Randomization Analysis , Osteoporosis/genetics , Nonoxynol , Periodontitis/genetics , Polymorphism, Single Nucleotide/genetics
7.
Braz. j. med. biol. res ; 57: e12951, fev.2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1550148

ABSTRACT

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

8.
Virulence ; 15(1): 2319962, 2024 12.
Article in English | MEDLINE | ID: mdl-38380669

ABSTRACT

Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli (E. coli) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli's coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro. The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.


Subject(s)
Coinfection , Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/diagnosis , Interleukin-10/genetics , Human papillomavirus 16/genetics , Escherichia coli/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Retrospective Studies , Prospective Studies , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/pathology , Tumor Microenvironment
9.
Sci Rep ; 14(1): 3075, 2024 02 06.
Article in English | MEDLINE | ID: mdl-38321064

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and there is a huge unmet need to find safer and more effective drugs. Vitamin K has been found to regulate lipid metabolism in the liver. However, the effects of vitamin K2 on NAFLD is unclear. This study aims to evaluate the preventive and therapeutic effects of vitamin K2 in the process of fatty liver formation and to explore molecular mechanisms the associated with lipid metabolism. A non-alcoholic fatty liver model was established by high-fat diet administration for three months. Vitamin K2 significantly reduced the body weight, abdominal circumference and body fat percentage of NAFLD mice. Vitamin K2 also showed histological benefits in reducing hepatic steatosis. NAFLD mice induced by high-fat diet showed increased HMGR while vitamin K2 intervention could reverse the pathological lterations. Adiponectin (APN) is an endogenous bioactive polypeptide or protein secreted by adipocytes. We detected APN, SOD, AlaDH and other indicators that may affect the state of high-fat diet mice, but the experimental results showed that the above indicators did not change significantly. It is worth noting that the effect of vitamin K2 supplementation on the lipid-lowering effect of uc OC in vivo needs to be further explored. This study first reported the protective effect of vitamin K2 on high-fat diet-induced NAFLD in mice. The protective effect of vitamin K2 may be related to the improvement of lipid metabolism disorder in NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/pathology , Vitamin K 2/metabolism , Diet, High-Fat , Liver/metabolism , Lipid Metabolism , Adiponectin/metabolism , Mice, Inbred C57BL
10.
Adv Mater ; 36(16): e2311817, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38226720

ABSTRACT

Transparent bulk glass is highly demanded in devices and components of daily life to transmit light and protect against external temperature and mechanical hazards. However, the application of glass is impeded by its poor functional performance, especially in terms of thermal isolation and impact resistance. Here, a glass composite integrating the nacre-inspired structure and shear stiffening gel (SSG) material is proposed. Benefiting from the combination of these two elements, this nacre-inspired SSG/glass composite (NSG) exhibits superior thermal insulation and impact resistance while maintaining transparency simultaneously. Specifically, the low thermal conductivity of the SSG combined with the anisotropic heat transfer capability of the nacre-inspired structure enhances the out-of-plane thermal insulation of NSG. The deformations over large volumes in nacre-inspired facesheets promote the deformation region of the SSG core, synergistic effect of tablet sliding mechanism in nacre-inspired structure and strain-rate enhancement in SSG material cause the superior impact resistance of overall panels in a wide range of impact velocities. NSG demonstrates outstanding properties such as transparency, light weight, impact resistance, and thermal insulation, which are major concerns for the application in engineering fields. In conclusion, this bioinspired SSG/glass composite opens new avenues to achieve comprehensive performance improvements for transparent structural materials.

11.
Int J Biol Macromol ; 261(Pt 1): 129747, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38281536

ABSTRACT

Serpins are a protein superfamily of serine protease inhibitors. One of their functions is to participate in immune responses by inhibiting the activation of prophenoloxidase. To elucidate the immune role of serpin in Macrobrachium nipponense, a serpin gene (Mnserpin) was cloned from M. nipponense in this study. Mnserpin protein has an N-terminal signal peptide and a serpin domain that contains a hinge region, a signature sequence of serpin and a P1(arginine)-P1' scissile bond, and evolutionally closely related to the crustacean serpins. Mnserpin highly expressed in the hepatopancreas and gill. Mnserpin expression increased first and then decreased after Vibrio parahaemolyticus and Aeromonas hydrophila infection, and was knocked down by dsMnserpin injection with a maximum knockdown efficiency of 92 %. Mnserpin knockdown increased the expression of the clip domain serine protease and prophenoloxidase genes and phenoloxidase activity of M. nipponense as well as its mortality rate after V. parahaemolyticus and A. hydrophila infection. The recombinant Mnserpin (rMnserpin) showed bacteria-binding and bacteriostatic activity in vitro. Moreover, rMnserpin injection decreased the bacterial number and the mortality rate of M. nipponense post V. parahaemolyticus and A. hydrophila infection. These results suggested that Mnserpin plays a major role in the innate immune response of M. nipponense.


Subject(s)
Palaemonidae , Serpins , Animals , Serpins/genetics , Serpins/metabolism , Amino Acid Sequence , Base Sequence , Sequence Alignment , Arthropod Proteins/metabolism , Phylogeny
12.
Small ; 20(25): e2310268, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38195818

ABSTRACT

Electrocatalytic nitrogen reduction reaction (NRR) paves a sustainable way to produce NH3 but suffering from the relatively low NH3 yield and poor selectivity. High-performance NRR catalysts and a deep insight into the structure-performance relationship are higher desired. Herein, a molten-salt approach is developed to synthesize tiny CeO2 nanoparticles anchored by ultra-thin MoN nanosheets as advanced catalysts for NRR. Specifically, a considerably high NH3 yield rate of 27.5 µg h-1 mg-1 with 17.2% Faradaic efficiency (FE) can be achieved at -0.3 V vs (RHE) under ambient conditions. Experimental and density functional theory (DFT) calculations further point out that the incorporation of MoN with CeO2 can promotes the enlargement of the electron deficient area of nitrogen vacancy site. The enlarged electron deficient area contributes to the accommodation of lone pair electrons of N2, which dramatically improves the N2 adsorption/activation and the key intermediates (*NNH and *NH3) generation, thus boosting the NRR performance.

13.
Ann Hematol ; 103(4): 1305-1315, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38049586

ABSTRACT

Prognostic significance of multiple immune antigens in multiple myeloma has been well established. However, a level of uncertainty remains regarding the intrinsic relationship between immunophenotypes and cytogenetic stability and precise risk stratification. To address these unresolved issues, we conducted a study involving 1389 patients enrolled in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Our results revealed that the correlation between antigen expression and cytogenetics is more prominent than cytopenia or organ dysfunction. Most immune antigens, apart from CD38, CD138, and CD81, exhibit significant associations with the incidence of at least one cytogenetic abnormality. In turn, we identified CD138-low/CD27-neg as specific adverse immunophenotypic profile, which remaining independent impact on progression-free survival (HR, 1.49; P = 0.007) and overall survival (HR, 1.77; P < 0.001) even in the context of cytogenetics. Importantly, CD138-low/CD27-neg profile was also associated with inferior survival after first relapse (P < 0.001). Moreover, the antigen expression profiles were not strictly similar when comparing diagnosis and relapse; in particular, the CD138-low/CD27-neg pattern was notably increased after disease progression (19.1 to 29.1%; P = 0.005). Overall, our study demonstrates that diverse immune profiles are strongly associated with cytogenetic stability, and a specific immunophenotype (CD138-low/CD27-neg) could effectively predict prognoses across different disease stages.


Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Prognosis , Chromosome Aberrations , Cytogenetic Analysis , Recurrence
14.
Int J Biol Macromol ; 254(Pt 2): 127934, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37939777

ABSTRACT

Ribosomal proteins (RPs) have mang extraribosomal functions including regulation of ovarian development in some organisms. In order to solve the problem of rapid ovarian maturation in Macrobrachium nipponense aquaculture, this study identified a RPS24 (MnRPS24) gene from M. nipponense, which encodes a protein of ßßαßαααα folding structure type. MnRPS24 exhibited the greatest expressions in the female adult stage among the six growth stages, in the ovary among the nine tissues, and in the stage I ovary among the six ovarian development stages. The MnRPS24 protein located in the cytoplasm of oogonia, previtellogenic and early-vitellogenic oocytes, and the follicular cells surrounding the oocytes. The expression of the vitellogenin (MnVg), vitellogenin receptor (MnVgr), cell cycle protein B (MnCyclin B) and cell division cyclin 2 (MnCdc2) genes were increased by recombinant MnRPS24 protein incubation. Conversely, the expression of the Wee1 kinase (MnWee1) gene was decreased. MnRPS24 gene silencing downregulated the expression for MnVg, MnVgr, MnCyclin B and MnCdc2 and upregulated the expression for MnWee1. Furthermore, MnRPS24 gene silencing delayed the vitellogenesis of oocytes, halting the progression of ovarian development. The findings of this research demonstrate that MnRPS24 could potentially function as a stimulator in promoting the development of ovaries in M. nipponense.


Subject(s)
Palaemonidae , Animals , Female , Oocytes , Ovary/metabolism , Ribosomes
15.
Bone Res ; 11(1): 64, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38097598

ABSTRACT

Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.


Subject(s)
Bone Resorption , Osteogenesis , Humans , Peptidylprolyl Isomerase/metabolism , Osteoclasts/metabolism , Bone Resorption/metabolism
16.
PeerJ ; 11: e16635, 2023.
Article in English | MEDLINE | ID: mdl-38107562

ABSTRACT

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase widely expressed in various tissues and organs. Unlike other kinases, GSK-3 is active under resting conditions and is inactivated upon stimulation. In mammals, GSK-3 includes GSK-3 α and GSK-3ß isoforms encoded by two homologous genes, namely, GSK3A and GSK3B. GSK-3ß is essential for the control of glucose metabolism, signal transduction, and tissue homeostasis. As more than 100 known proteins have been identified as GSK-3ß substrates, it is sometimes referred to as a moonlighting kinase. Previous studies have elucidated the regulation modes of GSK-3ß. GSK-3ß is involved in almost all aspects of brain functions, such as neuronal morphology, synapse formation, neuroinflammation, and neurological disorders. Recently, several comparatively specific small molecules have facilitated the chemical manipulation of this enzyme within cellular systems, leading to the discovery of novel inhibitors for GSK-3ß. Despite these advancements, the therapeutic significance of GSK-3ß as a drug target is still complicated by uncertainties surrounding the potential of inhibitors to stimulate tumorigenesis. This review provides a comprehensive overview of the intricate mechanisms of this enzyme and evaluates the existing evidence regarding the therapeutic potential of GSK-3ß in brain diseases, including Alzheimer's disease, Parkinson's disease, mood disorders, and glioblastoma.


Subject(s)
Neurodegenerative Diseases , Animals , Glycogen Synthase Kinase 3 beta/genetics , Neurodegenerative Diseases/drug therapy , Glycogen Synthase Kinase 3/genetics , Brain , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Mammals
17.
Exp Biol Med (Maywood) ; 248(20): 1864-1876, 2023 10.
Article in English | MEDLINE | ID: mdl-38031247

ABSTRACT

Excessive acetaminophen (APAP) application is a major cause of drug-induced liver injury (DILI). Febuxostat (Feb), a drug for reducing uric acid (UA) levels, was demonstrated to relieve hepatic inflammation and reverse organ functions. However, the effect of Feb on APAP-induced DILI and its mechanisms have not been fully explored. In this study, Feb (10 mg/kg) was given to mice by gavage 1 h after APAP (300 mg/kg, i.g.) induction. Serum and liver samples were collected 12 or 3 h after APAP challenge. Feb treatment was found to remarkably improve APAP-induced DILI, as evidenced by reduced serum ALT, AST and UA levels, pathomorphology, inflammatory, and oxidative responses. Consistently, treatment with Feb also reduced the cell injury induced by APAP in LO2 cells. Mechanistically, Feb induced GPX4 expression, activated the Keap1/Nrf2 pathway, and inhibited the TLR4/NF-κB p65 pathway. Feb also inhibited glutathione (GSH) depletion and Jun N-terminal kinase (JNK) activation in the early injury phase. Notably, pretreatment with Feb for 3 days also revealed preventive effects against APAP-induced DILI in mice. Overall, our data revealed a potential health impact of Feb on APAP-mediated DILI in vivo and in vitro, suggesting that Feb might be a potential candidate for treating DILI.


Subject(s)
Chemical and Drug Induced Liver Injury , Oxidative Stress , Animals , Mice , Acetaminophen/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Febuxostat/pharmacology , Febuxostat/metabolism , Glutathione/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Liver/metabolism , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism
18.
Physiol Plant ; 175(5): e14010, 2023.
Article in English | MEDLINE | ID: mdl-37882262

ABSTRACT

Fruits and leaves of Solanum khasianum C. B. Clarke have long been used as a common Chinese herbal medicine. Steroidal glycoalkaloids (SGAs), the main active ingredient in S. khasianum, exhibit various pharmacological effects. However, genes involved in the SGA biosynthetic pathway in S. khasianum have not yet been identified. Genes encoding potential key SGA biosynthesis enzymes were identified through comprehensive RNA sequencing analysis (RNA-seq) of S. khasianum leaves, stems, and fruits. A total of 123,704 unigenes were obtained, of which 109,775 (88.74%) were annotated in seven public databases. Among these, 54 unigenes potentially involved in SGA biosynthesis were identified. Additionally, 23,636 differentially expressed genes were identified by comparing gene expression levels among the fruits, stems, and leaves of S. khasianum. The structural characteristics and phylogenetic relationship of cycloartenol synthase involved in SGA biosynthesis were further analyzed. Solasodine constituent was detected by high-performance liquid chromatography. This is the first study to report the comparative transcriptome analysis of different tissues of S. khasianum that identifies valuable genes potentially involved in SGA biosynthesis in this species.


Subject(s)
Solanum , Solanum/genetics , Phylogeny , Gene Expression Profiling , Transcriptome/genetics , RNA-Seq
19.
Bioorg Chem ; 139: 106699, 2023 10.
Article in English | MEDLINE | ID: mdl-37390633

ABSTRACT

A chemical investigation of the marine sponge Phakellia sp. from the South China Sea yielded five new cyclopeptides, phakellisins A-E (1-5). Structures of these compounds were determined by comprehensive analysis of 1D/2D NMR, HRESIMS/MS spectroscopic data and the advanced Marfey's method. All compounds were evaluated for their cytotoxic activity. Compound 1 showed a strong inhibitory activity against WSU-DLCL-2 cells with an IC50 value of 5.25 ± 0.2 µM by induction of G0/G1 cell cycle arrest and apoptosis.


Subject(s)
Peptides, Cyclic , Porifera , Animals , Chromatography, Liquid , Peptides, Cyclic/pharmacology , Peptides, Cyclic/chemistry , Tandem Mass Spectrometry , Porifera/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure
20.
PeerJ Comput Sci ; 9: e1349, 2023.
Article in English | MEDLINE | ID: mdl-37346720

ABSTRACT

Physical layer security (PLS) is considered one of the most promising solutions to solve the security problems of massive Internet of Things (IoTs) devices because of its lightweight and high efficiency. Significantly, the recent physical layer key generation (PLKG) scheme based on transmission delay proposed by Huang et al. (2021) does not have any restrictions on communication methods and can extend the traditional physical layer security based on wireless channels to the whole Internet scene. However, the secret-sharing strategy adopted in this scheme has hidden dangers of collusion attack, which may lead to security problems such as information tampering and privacy disclosure. By establishing a probability model, this article quantitatively analyzes the relationship between the number of malicious collusion nodes and the probability of key exposure, which proves the existence of this security problem. In order to solve the problem of collusion attack in Huang et al.'s scheme, this article proposes an anti-collusion attack defense method, which minimizes the influence of collusion attack on key security by optimizing parameters including the number of the middle forwarding nodes, the random forwarding times, the time delay measurement times and the out-of-control rate of forwarding nodes. Finally, based on the game model, we prove that the defense method proposed in this article can reduce the risk of key leakage to zero under the scenario of the "Careless Defender" and "Cautious Defender" respectively.

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