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2.
Front Immunol ; 15: 1323199, 2024.
Article in English | MEDLINE | ID: mdl-38742112

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. PANoptosis is a recently unveiled programmed cell death pathway, Nonetheless, the precise implications of PANoptosis within the context of HCC remain incompletely elucidated. Methods: We conducted a comprehensive bioinformatics analysis to evaluate both the expression and mutation patterns of PANoptosis-related genes (PRGs). We categorized HCC into two clusters and identified differentially expressed PANoptosis-related genes (DEPRGs). Next, a PANoptosis risk model was constructed using LASSO and multivariate Cox regression analyses. The relationship between PRGs, risk genes, the risk model, and the immune microenvironment was studies. In addition, drug sensitivity between high- and low-risk groups was examined. The expression profiles of these four risk genes were elucidate by qRT-PCR or immunohistochemical (IHC). Furthermore, the effect of CTSC knock down on HCC cell behavior was verified using in vitro experiments. Results: We constructed a prognostic signature of four DEPRGs (CTSC, CDCA8, G6PD, and CXCL9). Receiver operating characteristic curve analyses underscored the superior prognostic capacity of this signature in assessing the outcomes of HCC patients. Subsequently, patients were stratified based on their risk scores, which revealed that the low-risk group had better prognosis than those in the high-risk group. High-risk group displayed a lower Stromal Score, Immune Score, ESTIMATE score, and higher cancer stem cell content, tumor mutation burden (TMB) values. Furthermore, a correlation was noted between the risk model and the sensitivity to 56 chemotherapeutic agents, as well as immunotherapy efficacy, in patient with. These findings provide valuable guidance for personalized clinical treatment strategies. The qRT-PCR analysis revealed that upregulated expression of CTSC, CDCA8, and G6PD, whereas downregulated expression of CXCL9 in HCC compared with adjacent tumor tissue and normal liver cell lines. The knockdown of CTSC significantly reduced both HCC cell proliferation and migration. Conclusion: Our study underscores the promise of PANoptosis-based molecular clustering and prognostic signatures in predicting patient survival and discerning the intricacies of the tumor microenvironment within the context of HCC. These insights hold the potential to advance our comprehension of the therapeutic contribution of PANoptosis plays in HCC and pave the way for generating more efficacious treatment strategies.


Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular , Computational Biology , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Tumor Microenvironment , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Humans , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Computational Biology/methods , Prognosis , Biomarkers, Tumor/genetics , Cell Line, Tumor , Chemokine CXCL9/genetics , Gene Expression Profiling , Male , Female , Transcriptome
3.
J Photochem Photobiol B ; 254: 112903, 2024 May.
Article in English | MEDLINE | ID: mdl-38608335

ABSTRACT

This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were prepared: cellular vesicles (CVs) were fabricated by sonication-mediated nanosizing of cholangiocarcinoma (TFK-1) cells, whereas cell membrane vesicles (CMVs) were produced by TFK-1 cell and organelle membrane isolation and subsequent nanovesicularization by sonication. The bionanovesicles were loaded with zinc phthalocyanine (ZnPC). The CVs and CMVs were characterized (size, polydispersity index, zeta potential, stability, ZnPC encapsulation efficiency, spectral properties) and assayed for tumor (TFK-1) cell association and uptake (flow cytometry, confocal microscopy), intracellular ZnPC distribution (confocal microscopy), dark toxicity (MTS assay), and PDT efficacy (MTS assay). The mean ±â€¯SD diameter, polydispersity index, and zeta potential were 134 ±â€¯1 nm, -16.1 ±â€¯0.9, and 0.220 ±â€¯0.013, respectively, for CVs and 172 ±â€¯3 nm, -16.4 ±â€¯1.1, and 0.167 ±â€¯0.022, respectively, for CMVs. Cold storage for 1 wk and incorporation of ZnPC increased bionanovesicular diameter slightly but size remained within the recommended range for in vivo application (136-220 nm). ZnPC was incorporated into CVs and CMVs at an optimal photosensitizer:lipid molar ratio of 0.006 and 0.01, respectively. Both bionanovesicles were avidly taken up by TFK-1 cells, resulting in homogenous intracellular ZnPC dispersion. Photosensitization of TFK-1 cells did not cause dark toxicity, while illumination at 671 nm (35.3 J/cm2) produced LC50 values of 1.11 µM (CVs) and 0.51 µM (CMVs) at 24 h post-PDT, which is superior to most LC50 values generated in tumor cells photosensitized with liposomal ZnPC. In conclusion, CVs and CMVs constitute a potent photosensitizer platform with no inherent cytotoxicity and high PDT efficacy in vitro.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Organometallic Compounds , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Cholangiocarcinoma/drug therapy , Bile Duct Neoplasms/drug therapy , Bile Ducts, Intrahepatic , Organometallic Compounds/pharmacology , Zinc Compounds , Cell Line, Tumor
4.
Int Immunopharmacol ; 129: 111658, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38359663

ABSTRACT

BACKGROUND: Chronic periodontitis triggers an increase in osteoclastogenesis, with glycolysis playing a crucial role in this process. Pyruvate kinase M2 (PKM2) is a critical enzyme involved in glycolysis and pyruvate metabolism. Yet, the precise function of PKM2 in osteoclasts and their formation remains unclear and requires further investigation. METHODS: Bioinformatics was used to investigate critical biological processes in osteoclastogenesis. In vitro, osteoclastogenesis was analyzed using tartrate-resistant acid phosphatase (TRAP) staining, phalloidin staining, quantitative real­time PCR (RT-qPCR), and Western blotting. Small interfering RNA (siRNA) of PKM2 and Shikonin, a specific inhibitor of PKM2, were used to verify the role of PKM2 in osteoclastogenesis. The mouse model of periodontitis was used to assess the effect of shikonin on bone loss. Analyses included micro computed tomography, immunohistochemistry, flow cytometry, TRAP staining and HE staining. RESULTS: Bioinformatic analysis revealed a significant impact of glycolysis and pyruvate metabolism on osteoclastogenesis. Inhibition of PKM2 leads to a significant reduction in osteoclastogenesis. In vitro, co-culture of the heat-killed Porphyromonas gingivalis significantly promoted osteoclastogenesis, concomitant with an increased PKM2 expression in osteoclasts. Shikonin weakened the promoting effect of porphyromonas gingivalis on osteoclastogenesis. In vivo experiments demonstrated that inhibition of PKM2 by shikonin alleviated bone loss induced by periodontitis, suppressed excessive osteoclastogenesis in alveolar bone, and reduced tissue inflammation to some extent. CONCLUSION: PKM2 inhibition by shikonin, a specific inhibitor of this enzyme, attenuated osteoclastogenesis and bone resorption in periodontitis. Shikonin appears to be a promising therapeutic agent for treating periodontitis.


Subject(s)
Naphthoquinones , Osteogenesis , Periodontitis , Mice , Animals , X-Ray Microtomography , Osteoclasts , Periodontitis/drug therapy , Periodontitis/metabolism , Pyruvates/pharmacology
6.
Eur J Orthod ; 46(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38168816

ABSTRACT

BACKGROUND: Agenesis of third molar agenesis has a higher incidence than other tooth development anomalies. Previous research identified a potential correlation between third molar agenesis and specific craniofacial morphology; however, no systematic review and meta-analysis on this topic currently exists. OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the association between third molar agenesis and craniofacial sagittal and vertical morphology. SEARCH METHODS: An electronic search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library without restrictions on publication year or language; this was supplemented by the manual retrieval of relevant literature. SELECTION CRITERIA: Cross-sectional studies that compared craniofacial morphology using angular and linear measurements obtained from lateral cephalography between patients with third molar agenesis and those without were included. DATA COLLECTION AND ANALYSIS: The quality assessment of the enrolled articles was evaluated by the Joanna Briggs Institute critical appraisal tool. Meta-analysis and sensitivity analysis were performed by Review Manager software (The Cochrane Collaborative, version 5.4, Cochrane IMS). RESULTS: A total of seven studies were included. Meta-analysis demonstrated that the ANB (mean differences (MD) = -0.75, 95% CI: -1.31 to -0.19, P < 0.01), palate length (ANS-PNS, MD = -1.68, 95% CI: -2.24 to -1.11, P < 0.01), and mandibular length (Go-Pog, MD = -0.36, 95% CI: -0.59 to -0.13, P < 0.01) were smaller in patients with third molar agenesis. With regard to vertical craniofacial morphology, the mandibular plane angle (MP-FH; MD = -1.88, 95% CI: -3.45 to -0.31, P = 0.02), gonial angle (gonial angle; MD = -1.73, 95% CI: -2.69 to -0.77, P < 0.01) and lower face height (lower face heigh angle; MD = -1.36, 95% CI: -1.94 to -0.77, P < 0.01) were smaller in patients with third molar agenesis, indicating a flatter or brachyfacial skeletal pattern. CONCLUSIONS: The results of this study suggest that third molar agenesis maybe associated with a reduced maxillary length and a flatter mandible. However, these findings need to be interpreted with caution due to inconsistencies in the certainty of evidence. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42023448226).


Subject(s)
Maxilla , Molar, Third , Humans , Molar, Third/diagnostic imaging , Molar, Third/abnormalities , Cross-Sectional Studies , Mandible , Palate
7.
New Phytol ; 241(3): 1250-1265, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38009305

ABSTRACT

Sugar transporter proteins (STPs) play critical roles in regulating plant stress tolerance, growth, and development. However, the role of STPs in regulating crop yield is poorly understood. This study elucidates the mechanism by which knockout of the sugar transporter OsSTP15 enhances grain yield via increasing the tiller number in rice. We found that OsSTP15 is specifically expressed in the shoot base and vascular bundle sheath of seedlings and encodes a plasma membrane-localized high-affinity glucose efflux transporter. OsSTP15 knockout enhanced sucrose and trehalose-6-phosphate (Tre6P) synthesis in leaves and improved sucrose transport to the shoot base by inducing the expression of sucrose transporters. Higher glucose, sucrose, and Tre6P contents were observed at the shoot base of stp15 plants. Transcriptome and metabolome analyses of the shoot base demonstrated that OsSTP15 knockout upregulated the expression of cytokinin (CK) synthesis- and signaling pathway-related genes and increased CK levels. These findings suggest that OsSTP15 knockout represses glucose export from the cytoplasm and simultaneously enhances sugar transport from source leaves to the shoot base by promoting the synthesis of sucrose and Tre6P in leaves. Subsequent accumulation of glucose, sucrose, and Tre6P in the shoot base promotes tillering by stimulating the CK signaling pathway.


Subject(s)
Oryza , Oryza/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Edible Grain , Glucose/metabolism , Sucrose/metabolism , Sugars/metabolism
8.
J Stomatol Oral Maxillofac Surg ; : 101747, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38141825

ABSTRACT

OBJECTIVE: The preoperative inclination angle of mandibular incisors was crucial for surgical and postoperative stability while the effect of proclined mandibular incisors on skeletal stability has not been investigated. This study aimed to evaluate the effects of differences in presurgical mandibular incisor inclination on skeletal stability after orthognathic surgery in patients with skeletal Class III malocclusion. METHODS: A retrospective cohort study of 80 consecutive patients with skeletal Class III malocclusion who underwent bimaxillary orthognathic surgery was conducted. According to incisor mandibular plane angle (IMPA), patients were divided into 3 groups: retroclined inclination (IMPA < 87°), normal inclination (87° ≤ IMPA < 93°) and proclined inclination (IMPA ≥ 93°). Preoperative characteristics, surgical changes and postoperative stability were compared based on lateral cephalograms obtained 1 week before surgery (T0), 1 week after surgery (T1), and at 6 to 12 months postoperatively (T2). RESULTS: The mandible demonstrated a forward and upward relapse in all three groups. No significant differences in skeletal relapse were observed in the 3 groups of patients. However, the proclined inclination group showed a negative overbite tendency postoperatively compared with the other two groups and a clinically significant mandibular relapse pattern. Proclined IMPA both pre- and postoperatively was correlated with mandibular relapse. CONCLUSION: Sufficient presurgical mandibular incisor decompensation was of crucial importance for the maintenance of skeletal stability in patients with skeletal Class III malocclusion who subsequently underwent orthognathic surgery.

9.
Foods ; 12(19)2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37835238

ABSTRACT

Cassava flour (CF) was used as a raw material to replace wheat flour (WF) at levels of 0% (control), 10%, 20%, 30%, 40%, and 50% to prepare wheat-cassava composite flour (W-CF) and dough. The effects of different CF substituting levels on the functional properties of the W-CF and dough were investigated. The results show that an increase in CF led to a decrease in the moisture, protein, fat, and b* values of W-CF. The crude fiber, ash, starch, L*, a* values, iodine blue value (IBV), and swelling power (SP) of the composite flour increased gradually. It was found that the water absorption, hardness, and chewiness of the W-CF dough increased with an increase in the CF substitution level. A different trend could be observed with the springiness and cohesiveness of the W-CF dough. The resistance to extension, extensibility, and the extended area of the W-CF dough at all substitution levels was significantly lower than that of the WF dough. The elasticity and cohesiveness of the dough tended to increase for CF content from 10% to 30%, followed by a decrease at a higher replacement. Pearson correlation analysis indicated that the substitution levels of CF had a significant influence on the proximate analysis and functional properties of the W-CF and dough. This study will provide important information on choosing CF substitution levels for different products.

10.
Shock ; 60(5): 698-706, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37695737

ABSTRACT

ABSTRACT: Purpose: Intensive care unit-acquired weakness (ICUAW) is a severe neuromuscular complication that frequently occurs in patients with sepsis. The precise molecular pathophysiology of mitochondrial calcium uptake 1 (MICU1) and mitochondrial calcium uniporter (MCU) in ICUAW has not been fully elucidated. Here, we speculate that ICUAW is associated with MICU1:MCU protein ratio-mediated mitochondrial calcium ([Ca 2+ ] m ) uptake dysfunction. Methods: Cecal ligation and perforation (CLP) was performed on C57BL/6J mice to induce sepsis. Sham-operated animals were used as controls. Lipopolysaccharide (LPS) (5 µg/mL) was used to induce inflammation in differentiated C2C12 myoblasts. Compound muscle action potential (CMAP) was detected using a biological signal acquisition system. Grip strength was measured using a grip-strength meter. Skeletal muscle inflammatory factors were detected using ELISA kits. The cross-sectional area (CSA) of the tibialis anterior (TA) muscle was detected by hematoxylin and eosin staining. Cytosolic calcium ([Ca 2+ ] c ) levels were measured using Fluo-4 AM. Adeno-associated virus (AAV) was injected into TA muscles for 4 weeks to overexpress MICU1 prophylactically. A lentivirus was used to infect C2C12 cells to increase MICU1 expression prophylactically. Findings: The results suggest that sepsis induces [Ca 2+ ] m uptake disorder by reducing the MICU1:MCU protein ratio, resulting in skeletal muscle weakness and muscle fiber atrophy. However, MICU1 prophylactic overexpression reversed these effects by increasing the MICU1:MCU protein ratio. Conclusions: ICUAW is associated with impaired [Ca 2+ ] m uptake caused by a decreased MICU1:MCU protein ratio. MICU1 overexpression improves sepsis-induced skeletal muscle weakness and atrophy by ameliorating the [Ca 2+ ] m uptake disorder.


Subject(s)
Cation Transport Proteins , Sepsis , Animals , Mice , Atrophy/metabolism , Calcium/metabolism , Calcium-Binding Proteins/metabolism , Cation Transport Proteins/metabolism , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Muscle Weakness/etiology , Muscle, Skeletal/metabolism , Sepsis/metabolism
12.
Drug Des Devel Ther ; 17: 2087-2106, 2023.
Article in English | MEDLINE | ID: mdl-37489176

ABSTRACT

Purpose: Malignant melanoma (MM), the most lethal skin cancer, is highly invasive and metastatic. These qualities are related to not only genetic mutations in MM itself but also the interaction of MM cells with the immune system and microenvironment. This study aimed to construct a combined immunotherapy and gene therapy drug delivery system for the effective treatment of MM. Methods: Mature dendritic cell (mDC) exosomes (mDexos) with immune induction functions were used as carriers. BRAF siRNA (siBRAF) with the ability to silence mutated BRAF in MM was encapsulated in mDexos by electroporation to construct a biomimetic nanosystem for the codelivery of immunotherapy and gene therapy drugs (siBRAF-mDexos) to the MM microenvironment. Then, we investigated the nanosystem's serum stability and biocompatibility, uptake efficiency in mouse melanoma cells (B16-F10 cells), cytotoxicity against B16-F10 cells and inhibitory effect on BRAF expression. Furthermore, we evaluated its antimelanoma activity and safety in vivo. Results: SiBRAF-mDexos were nanosized. Compared to siBRAF, siBRAF-mDexos displayed significantly increased serum stability, biocompatibility, uptake efficiency in B16-F10 cells, and cytotoxicity to B16-F10 melanoma cells; they also had a significantly greater inhibitory effect on BRAF expression and induced T-lymphocyte proliferation. Moreover, compared with siBRAF, siBRAF-mDexos showed significantly enhanced anti-MM activity and a high level of safety in vivo. Conclusion: The study suggests that the siBRAF-mDexo biomimetic drug codelivery system can be used to effectively treat MM, which provides a new strategy for combined gene therapy and immunotherapy for MM.


Subject(s)
Exosomes , Melanoma, Experimental , Skin Neoplasms , Animals , Mice , Biomimetics , Proto-Oncogene Proteins B-raf , Immunotherapy , Drug Delivery Systems , Genetic Therapy , Dendritic Cells , Tumor Microenvironment , Melanoma, Cutaneous Malignant
13.
Front Cell Dev Biol ; 11: 1054381, 2023.
Article in English | MEDLINE | ID: mdl-37009477

ABSTRACT

Introduction: Maternal immune activation (MIA) is closely related to the onset of autism-like behaviors in offspring, but the mechanism remains unclear. Maternal behaviors can influence offspring's development and behaviors, as indicated in both human and animal studies. We hypothesized that abnormal maternal behaviors in MIA dams might be other factors leading to delayed development and abnormal behaviors in offspring. Methods: To verify our hypothesis, we analyzed poly(I:C)-induced MIA dam's postpartum maternal behavior and serum levels of several hormones related to maternal behavior. Pup's developmental milestones and early social communication were recorded and evaluated in infancy. Other behavioral tests, including three-chamber test, self-grooming test, open field test, novel object recognition test, rotarod test and maximum grip test, were performed in adolescence of pups. Results: Our results showed that MIA dams exhibit abnormal static nursing behavior but normal basic care and dynamic nursing behavior. The serum levels of testosterone and arginine vasopressin in MIA dams were significantly reduced compared with control dams. The developmental milestones, including pinna detachment, incisor eruption and eye opening, were significantly delayed in MIA offspring compared with control offspring, while the weight and early social communication showed no significant differences between the two groups. Behavioral tests performed in adolescence showed that only male MIA offspring display elevated self-grooming behaviors and reduced maximum grip. Discussion: In conclusion, MIA dams display abnormal postpartum static nursing behavior concomitantly with reduced serum levels of testosterone and arginine vasopressin, possibly involving in the pathogenesis of delayed development and elevated self-grooming in male offspring. These findings hint that improving dam's postpartum maternal behavior might be a potential regime to counteract delayed development and elevated self-grooming in male MIA offspring.

14.
Zool Res ; 44(3): 522-524, 2023 05 18.
Article in English | MEDLINE | ID: mdl-37070576
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(2): 209-211, 2023 Feb.
Article in Chinese | MEDLINE | ID: mdl-36916384

ABSTRACT

In the process of continuous renal replacement therapy (CRRT), various factors such as the temperature of replacement fluid, the flow of fluid and the circulation of blood in cardiopulmonary bypass, lead to the temperature of the blood injected back into the body is often lower than normal. It leads to the decrease of body temperature and the occurrence of hypothermia, which can be life-threatening in severe cases. In clinical practice, medical staff mostly reduces the occurrence of hypothermia in patients with CRRT by means of the heating device of the machine, the heating of the liquid temperature box for cardiopulmonary bypass, and the application of heating blankets, but the effect is not ideal. Therefore, medical staff of the department of critical care medicine of the Second Affiliated Hospital of Anhui Medical University designed a heating device and temperature control system for CRRT dialysis fluid bag, and obtained the National Invention Patent of China (ZL 2021 1 0334906.7). The device includes a heating and thermal insulation device and a temperature control system, wherein the heating and thermal insulation device is composed of the body of the heating dialysis fluid bag and the temperature control structure, which solves the problems of safe and efficient liquid heating and thermal insulation during the CRRT process. The temperature control system can display the dynamic state of the patient's body temperature, adjust the temperature of the dialysis fluid bag in time, and monitor the temperature of the blood transfusion in real time through the cooperation of the five modules of data collection, data handle, data analysis, regulation and display. This design is applied to CRRT, which can achieve precise control of body temperature of critically ill patients, and has certain clinical significance.


Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Hypothermia , Humans , Renal Replacement Therapy , Renal Dialysis , Temperature , Heating , Acute Kidney Injury/therapy , Critical Illness/therapy
16.
J Clin Monit Comput ; 37(2): 365-377, 2023 04.
Article in English | MEDLINE | ID: mdl-36607532

ABSTRACT

The optimization of positive end-expiratory pressure (PEEP) according to respiratory mechanics [driving pressure or respiratory system compliance (Crs)] is a simple and straightforward strategy. However, its validity to prevent postoperative pulmonary complications (PPCs) remains unclear. Here, we performed a meta-analysis to assess such efficacy. We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) that compared personalized PEEP based on respiratory mechanics and constant PEEP to prevent PPCs in adults. The primary outcome was PPCs. Fourteen studies with 1105 patients were included. Compared with those who received constant PEEP, patients who received optimized PEEP exhibited a significant reduction in the incidence of PPCs (RR = 0.54, 95% CI 0.42 to 0.69). The results of commonly happened PPCs (pulmonary infections, hypoxemia, and atelectasis but not pleural effusion) also supported individualized PEEP group. Moreover, the application of PEEP based on respiratory mechanics improved intraoperative respiratory mechanics (driving pressure and Crs) and oxygenation. The PEEP titration method based on respiratory mechanics seems to work positively for lung protection in surgical patients undergoing general anesthesia.


Subject(s)
Lung , Pulmonary Atelectasis , Adult , Humans , Positive-Pressure Respiration/methods , Pulmonary Atelectasis/prevention & control , Pulmonary Atelectasis/etiology , Anesthesia, General/adverse effects , Postoperative Complications/prevention & control , Respiratory Mechanics
17.
CNS Neurosci Ther ; 29(1): 78-90, 2023 01.
Article in English | MEDLINE | ID: mdl-36221783

ABSTRACT

INTRODUCTION: SHANK3 is an important excitatory postsynaptic scaffold protein, and its mutations lead to genetic cause of neurodevelopmental diseases including autism spectrum disorders (ASD), Philan McDermid syndrome (PMS), and intellectual disability (ID). Early prevention and treatment are important for Shank3 gene mutation disease. Swimming has been proven to have a positive effect on neurodegenerative diseases. METHODS: Shank3 gene exon 11-21 knockout rats were intervened by a 40 min/day, 5 day/week for 8-week protocol. After the intervention, the rats were tested to behavioral measures such as learning and memory, and the volume and H-spectrum of the brain were measured using MRI; hippocampal dendritic spines were measured using Golgi staining and laser confocal. RESULTS: The results showed that Shank3-deficient rats had significant deficits in social memory, object recognition, and water maze learning decreased hippocampal volume and number of neurons, and lower levels of related scaffold proteins and receptor proteins were found in Shank3-deficient rats. CONCLUSION: It is suggested that early swimming exercise has a positive effect on Shank3 gene-deficient rats, which provides a new therapeutic strategy for the prevention and recovery of neurodevelopmental disorders.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Physical Conditioning, Animal , Animals , Rats , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/therapy , Autistic Disorder/genetics , Autistic Disorder/therapy , Behavior, Animal , Mutation , Nerve Tissue Proteins/genetics , Swimming
18.
Curr Pharm Biotechnol ; 24(4): 589-598, 2023.
Article in English | MEDLINE | ID: mdl-36043717

ABSTRACT

BACKGROUND: Multidrug-resistant tumor cells have special drug detoxification/inactivation mechanisms. The terminal amino groups of the polyamidoamine (PAMAM-NH2), which is cytotoxic to tumor sensitive cells, may have no cytotoxicity in tumor resistant cells with a mechanism different from tumor sensitive cells. OBJECTIVE: This study aimed to investigate the cytotoxic effects of PAMAM-G4-NH2 on human multidrug- resistant breast cancer cells (MCF-7/ADR cells) and identify the possible molecular mechanisms. METHODS: The cytotoxicity of PAMAM-G4-NH2 (10-1000 µg/mL) against MCF-7 and MCF-7/ADR cells was detected. Then, MCF-7 and MCF-7/ADR cells were treated with PAMAM-G4-NH2 (10, 100 and 1000 µg/mL), and apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), activities of caspase-3, -8 and -9 and cell cycle distribution were determined. RESULTS: Within 48 h, the cell viabilities in MCF-7/ADR cells after treatment with PAMAM-G4-NH2 were significantly higher than that in MCF-7 cells in the concentration range of 200-500 µg/mL (P < 0.05). Viabilities of MCF-7/ADR cells treated with PAMAM-G4-OH and PAMAM-G4-COOH for 48 and 72 h were much higher than that of MCF-7/ADR cells treated with PAMAM-G4-NH2. Treated with high concentration (1000 µg/mL) of PAMAM-G4-NH2 for 24 h, the apoptosis ratio, ROS levels, as well as caspase-3 and -9 activities in MCF-7 and MCF-7/ADR cells increased, while MMP decreased, and the cells were arrested in the G0/G1 phase. CONCLUSION: PAMAM-G4-NH2 induced concentration-dependent cytotoxicity in MCF-7/ADR cells via G0/G1 arrest, and acted through h the mitochondria-dependent apoptotic pathway, which was similar to those in tumor sensitive cell, MCF-7 cells. The results suggest that PAMAM-G4-NH2, instead of PAMAM-G4-OH and PAMAM-G4-COOH, can be used as a carrier for drug delivery, concomitantly, it can also induce apoptosis in multidrug-resistant cancer cells in combination with the loaded drug through multiple apoptotic pathways.


Subject(s)
Breast Neoplasms , Dendrimers , Humans , Female , Dendrimers/pharmacology , Caspase 3 , Drug Resistance, Multiple , Reactive Oxygen Species , Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm , Apoptosis , MCF-7 Cells , G1 Phase
19.
Front Nutr ; 9: 1003657, 2022.
Article in English | MEDLINE | ID: mdl-36118753

ABSTRACT

The study aims to evaluate the relationships between characteristics of regional rice raw material and resulting quality of rice noodles. Four of most commonly used rice cultivars in Guangxi for noodles production were investigated. The results showed that compositions of rice flour primarily affected gelatinization and retrogradation, which then influenced the textural and sensory properties of rice noodles. Amylose content had strong positive correlation with peak viscosity (PV) and trough viscosity (TV) of rice flour (P < 0.01). PV and TV had strong negative correlations with adhesive strength (P < 0.01) and positive correlations with chewiness (P < 0.05), hardness, peak load and deformation at peak of rice noodles (P < 0.01). Protein content had positive correlation with the Setback of rice flour (P < 0.05), which is known to have influences on retrogradation. In addition, solubility had positive correlations with cooking loss (P < 0.01) and broken rate (P < 0.05) of rice noodles and strong negative correlation with its springiness (P < 0.01). Swelling power had negative correlation with broken rate (P < 0.05). As sensory score of rice noodles was negatively correlated with broken rate (P < 0.05) and cooking loss (P < 0.01) and positively correlated with springiness (P < 0.01), solubility and swelling power of rice flours were presumed to be useful for predicting consumer acceptability of rice noodles.

20.
Neurosci Lett ; 784: 136734, 2022 07 27.
Article in English | MEDLINE | ID: mdl-35709878

ABSTRACT

OBJECTIVE: As a typical member of the ABC transporter superfamily, ABCA7 has been shown to play an important role in stalling the pathogenesis of neurodegenerative disorders through maintaining the normal microglial function, regulating cellular responses to inflammation and ER stress, and modulating lipid metabolism. Variants in the ABCA7 locus have been hypothesized to be correlated with the genetic predisposition of several neurodegenerative disorders. The goal of this study was to examine whether there is a link between three specific single nucleotide polymorphisms in the ABCA7 gene, namely, rs3764650, rs4147929, and rs3752246, with the risk of developing Parkinson's disease (PD) in a northern Chinese Han community. METHODS: In this case-control study, we recruited 821 participants, including 411 patients with sporadic PD and 410 independent, healthy controls. A Polymerase Chain Reaction-Restriction Fragment Length Polymorphism genotyping assay was used to identify polymorphisms of the three selected single nucleotide polymorphisms (rs3764650, rs4147929, and rs3752246) of the ABCA7 gene. Sanger sequencing was further applied to identify the accuracy of the genotyping results. The chi-square test was used to compare the frequencies of alleles and genotypes in patients and controls. Odds ratios and 95% confidence intervals were calculated using logistic regression. RESULTS: We found significant between-group differences in the alleles (A vs. G, nominal P = 0.014) and dominant models (AA + GA vs. GG, nominal P = 0.015) of rs4147929. Subgroup analysis showed that the frequency of the rs4147929 A allele in male patients with PD was significantly higher than that in male controls (nominal P = 0.036). For the rs3752246 polymorphism, the frequency of the G allele was significantly higher in patients with PD than in controls, and the dominant model fit the data best when considering the nominal P-values (nominal P = 0.019, nominal P = 0.033, respectively). Differences in G allele and genotypes frequencies between patients and controls remained significant in women (nominal P = 0.032 for allele, nominal P = 0.015 for genotype), as well as in individuals aged more than 50 years (nominal P = 0.044, nominal P = 0.020, respectively). No significant differences were observed in allele or genotype frequencies between patients with PD and healthy controls for rs3764650. The frequency of the TCG (rs3764650-rs3752246-rs4147929) haplotype was significantly lower in the PD group than in the healthy control group (odds ratio = 0.772; 95% confidence interval = 0.634-0.940; P = 0.011). CONCLUSION: The rs4147929 polymorphism was significantly associated with PD susceptibility in the northern Chinese Han population. The A allele of rs4147929 was a risk factor for developing PD. The TCG haplotype presented a protective role in the pathogenesis of PD. Further studies using larger sample sizes, considering different clinical and biochemical parameters such as the cognitive status of subjects at the same time, are warranted to better clarify the effects of these common variants on the pathogenesis and development of PD.


Subject(s)
ATP-Binding Cassette Transporters , Genetic Predisposition to Disease , Parkinson Disease , ATP-Binding Cassette Transporters/genetics , Case-Control Studies , China , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Male , Parkinson Disease/genetics , Polymorphism, Single Nucleotide
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