Search

BACKGROUND: The extracellular-regulated protein kinase 5 (ERK5) signaling protein is essential for the survival of organisms, and resveratrol can promote osteoblast proliferation through various pathways. However, whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE: To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins, and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS: Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium, XMD8-92 (an ERK5 inhibitor), epidermal growth factor (an ERK5 activator), resveratrol alone, XMD8-92+EGF, and resveratrol+XMD8-92, respectively. Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins, proliferation-related proteins Cyclin D1, CDK4 and PCNA, and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group. The fluorescence intensity of ERK5, osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining, and cell proliferation was detected by EdU staining, respectively. The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION: The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells, up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio. The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours, respectively. Resveratrol could activate ERK5 signaling protein, thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio. All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/ RANKL ratio by activating the ERK5 signaling protein. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influences of asiaticoside (AS) on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis (MsPGN) by regulating the rat sarcoma (Ras) /extracellular signal regulated kinase (ERK) /mitogen activated protein kinase (MAPK) signaling pathway. Methods: Sixty SPF SD rats were randomly divided into sham operation group (Sham group), MsPGN model group (Model group), low-dose AS group (AS-L group, 40 mg/kg), high-dose AS group (AS-H group, 80 mg/kg), high-dose AS+Ras/ERK/MAPK signaling pathway activator group (AS-H+anisomycin group, 80 mg/kg AS+10 mg/kg anisomycin), with 12 rats in each group. Rat model of MsPGN was established by modified serum immunization. The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method. HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group. TUNEL staining was used to detect apoptosis of rat glomerular cells in each group. Levels of serum creatinine (Scr), superoxide dismutase (SOD), blood urea nitrogen (BUN), malondialdehyde (MDA), and levels of IL-18, IL-1β, TNF-α, SOD and MDA in renal tissues were measured by ELISA. Protein levels of Ras, pERK1/2, ERK1/2, MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot. Results: ①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats. Compared with Sham group, 24 h urine protein content, glomerular cell apoptosis rate, serum Scr, BUN, MDA levels, renal tissue IL-18, IL-1β, TNF-α, MDA levels in model group were significantly increased (P<0.05), while SOD level in serum and renal tissue was significantly decreased (P<0.05) . HE staining showed that the glomerulus of rats had severe mesangial hyperplasia, a large amount of matrix deposition, and the basement membrane was significantly thickened. Compared with model group, 24 h urine protein content, glomerular cell apoptosis rate, serum Scr, BUN, MDA levels, renal tissue IL-18, IL-1β, TNF-α, MDA levels in AS-H group rats were significantly decreased (P<0.05), while SOD level in serum and renal tissue was significantly increased (P<0.05), HE staining showed alleviated mesangial hyperplasia injury. ②AS downregulated the Ras/ERK/MAPK signaling pathway. Compared with Sham group, expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased (P<0.05); compared with Model group, expression of Ras protein, phosphorylation level of ERK1/2 and MAPK in AS-H group were significantly decreased (P<0.05), and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats (P<0.05) . Conclusion: AS may reduce the inflammatory reaction and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Defective outgrowth of chondrocyte mitophagy causes degenerative chondrocyte pathological changes such as apoptosis and matrix loss. OBJECTIVE: To investigate the effects and possible mechanism of Juanbi Decoction-containing serum on interleukin-1β-induced inflammatory response and apoptosis of rat knee joint chondrocytes. METHODS: Fifty male Sprague-Dawley rats were randomly given saline, Juanbi Decoction in low, medium and high doses (1.24, 2.48 and 4.96 g/kg), and celecoxib (positive drug) group. Drug-containing serum was obtained by continuous gavage for 2 weeks. (1) Chondrocytes were isolated and randomly divided into control group, interleukin-1β group, Juanbi Decoction low, medium and high dose containing serum groups and positive drug serum group. Cell counting kit-8 assay was used to detect cell viability; immunofluorescence double staining was used to detect mitophagy level; immunofluorescence was used to detect the phosphorylated AMP-activated protein kinase level; western blot was used to detect the expression of PTEN induced putative kinase 1/Parkin pathwayrelated protein and cleaved caspase-3; and ELISA was used to detect inflammatory factor level. (2) PTEN induced putative kinase 1 siRNA and Compound C were used for intervention to explore the role of AMP-activated protein kinase/PTEN induced putative kinase 1/Parkin pathway in the regulation of mitophagy by Juanbi Decoction-containing serum. RESULTS AND CONCLUSION: (1) Compared with the control group, chondrocyte survival, type II collagen, phosphorylated AMP-activated protein kinase, PTEN induced putative kinase 1, Parkin, and microtubule-associated proteins 1 light chain 3 protein levels, and mitophagy levels were significantly lower in the interleukin-1β group (P < 0.05), while cleaved caspase-3 protein levels, interleukin-6, interleukin-8 and tumor necrosis factor-α levels were significantly higher (P < 0.05). Compared with the interleukin-1β group, opposite changes in all the above indexes were observed in Juanbi Decoction low, medium and high dose containing serum groups and positive drug serum group (P < 0.05). (2) PTEN induced putative kinase 1 siRNA significantly inhibited the effect of Juanbi Decoction-containing serum on mitophagy in interleukin-1β-treated chondrocytes and reduced the protective effect of Juanbi Decoction-containing serum on interleukin-1β-induced inflammation and apoptosis in chondrocytes; Compound C reversed the effect of Juanbi Decoction-containing serum on the PTEN induced putative kinase 1/Parkin signaling pathway in interleukin-1β-treated chondrocytes. To conclude, Juanbi Decoction-containing serum inhibits chondrocyte inflammation and apoptosis by affecting the level of mitochondrial autophagy, thereby attenuating interleukin-1β-induced chondrocyte degradation by a mechanism that may be related to the regulation of the AMP-activated protein kinase/PTEN induced putative kinase 1/Parkin pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, with the deepening of cell death research, necroptosis has gradually become a hot and difficult topic in academic research. Its various signaling pathways and proteins play an important role in the occurrence and development of periodontitis. People try to delay the process of periodontal tissue inflammation by preventing the occurrence of necroptosis. OBJECTIVE: To provide a review on the molecular mechanism of necroptosis and its correlation with periodontitis in the hope of providing new ideas and directions for the prevention, diagnosis, treatment and evaluation of periodontitis. METHODS: The first author searched PubMed, CNKI, and other databases in October 2023 for relevant literature published up to April 2024 with the search terms of “necroptosis, programmed cell death, periodontitis, periodontal, immunity, inflammation, receptor interacting protein kinase 1, receptor interacting protein kinase 3, mixed lineage kinase domain-like” in Chinese and “necroptosis, programmed cell death, periodontitis, periodontal, immunity, inflammation, RIP1, RIP3, MLKL” in English, respectively. The titles and abstracts of each document were read for preliminary screening, and 56 documents were finally selected for generalization and analysis. RESULTS AND CONCLUSION: (1) The main pathogenesis of periodontitis is that periodontal pathogenic bacteria stimulate the organism, leading to changes in the periodontal microenvironment, breaking the original immune balance and releasing a variety of inflammatory factors, triggering an inflammatory response resulting in destruction of periodontal tissues. Necroptosis can modulate the immuno-inflammation in periodontal tissues, thus affecting the development of periodontitis. (2) The occurrence of necroptosis is related to a variety of proteins, signaling pathways, and signaling molecules. Animal experiments have confirmed that the expression of phosphorylated mixed lineage kinase domain-like protein (pMLKL) is related to the degree of inflammation, and RIP3 and pMLKL are highly expressed in the periodontal tissues of mice suffering from periodontitis. Blocking the RIP3/MLKL pathway is conducive to the reduction of inflammation in periodontal tissues and the control of periodontitis progression. (3) To explore whether pMLKL can be used as a diagnostic indicator of periodontitis is of great value in the prevention, diagnosis and treatment of periodontitis. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism. Under non-physiological conditions, mitophagy breaks the balance of bone metabolism and triggers metabolism disorders, which affect osteoblasts, osteoclasts, osteocytes, chondrocytes, bone marrow mesenchymal stem cells, etc. OBJECTIVE: To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS: PubMed, Web of Science, CNKI, WanFang and VIP databases were searched by computer using the keywords of “mitophagy, bone metabolism, osteoblasts, osteoclasts, osteocytes, chondrocytes, bone marrow mesenchymal stem cells” in English and Chinese. The search time was from 2008 to 2023. According to the inclusion criteria, 90 articles were finally included for review and analysis. RESULTS AND CONCLUSION: Mitophagy promotes the generation of osteoblasts through SIRT1, PINK1/Parkin, FOXO3 and PI3K signaling pathways, while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways. Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue. Mitophagy improves the function of chondrocytes through PINK1/Parkin, PI3K/AKT/mTOR and AMPK signaling pathways. Modulation of mitophagy shows great potential in the treatment of bone diseases, but there are still some issues to be further explored, such as different stages of drug-activated mitophagy, and the regulatory mechanisms of different signaling pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Multiple studies have confirmed that mitogen-activated protein kinase (MAPK) signaling pathway is involved in cell proliferation, and microRNA (miR) is involved in the occurrence and development of hypertrophic scars. Therefore, the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE: To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS: The primary fibroblasts were isolated and collected from the skin samples. The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence. The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR. The target genes of hsa-miR-27a-3p were predicted using the database, and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes. There were seven groups: blank control, negative control, miR-27a-3p mimic, miR-27a-3p inhibitor, miR-27a-3p mimic+p38 MAPK inhibitor, miR-27a-3p mimic+extracellular regulated protein kinase inhibitor, miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor. Western blot was used to detect the levels of extracellular regulated protein kinase, c-Jun N-terminal kinase inhibitor. and p38 kinase and their phosphorylation levels. Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION: Compared with normal skin fibroblasts, hypertrophic scar fibroblasts had stronger proliferative activity (P < 0.05) and faster proliferation level (P < 0.001). Compared with normal skin, miR-27a-3p was highly expressed in hypertrophic scars (P < 0.001). Compared with the negative control group, overexpression of miR-27a-3p could promote cell proliferation activity (P < 0.001) and proliferation levels (P < 0.001). Compared with the negative control group, knockdown of miR-27a-3p could inhibit the proliferation activity (P < 0.05) and proliferation levels (P < 0.001). Compared with the negative control group, overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase (P < 0.05). Compared with the negative control group, knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase, c-Jun N-terminal kinase, and p38 MAPK (P < 0.05). Compared with the miR-27a-3p mimic group, specific inhibitors of extracellular regulated protein kinase, c-Jun N-terminal kinase, and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity (P < 0.01) and proliferation level (P < 0.001) of fibroblasts. To conclude, these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate protective effect of wogonin on myocardial ischemia/reperfusion (MI/R) injury in rats, and to analyze its potential mechanism. Methods: SD rats were randomly separated into sham operation group, MI/R group, trimetazi- dine group (10 mg/kg), wogonin low, medium and high doses groups (5, 10, 20 mg/kg), with 12 rars per group. MI/R model was established by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h. Echocardiography was applied to detect cardiac function in rats, ELISA was applied to detect activities of serum lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and levels of TNF-a, 1L-6 and IL-l(i in rats; TTC staining was applied to detect myocardial infarct size; HE staining was applied to detect myocardial histo pathological changes; TUN EL staining was applied to detect apoptosis level of cardiomyocytes; immunohistochemistry (IHC) method was applied to detect expression of nuclear factor-KB (NF-KB) p65 in myocardial tissue; Western blot was applied to detect myocardial apoptosis and expressions of NF-KB/mitogen-activated protein kinase (MAPK) pathway- related proteins. Results:Compared with sham operation group, LVESD, LVEDD, serum CK-MB and LDH activities, levels of IL-6, IL-1β and TNF-α, myocardial infarction area percentage, myocardial cell apoptosis rate, protein level of Bax, expression of nuclear NF-κB p65, and Cleaved-Caspase-3/Caspase-3, p-P38 MAPK/P38 MAPK in MI/R group were obviously increased, EF, FS and protein levels of Bcl-2 were obviously decreased (P<0.05), myocardial fibers were disordered, and a large number of inflammatory cells were infiltrated; compared with MI/R group, LVESD, LVEDD, serum CK-MB and LDH activities, levels of IL-6, IL-1β and TNF-α, myocardial infarction area percentage, myocardial cell apoptosis rate, protein level of Bax, expression of nuclear NF-KB p65, and Cleaved-Caspase-3/Caspase-3 and p-P38 MAPK/P38 MAPK in trimetazidine group and wogonin high, medium and low doses groups were obviously decreased, EF, FS and protein levels of Bcl-2 were obviously increased (P<0.05), myocardial inflammatory cell infiltration and muscle fiber fragmentation were reduced in a dose-dependent manner. Conclusion: Wogonin may improve MI/R injury in rats by inhibiting NF-κB/MAPK signaling pathway, inhibiting inflammatory response and cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: According to research methods of data mining and network pharmacology, to probe into the medication rules and mechanism of ancient traditional Chinese medicine prescription in the treatment of coronary heart disease from the theory of “ Stasis Toxin”, and to explore its core traditional Chinese medicine group and mechanism of action. METHODS: The ancient prescriptions extracted from the literature database were data-mined by using the Cloud Platform of Ancient and Modern Medical Cases, and the core group of traditional Chinese medicines was extracted. The mechanism in the treatment of coronary heart disease was investigated by network pharmacology. RESULTS: Totally 208 ancient prescriptions were extracted. Among them, the top three ranked by frequency of traditional Chinese medicines were Angelicae sinensis radix, Chuanxiong rhizoma, and Panax ginseng C. A. Mey. The four Qi contained warmth, calmness, slight coldness, coldness, and slight warmth. The five flavors were mainly pungent, bitter, and sweet, with the liver meridian and the spleen meridian as the main meridian. The core group of traditional Chinese medicine was Panax ginseng C. A. Mey, Angelicae sinensis radix, and Chuanxiong rhizoma. There were 28 traditional Chinese medicine active components, 685 traditional Chinese medicine active component targets, 1 450 disease targets and 190 common targets in the core group of traditional Chinese medicine. There were 40 core targets, including interleukin 6, tumor necrosis factor, protein kinase B1 and PPARG. Angelicae sinensis radix-Panax ginseng C. A. Mey-Chuanxiong rhizoma plays a role in the treatment of coronary heart disease through multiple pathways. CONCLUSIONS: Ancient prescription in the treatment of coronary heart disease from the theory of “Stasis Toxin” plays a role in the treatment of coronary heart disease through multi-components, multi-targets and multi-pathways, and its mechanism has similarities with the “ Theory of Stasis Toxin” and “ Theory of Inflammation” in modern research, which provides reliable theoretical basis for future related research. [ABSTRACT FROM AUTHOR]

Background and objective Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs. In this study, we constructed a clinically relevant PC-9 EGFRD19/T790M/C797S cellular model featuring the mutation type within the EGFRD19/T790M/C797S. This model aims to investigate the inhibitory effects of small-molecule EGFR-TKIs and to provide a cellular platform for developing a new generation of innovative drugs that target resistance associated with EGFR mutations. Methods Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology was employed to knock in the EGFRT790M/C797S mutant fragment into NSCLC PC-9 cells, originally harboring the EGFRD19 mutation, to generate the PC-9 EGFRD19/T790M/C797S cell model. This model, with the EGFRD19/T790M/C797S mutant, was used to investigate the inhibitory effects of EGFR-TKIs on cell proliferation through MTS assay. Additionally, Western blot analysis was conducted to assess the regulation of EGFR protein expression and the phosphorylation levels of downstream signaling molecules, including protein kinase B (AKT) and mitogen-activated protein kinase (MAPK). Results PC-9 EGFRD19/T790M/C797S cells, with the EGFRD19/T790M/C797S mutation, were successfully generated using CRISPR/Cas9 technology. In terms of proliferation inhibition, the marketed first-, second-, and third-generation EGFR-TKIs that were ineffective against the EGFRD19/T790M/C797S mutation showed weak proliferation inhibitory activity against this cell line, and the proliferation inhibition (half maximal inhibitory concentration, IC50)>1000 nmol/L; in contrast, the fourth-generation EGFR-TKIs in development, which have better efficacy against the EGFRD19/T790M/C797S mutation, showed strong proliferation inhibition in this cell model. On mechanistic validation, the first-, second-, and third-generation EGFR-TKIs had weak inhibitory activity on the phosphorylation of EGFR and the downstream AKT/MAPK signaling pathway in this cell line, whereas the fourth generation of EGFR-TKIs under development significantly inhibited the phosphorylation of EGFR and the downstream AKT/MAPK signaling pathway in this cell line. Conclusion Using CRISPR/Cas9 technology, the EGFRT790M/C797S mutant fragment was successfully knocked into PC-9 cells to create cell lines harboring the EGFRD19/T790M/C797S mutation. The study demonstrated that the EGFR-TKIs showed different sensitivities to whether the EGFRD19/T790M/C797S mutation was effective or not and different inhibitory effects on the phosphorylation of EGFR and downstream pathways, which demonstrated that this cell line depended on the activation of the EGFRD19/T790M/C797S mutation and EGFR/AKT/MAPK signaling pathway for proliferation. This study provides a clinically relevant cellular evaluation and mechanism validation system for the development of a new generation of innovative drugs targeting EGFR mutation resistance. [ABSTRACT FROM AUTHOR]

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Chongqing Medical University is the property of Journal of Chongqing Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Dermatovenereology is the property of Xi'an Jiaotong University Periodicals Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Henan Agricultural Sciences is the property of Editorial Board of Journal of Henan Agricultural Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate the effect of wogonin (WOG) on hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis by regulating adenosine monophosphate-activated protein kinase (AMPK)/NOD-like receptor protein 3 (NLRP3) signaling pathway. Methods: H9C2 cells were divided into Control group (normal culture), H/R group (H/R induction), L (low dose)-WOG group, M (medium dose)-WOG group, H (high dose)-WOG group (40, 80, 120 µmol/L WOG were added on the basis of H/R induction), WOG+Compound C group (10 µmol/L AMPK inhibitor Compound C was added on the basis of H-WOG group). The effect of WOG on the proliferation of H9C2 cells was detected by methyl thiazolyl tetrazolium (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining. The effect of WOG on apoptosis of H9C2 cells was detected by flow cytometry. The levels of serum oxidative stress indexes [malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD)] and inflammatory factors [interleukin (IL)-1B, IL-18] in H9C2 cells were detected by enzyme-linked immunosorbent assay (ELISA). The expression of AMPK, NLRP3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in H9C2 cells was detected by Western blot (WB). Results: The optical density (OD), EdU positive cell rate, SOD, AMPK and Bcl-2 of H9C2 cells in H/R group were lower than those in Control group, and the apoptosis rate, IL-1B, IL-18, ROS, MDA, NLRP3 and Bax were higher than those in Control group (P<0.05). Compared with H/R group, OD490, EdU positive cell rate, SOD, AMPK and Bcl-2 expression in L-WOG group, M-WOG group and H-WOG group increased, while apoptosis rate, IL-1B, IL-18, ROS, MDA, NLRP3 and Bax decreased (P<0.05). The OD, EdU positive cell rate, SOD, AMPK and Bcl-2 in WOG+Compound C group were lower than those in H-WOG group, and the apoptosis rate, IL-1B, IL-18, ROS, MDA, NLRP3 and Bax expression were higher than those in H-WOG group (P<0.05). Conclusion: WOG can inhibit H/R-induced cardiomyocyte apoptosis, which may be relate to the AMPK/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To discuss the protective effect of carnosine (CAR) against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced astrocyte (AS) injury, and to clarify its possible mechanism. Methods: The AS were divided into control group, model group (OGD/R group), OGD/R+CAR group (CAR group), and OGD/R+CAR+AMP-activated protein kinase (AMPK) activator AICAR group (CAR+AICAR group). MTT assay and green cyanine staining method were used to detect the survival rates and green cyanine staining positive rates of the AS in various groups; Annexin Ⅴ-FITC/PI method and flow cytometry were used to detect the apoptotic rates of the AS in various groups; Western blotting method was used to detect the expression levels of AMPK, phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), microtubule-associated protein light chain 3B (LC3B), Beclin-1, and P62 proteins in the AS in various groups; immunofluorescence staining was used to observe the LC3B positive fluorescence intensities in the AS in various groups. Results : Compared with control group, the survival rate and green cyanine staining positive rate of the AS in OGD/R group were decreased (P<0. 01), the apoptotic rate of the AS was increased (P< 0. 01), the ratios of p-AMPK/AMPK and LC3BⅡ/LC3BⅠ and the expression level of Beclin-1 protein were increased (P<0. 01), and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased (P<0. 01). Compared with OGD/R group, the survival rate and green cyanine staining positive rate of the AS in CAR group were increased (P<0. 01), the apoptotic rate of the AS was decreased (P<0. 01), the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were decreased (P<0. 01), and the ratio of p-mTOR/mTOR and the expression level of P62 protein were increased (P<0. 01). Compared with CAR group, the survival rate and green cyanine staining positive rate of the AS in CAR+AICAR group were decreased (P<0. 01), the apoptotic rate of the AS was increased (P<0. 01), the ratios of p-AMPK/AMPK and LC3B Ⅱ/ LC3BⅠ and the expression level of Beclin-1 protein were increased (P<0. 01), and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased (P<0. 01). The LC3B immunofluorescence staining results were consistent with the Western blotting results. Conclusion: CAR has the protective effect on injury of the AS induced by OGD/R, and its molecular mechanism may be related to the inhibition of the AMPK/mTOR signaling pathway, thereby inhibiting autophagy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim To investigate whether SIRT6 overexpression inhibits angiotensin Ⅱ (AngⅡ)-induced cardiomyocyte apoptosis by activating adenosine 5′-monophosphate-activated protein kinase / nuclear factor erythroid 2-related factor 2 / heme oxygenase-1(AMPK/ Nrf2 / HO-1) signaling pathway. Methods The experiment was divided into 4 groups: control group, AngⅡ group,AngⅡ+SIRT6 group, AngⅡ+empty vector (EV) group. The mRNA level of SIRT6 was detected by RT-PCR. The cell activity was measured by MTT assay. The cell apoptosis was analyzed by flow cytometry. SIRT6, cardiomyocyte apoptosis related proteins (Bax, cleaved Caspase-3, Bcl-2), DNA damage related proteins (γ-H2AX, p-ATM), AMPK/ Nrf2 / HO-1 signaling pathway related proteins (p-AMPK, Nrf2, HO-1) were measured by Western blot. The reactive oxygen species (ROS) content was determined by DCFH-DA staining. The changes of the above indexes among the groups were observed. Results Compared with control group, the mRNA and protein expression levels of SIRT6 and cell activity were significantly decreased in AngⅡ group. Apoptosis rate, the expressions of Bax, cleaved Caspase-3 were increased, and the expression of Bcl-2 was decreased. The expressions of γ-H2AX and pATM were increased, and the expressions of p-AMPK, Nrf2, HO-1 were decreased. The activity of ROS was increased (P<0. 01). Compared with AngⅡ+EV group, the expression of SIRT6 and cell activity were significantly increased in AngⅡ+SIRT6 group. Apoptosis rate, the expressions of Bax and cleaved Caspase-3 were decreased, and the expression of Bcl-2 was increased. The expressions of γ-H2AX and p-ATM were decreased, the expressions of p-AMPK, Nrf2, HO-1 were increased. The activity of ROS was decreased (P<0. 01). Conclusion SIRT6 overexpression inhibits AngⅡ- induced cardiomyocyte apoptosis through activation of AMPK/ Nrf2 / HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Abnormal activation of osteoclasts plays an important role in the bone destruction due to spinal tuberculosis. During the pathogenesis of osteoporosis, miR-155 knockdown activates adenosine phosphate-dependent protein kinase (AMPK) by increasing the expression of leptin receptors, thereby inhibiting osteoclast differentiation and bone resorption. However, the role of miR-155/leptin receptor(LEPR)/AMPK axis in the bone destruction due to spinal tuberculosis remains unclear. OBJECTIVE: To investigate the role and mechanism of miR-155/LEPR/AMPK axis in tuberculin-induced osteoclast formation. METHODS: RAW264.7 cells were cultured and treated with different concentrations of purified protein derivative (PPD) (1.0, 2.5, 5.0, 10.0 IU/mL) and transfected with negative control (NC) sequence or miR-155 inhibitor, NC siRNA sequence or LEPR siRNA sequence. Tartrate resistant acid phosphatase staining was used to detect the number of osteoclasts. Fluorescence quantitative PCR was used to detect the expression of miR-155. Western blot was used to detect the expression of LEPR and p-AMPK. Double luciferase reporter gene was used to verify miR-155 targeting LEPR. RESULTS AND CONCLUSION: Compared with the control group, the number of osteoclasts and the expression level of miR-155 significantly increased, while the expression level of LEPR and p-AMPK significantly decreased in 2.5, 5.0, and 10.0 IU/mL PPD groups (P < 0.05). Compared with NC+5.0 IU/mL PPD group, the number of osteoclasts and the expression level of miR-155 significantly decreased, while the expression level of LEPR and p-AMPK significantly increased in the miR-155 inhibitor+5.0 IU/mL PPD group (P < 0.05). Compared with the NC group, the fluorescence activity of LEPR wild-type double luciferase reporter gene was increased in the miR-155 inhibitor group, and decreased in the miR-155 mimic group (P < 0.05). Compared with si-NC+miR-155 inhibitor+5.0 IU/ mL PPD group, the expression level of miR-155 had no significant change, the number of osteoclasts significantly increased, and the expression levels of LEPR and p-AMPL significantly decreased in si-LEPR+miR-155 inhibitor+5.0 IU/mL PPD group (P < 0.05). To conclude, tuberculin can induce osteoclast formation by increasing miR-155 expression and inhibiting downstream LEPR expression and AMPK activation. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a chronic pain condition caused by damage or dysfunction of the nervous system. Symptoms of neuropathic pain include spontaneous pain, hyperalgesia, and sensory abnormalities. AMP-activated protein kinase (AMPK) is a key energy regulator that maintains cellular homeostasis by modulating carbohydrate and lipid metabolism. Recent studies have highlighted its role in synaptic plasticity and glial cell function, suggesting that AMPK signaling pathways contribute to the onset and progression of neurological disorders. Investigations using animal models of neuropathic pain as well as clinical research have illustrated aberrations in AMPK expression and activity at various sites along sensory conduction pathways. Treatment with AMPK agonists has been shown to alleviate pain symptoms, suggesting that dysregulation of AMPK expression/function contributes to the development and persistence of neuropathic pain. Therefore, the development of analgesics targeting AMPK has garnered considerable attention worldwide. This article provides a comprehensive review of the mechanisms by which AMPK participates in neuropathic pain, with the aim of guiding the development of related analgesic drugs. [ABSTRACT FROM AUTHOR]

As the main staple food for over one-third of the world’s population, rice (Oryza sativa L.) is the crucial material foundation and guarantee for human survival and productivity. However, most of rice-producing regions are facing serious water scarcity issues, which severely restrict rice growth, leading to a sharp decrease in rice yield and posing a threat to food security. Therefore, studies of drought resistance mechanisms as well as breeding and application of water-saving and drought-resistant rice varieties are not only beneficial for utilizing freshwater resources in a sustainable manner, it also holds significant importance for ensuring food security. Breeders have screened and bred water-saving and drought-resistant varieties through the evaluation of morphological traits, physiological-biochemical and yield indexes, and even have promoted them. Researchers have identified many drought genes related to transcription factors, transport proteins, ubiquitin ligases, proteases and protein kinases by using genetic mapping, GWAS, expression profiling and multi-omics integrative analysis, indicating that drought resistance of rice is a complex quantitative trait controlled by multiple genes. They also demonstrated the mechanisms including hormone regulation, reactive oxygen scavenging, osmotic regulation, cuticular wax deposition and root architecture improvement. However, the number of water-saving and drought-resistant varieties cannot meet the urgent need for our country, the drought resistant genes are still need to be mined and demonstrated. In this article, we collected and reviewed literature related to rice drought resistance over the past two decades in China and abroad. And then summarized three types of conventional identification indexes for rice drought resistance, and comprehensively analyzed the latest progress of important mechanisms and key genes (QTLs) for rice drought resistance. [ABSTRACT FROM AUTHOR]

[Objective] Trehalase (Tre) is a key enzyme in trehalose metabolism of Conopomorpha sinensis Bradley, which plays an important role in energy metabolism and growth development by specifically hydrolyzing trehalose into glucose. The study aims to clone two trehalase genes (CsTre1 and CsTre2) from Conopomorpha sinensis Bradley, to clarify its expression patterns in different developmental stages and tissues, and to analyze the molecular characteristics of the two genes and their enzyme proteins.[Method] Based on the transcriptome data of C. sinensis, the full-length cDNA sequences of CsTre1 and CsTre2 were cloned with the rapid amplification of cDNA ends (RACE)-PCR. Bioinformatics analysis was performed with software such as ORF Finder, ProtParam, SignalP 4.1, ProtScale, NetPhos2.0 Server and IQ TREE. The mRNA expression patterns of CsTre1 and CsTre2 in different developmental stages and tissues of C. sinensis were detected by using real-time quantitative PCR (RT-qPCR).[Result] The open reading frame of CsTre1 was 1 701 bp, encoding 566 amino acids, and the protein molecular weight was 64.53 kD. The open reading frame length of CsTre2 was 1 821 bp, encoding 606 amino acids, and the protein molecular weight was 69.08 kD. Signal peptide prediction analysis showed that both front-ends of CsTre1 and CsTre2 had a signal peptide, with positions of 1-16 and 1-17, respectively. The analysis on the secondary structure of the sequence showed that both CsTre1 and CsTre2 were mainly composed of α-helix and random coil, CsTre1 had 24 Sers, 15 Tyrs, and 10 Thrs that may serve as binding sites for protein kinases, while CsTre2 had 27 Sers, 10 Tyrs, and 13 Thrs that may serve as binding sites for protein kinases. The RT-qPCR results revealed that CsTre was expressed throughout all developmental stages of C. sinensis. In the expression pattern of adult stage, the expression level of CsTre1 was much higher than that of CsTre2, and the expression level of male adults of CsTre1 dropped sharply after the fourth day.[Conclusion] The study successfully cloned two trehalose genes of Conopomorpha sinensis Bradley. According to the results of analysis on their molecular characteristics and expression patterns, CsTre1 may be the main gene regulating trehalose metabolism in Conopomorpha sinensis Bradley. The research results provide important clues for elucidating the function of trehalase genes, which lay a solid foundation for the development pest control strategies. [ABSTRACT FROM AUTHOR]

Objective To detect the level of related indexes of energy metabolism in liver tissue of alcoholic liver disease (ALD) mice, and to explore the intervention effect of Gehua Jiejiu Dizhi Decoction.Methods Forty male C57BL/6J mice were randomly divided into the normal control group, the model group, the Gehua Jiejiu Dizhi Decoction high-dose group (4.94 g/kg), the Gehua Jiejiu Dizhi Decoction low-dose group (2.47 g/kg), and the resveratrol group (0.40 g/kg), with 8 mice in each group.Except the normal control group, the mice in other groups were fed with Lieber-DeCarli control liquid diet for five days, followed by Lieber-DeCarli alcohol liquid diet for ten days, and on the 16th day, the mice were given 31.5%alcohol solution through gavage to establish the ALD model.From the second day after modeling, the rats in the intervention groups were given the corresponding drugs by gavage once a day for nine consecutive days.Hematoxylin and eosin staining and oil red O staining were used to observe the liver steatosis in liver tissue.The activities of Na+K+-ATPase and Ca2+Mg2+-ATPase, and the contents of succinate dehydrogenase (SDH) and hepatic glycogen in liver tissue were detected using spectrophotometry.The contents of ATP, ADP, AMP, the AMP/ATP value, total adenosine pool (TAN) content, and energy charge (EC) in liver tissue were detected by reversed phase high performance liquid chromatography method.The mRNA expressions of NAD dependent deacetylase Sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) a2 in liver tissue were detected by real-time PCR.The protein expressions of SIRT1, AMPKa2, and AMPKTNF-β1 in liver tissue were detected by Western blotting.Results Compared with the normal control group, the model group mice showed significant hepatic steatosis, significantly decreased Ca2+Mg2+-ATPase activity and SDH content in liver tissue, significantly increased hepatic glycogen content, significantly decreased EC and AMP/ATP value, significantly increased ATP, ADP, AMP, and TAN content, significantly decreased mRNA expressions of SIRT1 and AMPKa2, significantly increased protein expression of AMPKTNF-β1 (P < 0.05). Compared with the model group, the Gehua Jiejiu Dizhi Decoction high-and low-dose groups significantly reduced liver tissue steatosis, and the activity of Na+K+-ATPase in liver tissue was significantly reduced, the EC and the mRNA expressions of SIRT1 and AMPKa2 were increased (P < 0.05); the activity of Ca2+Mg2+-ATPase, SDH and ATP contents were increased in the Gehua Jiejiu Dizhi Decoction low-dose group (P < 0.05); the AMP/ATP value was increased in the Gehua Jiejiu Dizhi Decoction high-dose group (P < 0.05); and the protein expression of SIRT1 was increased in the the Gehua Jiejiu Dizhi Decoction high-and low-dose groups and the resveratrol group (P < 0.05); the protein expression of AMPKa2 in the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group was increased (P < 0.05). Compared with the Gehua Jiejiu Dizhi Decoction high-dose group, the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group showed a significant increase in ATP, TAN contents, and EC in liver tissue, while the AMP/ATP value decreased (P < 0.05); mRNA expressionin of AMPKa2 in the Gehua Jiejiu Dizhi Decoction low-dose group was decreased (P < 0.05); and the protein expressions of SIRT1 and AMPKa2 in the resveratrol group were increased (P < 0.05). Compared with the Gehua Jiejiu Dizhi Decoction low-dose group, the protein expression of AMPKTNF-β1 was decreased in the resveratrol group (P < 0.05). Conclusion The changes of energy metabolism caused by chronic alcohol intake may be related to the occurrence of ALD, and the intervention of Gehua Jiejiu Dizhi Decoction can improve the abnormal energy metabolism in the liver of ALD mice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Reactive oxygen species may be closely related to the occurrence and development of tendinopathy, but its exact role and related signal transduction mechanism have not been fully summarized. OBJECTIVE: To review current clinical or preclinical original studies, summarize the role of reactive oxygen species in tendinopathy and related signal transduction pathways and to explore its characteristics and whether there is a unified downstream pathway. METHODS: Relevant original studies in PubMed, Embase, Web of Science, as well as CNKI, WanFang, and VIP databases were searched by computer and the search results were screened and excluded according to the inclusion criteria. Ninety articles were finally included for review and analysis. RESULTS AND CONCLUSION: Reactive oxygen species affects the direction of tendon healing by simultaneously acting on tendon cells and the extracellular matrix, and it exhibits a bifacial effect in the treatment of tendinopathy. Concentration of reactive oxygen species may be the key to determining its direction of action. The possibility that low-dose reactive oxygen species can participate in the normal physiological healing of tendons or that tendon tissues are adaptive to stimulations may be the underlying mechanism that produces this characteristic effect. Reactive oxygen species affect the composition and structure of the extracellular matrix and normal tendon repair as well as maintain viability in response to external stimulations through matrix metalloproteinases, mitogenactivated protein kinases, mitochondrial apoptosis, the forkhead transcription factor O family, autophagy, inflammation, and antioxidant signaling pathways. Different reactive oxygen species stimulation intensities, durations, and external environments may cause different alterations in downstream molecular pathways and thus have different effects on the tendon. Due to the large gap in the number of literature included in the evaluation of the positive and negative effects of reactive oxygen species, it may cause some analytical error in the search for factors behind the characteristics of the action of reactive oxygen species in tendon. In addition, most experimental intervention conditions and results of interest are relatively homogeneous; therefore, the temporal and quantitative mechanisms of reactive oxygen species and the synergistic effects with other intervention factors have not been clarified, and the overall system of molecular actions of reactive oxygen species in tendinopathy has not been constructed. To conclude, reactive oxygen species might be involved in the treatment and prevention of tendinopathies as a beneficial factor in the future, and facilitate the exploration of oxidative stress signaling pathways and overall molecular action systems in tendinopathies thereafter, as well as lay the foundation for research on the therapeutic strategies of different antioxidants in tendinopathies to better prevent and treat tendon injury and degeneration. [ABSTRACT FROM AUTHOR]

Objective: To investigate effect of acacetin on alveolar epithelial cell damage caused by Streptococcus pneumoniae (SP) infection by regulating sirtuin 1 (Sirtl)-mediated 5'-AMP activated protein kinase (AMPK)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway. Methods: Alveolar epithelial cells A549 cultured in vitro were infected with SP to establish a cell damage model. After treatment with acacetin at final concentrations of 0, 5, 25, 50, 100, 150, 200 µmol/L, CCK-8 was performed to detect cell viability of each treatment group and optimal concentration of acacetin was screened. A549 cells cultured in vitro were randomly separated into five groups: control group, model group, acacetin (150 µmol/L) group, EX527 (Sirtl inhibitor, 40 µmol/L) group, acacetin (150 µmol/L) +EX527 (40 (JLmol/L) group, control group was not treated, other groups were infected with SP to establish a cell damage model, and then treated with 150 µmol/L acacetin and 40 µmol/L EX527, CCK-8 and flow cytometry were performed to measure cell viability and apoptosis rate in each group; kits were performed to measure levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH) and IL-10, IL-1 β, TNF-α levels of cells in each group; Western blot was performed to measure proliferation-related proteins Ki-67, proliferating cell nuclear antigen (PCNA), apoptosis-related proteins caspase-9, Bax, Sirt1 and AMPK/Nrf2 signaling pathway proteins p-AMPK/AMPK, Nrf2 expressions of cells in each group. Results: Model group had decreased A549 cell viability, SOD and IL-10 levels, p-AMPK/AMPK, Sirtl, Nrf2, Ki-67 and PCNA protein expressions (P<0.05), and increased apoptosis rate, MDA, LDH, ROS, IL-1β and TNF-α levels than control group (P<0.05). Compared with model group and acacetin+EX527 group, acacetin group had increased A549 cell viability, SOD and IL-10 levels, p-AMPK/AMPK, Sirt1, Nrf2, Ki-67 and PCNA protein expressions (P<0.05), and decreased apoptosis rate, MDA, LDH, ROS, IL-1β and TNF-α levels (P<0.05) ; EX527 group had decreased A549 cell viability, SOD and IL-10 levels, p-AMPK/AMPK, Sirtl, Nrf2, Ki-67 and PCNA protein expressions (P<0.05), and increased apoptosis rate, MDA, LDH, ROS, IL-1β and TNF-α levels (P<0.05). Conclusion: Acnestin can activate AMPK/Nrf2 signaling by up-regulating Sirt1 expression, thereby promoting secretion of anti-inflammatory factors, reducing production of ROS and pro-inflammatory factors, reducing inflammation and oxidative stress, and finally alleviating neuronal damage. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of resveratrol on apoptosis of chondrocytes in rats with knee osteoarthritis (KOA) through autophagy mediated by silent information regulator 1 (SIRT1)/adenylate activated protein kinase (AMPK) signaling pathway. Methods: Fifty healthy Wistar rats were randomly separated into control group, model group, resveratrol group, resveratrol+ SIRT1 inhibitor group, and autophagy activator group, with 10 rats per group. Except for the control group, the other rats were injected with Freund's complete adjuvant to establish the KOA rat model, resveratrol group, resveratrol+AMPK inhibitor group, and autophagy activator group were treated with 10 µmol/kg resveratrol, 10 µmol/kg resveratrol+10 mg/kg EX527, 2 mg/kg rapamycin, respectively. After 4 weeks, the grade of Lequesne MG knee joint of rats were observed; the levels of IL-6 and tumor necrosis factor-β (TNF-β) in rat knee joint fluid were measured; HE staining and TUNEL staining were used to observe the morphology and apoptosis of rat knee cartilage; transmission electron microscope was used to observe the autophagy in rat chondrocytes; Western blot was performed to determine the protein expressions of SIRT1, p-AMPK, AMPK, LC3 and Beclin-1. Results: Compared with control group, the local reaction, gait reaction, joint activity, and joint swelling of model group were increased; compared with model group, the local response, gait response (P<0.05), joint activity, and joint swelling in resveratrol group and autophagy activator group were reduced (P<0.05). Compared with control group, the cartilage tissue cells in model group were disordered and rough, with fibrotic degeneration, marginal humeral bulge, reduced organelles, and vacuolar degeneration, the number of autophagosomes was increased, the levels of IL-6 and TNF-β in knee joint fluid, chondrocyte apoptosis rate, Beclin-1 and LC3B/A were increased (P<0.05), the SIRT1 and p-AMPK/AMPK in cartilage tissue were decreased (P<0.05) ; compared with model group, resveratrol group and autophagy activator group showed improvement in the disordered arrangement of cartilage tissue cells and the marginal humeral bulge, the number of autophago-somes was increased, the levels of IL-6 and TNF-β in knee joint fluid, and the apoptosis rate of chondrocytes were decreased (P< 0.05), the levels of SIRT1, p-AMPK/AMPK, Beclin-1 and LC3B/A in cartilage tissue were increased (P<0.05) ; SIRT1 inhibitor could reverse the protective effect of resveratrol group on rat chondrocytes. Conclusion: Resveratrol maybe autophagic KOA rat chon-drocyte apoptosis mediated by activating SIRT1/AMPK pathway, which can be reversed by SIRT1 inhibitor. [ABSTRACT FROM AUTHOR]

Chronic inflammation is the pathological basis for the development of cardiovascular diseases. Immune cells dominated by T cells can secrete pro-inflammatory factors to mediate inflammation and affect the progress of cardiovascular diseases. The co-stimulatory signals is the second signal of T cell activation, which can enhance or inhibit the signal transmission of T cell antigen receptor (TCR) by Phosphatidylinositol 3-kinase (PI3K), mitogen activated protein kinase (MAPK) and C-Jun N-terminal kinases (JNK), which play an important role in cardiovascular disease by regulating T cell immune function, the release of inflammatory cytokines, and the production of extracellular matrix. This article describes the transmission mechanism of costimulatory signals and their correlation with cardiovascular diseases, in order to provide new ideas for immunotherapy of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of Toll-like receptor 4 (TLR4) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) in decidua tissue of patients with unexplained spontaneous abortion and their correlation. Methods: The expressions of TLR4, ERK1/2 and p-ERK1/2 in decidua tissues of 32 patients with unexplained spontaneous abortion (abortion group) and 32 normal pregnancy (control group) were detected by immunohistochemistry and Western blot, respectively. The correlation between TLR4 and p-ERK1/2 in abortion group were analyzed by Pearson hierarchical correlation analysis. Results: In immunohistochemical experiments, the cytoplasm of decidua cells in the two groups is the expression locus of TLR4, ERK1/2 and p-ERK1/2, the expression of the three proteins were different, and the expressions of TLR4 and p-ERK1/2 in abortion group were significantly higher than that in control group (P<0.01). There was no significant difference in ERK1/2 expression between abortion group and control group (P> 0.05 ); In decidua tissue samples of abortion group, the protein level of TLR4 was higher than that of control group (P<0.05) ; the protein level of p-ERK1/2 was significantly higher than that of control group (P<0.01), and the protein level of ERK1/2 in decidua tissue of abortion group was not statistically different from that of control group (P>0.05). TLR4 was positively correlated with p-ERK1/2 expression in abortion group (r=0.890, P<0.01). Conclusion: Abnormal activation of TLR4/ERK1/2 signaling pathway may be one of the mechanisms of unexplained spontaneous abortion. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AimTo investigate the effect of butorphanol on neuronal pyroptosis in ischemic stroke rats and its role in protein kinase A (PKA) / cyclic adenosine phosphate (cAMP) response element binding protein (CREB). Methods A rat model of ischemic stroke was established using SD rats. All rats were divided into control group, model group, butorphanol low-dose group (butorphanol L group), butorphanol high-dose group (butorphanol H group) and butorphanol+ PKA inhibitor (H-89) group. Neurological function was scored, TTC staining was used to detect cerebral infarction volume, and pathological characteristics of brain tissue were detected by HE staining. Neuronal pyroptosis was observed by uranium lead double staining in hippocampus. The expression of inflammassome NOD-like receptor thermal protein domain associated protein 3(NLRP3) and Caspase-1 were detected by immunofluorescence, and the contents of interleukin-1β (IL-1β), IL-18 and cAMP were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of phosphorylated PKA (p-PKA), PKA, p-CREB and CREB protein were detected by Western blot. Results Compared with the control group, the brain space of rats in the model group was enlarged, the neuron cell membrane was defective, the nucleus and nuclear membrane were sunken and constricted, and the nerve function scores, cerebral infarction volume, NLRP3, Caspase-1, IL-1β and IL-18 levels were increased; the expression levels of cAMP, p-PKA/PKA and p-CREB/CREB protein were decreased (P<0. 05). Compared with the model group, the brain structure of butorphanol L and H groups was more complete, the neuronal cell structure was improved, the neural function scores, cerebral infarction volume, NLRP3, Caspase-1, IL-1β and IL-18 levels were decreased, and the protein expression levels of cAMP, p-PKA/PKA and p-CREB/CREB were increased (P<0. 05). Compared with butorphanol H group, butorphanol+H-89 group increased vacuolar degeneration of brain tissue, abnormal neuronal structure, neural function scores, cerebral infarction volume, NLRP3, Caspase-1, IL-1β and IL-18 levels; and the expression levels of cAMP, p-PKA/PKA and p-CREB/CREB protein were decreased (P<0. 05). Conclusion Butorphanol significantly inhibits neuronal pyroptosis in ischemic stroke rats, which may be related to the activation of PKA/CREB signaling pathway. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Bushen Yiqi Huayu granule has the effect of replenishing qi and eliminating blood stasis, tonifying kidney and smoothing collages, and is often used in the treatment of osteoporosis. At present, there are few studies on the effect of Bushen Yiqi Huayu granule on the callus angiogenesis of osteoporotic fractures. OBJECTIVE: To explore the mechanism of Bushen Yiqi Huayu granule by up-regulating extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK) signaling pathway to improve callus angiogenesis after fracturing in osteoporotic rats. METHODS: (1) Bone marrow mesenchymal stem cells from osteoporotic SD rats and bone marrow monocytes from C57BL/6 mice were collected. MTT assay was used to detect different doses of Bushen Yiqi Huayu granule on bone mesenchymal stem cell toxicity. Bone mesenchymal stem cells and bone marrow monocytes were cultured in the medium supplemented with 0 and 1.5 mg/mL Bushen Yiqi Huayu granules, respectively, and osteogenic differentiation and osteoclast differentiation were carried out in vitro. (2) 144 SD rats were randomly divided into sham operation group, model group, granule group and granule+PD98059 group with 36 rats in each group. The osteoporotic model was established in the model group, granule group and granule+PD98059 group, and only part of the adipose tissue near the ovary was removed in the sham operation group. 8 weeks later, all rats received left tibial osteotomy. In the granule+PD98059 group, 5 g/kg Bushen Yiqi Huayu granule was given intragastrically, and 0.3 mg/kg PD98059 was injected into the tail vein. The granule group was given 5 g/kg Bushen Yiqi Huayu granule, and the same volume of normal saline was injected into the tail vein. The sham operation group and model group were given an equal volume of normal saline, and the caudal vein was injected with an equal volume of normal saline. Drug administration was conducted once a day for 8 weeks. Fracture healing and callus angiogenesis were observed by X-ray, micro-computed tomography and microvascular perfusion angiography. Bone mineral density and mechanical strength of the callus were measured. The tibia was observed by hematoxylin-eosin staining and Masson staining. Western blot assay and immunohistochemistry were used to examine the expression of ERK/MAPK signaling pathway-related molecules. RESULTS AND CONCLUSION: (1) Compared with the 0 mg/mL group, the alkaline phosphatase activity, mineralization level, p-ERK1/2 and p-p38 MAPK expression levels of osteocytes increased (P < 0.05), while the density and volume of osteoclasts decreased in the 1.5 mg/mL group (P < 0.05). (2) Compared with the sham operation group, the fracture healing degree of the granule group was similar at 4 and 8 weeks, but there was no significant difference in LaneSandhu score, total callus volume, mineralized callus volume, mineralized callus volume/total callus volume, trabecular thickness, vascular number, spacing, thickness, vascular volume/total volume, bone mineral density, ultimate load of callus, stiffness, p-ERK1/2, p-p38 MAPK, p-IκB-α, and p-p65 expression levels (P > 0.05). In the model group and granule+PD98059 group, fracture healing was slow, Lane-Sandhu score, total callus volume, mineralized callus volume, mineralized callus volume/total callus volume, trabecular thickness, vascular number, thickness, vascular volume/total volume, bone mineral density, ultimate load of callus, stiffness, p-ERK1/2, p-p38 MAPK, p-IκB-α, and p-p65 expression levels decreased (P < 0.05), and vascular spacing increased (P < 0.05), compared with the sham operation group. (3) It is indicated that Bushen Yiqi Huayu granule can improve fracture healing, promote callus angiogenesis and alleviate the symptoms of osteoporosis by enhancing the expression of the ERK/MAPK signaling pathway-related molecules in osteoporotic rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circadian rhythms are closely related to the life activities of most mammals and insects. Timless gene plays a crucial role in the generation of circadian rhythms as key components encoding the Timeless/Period gene complex. However, its specific mechanism in circadian rhythms is still unclear. OBJECTIVE: To study the relationship between Timless protein gene, Period gene, circadian rhythm, environment and cryptochrome gene, so as to have a more comprehensive understanding of the nucleation and accumulation mechanism of circadian cycle and the influence of environment on circadian rhythm. METHODS: Literature retrieval was conducted in the Web of science Core Collection database, PubMed and CNKI, and the relevant literature was searched, consulted and screened after the keyword was set as "Timless, Period, circadian rhythm, environment" in English and Chinese. Non-relevant literature was progressively excluded through full-text reading, and 126 papers were finally included for the review. RESULTS AND CONCLUSION: In the circadian clock, the circadian spontaneous output of the cyclins kaput and CYCLE activate the Timeless/Period gene, Timeless gene regulates the nucleation mechanism and stability of Period gene, and Period gene can also be nucleated individually by a number of mechanisms. Casein kinase 2, Shaggy protein kinase and double time genes can regulate circadian rhythms and participate in transcription by phosphorylating Timeless gene/Period gene. Cryptochrome gene-mediated degradation of Timeless gene has a very important role in transcriptional integrity. External factors such as environmental factors and dietary patterns can influence circadian rhythms through the Timeless gene/Period gene. Interestingly, time-restricted eating can be used as an effective way to improve circadian rhythm disturbances. [ABSTRACT FROM AUTHOR]

Sestrin 3 （Sesn3） is a highly conserved stress-inducible protein that is stimulated during various stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum stress and inflammation, to protect organisms against different types of stimuli. Sesn3 is regulated by forkhead box O transcription factors, which activates both AMP-activated protein kinase and mammalian target of rapamycin complex 2（ mTORC2） and suppresses mTORC1. Moreover, Sesn3 can directly or indirectly scavenge reactive oxygen species to alleviate cellular oxidative damage. Sesn3 also plays an important role in the development of multiple diseases by participating in biological processes such as antioxidation, anti-aging, nutrient sensing, and maintenance of metabolic homeostasis. This study reviews the role of Sesn3 in cardiovascular and fatty liver diseases, diabetes mellitus, malignancies and epilepsy to explore novel concepts and potential therapeutic targets for addressing related diseases. [ABSTRACT FROM AUTHOR]

Mixed lineage kinase domain-like protein （MLKL） serves as the terminal effector in the necroptosis pathway. Upon phosphorylation by receptor-interacting protein kinase 3 （RIPK3）, MLKL translocates to the plasma membrane, compromising the membrane integrity, thus inducing lytic cell death. This process epitomizes the classical mechanism of MLKL-driven necroptosis. Additionally, MLKL possesses several non-necroptotic functions, such as the regulation of autophagy and endosomal transport. This review summarizes the structural characteristics of MLKL, its mechanism in mediating necroptosis and recent research advances in its non-necroptotic functions, as well as the diverse functionalities of MLKL in connection with its phosphorylation sites, subcellular location, and non-RIPK3-dependent activation pathways. [ABSTRACT FROM AUTHOR]

AIM: To investigate the role of inositol 1, 4, 5-trisphosphate receptor type 1（ IP3R1） in the regulation of calcium/calmodulin-dependent protein kinase II （CaMKII） and voltage-dependent anion channel 1 （VDAC1） in heroin （HE）-induced cardiomyocyte rhythm abnormalities. METHODS: In this study, we analysed arrhythmia microarray data by combining proteomics and Gene Expression Omnibus （GEO） to search for key regulators. Lentiviral vector with knockdown of IP3R1 gene was constructed, and used to infect neonatal rat cardiomyocytes （NRCMs）. The cells were divided into control group, HE group, and HE+shIP3R1 group. Crystal violet staining was used to observe the morphology of cardiomyocytes. Lactate dehydrogenase （LDH） and aspartate aminotransferase （AST） levels were detected by ELISA. Transmission electron microscopy was used to observe the morphological changes of mitochondria. Intracellular Ca2+ concentration was detected by Fluo-4/AM probe method. Intracellular reactive oxygen species （ROS） content was detected by DCFH-DA fluorescent probe. Mitochondrial membrane potential （MMP） level was detected by JC-1 staining method. Intracellular ATP level was detected by ATP assay kit. The interaction between IP3R1 and CaMKIIδ/VDAC1 was verified by co-immunoprecipitation （Co-IP） detection. The protein levels of IP3R1, CaMKIIδ and p-CaMKIIδ （T287） and VDAC1 were detected by Western blot. RESULTS: Combined with proteomics and gene expression profiling dataset GSE89410 analysis, 80 differentially co-expressed molecules were screened. Based on the results of Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis, the key factor IP3R1 was finally screened out, and IP3R1-binding proteins were obtained from the STRING database: CaMKIIδ and VDAC1. Moreover, the Co-IP results verified the interaction between IP3R1 and CaMKIIδ/VDAC1, and the interaction between IP3R1 and CaMKIIδ/VDAC1 was increased in the NRCMs after HE intervention. In vitro cellular experiments showed that compared with control group, the number of NRCMs in HE group was drastically reduced, the cell membrane was narrowed, the pseudopods were reduced, and the structure of the nucleus was blurred. The levels of both LDH and AST were significantly increased （P<0. 05）, and the mitochondrial ultrastructural damage was severe. It was confirmed that HE enhanced the cardiotoxic effects and mitochondrial damage in NRCMs. Compared with control group, intracardiomyocyte Ca2+ concentration, ROS levels, MMP, and IP3R1, p-CaMKIIδ （T287） and VDAC1 protein levels were significantly elevated in HE group（ P<0. 05） and significantly attenuated in HE+shIP3R1 group（ P<0. 05）, but the ATP level was the opposite. It was confirmed that silencing of IP3R1 attenuated cellular calcium overload and mitochondrial damage in NRCMs after HE intervention. CONCLUSION: The IP3R1 is involved in HE-induced cardiomyocyte rhythm abnormality by regulating CaMKII and VDAC1 to cause cardiomyocyte calcium overload and increased ROS production. [ABSTRACT FROM AUTHOR]

Objective.To investigate the impacts of chlorprothixene on autophagy and apoptosis in human acute myeloid leukemia (AML) cells by regulating the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Methods.Two cell lines, SKNO-1 and MOLM-13, were used as the research objects, and they were treated with (0, 20, 40, 60) μmol/L chlorprothixene for (6, 12, 24) h, respectively, CCK-8 was performed to detect cell proliferation.Experiments were divided into control group (normal culture), SC79 group (5 mg/L SC79 treated cells for 2 h),chlorprothixene group (40 μmol/L chloroprotixol treated cells for 12 h), chlorprothixene + SC79 group (40 μmol/L chlorprothixene was added to the cells for 12 h on the basis of the group), monodansylcadaverine (MDC) staining was performed to measure the occurrence of autophagy,flow cytometry was performed to measure cell apoptosis rate,Western blot was performed to measure autophagy-related protein SQSTM1/ p62, microtubule-related protein 1 light chain 3B (LC3B), apoptosis-related protein poly (ADP-ribosyltransferase) (PARP), aspartate-specific cysteine protease 3 (caspase3), activated caspase3 (cleaved caspase3) and Akt/mTOR signaling pathway related proteins Akt, phosphorylated (p)-Akt, mTOR and p-mTOR. Results.In SKNO-1 and MOLM-13 cells, at (6, 12, 24) h, compared with 0 μmol/L chlorprothixene, (20, 40, 60) μmol/L chlorprothixene treatment increased the inhibition rate of cell proliferation (P < 0.05),at the same time point, as the concentration of chlorprothixene increased, the inhibition rate of cell proliferation increased, and 40 μmol/L chlorprothixene treatment for 12 h was used for the next study.In SKNO-1 and MOLM-13 cells, compared with the control group, the apoptosis rate, autophagosome positive rate, LC3B, PARP, cleaved caspase3/caspase3 protein expression levels in SC79 group decreased (P < 0.05), the SQSTM1/p62, p-Akt/Akt and p-mTOR/mTOR protein expression levels increased (P < 0.05),the chlorprothixene group showed the opposite trends (P < 0.05),after adding chlorprothix ene on the basis of SC79 group, the apoptosis rate, autophagosome positive rate, LC3B, PARP, cleaved caspase3/ caspase3 protein expression levels decreased than chlorprothixene group (P < 0.05), the protein expression levels of SQSTM1/p62, p-Akt/Akt and p-mTOR/mTOR increased (P < 0.05). Conclusion.Chlorprothixene can inhibit the Akt/mTOR pathway and promote autophagy and apoptosis in human AML cells. [ABSTRACT FROM AUTHOR]

Background and objective Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, and its treatment and diagnosis remain a hot research topic. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is highly expressed in a variety of cancer cells and may be associated with the progression of LUAD. This study aimed to investigate the effect of TPX2 on the malignant progression of LUAD cells and the regulatory mechanisms. Methods The expression of gene TPX2 in LUAD tissues from The Cancer Genome Atlas (TCGA) database was analyzed by bioinformatics analysis techniques. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of TPX2 and miR-218-5p in human lung normal cell lines and human LUAD cell lines. Western blot was used to detect TPX2 protein expression in cell lines and its effect on the expression of key proteins in the p53 signaling pathway. The relationship between TPX2 and miR-218-5p was predicted using bioinformatics and verified by dual luciferase reporter gene assay. Cell counting kit-8 (CCK-8) assay, cell clone formation, cell scratching, Transwell assay, and flow cytometry were used to detect the effects of miR-218-5p and TPX2 on LUAD cell function. Results TPX2 was significantly overexpressed in LUAD cells, and knockdown of TPX2 inhibited LUAD cell proliferation, migration, and invasion, promoted apoptosis and induced G2/M phase block, and promoted the expression of key proteins in the p53 signaling pathway. miR-218-5p, an upstream regulator of TPX2, could inhibit its expression. Overexpression of miR-218-5p eliminated the malignant development caused by high expression of TPX2, inhibited the malignant processes of LUAD cells such as proliferation and migration as well as promoted the p53 signaling pathway. Conclu- sion miR-218-5p targets and inhibits TPX2 expression and exerts an inhibitory effect on the malignant progression of LUAD cells via p53. [ABSTRACT FROM AUTHOR]

Necroptosis is a major discovery in the field of cell death in recent decades. At present, in the field of ophthalmology, the activation of necroptosis pathway has been found from corneal diseases, glaucoma, retinal diseases and so on. In addition to Necrostatin-1（Nec-1）, a necroptosis inhibitor targeting receptor-interacting protein1（RIP1）, drugs such as GSK2399872A（GSK872）, a receptor-interacting protein3（RIP3） inhibitor, and TC13172, a novel inhibitor targeting mixed lineage kinase domain-like protein （MLKL）, have made major breakthroughs in cell death mechanisms. Currently in the field of ophthalmology, necroptosis inhibitors have demonstrated their protective effects in a variety of disease models. This article focuses on the molecular mechanism of necroptosis and the research results of its inhibitors in ophthalmology, discusses the potential of necroptosis as a new target for the treatment of ophthalmic diseases, and puts forward suggestions for its further research in the field of ophthalmology. [ABSTRACT FROM AUTHOR]

AIM: To investigate whether thyroid hormone can reduce the damage of type II alveolar epithelial cells and lung tissue in rats under high-altitude hypoxic environment, and to explore its mechanism. METHODS: Eight-week-old male SPF SD rats were divided into a normal control group and a plateau model group, with 10 rats in each group. The former group lived at an altitude consistent with local area, while the latter group was placed in a cabin that simulated the hypoxic environment at an altitude of 6 000 m to establish a plateau hypoxia model. After modeling, the serum and lung tissue samples of two-group animals were collected at normal altitudes. Apoptosis of rat lung tissue cells was observed with electron microscopy and TUNEL staining method. The expression levels of glucose-regulated protein 78 (GRP78), inositol-requiring enzyme lot (iRElot), protein kinase R-like endoplasmic reticulum kinase(PERK)and acti-vating transcription factor 6 (ATF6)in rat lung tissues were detected by RT-qP(Jl< and Western blot. The thyroid follicular epithelial cells were divided into a normoxic group and a hypoxic group, and cultured in normoxic or hypoxia condition for 24 h, respectively. The cell proliferation rate was detected using the CCK・8 method. The content of lactate dehydrogenase (LDH), T3 and T4 were detected using ELISA. Rat type 11 alveolar epithelial cells were divided into normoxic group, nor-moxia+thyroid hormone (T3)group, hypoxic group, and liypoxia+T3 group, before hypoxia treatment was catTicd out. The cell proliferation rate was detected using CCK-8 method. The proportion of living and dead cells was observed using cell staining. The LDH content of the cells was detected using ELISA. Apoptosis was observed using TL J\EL staining. The expression of (;RP78, 11出la, PERK and ATt'6 niRAA and proteins in rat lung tissues were detected by RT-qP(Jl< and Western blot. (;RP78, ATF6 and Bax were detected using immunofluorcsccncc. RESULTS: The number of apoptot-ic cells in lung tissue of rats in the plateau model group increased, and their expression of (;RP78, IRE la, PERK and ATF6 niRA A and proteins was significantly increased (PvO. 01). After hypoxic culture, the proliferation rate and the contents of T3 and T4 decreased, while the LDH content significantly increased (P<0. 01). Compared with the hypoxic group, the cell proliferation rate of hypoxia+T3 group was significantly increased, while the apoptosis rate and LDH content significantly decreased, and the expression of GRP78, 1RE1 a, PERK and ATF6 mRA A and proteins was significantly decreased 01). CONCLUSION: Exogenous thyroid hormones can alleviate hypoxia-induced type 11 alveolar epithelial cells injuiy in rats, possibly by iiihihiting the mRAA and proteins of the endoplasmic reticulum stress pathway in alveolar epithelial cells. [ABSTRACT FROM AUTHOR]

Background and objective The biological and molecular characteristics of spread through air spaces (STAS), a newly recognized invasive mode of lung cancer, remain controversial. The aim of this study was to investigate the clinicopathological features and molecular characteristics of STAS in patients with pulmonary adenocar-cinoma. Methods A total of 694 resected invasive non-mucinous lung adenocarcinomas diagnosed by clinicopathology from July 2019 to March 2021 in the First Affiliated Hospital of Guangzhou Medical University were collected, and the relationship between STAS and clinicopathological factors was analyzed. The state of protein expression of anaplastic lymphoma kinase (ALK) was detected by immunohistochemical method. Epidermal growth factor receptor (EGFR) was detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). ROS proto-onco-gene 1-receptor (ROS1) was detected by reverse transcription-PCR (RT-PCR). Results A total of 344 STAS positive cases and 350 STAS negative cases were collected. By univariate analysis, STAS positivity was statistically associated with tumor maximum diameter (P<0.001), pleural invasion (P<0.001), lymphovascular invasion (P<0.001), nerve invasion (P=0.013), lymph node metastasis (P<0.001), clinical stage (P<0.001) and histological type (P<0.001). There was a statistical correlation between STAS and ALK protein expression (P=0.001). Multivariate analysis showed that STAS positive was correlated with pleural invasion (P=0.001), vascular invasion (P<0.001), lymph node metastasis (P=0.005)and ALK protein expression (P=0.032). Conclusion STAS is associated with highly aggressive biological behavior of lung adenocarcinoma, suggesting a poor prognosis. [ABSTRACT FROM AUTHOR]

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate and analysis the effects of ginsenoside Rg1 on depression behavior, hippocampal neuron damage, protein kinase A (PKA) and protein kinase C (PKC) in rats with depression. Methods: 48 cases of rats with depression were randomly divided into three groups: model group, experimental group 1 and experimental group 2, with 16 rats in each group. Experiment group 1 and experiment group 2 were administered twice a day by gavage (1 mg/mL, 4 mg/ml ginsenoside Rg1) with a dose volume of 10ml; The model group were given double distilled water according to body weight in the same way. The depression behavior, hippocampal neuron injury, PKA and PKC expression were observed and recorded. Results: The escape latency of experimental group 1 and experimental group 2 on the 7th and 14th day of treatment were lower than that of model group, and the escape latency of experimental group 2 were also significantly shorter than that of experimental group 1 (P<0.05). The sugar preference rate of experimental group 1 and experimental group 2 on the 7th and 14th day of treatment were higher than that of model group, and the sugar preference rate of experimental group 2 were also higher than that of experimental group 1 (P<0.05). The serum 5-hydroxytryptamine level of experimental group 1 and experimental group 2 on the 7th and 14th day of treatment were higher than that of model group, and the serum corticosterone level were significantly lower than that of model group. There were also difference compared between experimental group 2 and experimental group 1(P<0.05). The relative expression levels of PKA and PKC protein in the hippocampal neurons of the experimental group 1 and the experimental group 2 on the 7th and 14th day of treatment were lower than that of the model group, and the experimental group 2 were also shorter than that of the experimental group 1(P<0.05). Conclusion: The application of ginsenoside Rg1 in rats with depression can improve the depressive behavior, increase the preference rate of sugar water, reduce the escape latency, increase the content of serum serotonin, reduce the content of serum corticosterone, and reduce the level of PKA and PKC protein expression in hippocampal neurons. [ABSTRACT FROM AUTHOR]