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The levels of nicotinamide adenine dinucleotide (NADH) dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUFS2, a subunit of NADH dehydrogenase) decrease in aged tissues, and these reductions may be partly associated with age-related conditions such as Parkinson's disease. Aging leads to many mitochondrial defects, such as biogenesis disruption, dysfunction, defects in the mitochondrial membrane potential, and production of reactive oxygen species, that may be highly related to NDUFS2 expression. The relationship between NDUFS2 and postovulatory oocyte aging in pigs remains unknown. In this study, we investigated changes in NDUFS2 expression during postovulatory aging (POA). Furthermore, NDUFS2 was knocked down via dsRNA microinjection at the MII stage to evaluate the effects on mitochondrial-related processes during POA. The mRNA expression of NDUFS2 decreased significantly after 48-h aging compared with that in fresh oocytes. NDUFS2 knockdown (KD) significantly impaired the maintenance of oocyte morphology and blastocyst development of embryos after POA. The levels of PGC1α (mitochondrial biogenesis-related proteins) decreased significantly after NDUFS2 KD, while the level of GSNOR, a protein denitrosylase, was reduced by NDUFS2 KD after 48 h of aging. These data suggest that NDUFS2 is vital for maintaining the oocyte quality during POA in pigs.

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Methionine adenosyltransferase 2A (MAT2A) is an essential enzyme in the methionine cycle that generates S-adenosylmethionine (SAM) by reacting with methionine and ATP. SAM acts as a methyl donors for histone and DNA methylation, which plays key roles in zygotic genome activation (ZGA). However, the effects of MAT2A on porcine ZGA remain unclear. To investigate the function of MAT2A and its underlying mechanism in porcine ZGA, MAT2A was knocked down by double-stranded RNA injection at the 1-cell stage. MAT2A is highly expressed at every stage of porcine embryo development. The percentages of four-cell-stage embryos and blastocysts were lower in the MAT2A-knockdown (KD) group than in the control group. Notably, depletion of MAT2A decreased the levels of H3K4me2, H3K9me2/3, and H3K27me3 at the four-cell stage, whereas MAT2A KD reduced the transcriptional activity of ZGA genes. MAT2A KD decreased embryonic ectoderm development (EED) and enhancer of zeste homolog 2 (EZH2) expression. Exogenous SAM supplementation rescued histone methylation levels and developmental arrest induced by MAT2A KD. Additionally, MAT2A KD significantly increased DNA damage and apoptosis. In conclusion, MAT2A is involved in regulating transcriptional activity and is essential for regulating histone methylation during porcine ZGA.

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G-protein-coupled receptor kinase 2 (GRK2) interacts with Gßγ and Gαq, subunits of G-protein alpha, to regulate cell signalling. The second messenger inositol trisphosphate, produced by activated Gαq, promotes calcium release from the endoplasmic reticulum (ER) and regulates maturation-promoting factor (MPF) activity. This study aimed to investigate the role of GRK2 in MPF activity during the meiotic maturation of porcine oocytes. A specific inhibitor of GRK2 (ßi) was used in this study. The present study showed that GRK2 inhibition increased the percentage of oocyte arrest at the metaphase I (MI) stage (control: 13.84 ± 0.95%; ßi: 31.30 ± 4.18%), which resulted in the reduction of the maturation rate (control: 80.36 ± 1.94%; ßi: 65.40 ± 1.14%). The level of phospho-GRK2 decreased in the treated group, suggesting that GRK2 activity was reduced upon GRK2 inhibition. Furthermore, the addition of ßi decreased Ca2+ release from the ER. The protein levels of cyclin B and cyclin-dependent kinase 1 were higher in the treatment group than those in the control group, indicating that GRK2 inhibition prevented a decrease in MPF activity. Collectively, GRK2 inhibition induced meiotic arrest at the MI stage in porcine oocytes by preventing a decrease in MPF activity, suggesting that GRK2 is essential for oocyte meiotic maturation in pigs.

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OBJECTIVES: Unique lifestyle and cultural factors in China may lead to distinct patterns of risk factors for oral frailty among older adults, especially in regions inhabited by northeastern border minority groups. METHODS: From July to November 2023, a convenience sampling method was employed to select older adults from three communities in Yanji City as the subjects. Data were collected by a set of questionnaires. RESULTS: A total of 478 older adults were included, revealing a prevalence rate of 71.6 % for oral frailty. Factors influencing were found to include age, ethnicity, gender, income, number of chronic diseases, body mass index, drinking, physical frailty, sleep disorders, and attitudes towards aging (p < 0.05). CONCLUSIONS: There is a higher prevalence of oral frailty. It is crucial to prioritize the oral health issues of older adults with high-risk factors and implement targeted intervention measures to reduce and control the occurrence and progression of oral frailty.

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In chicken, primordial germ cells (PGC) are crucial for the preservation and manipulation of genetic resources in poultry production. The HiS and FAcs culture systems are two important methods for the in vitro cultivation of chicken PGCs. The purpose of this study was to compare and analyze the two cultivation systems for PGCs (His and FAcs culture systems) to assess their efficacy and applicability in supporting PGC growth, maintaining PGC characteristics, and lineage transmission ability. The study found that both HiS and FAcs culture systems could maintain the basic biological characteristics of chicken PGCs, including the simultaneous expression of pluripotency and reproductive marker genes, as well as the presence of abundant glycogen granules. Subsequently, we identified 2,145 differentially expressed genes (DEG) through RNA sequencing. GO and KEGG analysis revealed a large number of DEGs enriched in the cell adhesion and calcium ion binding pathways, and the analysis found that these genes maintained a higher level in HiS-PGCs. Further personalized analysis found that the regulatory genes for maintaining PGC pluripotency were highly expressed in HiS-PGCs, while germ cell-related genes showed similar expression in both systems. Additionally, through RNA sequencing data and cell proliferation ability, it was found that PGCs in the FAcs system had a higher proliferation rate and a faster cell cycle. Finally, it was discovered that the expression of cell migration-related genes was maintained at a higher level in HiS-PGCs, but the migration efficiency of HiS-PGCs did not show a significant difference compared to FAcs-PGCs. These results suggest that both HiS and FAcs culture systems can maintain the proliferation and basic characteristics of chicken PGCs, but differences exist in cell proliferation, pluripotency regulation, and cell adhesion. These findings provide new information for optimizing PGC cultivation systems and are important for the preservation and genetic improvement of chicken PGCs.

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Myoblast is a kind of activated muscle stem cell. Its biological activities, such as proliferation, migration, differentiation, and fusion, play a crucial role in maintaining the integrity of the skeletal muscle system. These activities of myoblasts can be significantly influenced by the extracellular matrix. Collagen, being a principal constituent of the extracellular matrix, substantially influences these biological activities. In skeletal muscle, collagen I and III are two kinds of primary collagen types. Their influence on myoblasts and the difference between them remain ambiguous. The purpose of this study is to discover the influence of collagen I and III on biological function of myoblasts and compare their differences. We used C2C12 cell line and primary myoblasts to discover the effect of collagen I and III on proliferation, migration and differentiation of myoblasts and then performed the transcriptome sequencing and analysis. The results showed that both collagen I and III enhanced the proliferation of myoblasts, with no statistical difference between them. Similarly, collagen I and III enhanced the migration of myoblasts, with collagen I was more pronounced in Transwell assay. On the contrary, collagen I and III inhibited myoblasts differentiation, with collagen III was more pronounced at gene expression level. The transcriptome sequencing identified DEGs and enrichment analysis elucidated different terms between Type I and III collagen. Collectively, our research preliminarily elucidated the influence of collagen I and III on myoblasts and their difference and provided the preliminary experimental foundation for subsequent research.

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OBJECTIVE: To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL) training injuries. METHODS: Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed. All the cases were underwent ligament reconstruction surgery. Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group, including 13 males and 1 female, aged from 22 to 31 years old with an average of (27.07±7.28) years old, autogenous hamstring tendon was used for ligament reconstruction. There were 15 patients in the enhanced reconstruction group, including 13 males and 2 females, aged from 25 to 34 years old with an average of (29.06±4.23) years old, double tunnel ligament reconstruction, the autogenous hamstring muscle was used as the anteromedial bundle, and the posterolateral bundle was replaced by a high-strength line. The difference between knee tibial anterior distance, Lysholm score, International Knee Literature Committee (IKDC) subjective score, Tegner motor level score and visual analog scale (VAS) at 6th and 12th months after the surgery, limb symmetry index (LSI) were recorded at the last follow-up and surgery-related adverse effects during follow-up. RESULTS: All patients were followed up, ranged from 13 to 15 months with an average of (13.7±0.8) months. There were no serious adverse reactions related to surgery during the period. There was no statistical difference between the preoperative general data and the observation index of the two groups (P>0.05). The difference in tibial anterior distance at 6 and 12 months in the enhanced reconstruction group (1.45±0.62) mm and (1.74±0.78) mm which were lower those that in the conventional reconstruction group (2.42±0.60) mm and (2.51±0.63) mm(P<0.05). There was no significant difference in postoperative Lysholm score, Tegner motor level score, IKDC score, VAS, and limb symmetry index at the last follow-up(P>0.05). CONCLUSION: The enhanced reconstruction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique. The short-term curative effect is satisfactory, and it is suitable for the group with high sports demand.

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ABSTRACT: Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R+) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R+ neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R+ neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor-positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R+ neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R+ neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R+ neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.

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In brief: GRK2 deficiency disrupts the early embryonic development in pigs. The regulation of GRK2 on HSP90 and AKT may also play an important role during embryo development and tumor formation. Abstract: Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination, G-protein-coupled receptor kinase 2 (GRK2) binds to HSP90 in response to hypoxia or other stresses. In this study, we investigated the effects of GRK2 knockdown and inhibition on porcine embryonic development from the zygote stage. Immunofluorescence and western blotting were used to determine the localization and expression, respectively, of GRK2 and related proteins. First, GRK2 and p-GRK2 were expressed in both the cytoplasm and membrane and co-localized with HSP90 on the membrane. The mRNA level of GRK2 increased until the 8C-morula stage, suggesting that GRK2 may play an essential role during the early development of the porcine embryos. GRK2 knockdown reduced porcine embryo development capacity and led to significantly decreased blastocyst quality. In addition, inhibition of GRK2 also induced poor ability of embryo development at an early stage, indicating that GRK2 is critical for embryonic cleavage in pigs. Knockdown and inhibition of GRK2 reduced HSP90 expression, AKT activation, and cAMP levels. Additionally, GRK2 deficiency increased LC3 expression, suggesting enhanced autophagy during embryo development. In summary, we showed that GRK2 binds to HSP90 on the membrane to regulate embryonic cleavage and AKT activation during embryonic development in pigs.

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Recent studies have highlighted the immunomodulatory effects of acupuncture on sepsis and proposed novel non-pharmacological or bioelectronic approaches to managing inflammatory illnesses. Establishing rules for selectively activating sympathetic or vagal nerve-mediated anti-inflammatory pathways using acupuncture has valuable clinical applications. Over the years, studies have revealed the segmental modulatory role of acupuncture in regulating visceral function by targeting the autonomic nervous system (ANS). In this review, we aim to summarize recent findings on acupuncture in treating sepsis, focusing on the underlying ANS mechanism, as well as the rules of acupoint specificity, intensity, frequency, and other parameters utilized in these studies. Mechanistically, the immunomodulatory properties of the sympathetic nervous system have been highlighted. Furthermore, we explore the immunotherapeutic benefits of acupuncture in treating sepsis. A better understanding of the immunoregulatory mechanism of sympathetic nervous system may offer novel approaches for the development of therapeutics to treat or prevent a variety of inflammatory diseases.

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Assisted reproduction technology (ART) procedures are often impacted by post-ovulatory aging (POA), which can lead to reduced fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte (A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte (A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched Gene Ontology (GO) terms. The expression of genes related to the "electron transport chain" and "cell redox homeostasis" pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. Weighted correlation network analysis was carried out to explore gene expression modules specific to A_vivo. Trait-module association analysis showed that the red modules were most associated with in vivo aging. There are 959 genes in the red module, mainly enriched in "RNA binding", "mRNA metabolic process", etc., as well as in GO terms, and "spliceosome" and "nucleotide excision repair" pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. Subsequently, the functions of DDX18 and DNAJC7 were verified by knocking down their expression at the germinal vesicle (GV) and Metaphase II (MII) stages, respectively. Knockdown at the GV stage caused cell cycle disorders and increase the rate of abnormal spindle. Knockdown at the MII stage resulted in the inefficiency of the antioxidant melatonin, increasing the level of intracellular oxidative stress, and in mitochondrial dysfunction. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study provides a better understanding of the detailed mechanism of POA and potential strategies for improving the success rates of assisted reproductive technologies in pigs and other mammalian species.

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The ongoing and progressive evolution of antibiotic resistance presents escalating challenges for the clinical management and prevention of bacterial infections. Understanding the makeup of resistance genomes and accurately quantifying the current abundance of antibiotic resistance genes (ARGs) are crucial for assessing the threat of antimicrobial resistance (AMR) to public health. This comprehensive study investigated the distribution and diversity of bacterial community composition, ARGs, and virulence factors (VFs) across human, chicken, pig fecal, and soil microbiomes in various provinces of China. As a result, multidrug resistance was identified across all samples. Core ARGs primarily related to multidrug, MLS (Macrolides-Lincosamide-Streptogramins), and tetracycline resistance were characterized. A significant correlation between ARGs and bacterial taxa was observed, especially in soil samples. Probiotic strains such as Lactobacillus harbored ARGs, potentially contributing to the dissemination of antibiotic resistance. We screened subsets of ARGs from samples from different sources as indicators to assess the level of ARGs contamination in samples, with high accuracy. These results underline the complex relationship between microbial communities, resistance mechanisms, and environmental factors, emphasizing the importance of continued research and monitoring to better understand these dynamics.

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Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.

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The utilization of chicken embryonic-derived pluripotent stem cell (PSC) lines is crucial in various fields, including growth and development, vaccine and protein production, and germplasm resource protection. However, the research foundation for chicken PSCs is relatively weak, and there are still challenges in establishing a stable and efficient PSC culture system. Therefore, this study aims to investigate the effects of the FGF2/ERK and WNT/ß-catenin signaling pathways, as well as different feeder layers, on the derivation and maintenance of chicken embryonic-derived PSCs. The results of this study demonstrate that the use of STO cells as feeder layers, along with the addition of FGF2, IWR-1, and XAV-939 (FIX), allows for the efficient derivation of chicken PSC-like cells. Under the FIX culture conditions, chicken PSCs express key pluripotency genes, such as POUV, SOX2, and NANOG, as well as specific proteins SSEA-1, C-KIT, and SOX2, indicating their pluripotent nature. Additionally, the embryoid body experiment confirms that these PSC-like cells can differentiate into cells of three germ layers in vitro, highlighting their potential for multilineage differentiation. Furthermore, this study reveals that chicken Eyal-Giladi and Kochav stage X blastodermal cells express genes related to the primed state of PSCs, and the FIX culture system established in this research maintains the expression of these genes in vitro. These findings contribute significantly to the understanding and optimization of chicken PSC culture conditions and provide a foundation for further exploration of the biomedical research and biotechnological applications of chicken PSCs.

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ABSTRACT: Many medications commonly used to treat neuropathic pain are associated with significant, dose-limiting adverse effects, including sedation, dizziness, and fatigue. These adverse effects are due to the activity of these medications within the central nervous system. The objective of this work was to investigate the interactions between peripherally restricted cannabinoid receptor and mu-opioid receptor (MOR) agonists on ongoing and evoked neuropathic pain behaviors in mouse models. RNAscope analysis of cannabinoid receptor type 1 (CB1R) and MOR mRNA demonstrated that the mRNA of both receptors is colocalized in both mouse and human dorsal root ganglion. Single-cell RNAseq of dorsal root ganglion from chronic constriction injury mice showed that the mRNA of both receptors (Cnr1 and Oprm1) is coexpressed across different neuron clusters. Myc-CB1R and FLAG-MOR were cotransfected into immortalized HEK-293T cells and were found to interact at a subcellular level. We also find that CB-13 (a peripherally restricted dual CB1R and cannabinoid receptor type 2 agonist) and DALDA (a peripherally restricted MOR agonist) both attenuate mechanical hypersensitivity in a murine model of neuropathic pain. Using isobolographic analysis, we demonstrate that when coadministered, these agents synergistically attenuate mechanical hypersensitivity. Importantly, combination dosing of these agents does not cause any detectable preferential behaviors or motor impairment. However, repeated dosing of these agents is associated with the development of tolerance to these drugs. Collectively, these findings suggest that leveraging synergistic pain inhibition between cannabinoid receptor and MOR agonists in peripheral sensory neurons may be worth examining in patients with neuropathic pain.

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ETHNOPHARMACOLOGICAL RELEVANCE: Shugan Xiaozhi (SGXZ) decoction is a traditional Chinese medicine used for treating nonalcoholic steatohepatitis (NASH). It has been used clinically for over 20 years and proved to be effective; however, the molecular mechanism underlying the effects of SGXZ decoction remains unclear. AIM OF THE STUDY: We analyzed the chemical components, core targets, and molecular mechanisms of SGXZ decoction to improve NASH through network pharmacology and in vivo experiments. MATERIALS AND METHODS: The chemical components, core targets, and related signaling pathways of SGXZ decoction intervention in NASH were predicted using network pharmacology. Molecular docking was performed to verify chemical components and their core targets. The results were validated in the NASH model treated with SGXZ decoction. Mouse liver function was assessed by measuring ALT and AST levels. TC and TG levels were determined to evaluate lipid metabolism, and lipid deposition was assessed via oil red O staining. Mouse liver damage was determined via microscopy following hematoxylin and eosin staining. Liver fibrosis was assessed via Masson staining. Western blot (WB) and immunohistochemical (IHC) analyses were performed to detect inflammation and the expression of apoptosis-related proteins, including IL-1ß, IL-6, IL-18, TNF-α, MCP1, p53, FAS, Caspase-8, Caspase-3, Caspase-9, Bax, Bid, Cytochrome c, Bcl-2, and Bcl-XL. In addition, WB and IHC were used to assess protein expression associated with the TLR4/MyD88/NF-κB pathway. RESULTS: Quercetin, luteolin, kaempferol, naringenin, and nobiletin in SGXZ decoction were effective chemical components in improving NASH, and TNF-α, IL-6, and IL-1ß were the major core targets. Molecular docking indicated that these chemical components and major core targets might interact. KEGG pathway analysis showed that the pathways affected by SGXZ decoction, primarily including apoptosis and TLR4/NF-κB signaling pathways, interfere with NASH. In vivo experiments indicated that SGXZ decoction considerably ameliorated liver damage, fibrosis, and lipid metabolism disorder in MCD-induced NASH mouse models. In addition, WB and IHC verified the underlying molecular mechanisms of SGXZ decoction as predicted via network pharmacology. SGXZ decoction inhibited the activation of apoptosis-related pathways in MCD-induced NASH mice. Moreover, SGXZ decoction suppressed the activation of TLR4/MyD88/NF-κB pathway in MCD-induced NASH mice. CONCLUSION: SGXZ decoction can treat NASH through multiple targets and pathways. These findings provide new insights into the effective treatment of NASH using SGXZ decoction.

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BACKGROUND: Peripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of PENS on autonomic and cardiac function based on cardiac self-repair is not well understood. OBJECTIVES: This study aimed to explore the relationship between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS. METHODS: The activities of the superior cervical cardiac sympathetic nerve and vagus nerve were recorded to evaluate the autonomic tone directly. The pressure-volume loop system was used for left ventricular diastolic and systolic function. Noninvasive continuous electrocardiography and echocardiography were performed to analyze heart rate, heart rate variability, and left ventricular function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested. RESULTS: Sympathetic nerve activity and vagus nerve activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS at acupoint PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS at acupoint ST36 had a limited effect. Both iPENS at PC6 and ST36 improved the autonomic and cardiac function of rats in the cPENS groups. CONCLUSION: Rats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. On the basis of cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation.

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BACKGROUND: Gastric cancer, characterized by a multifactorial etiology and high heterogeneity, continues to confound researchers in terms of its pathogenesis. Curcumin, a natural anticancer agent, exhibits therapeutic promise in gastric cancer. Its effects include promoting cell apoptosis, curtailing tumor angiogenesis, and enhancing sensitivity to radiation and chemotherapy. Long noncoding RNAs (lncRNAs) have garnered significant attention as biomarkers for early screening, diagnosis, treatment, and drug response because of their remarkable specificity and sensitivity. Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis, clinical staging, metastasis, drug sensitivity, and prognosis in gastric cancer. A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer development can provide novel insights for precision treatment and tailored management of patients with gastric cancer. This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregulating specific lncRNAs and modulating gastric cancer onset and progression. AIM: To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis, proliferation, and invasion. Furthermore, these findings were validated in clinical samples. METHODS: The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation, flow cytometry to investigate its effects on apoptosis, and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells. Western blotting was used to gauge changes in the protein expression levels of CDK6, CDK4, Bax, Bcl-2, caspase-3, P65, and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment. Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in BGC-823 and MGC-803 cells. AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis, proliferation, migration, and invasion of gastric cancer cells. Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways. RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics. RESULTS: Curcumin induced apoptosis and hindered proliferation, migration, and invasion of gastric cancer cells in a dose- and time-dependent manner. LncRNA AC022424.2 was upregulated after curcumin treatment, and its knockdown enhanced cancer cell aggressiveness. LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways. LncRNA AC022424.2 downregulation was correlated with lymph node metastasis, making it a potential diagnostic and prognostic marker. CONCLUSION: Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2. This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation. The results of this study enhance our understanding of gastric cancer development and precision treatment.

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Nobiletin is a natural flavonoid found in citrus fruits with beneficial effects, including anti-inflammatory, anti-cancer and anti-oxidation effects. The aim of this study was to investigate whether nobiletin improves mitochondrial function in porcine oocytes and examine the underlying mechanism. Oocytes enclosed by cumulus cells were cultured in TCM-199 for 44 h with 0.1% dimethyl sulfoxide (control), or supplemented with 5, 10, 25, and 50 µM of nobiletin (Nob5, Nob10, Nob25, and Nob50, respectively). Oocyte maturation rate was significantly enhanced in Nob10 (70.26 ± 0.45%) compared to the other groups (control: 60.12 ± 0.47%; Nob5: 59.44 ± 1.63%; Nob25: 63.15 ± 1.38%; Nob50: 46.57 ± 1.19%). The addition of nobiletin reduced the levels of reactive oxygen species and increased glutathione levels. Moreover, Nob10 promoted mitochondrial biogenesis by upregulating the protein levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α). This resulted in an increase in the number of active mitochondria, mitochondrial DNA copy number, mitochondrial membrane potential, and ATP production, thereby enhancing mitochondrial function. The protein level of p53 decreased, followed by the phosphorylation of B-cell lymphoma 2, suggesting a reduction in mitochondria-mediated apoptosis in the Nob10 group. Additionally, the release of cytochrome c from the mitochondria was significantly diminished along with a decrease in the protein expression of caspase 3. Thus, nobiletin has a great potential to promote the in vitro maturation of porcine oocytes by suppressing oxidative stress and promoting mitochondrial function through the upregulation of the SIRT1/PGC-1α signaling pathway.

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