Photothermal enhanced antibacterial chitosan-based polydopamine composite hydrogel for hemostasis and burn wound repairing.

Bleeding and bacterial infection are common problems associated with wound treatment, while effective blood clotting and vessel regeneration promotion are the primary considerations to design the wound dressing materials. This research presents a chitosan-based hydrogel with grafted quaternary ammonium and polyphosphate (QCSP hydrogel) as the antibacterial hemostatic dressing to achieve burn wound treatment. The tissue adhesion of the hydrogel sealed the blood flow and the polyphosphate grafted to the chitosan promoted the activation of coagulation factor V to enhance the hemostasis. At the same time, the grafted quaternary ammonium enhanced the antibacterial ability of the biodegradable hydrogel wound dressing. In addition, the polydopamine as a photothermal agent was composited into the hydrogel to enhance the antibacterial and reactive oxygen scavenging performance. The in vivo hemostasis experiment proved the polyphosphate enhanced the coagulation property. Moreover, this photothermal property of the composite hydrogel enhanced the burn wound repairing rate combined with the NIR stimulus. As a result, this hydrogel could have potential application in clinic as dressing material for hemostasis and infection prone would repairing.

Anticancer Tetranuclear Cu(I) Complex Catalyzes a Click Reaction to Synthesize a Chemotherapeutic Agent in situ to Achieve Targeted Dual-Agent Combination Therapy for Cancer.

To develop next-generation metal-based drugs and dual-drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual-agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). We also constructed an apoferritin (AFt)-Cu4 nanoparticles (NPs) delivery system. AFt-Cu4 NPs not only showed an enhanced performance of tumor growth inhibition, but also improved the targeting ability and reduced the systemic toxicity of Cu4 in vivo. Importantly, the anticancer effect was enhanced by combining the AFt-Cu4 NPs with the resveratrol analogue obtained from the CuAAC reaction in situ. Finally, we revealed the anticancer mechanism of the Cu4/AFt-Cu4 NPs, which involves both cuproptosis and cuproptosis-induced systemic immune response.

Mitigation of lipopolysaccharide-induced intestinal injury in rats by Chimonanthus nitens Oliv. essential oil via suppression of mitochondrial fusion protein mitofusin 2 (MFN2)-mediated mitochondrial-associated endoplasmic reticulum membranes (MAMs) formation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chimonanthus nitens Oliv. is a traditional Chinese medicine with anti-inflammatory and antioxidant properties that has commonly been used for colds, fevers, and other diseases. However, its role and specific mechanism in sepsis-associated intestinal injury have not been reported. AIM OF THE STUDY: C. nitens Oliv. essential oil (CEO), an organic active compound extracted from the traditional Chinese medicine C. nitens Oliv. exhibits notable anti-inflammatory and antioxidant properties. Nevertheless, the therapeutic potential of CEO for septic intestinal injury remains undocumented. This study thus aims to elucidate the anti-inflammatory and antioxidant effects of CEO in the context of acute intestinal injury and to investigate its mechanisms of action in septic rats. MATERIALS AND METHODS: Cell and animal models were established using LPS to investigate the impact of CEO on LPS-induced intestinal pathological injury and the secretion of inflammatory factor IL-1ß. The effects of CEO on the expression of NLRP3, caspase-1, and MFN2, p-p65 protein were also examined, as well as its influence on oxidative stress injury and mitochondrial-associated endoplasmic reticulum membrane (MAM) formation. Generation of an MFN2 knockout IEC-6 cell line allowed comprehensive investigation of the protective mechanism of CEO. RESULTS: In rat models, CEO reduced IL-1ß secretion, inhibited caspase-1, ZO-1 expression and NF-κB p65 phosphorylation, while also decreasing malondialdehyde levels and enhancing superoxide dismutase activity in intestinal tissues. Cellular experiments demonstrated its ability to decrease IL-1ß secretion; NLRP3, caspase-1, and MFN2 expression; NF-κB p65 phosphorylation; reactive oxygen species (ROS) production, and mitochondrial dysfunction. MFN2 knockdown enhanced these effects synergistically with CEO, indicating potential therapeutic synergy. Further, MFN2 knockdown significantly mitigated LPS-induced NLRP3 and caspase-1 expression, IL-1ß secretion, ROS production, NF-κB p65 phosphorylation and MMP reduction in IEC-6 cells, while inhibiting MAM formation and NLRP3 localization on MAMs. Importantly, MFN2 downregulation and CEO synergistically reduced LPS-induced IL-1ß secretion and ROS production while inhibiting MAM formation in IEC-6 cells, thus inhibiting NLRP3 inflammasome activation. CONCLUSION: CEO mitigates inflammation and oxidative stress by inhibiting MAM formation and is thus a promising intervention for septic intestinal injury.

Developing a Palladium(II) Agent to Overcome Multidrug Resistance and Metastasis of Liver Tumor by Targeted Multiacting on Tumor Cell, Inactivating Cancer-Associated Fibroblast and Activating Immune Response.

To targeted overcome the multidrug resistance (MDR) and metastasis of liver tumors, we proposed to develop a palladium (Pd) agent based on a specific residue of human serum albumin (HSA) for multiacting on tumor cell and other components in the tumor microenvironment. To this end, a series of Pd(II) 2-acetylpyridine thiosemicarbazone compounds were optimized to obtain a Pd(II) compound (5b) with significant cytotoxicity against HepG2/ADM cells. Subsequently, we constructed a HSA-5b complex delivery system and revealed the structural mechanism of HSA delivering 5b. Importantly, 5b/HSA-5b effectively inhibited the growth and metastasis of multidrug resistant liver tumors, and HSA enhanced the targeting ability of 5b and reduced its side effects in vivo. Furthermore, we confirmed the mechanisms of 5b/HSA-5b integrating to overcome MDR and metastasis of liver tumors: multiacting on cancer cell, activating immune response, and inactivating cancer-associated fibroblasts.

Identification and expression profiling of the bone morphogenetic protein gene family based on pearl culture in mantle and visceral mass of Hyriopsis cumingii.

Bone morphogenetic proteins (BMPs) play an important biological role in pearl biomineralization in pearl mussels. In this study, based on the genome data of the triangular sail mussel (Hyriopsis cumingii), the genome-wide identification and bioinformatic analysis of BMP gene family were performed, and the expression pattern of the BMP genes was investigated by the insertion experiments. The results showed that a total of 12 BMP gene family members (BMP2a/2b, BMP3, BMP5a/5b, BMP7a/7b/7c, BMP9, BMP10a/10b, and BMP11) were identified, which were unevenly distributed on chromosome 3/14/18, encoding 169-583 amino acids, with molecular weights ranging from 19.32 to 65.99 kDa. BMP2a, BMP7b, and BMP10a were distributed, respectively, in the cytoplasm, endoplasmic reticulum and mitochondria, others were distributed in the nucleus. qRT-PCR results showed the significant tissue specificity in BMPs gene expression. The HcBMPs were differentially expressed in the mantle and visceral mass, and the expression level was higher in the visceral mass. The expressing trends of HcBMPs were not consistent between the mantle and visceral mass insertion, suggesting that HcBMPs may perform different functions. We also found that insertion surgery in the mantle and visceral mass significantly alters the expression profiling of the BMP gene family. Insertion of the mantle induced the biomineralization function of BMP2a, BMP7a, and BMP7b, while BMP3 and BMP10b played opposite roles in visceral mass insertion. Visceral mass insertion could suppress BMP9 expression at 5 d and BMP5b expression at 90 d after insertion This work lays the foundation and data support for the preliminary elucidation of regulatory role and mechanism of HcBMPs in the pearl-cultivating process of mantle and visceral mass.

Path analysis of influencing factors for anxiety and depression among first-trimester pregnant women.

Background: Prenatal anxiety and depression exert a significant influence on the physiological and psychological health outcomes of both expectant mothers and their infants. The aim of this study was to explore the intrinsic relationships between maternal anxiety, depression in early pregnancy, and their influencing factors. The findings of this study provide scientific basis for developing targeted preventive interventions. Methods: The study involved 887 expectant mothers in the early stages of pregnancy residing in Changsha City from March to August 2022. The sociodemographic characteristics, health and lifestyle factors, and pregnancy-related factors of participants were collected. The Edinburgh Postnatal Depression Scale and the Self-Rating Anxiety Scale were used to assess depression and anxiety, respectively. Chi-square tests and multivariate logistic regression models using SPSS 26.0 were used to assess factors impacting early pregnancy anxiety and depression. Amos 23.0 was used to construct a path model to determine the potential pathways of the influencing factors. Results: In early pregnancy, the prevalence of depression and anxiety were 17.4% and 15.8%, respectively. Path analysis showed that early pregnancy anxiety and illness during pregnancy had a direct effect on early pregnancy depression. Anxiety had the greatest overall impact on early pregnancy depression. Education, maternal comorbidities, symptoms of pregnancy, electronic device usage time, work stress, active smoking in the 6 months before pregnancy, and sleep quality were found to solely exert indirect effects on early pregnancy depression. Sleep quality had the greatest overall impact on early pregnancy anxiety. Active smoking in the 6 months before pregnancy, sleep quality, and work stress only had a direct impact on early pregnancy anxiety. Additionally, electronic device usage duration and monthly per capita household income exclusively indirectly impacted symptoms of early pregnancy anxiety. Conclusion: The study highlights the importance of targeted interventions in early screening. Avoiding excessive use of electronic devices and active smoking in the 6 months before pregnancy, alleviating work stress and symptoms of pregnancy, increasing education levels and monthly per capita household income, improving sleep quality, and actively preventing illnesses during pregnancy and maternal comorbidities might reduce anxiety and depression in early pregnancy.

Developing a Rhodium(III) Complex to Reprogram the Tumor Immune and Metabolic Microenvironments: Overcoming Multidrug Resistance and Metastasis in Non-Small Cell Lung Cancer.

To effectively inhibit the growth and metastasis of non-small cell lung cancer (NSCLC) and overcome its multidrug resistance (MDR), we designed and synthesized a series of rhodium (Rh, III) 2-benzoylpyridine thiosemicarbazone complexes. Through studying their structure-activity relationships, we identified the Rh(III) complex (Rh4) with excellent cytotoxicity against multidrug-resistant lung cancer cells (A549/ADR cells). Additionally, we successfully constructed an apoferritin (AFt) nanoparticle (NP) delivery system (AFt-Rh4 NPs). Importantly, AFt-Rh4 NPs not only exhibited excellent antitumor and antimetastatic capabilities against multidrug-resistant NSCLC in vivo but also demonstrated enhanced targeting ability and reduced systemic toxicity and adverse effects. Furthermore, we confirmed and elucidated the mechanisms by which Rh4/AFt-Rh4 NPs inhibit tumor metastasis and reverse MDR in NSCLC. This was achieved by reprogramming the immune and metabolic tumor microenvironments through induction of immunogenic cell death and inhibition of dual-energy metabolism.

Rational Design of a Hetero-multinuclear Gadolinium(III)-Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer.

For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)-Cu(II) thiosemicarbazone complex (Gd-2Cu) and then constructed a Gd-2Cu@AFt nanoparticle (NP) delivery system. Gd-2Cu/Gd-2Cu@AFt NPs not only had significant T1-weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy. Gd-2Cu@AFt NPs optimized the behavior of imaging diagnosis and therapy of Gd-2Cu, improved its targeting ability, and reduced the side effects in vivo. Besides, we revealed and clarified the anticancer mechanism of Gd-2Cu: interrupting energy metabolism of the tumor cell, inducing apoptosis of the tumor cell, and activating a systemic immune response by inducing immunogenic cell death of cancer cells.

Evolution, classification, structure, and functional diversification of steroid 5α-reductase family in eukaryotes.

Steroid 5α-reductase1/2 (SRD5A1/2) is an androgen protein that resembles the plant DET2 and is responsible for the conversion of testosterone to the more active dihydrotestosterone (DHT). Both proteins share functional homology and have a common ancestor. In mammals, the SRD5A1/2 can reduce a wide range of steroid substrates, such as testosterone, progesterone, and aldosterone, by reducing the Δ4 in ring A. The plant DET2 catalyzes the conversion of campesterol (CR) to campestanol (CN) by reducing the Δ5 in ring B during brassinosteroid (BRs) biosynthesis. We compared the evolution, structural, and functional homology of the SRD5A family and tried to identify the origin and functional diversification of duplicated genes in eukaryotes. We presented a detailed phylogeny that includes representative species from all eukaryotic groups. Our study indicated that protist is a common ancestor for all the subgroups of the SRD5A family. However, not all protists possess SRD5A1/2/DET2 or other homologs, suggesting that some protists may have lost these gene families during evolution. Lineage-specific duplication leads Caenorhabditis elegance to have three SRD5A1/2 genes but none was found in Drosophila melanogaster. We also identified a new subclass, DET2-like (DET2L), in plants that closely resemble SRD5A1/2/DET2. The hypothesized reductase DET2L showed no phenotypic enhancement when expressed in Arabidopsis det 2 mutants, suggesting its possible role in the reduction of polyprenol or other substrates.

Life's Essential 8 in Relation to Cardiovascular Disease and Mortality in Individuals With Diabetes.

Background: Evidence regarding the potential health effects of Life's Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited. Objectives: The purpose of this study was to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality among individuals with T2D. Methods: We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations. Results: During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted HRs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (95% CI: 0.53-0.59) for CVD, 0.57 (95% CI: 0.53-0.62) for heart disease, 0.53 (95% CI: 0.49-0.57) for stroke, and 0.73 (95% CI: 0.69-0.78) for total mortality (all P trend <0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17% to 42% lower risk of CVD, heart disease, stroke, and mortality. Conclusions: A higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D.

Polyphenol (-)-Epigallocatechin Gallate (EGCG) mitigated kidney injury by regulating metabolic homeostasis and mitochondrial dynamics involvement with Drp1-mediated mitochondrial fission in mice.

The study aimed to examine effects of (-)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury.

Feasibility and value of modular splenic hilar lymphadenectomy technique in laparoscopic total gastrectomy: a retrospective-controlled research.

BACKGROUND: This study aims to investigate the feasibility and value of modular splenic hilar lymphadenectomy (MSHL) in LTG for advanced PGC located at the greater curvature. STUDY DESIGN: A retrospective-controlled research included 54 patients diagnosed with advanced PGC located at the greater curvature who underwent LTG combined with spleen-preserving hilar lymphadenectomy between January 2020 and December 2022 at the same treatment center. A total of 20 patients underwent classic splenic hilar lymphadenectomy (CSHL) using a medial approach (classic group), while 34 patients underwent MSHL (modular group). We summarized the technical points, caveats, and critical steps of the MSHL technique and observed and compared clinical indexes between the two groups. RESULTS: All operations were successful without conversion to laparotomy. The mean operation time, mean splenic hilar lymph node dissection (LND) time, median intraoperative blood loss, and blood loss from splenic hilar LND were all significantly lower in the modular group than in the classic group (p < 0.05). The amount of NO.10 lymph nodes (LNs) was significantly higher in the modular group than in the classic group (p < 0.05). In the classic group, one patient experienced intraoperative splenic vein injury, and one experienced spleen laceration, whereas no intraoperative complications occurred in the modular group. The median postoperative feeding time, exhaust time, defecation time, and postoperative stay were all significantly lower in the modular group compared to the classic group (p < 0.05). In the modular group, one patient experienced Clavien-Dindo I complication and one Clavien-Dindo II complication, while in the classic group, one patient experienced Clavien-Dindo II complication and one Clavien-Dindo IIIa complication. There were no patient was re-hospitalized within 30 days after surgery. CONCLUSION: The modular splenic hilar LND technique can simplify complicated surgical procedures in SPSHL and reduce the risk of intraoperative bleeding and collateral damage.

Andrographolide ameliorates sepsis-induced acute lung injury by promoting autophagy in alveolar macrophages via the RAGE/PI3K/AKT/mTOR pathway.

Autophagy in alveolar macrophages (AMs) is an important mechanism for maintaining immune homeostasis and normal lung tissue function, and insufficient autophagy in AMs may mediate the development of sepsis-induced acute lung injury (SALI). Insufficient autophagy in AMs and the activation of the NLRP3 inflammasome were observed in a mouse model with SALI induced by cecal ligation and puncture (CLP), resulting in the release of a substantial quantity of proinflammatory factors and the formation of SALI. However, after andrographolide (AG) intervention, autophagy in AMs was significantly promoted, the activation of the NLRP3 inflammasome was inhibited, the release of proinflammatory factors and pyroptosis were suppressed, and SALI was then ameliorated. In the MH-S cell model stimulated with LPS, insufficient autophagy was discovered to promote the overactivation of the NLRP3 inflammasome. AG was found to significantly promote autophagy, inhibit the activation of the NLRP3 inflammasome, and attenuate the release of proinflammatory factors. The primary mechanism of AG promoting autophagy was to inhibit the activation of the PI3K/AKT/mTOR pathway by binding RAGE to the membrane. In addition, it inhibited the activation of the NLRP3 inflammasome to ameliorate SALI. Our findings suggest that AG promotes autophagy in AMs through the RAGE/PI3K/AKT/mTOR pathway to inhibit the activation of the NLRP3 inflammasome, remodel the functional homeostasis of AMs in SALI, and exert anti-inflammatory and lung-protective effects. It has also been the first to suggest that RAGE is likely a direct target through which AG regulates autophagy, providing theoretical support for a novel therapeutic strategy in sepsis.

A single-cell chromatin accessibility dataset of human primed and naïve pluripotent stem cell-derived teratoma.

Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.

Innovative pancreas-guided technique for splenic flexure mobilization in laparoscopic left hemicolectomy.

OBJECTIVE: Splenic flexure mobilization (SFM) is a major challenge in laparoscopic left hemicolectomy. This study aims to assess the safety and effectiveness of the pancreas-guided SFM technique during laparoscopic left hemicolectomy. METHODS: From January 2018 to December 2023, 352 patients with left-sided colon cancer underwent laparoscopic left hemicolectomy. Based on the SFM method used, the patients were divided into the pancreas-guided group (167 cases) or the "Three Approaches Roundabout"/classic group (185 cases). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups. RESULTS: The two groups had no significant differences in baseline indicators (P > 0.05). All surgeries were successful without needing to convert to laparotomy, and there were no combined organ resections involving the spleen or pancreas in either group. The mean duration of surgery was significantly lower in the pancreas-guided group than in the classic group (P < 0.01). The median volume of intraoperative blood loss in the pancreas-guided group was lower than that in the classic group (P < 0.01). Through video playback, it was found that the retro-pancreatic space had been entered during operation in 8 cases (4.3%) in the classic group, while there were no such occurrences in the pancreas-guided group. This difference was statistically significant (P < 0.05). The difference in the number of lymph nodes cleared, postoperative hospital stays, and incidence of complications were not statistically significant (all P > 0.05) between the groups. CONCLUSION: The pancreas-guided SFM technique is a safe and feasible option for laparoscopic left hemicolectomy. Our study's findings suggest that this approach facilitates accurate access to the correct anatomic plane, potentially improving surgical efficiency.

PGM5-AS1 Promotes Progression of Diffuse Large B-Cell Lymphoma and Immune Escape by Regulating miR-503-5p.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a prevalent malignant condition with a dismal prognosis. LncRNA PGM5 antisense RNA 1 (PGM5-AS1) appears to be intricately involved in the progression of DLBCL, yet the modulatory mechanism remains unclear. The purpose of this study was to explore the expression of lncRNA PGM5-AS1 in DLBCL and its effect on the disease progression of DLBCL, as well as to explore its mechanisms. Patients and Methods: A total of 35 patients were included in the study. The expression levels of PGM5-AS1 and miR-503-5p in DLBCL tumor tissues and cell lines were detected by RT-qPCR. Cell proliferation was assessed using CCK8. Apoptosis rate was determined by flow cytometry. Cell invasion was examined by transwell assays. The specific interaction between PGM5-AS1 and miR-503-5p was verified through dual luciferase reporter gene assays. The immune related factors were detected by ELASA kits. The CD8+ T cells cytotoxicity was evaluated by LDH cytotoxicity kit. Results: In DLBCL tumor tissues and cells, upregulated PGM5-AS1 expression, downregulated miR-503-5p expression, and elevated PD-L1 expression were observed. PGM5-AS1 functioned as a regulator in controlling DLBCL cell proliferation, apoptosis, and invasion by downregulating miR-503-5p expression. When CD8+ T cells were co-cultured with cells transfected with si-PGM5-AS1, the secretion of immunoregulatory factors increased, and the cytotoxicity of CD8+ T cells increased. These effects were mitigated by miR-503-5p inhibitors. Conclusion: PGM5-AS1 accelerated DLBCL development and facilitated tumor immune escape through the miR-503-5p. Our discoveries offered an insight into lncRNA PGM5-AS1 serving as a prospective therapeutic target for DLBCL.

Ebselen improves lipid metabolism by activating PI3K/Akt and inhibiting TLR4/JNK signaling pathway to alleviate nonalcoholic fatty liver.

Nonalcoholic fatty liver disease (NAFLD), a metabolic disease associated with obesity and type 2 diabetes. Due to its complex pathogenesis, there are still limitations in the knowledge of the disease. To date, no drug has been approved to treat NAFLD. This study aims to explore the role and mechanism of Ebselen (EbSe) in NAFLD. A high-fat diet-induced mouse model of NAFLD was employed to investigate EbSe function in NAFLD mice by EbSe gavage and to regularly monitor the mouse body weight. HE and oil red O staining were performed, respectively, to detect the pathological damage and lipid accumulation in mouse liver tissues. The biochemical and ELISA kits were employed to measure the levels of ALT, AST, TG, TC, LDL-C, HDL-C and pro-inflammatory cytokines within mouse serum or liver tissue. The expression of key proteins of PPARα, fatty acid ß oxidation-related protein, PI3K/Akt and TLR4/JNK signaling pathway was detected by western blot. EbSe significantly downregulated body weight, liver weight and liver lipid accumulation in NAFLD mice and downregulated ALT, AST, TG, TC, LDL-C and increased HDL-C serum levels. EbSe upregulated the expression levels of PPARα and fatty acid ß oxidation-associated proteins CPT1α, ACOX1, UCP2 and PGC1α. EbSe promoted Akt and PI3K phosphorylation, and inhibited TLR4 expression and JNK phosphorylation. EbSe can upregulate PPARα to promote fatty acid ß-oxidation and improve hepatic lipid metabolism. Meanwhile, EbSe also activated PI3K/Akt and inhibited TLR4/JNK signaling pathway. EbSe is predicted to be an effective therapeutic drug for treating NAFLD.

A CARM1 Inhibitor Potently Suppresses Breast Cancer Both In Vitro and In Vivo.

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

Neurofibromatosis type 1 with huge intrathoracic meningoceles misdiagnosed as pleural effusion: A case report and literature review.

BACKGROUND: Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare intrathoracic meningoceles often occur alongside bone dysplasia. These meningoceles contain cerebrospinal fluid and can be mistakenly diagnosed as 'pleural effusion'. CASE PRESENTATION: In this case report, we mistakenly identified 'cerebrospinal fluid' as 'pleural effusion' and proceeded with drainage. This error posed significant risks to the patient and holds valuable implications for the future diagnosis and treatment of similar patients. CONCLUSIONS: In patients with Neurofibromatosis type 1 complicated by spinal deformity, there is a high incidence of intrathoracic meningoceles. Treatment strategies may differ based on the specific features of the lesions, and collaboration among multiple disciplines can significantly improve patient outcomes.

Withaferin A Inhibits Liver Cancer Tumorigenesis by Suppressing Aerobic Glycolysis through the p53/IDH1/HIF-1α Signaling Axis.

BACKGROUND: The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from Withania somnifera, suppresses skin carcinogenesis at least partially by stabilizing IDH1 and promoting oxidative phosphorylation. Here, we have extended our studies to evaluate the anti-tumor effect of WA in liver cancer. METHODS: Differential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways. RESULTS: We first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia. CONCLUSION: Taken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.