Analysis of infrared radiation emitted by moxibustion devices made of different materials using Fourier transform infrared spectroscopy.

Moxibustion has a long history of use as a traditional Chinese medicine therapy. Infrared radiation is an important and effective factor in moxibustion. Instead of the time-consuming and laborious process of holding moxa sticks in the hand, moxibustion devices are commonly used as moxibustion methods and tools in modern times. With the publication of the international standard of moxibustion devices (ISO18666:2021, Traditional Chinese Medicine - General requirements of moxibustion devices) published, moxibustion devices of various materials are now sold in the pharmacies and online stores. However, the influence of moxibustion devices on the therapeutic effect of moxibustion has not been studied. Therefore, this research was aimed to evaluate the infrared radiation of moxibustion devices, in order to select the moxibustion device that delivered infrared radiation closest to that of moxa stick combustion. The combination of combustion stability and infrared radiation intensity showed that cardboard tubes and silicone were better materials for moxibustion devices. In the mid-far infrared wave band, the moxibustion devices made from cardboard tubes and silica gels can better maintain the thermal effect generated by moxibustion and enable it to be more easily absorbed by the human body. The infrared radiation intensity of the cardboard moxibustion devices increased rapidly and steadily and could be maintained for the longest time. In conclusion, cardboard tubes are the better material for moxibustion devices with respect to infrared radiation.

[Clinical Characteristics and Prognosis of Patients with Acute Leukemia Complicated with Mucormycosis after Chemotherapy].

OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.

20(R)-Panaxatriol enhances METTL3-mediated m6A modification of STUB1 to inhibit autophagy and exert antitumor effects in Triple-Negative Breast Cancer cells.

BACKGROUND: Aberrant activation of autophagy in triple-negative breast cancer (TNBC) has led researchers to investigate potential therapeutic strategies targeting this process. The regulation of autophagy is significantly influenced by METTL3. Our previous research has shown that the Panax ginseng-derived compound, 20(R)-panaxatriol (PT), has potential as an anti-tumor agent. However, it remains unclear whether PT can modulate autophagy through METTL3 to exert its anti-tumor effects. OBJECTIVE: Our objective is to investigate whether PT can regulate autophagy in TNBC cells and elucidate the molecular mechanisms. STUDY DESIGN: For in vitro experiments, we employed SUM-159-PT and MDA-MB-231 cells. While in vivo experiments involved BALB/c nude mice and NOD/SCID mice. METHODS: In vitro, TNBC cells were treated with PT, and cell lines with varying expression levels of METTL3 were established. We assessed the impact on tumor cell activity and autophagy by analyzing autophagic flux, Western Blot (WB), and methylation levels. In vivo, subcutaneous transplantation models were established in BALB/c nude and NOD/SCID mice to observe the effect of PT on TNBC growth. HE staining and immunofluorescence were employed to analyze histopathological changes in tumor tissues. MeRIP-seq and dual-luciferase reporter gene assays were used to identify key downstream targets. Additionally, the silencing of STIP1 Homology And U-Box Containing Protein 1 (STUB1) explored PT's effects. The mechanism of PT's action on STUB1 via METTL3 was elucidated through mRNA stability assays, mRNA alternative splicing analysis, and nuclear-cytoplasmic mRNA separation. RESULTS: In both in vivo and in vitro experiments, it was discovered that PT significantly upregulates the expression of METTL3, leading to autophagy inhibition and therapeutic effects in TNBC. Simultaneously, through MeRIP-seq analysis and dual-luciferase reporter gene assays, we have demonstrated that PT modulates STUB1 via METTL3, influencing autophagy in TNBC cells. Furthermore, intriguingly, PT extends the half-life of STUB1 mRNA by enhancing its methylation modification, thereby enhancing its stability. CONCLUSION: In summary, our research reveals that PT increases STUB1 m6A modification through a METTL3-mediated mechanism in TNBC cells, inhibiting autophagy and further accentuating its anti-tumor properties. Our study provides novel mechanistic insights into TNBC pathogenesis and potential drug targets for TNBC.

Unveiling the causal link between metabolic factors and ovarian cancer risk using Mendelian randomization analysis.

Background: Metabolic abnormalities are closely tied to the development of ovarian cancer (OC), yet the relationship between anthropometric indicators as risk indicators for metabolic abnormalities and OC lacks consistency. Method: The Mendelian randomization (MR) approach is a widely used methodology for determining causal relationships. Our study employed summary statistics from the genome-wide association studies (GWAS), and we used inverse variance weighting (IVW) together with MR-Egger and weighted median (WM) supplementary analyses to assess causal relationships between exposure and outcome. Furthermore, additional sensitivity studies, such as leave-one-out analyses and MR-PRESSO were used to assess the stability of the associations. Result: The IVW findings demonstrated a causal associations between 10 metabolic factors and an increased risk of OC. Including "Basal metabolic rate" (OR= 1.24, P= 6.86×10-4); "Body fat percentage" (OR= 1.22, P= 8.20×10-3); "Hip circumference" (OR= 1.20, P= 5.92×10-4); "Trunk fat mass" (OR= 1.15, P= 1.03×10-2); "Trunk fat percentage" (OR= 1.25, P= 8.55×10-4); "Waist circumference" (OR= 1.23, P= 3.28×10-3); "Weight" (OR= 1.21, P= 9.82×10-4); "Whole body fat mass" (OR= 1.21, P= 4.90×10-4); "Whole body fat-free mass" (OR= 1.19, P= 4.11×10-3) and "Whole body water mass" (OR= 1.21, P= 1.85×10-3). Conclusion: Several metabolic markers linked to altered fat accumulation and distribution are significantly associated with an increased risk of OC.

Bioaccessibility of Metallic Nickel and Nickel Oxide Nanoparticles in Four Simulated Biological Fluids.

Bioaccessibility of metals from substances and alloys is increasingly used as part of the assessment to predict potential toxicity. However, data are sparse on the metal bioaccessibility from nanoparticle (NP) size metal substances. This study examines nickel ion release from metallic nickel and nickel oxide micron particles (MPs) and NPs in simulated biological fluids at various timepoints including those relevant for specific routes of exposure. The results suggest that MPs of both metallic nickel and nickel oxide generally released more nickel ions in acidic simulated biological fluids (gastric and lysosomal) than NPs of the same substance, with the largest differences being for nickel oxide. In more neutral pH fluids (interstitial and perspiration), nickel metal NPs released more nickel ions than MPs, with nickel oxide results showing a higher release for MPs in interstitial fluid yet a lower release in perspiration fluid. Various experimental factors related to the particle, fluid, and extraction duration were identified that can have an impact on the particle dissolution and release of nickel ions. Overall, the results suggest that based on nickel release alone, nickel NPs are not inherently more hazardous than nickel MPs. Moreover, analyses should be performed on a case-by-case basis with consideration of various experimental factors and correlation with in vivo data.

Dapagliflozin Improves Angiogenesis after Hindlimb Ischemia through the PI3K-Akt-eNOS Pathway.

Recently, the vascular protective effect of anti-diabetic agents has been receiving much attention. Sodium glucose cotransporter 2 (SGLT2) inhibitors had demonstrated reductions in cardiovascular (CV) events. However, the therapeutic effect of dapagliflozin on angiogenesis in peripheral arterial disease was unclear. This study aimed to explore the effect and mechanism of dapagliflozin on angiogenesis after hindlimb ischemia. We first evaluated the effect of dapagliflozin on post-ischemic angiogenesis in the hindlimbs of rats. Laser doppler imaging was used to detect the hindlimb blood perfusion. In addition, we used immunohistochemistry to detect the density of new capillaries after ischemia. The relevant signaling pathways of dapagliflozin affecting post-ischemic angiogenesis were screened through phosphoproteomic detection, and then the mechanism of dapagliflozin affecting post-ischemic angiogenesis was verified at the level of human umbilical vein endothelial cells (HUVECs). After subjection to excision of the left femoral artery, all rats were randomly distributed into two groups: the dapagliflozin group (left femoral artery resection, receiving intragastric feeding with dapagliflozin (1 mg/kg/d), for 21 consecutive days) and the model group, that is, the positive control group (left femoral artery resection, receiving intragastric feeding with citric acid-sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days). In addition, the control group, that is the negative control group (without left femoral artery resection, receiving intragastric feeding with citric acid-sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days) was added. At day 21 post-surgery, the dapagliflozin-treatment group had the greatest blood perfusion, accompanied by elevated capillary density. The results showed that dapagliflozin could promote angiogenesis after hindlimb ischemia. Then, the ischemic hindlimb adductor-muscle tissue samples from three rats of model group and dapagliflozin group were taken for phosphoproteomic testing. The results showed that the PI3K-Akt-eNOS signaling pathway was closely related to the effect of dapagliflozin on post-ischemic angiogenesis. Our study intended to verify this mechanism from the perspective of endothelial cells. In vitro, dapagliflozin enhanced the tube formation, migration, and proliferation of HUVECs under ischemic and hypoxic conditions. Additionally, the dapagliflozin administration upregulated the expression of angiogenic factors phosphorylated Akt (p-Akt) and phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor A (VEGFA), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. dapagliflozin could promote angiogenesis after ischemia. This effect might be achieved by promoting the activation of the PI3K-Akt-eNOS signaling pathway. This study provided a new perspective, new ideas, and a theoretical basis for the treatment of peripheral arterial disease.

Evaluation of the horizontal approach to the medial malleolar facet in sagittal talar fractures through dorsiflexion and plantarflexion positions.

BACKGROUND: Talar fractures often require osteotomy during surgery to achieve reduction and screw fixation of the fractured fragments due to limited visualization and operating space of the talar articular surface. The objective of this study was to evaluate the horizontal approach to the medial malleolus facet by maximizing exposure through dorsiflexion and plantarflexion positions. METHODS: In dorsiflexion, plantarflexion, and functional foot positions, we respectively obtained the anterior and posterior edge lines of the projection of the medial malleolus on the medial malleolar facet. The talar model from Mimics was imported into Geomagic software for image refinement. Then Solidworks software was used to segment the medial surface of the talus and extend the edge lines from the three positions to project them onto the "semicircular" base for 2D projection. The exposed area in different positions, the percentage of total area it represents, and the anatomic location of the insertion point at the groove between the anteroposternal protrusions of the medial malleolus were calculated. RESULTS: The mean total area of the "semicircular" region on the medial malleolus surface of the talus was 542.10 ± 80.05 mm2. In the functional position, the exposed mean area of the medial malleolar facet around the medial malleolus both anteriorly and posteriorly was 141.22 ± 24.34 mm2, 167.58 ± 22.36mm2, respectively. In dorsiflexion, the mean area of the posterior aspect of the medial malleolar facet was 366.28 ± 48.12 mm2. In plantarflexion, the mean of the anterior aspect of the medial malleolar facet was 222.70 ± 35.32 mm2. The mean overlap area of unexposed area in both dorsiflexion and plantarflexion was 23.32 ± 5.94 mm2. The mean percentage of the increased exposure area in dorsiflexion and plantarflexion were 36.71 ± 3.25% and 15.13 ± 2.83%. The mean distance from the insertion point to the top of the talar dome was 10.69 ± 1.24 mm, to the medial malleolus facet border of the talar trochlea was 5.61 ± 0.96 mm, and to the tuberosity of the posterior tibiotalar portion of the deltoid ligament complex was 4.53 ± 0.64 mm. CONCLUSIONS: Within the 3D model, we measured the exposed area of the medial malleolus facet in different positions and the anatomic location of the insertion point at the medial malleolus groove. When the foot is in plantarflexion or dorsiflexion, a sufficiently large area and operating space can be exposed during surgery. The data regarding the exposed visualization area and virtual screws need to be combined with clinical experience for safer reduction and fixation of fracture fragments. Further validation of its intraoperative feasibility will require additional clinical research.

Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates inflammatory response ulcerative colitis through TLR4/NF-κB signaling pathway.

BACKGROUND: Ulcer colitis (UC) is a chronic, nonspecific, and noninfectious inflammatory bowel disease. Recently, Toll-like receptors (TLRs) have been found to be closely associated with clinical inflammatory diseases. Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging. Moreover, no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. AIM: To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. METHODS: This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021. The patients with UC were divided into two groups (control and experimental). The peripheral blood of the experimental and control groups were collected under aseptic conditions. The expression of TLR4 protein, NF-κB, IL-6, and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug. Linear correlation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17, and P < 0.05 was considered statistically significant. RESULTS: There were no significant differences in the patient characteristics between the control and experimental groups. The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group (P < 0.05). The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group (P < 0.05). The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17 (r = 0.823, P < 0.05). CONCLUSION: Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.

GSDMD in regulated cell death: A novel therapeutic target for sepsis.

Sepsis is a life-threatening multi-organ dysfunction syndrome caused by an abnormal host response to infection. Regulated cell death is essential for maintaining tissue homeostasis and eliminating damaged, infected, or aging cells in multicellular organisms. Gasdermin D, as a member of the gasdermin family, plays a crucial role in the formation of cytoplasmic membrane pores. Research has found that GSDMD plays important roles in various forms of regulated cell death such as pyroptosis, NETosis, and necroptosis. Therefore, through mediating regulated cell death, GSDMD regulates different stages of disease pathophysiology. This article mainly summarizes the concept of GSDMD, its role in regulated cell death, its involvement in organ damage associated with sepsis-related injuries mediated by regulated cell death via GSDMD activation and introduces potential drugs targeting GSDMD that may provide more effective treatment options for sepsis patients through drug modification.

Revealing prognostic insights of programmed cell death (PCD)-associated genes in advanced non-small cell lung cancer.

The management of patients with advanced non-small cell lung cancer (NSCLC) presents significant challenges due to cancer cells' intricate and heterogeneous nature. Programmed cell death (PCD) pathways are crucial in diverse biological processes. Nevertheless, the prognostic significance of cell death in NSCLC remains incompletely understood. Our study aims to investigate the prognostic importance of PCD genes and their ability to precisely stratify and evaluate the survival outcomes of patients with advanced NSCLC. We employed Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate Cox regression analyses for prognostic gene screening. Ultimately, we identified seven PCD-related genes to establish the PCD-related risk score for the advanced NSCLC model (PRAN), effectively stratifying overall survival (OS) in patients with advanced NSCLC. Multivariate Cox regression analysis revealed that the PRAN was the independent prognostic factor than clinical baseline factors. It was positively related to specific metabolic pathways, including hexosamine biosynthesis pathways, which play crucial roles in reprogramming cancer cell metabolism. Furthermore, drug prediction for different PRAN risk groups identified several sensitive drugs explicitly targeting the cell death pathway. Molecular docking analysis suggested the potential therapeutic efficacy of navitoclax in NSCLC, as it demonstrated strong binding with the amino acid residues of C-C motif chemokine ligand 14 (CCL14), carboxypeptidase A3 (CPA3), and C-X3-C motif chemokine receptor 1 (CX3CR1) proteins. The PRAN provides a robust personalized treatment and survival assessment tool in advanced NSCLC patients. Furthermore, identifying sensitive drugs for distinct PRAN risk groups holds promise for advancing targeted therapies in NSCLC.

Ligand-Free Iron-Catalyzed Construction of C-P Bonds via Phosphorylation of Alcohols: Synthesis of Phosphine Oxides and Phosphine Compounds.

An efficient method for the construction of C-P(V) and C-P(III) bonds via the iron-catalyzed phosphorylation of alcohols under ligand-free conditions is disclosed. This strategy represents a straightforward process to prepare a series of phosphine oxides and phosphine compounds in good to excellent yields from the readily available alcohols and P-H compounds. A plausible mechanism is also proposed. We anticipate that this mode of transforming simple alcohols would apply in chemical synthesis widely.

Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation.

Syndecan-binding protein (SDCBP) was reported to stimulate the advancement of esophageal squamous cell carcinoma (ESCC) and could potentially be a target for ESCC treatment. There is a growing corpus of research on the anti-tumor effects of iron chelators; however, very few studies have addressed the involvement of dexrazoxane in cancer. In this study, structure-based virtual screening was employed to select drugs targeting SDCBP from the Food and Drug Administration (FDA)-approved drug databases. The sepharose 4B beads pull-down assay revealed that dexrazoxane targeted SDCBP by interacting with its PDZ1 domain. Additionally, dexrazoxane inhibited ESCC cell proliferation and anchorage-independent colony formation via SDCBP. ESCC cell apoptosis and G2 phase arrest were induced as measured by the flow cytometry assay. Subsequent research revealed that dexrazoxane attenuated the binding ability between SDCBP and EGFR in an immunoprecipitation assay. Furthermore, dexrazoxane impaired EGFR membrane localization and inactivated the EGFR/PI3K/Akt pathway. In vivo, xenograft mouse experiments indicated that dexrazoxane suppressed ESCC tumor growth. These data indicate that dexrazoxane might be established as a potential anti-cancer agent in ESCC by targeting SDCBP.

Effect of ultrasound-guided stellate ganglion block on lung protection for patients undergoing one-lung ventilation.

OBJECTIVE: To explore the potential effect of ultrasound-guided stellate ganglion block (SGB) on lung protection for patients undergoing one-lung ventilation (OLV). METHODS: A total of 123 patients undergoing elective one-lung ventilation surgery were selected as research subjects in this prospective study. These patients were randomly divided into the SGB group, control group and blank group on average. Stellate ganglion block was carried out in the SGB and control groups. Patients in the SGB group were injected with 6 ml mixture of 0.25% ropivacaine hydrochloride and 1% lidocaine hydrochloride, while those in the control group were injected with 6 mL of 0.9% saline. Punctures weren't performed for patients in the blank group. The same induction and maintenance of general anesthesia was adopted for all three groups. Hemodynamics, respiratory parameters and arterial blood gas analysis were recorded after entering the operation room (T0), pre-OLV (T1), 30 min after OLV (T2), 60 min after OLV (T3), at the end of surgery (T4), and 30 min after extubation (T5). Oxygenation index (OI), pulmonary shunt fraction (Qs/Qt) and pH value were compared at different time points. Intravenous serum was collected at T0, T3 and T5 for the detection of surfactant proteins A (SP-A), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and interleukin-10 (IL-10) levels, respectively. The complications related to SGB after surgery and the postoperative pulmonary complications within 72 h were recorded. RESULTS: At T1, T2, and T3, MAP level in SGB group was lower than that in blank and control groups (P<0.05). At T2, and T3, SGB group had lower hear rate (HR), peak airway pressure (Ppeak) and tidal volume (TV) than blank and control groups (all P<0.05). From T2 to T5, SGB group had higher OI but lower Qs/Qt than blank and control groups (both P<0.05). At T3 and T5, SGB group had lower SP-A, IL-6, and MDA levels but higher IL-10 and SOD levels than blank and control groups (all P<0.05). There was one case of hypoxemia in the blank group within 72 h after surgery. CONCLUSION: Ultrasound-guided SGB has lung-protective effects on patients undergoing OLV, which significantly improves patients' OI, reduces intrapulmonary shunts, declines ventilator-induced lung damage, and inhibits inflammatory response as well as oxidative stress (China Clinical Trial Registry, registration number ChiCTR2000033385, https://www.chictr.org.cn).

Effect of ultrasound-guided stellate ganglion block on cerebral oxygen metabolism and S100B protein during carotid endarterectomy.

OBJECTIVE: To investigate the effect of ultrasound-guided stellate ganglion block (SGB) on cerebral oxygen metabolism and serum S100B during carotid endarterectomy (CEA). METHODS: Patients who were prospectively enrolled to receive CEA under elective general anesthesia were randomized into an SGB group and a control group (ChiCTR2000033385). Before anesthesia, the SGB group underwent ipsilateral SGB under ultrasound guidance, while the control group did not. Ultrasound-guided right subclavian internal jugular vein catheterization was performed under general anesthesia. Mean arterial pressure (MAP) and heart rate (HR) were monitored at various time points (T0-T4). Arterial and internal jugular venous bulb blood were collected for blood gas analysis, determining jugular venous oxygen saturation (SjvO2), arteriovenous oxygen difference (AVDO2), cerebral oxygen extraction ratio (COER), lactate production rate (LPR), and lactate-oxygen index (LOI). The serum concentration of S100B in the internal jugular venous bulb at each time point was measured. RESULTS: The results revealed significantly lower HR during anesthesia induction and surgery in the SGB group, with more stable MAP and HR during endotracheal intubation and surgery compared to the control group (P<0.05). The control group exhibited decreases at T3 and a slight increase at T4. SjvO2 was significantly higher in the SGB group, while AVDO2 and COER gradually decreased over time, but they were significantly higher in the control group (P<0.05). LPR and LOI in both groups peaked at T3 and were significantly different between T4 and T2 (P<0.05). Serum S100B levels in both groups rose and then decreased at each time point, but they were consistently lower in the SGB group (P<0.05). CONCLUSION: SGB before CEA effectively suppresses the stress response, maintains intraoperative hemodynamic stability, improves brain tissue oxygen supply, and demonstrates a neuroprotective effect.

LncRNA GAS5 restrains ISO-induced cardiac fibrosis by modulating mir-217 regulation of SIRT1.

Considering the effect of SIRT1 on improving myocardial fibrosis and GAS5 inhibiting occurrence and development of myocardial fibrosis at the cellular level, the aim of the present study was to investigate whether LncRNA GAS5 could attenuate cardiac fibrosis through regulating mir-217/SIRT1, and whether the NLRP3 inflammasome activation was involved in this process. Isoprenaline (ISO) was given subcutaneously to the male C57BL/6 mice to induce myocardial fibrosis and the AAV9 vectors were randomly injected into the left ventricle of each mouse to overexpress GAS5. Primary myocardial fibroblasts (MCFs) derived from neonatal C57BL/6 mice and TGF-ß1 were used to induce fibrosis. And the GAS5 overexpressed MCFs were treated with mir-217 mimics and mir-217 inhibitor respectively. Then the assays of expression levels of NLRP3, Caspase-1, IL-1ß and SIRT1 were conducted. The findings indicated that the overexpression of GAS5 reduced the expression levels of collagen, NLRP3, Capase-1, IL-1ß and SIRT1 in ISO treated mice and TGF-ß1 treated MCFs. However, this effect was significantly weakened after mir-217 overexpression, but was further enhanced after knockdown of mir-217. mir-217 down-regulates the expression of SIRT1, leading to increased activation of the NLRP3 inflammasome and subsequent pyroptosis. LncRNA GAS5 alleviates cardiac fibrosis induced via regulating mir-217/SIRT1 pathway.

The protective effects of Ninjin'yoeito against liver steatosis/fibrosis in a non-alcoholic steatohepatitis model mouse.

Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic form of non-alcoholic fatty liver disease. Liver fibrosis leads to liver cancer and cirrhosis, and drug therapy for NASH remains lacking. Ninjin'yoeito (NYT) has shown antifibrotic effects in a model of liver fibrosis without steatosis but has not been studied for NASH. Therefore, we evaluated the efficacy of NYT in mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a NASH model. Compared with the normal diet group, mice fed CDAHFD showed decreased body weight and increased white adipose tissue, liver weight, and triglyceride content in the liver. Furthermore, a substantial increase in the hepatic concentration of hydroxyproline, expression of α-smooth muscle actin (α-SMA), and transforming growth factor-ß was observed in CDAHFD-fed mice. Masson's trichrome and Picro-Sirius red staining revealed a remarkable increase in collagen fiber compared with the normal diet group. Compared with mice that received CDAHFD alone, those supplemented with NYT exhibited reduced hepatic triglyceride and hydroxyproline levels and α-SMA expression. Additionally, compared with the group fed CDAHFD alone, the stained liver tissues of NYT-treated mice exhibited a reduction in Masson's trichrome- and Picro-Sirius red-positive areas. Locomotor activity was significantly reduced in the CDAHFD-fed group compared with the normal diet group. In the NYT-treated group, the CDAHFD-induced decrease in locomotor activity was significantly suppressed. The findings indicate that NYT inhibited fatty and fibrotic changes in the livers of NASH mice and alleviated the decrease in locomotor activity. Therefore, NYT may serve as a novel therapeutic approach for NASH.

EIF4A3-negatively driven circular RNA ß-catenin (circß-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.

Potential therapeutic strategy for cancer: Multi-dimensional cross-talk between circRNAs and parental genes.

In many ways, circular RNAs (circRNAs) have been demonstrated to be crucial in the onset and advancement of cancer throughout the last ten years and have become a new focus of intense research in the field of RNAs. Accumulating studies have demonstrated that circRNAs can regulate parental gene expression via a variety of biological pathways. Furthermore, research into the complex interactions between circRNAs and their parental genes will shed light on their biological roles and open up new avenues for circRNAs' potential clinical translational uses. However, to date, multi-dimensional cross-talk between circRNAs and parental genes have not been systematically elucidated. Particularly intriguing is circRNA's exploration of tumor targeting, and potential therapeutic uses based on the parental gene regulation perspective. Here, we discuss their biogenesis, take a fresh look at the molecular mechanisms through which circRNAs control the expression of their parental genes in cancer. We further highlight We further highlight the latest circRNA clinical translational applications, including prognostic diagnostic markers, cancer vaccines, gDNA, and so on. Demonstrating the potential benefits and future applications of circRNA therapy.

Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma.

BACKGROUND: Neuroendocrine neoplasms of the female genital tract are rare. AIM: To enhance our clinical understanding of neuroendocrine carcinoma (NEC) of the ovary. METHODS: A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary, analyzing clinicopathological characteristics, treatment modalities, and survival status. RESULTS: The median age at diagnosis was 34.5 years (range: 20 to 62 years). Among the 12 cases, 9 were small cell carcinoma of the ovary and 3 were large cell NEC. Five cases were stage I tumors, one case was stage IV, and six cases were stage III. Eleven patients underwent surgery as part of their treatment. All patients received adjuvant chemotherapy. Among the 12 patients, one patient received radiotherapy, and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy. The median progression-free survival was 13 months, and the median overall survival was 19.5 months. Four cases remained disease-free, while eight cases experienced tumor recurrence, including three cases that resulted in death due to disease recurrence. CONCLUSION: NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes. Surgical resection remains the mainstay of treatment, with some patients benefiting from adjuvant chemoradiation therapy.