New Alkaloids and Steroids from Hydranth of Goniopora columna Corals and Their Inhibiting Lung Cancer Cell Activities.

A new alkaloids, aplysingoniopora A (1), and new configuration pregnane type steroid compound, 9,17-α-pregn-1,4,20-en-3-one (2), and two known pregnane type steroid compounds (3 and 4) were isolated from hydranth of Goniopora columna corals. The compounds structures and absolute configurations were determined by extensive spectroscopic analysis, MS data, single-crystal X-ray diffraction analysis and quantum chemical calculation. The anticancer effect of the compounds were explored in human non-small-cell lung cancer (NSCLC) A549 cell lines. As the results, the compound 3 and 4 induces toxicity and has proliferation inhibitory effects on A549 cells (IC50=58.99 µM and 58.77 µM, respectively) in vitro.

Clinical features and risk factors for postoperative recurrence in patients with Cushing's syndrome of different etiologies.

The clinical characteristics of Cushing's syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.

A Novel Polyamino Acid Sulfur Dioxide Prodrug Synergistically Elevates ROS with ß-Lapachone in Cancer Treatment.

Due to the distorted redox balance, cancer cells are considered more vulnerable to excessive reactive oxygen species (ROS). In a variety of oxidative stress-related therapies, gas therapy has emerged as a new therapeutic strategy owing to its efficacy and biosafety. Herein, a newly-discovered gasotransmitter sulfur dioxide (SO2) and a tumor specific ROS generation agent ß-lapachone (Lapa) were firstly combined for anticancer therapy. Firstly, amphiphilic glutathione (GSH) responsive polypeptide SO2 prodrug PEG-b-poly(Lys-DNs) was synthesized by ring opening polymerization of SO2-containing N-carboxyanhydride. Then, Lapa was encapsulated into the polymeric micelles with loading content of 8.6 % and loading efficiency of 51.6 %. The obtained drug-loaded nanoparticles (NPs(Lapa)) exhibited a fast release of Lapa and SO2 in the stimuli of 10 mM GSH in PBS. Subsequently, in vitro experiment showed that NPs(Lapa) exhibited obvious cytotoxicity towards 4 T1 cancer cells at a concentration of 2.0 µg/mL, which may be attributed to the depletion of intracellular GSH and upregulation of ROS level both by SO2 release and by the ROS generation from lapachone transformation. In vivo fluorescence imaging showed that the NPs were gradually enriched in tumor tissues in 24 h, probably due to the enhanced permeability and retention effect of NPs. Finally, NPs(Lapa) showed the best anticancer effect in 4 T1 tumor bearing mice with a tumor inhibiting rate (IRT) of 61 %, whereas IRT for free Lapa group was only 23.6 %. This work may be a new attempt to combine SO2 gas therapy with ROS inducer for anticancer therapy through oxidative stress.

Drug-coated balloons: A better revascularization strategy in patients with multivessel coronary artery disease undergoing one-stop hybrid coronary revascularization surgery.

BACKGROUND: The optimal revascularization strategy for non-left anterior descending coronary artery (LAD) lesions during one-stop hybrid coronary revascularization (HCR) surgery lacks current evidence. AIMS: This study aimed to compare the outcomes of the drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in patients with non-small non-LAD lesions undergoing one-stop HCR. METHODS: A total of 141 consecutive patients with multivessel coronary artery disease (MVCAD) undergoing one-stop HCR between June 1, 2018 and March 1, 2022 were retrospectively included in this study. In-hospital outcomes and mid-term major adverse cardiovascular and cerebrovascular events (MACCE) were observed. Kaplan-Meier curve analysis was used to evaluate the MACCE-free survival rate. The Cox proportional hazard model was used to identify risk factors of mid-term MACCE. RESULTS: Thirty-eight and 103 patients received only DCB or DES therapy, respectively, in this study. There were no significant differences in demographic characteristics and laboratory parameters between the two groups. The in-hospital MACCE rate in the DES group was numerically higher than that in the DCB group (9.7% vs. 5.3%, respectively), but the difference was not statistically significant (P = 0.4). The incidence of MACCE after patients' discharge was significantly higher in the DES group (22% vs. 5.3%, respectively, P = 0.02) during a median follow-up of 20 months. After multivariable Cox proportional hazard analysis, DCB therapy was independently associated with reduced risk of mid-term MACCE (hazard ratio, 0.21; 95% confidence interval, 0.06-0.91; P = 0.04). CONCLUSION: For patients with MVCAD undergoing one-stop HCR, DCB therapy may be the optimal revascularization strategy for non-small non-LAD coronary artery lesions with a significantly lower rate of mid-term MACCE.

Accuracy of liver metastasis detection and characterization: Dual-energy CT versus single-energy CT with deep learning reconstruction.

PURPOSE: To assess whether image quality differences between SECT (single-energy CT) and DECT (dual-energy CT 70 keV) with equivalent radiation doses result in altered detection and characterization accuracy of liver metastases when using deep learning image reconstruction (DLIR), and whether DECT spectral curve usage improves accuracy of indeterminate lesion characterization. METHODS: In this prospective Health Insurance Portability and Accountability Act-compliant study (March through August 2022), adult men and non-pregnant adult women with biopsy-proven colorectal cancer and liver metastases underwent SECT (120 kVp) and a DECT (70 keV) portovenous abdominal CT scan using DLIR in the same breath-hold (Revolution CT ES; GE Healthcare). Participants were excluded if consent could not be obtained, if there were nonequivalent radiation doses between the two scans, or if the examination was cancelled/rescheduled. Three radiologists independently performed lesion detection and characterization during two separate sessions (SECT DLIRmedium and DECT DLIRhigh) as well as reported lesion confidence and overall image quality. Hounsfield units were measured. Spectral HU curves were provided for any lesions rated as indeterminate. McNemar's test was used to test the marginal homogeneity in terms of diagnostic sensitivity, accuracy and lesion detection. A generalized estimating equation method was used for categorical outcomes. RESULTS: 30 participants (mean age, 58 years ± 11, 21 men) were evaluated. Mean CTDIvol was 34 mGy for both scans. 141 lesions (124 metastases, 17 benign) with a mean size of 0.8 cm ± 0.3 cm were identified. High scores for image quality (scores of 4 or 5) were not significantly different between DECT (N = 71 out of 90 total scores from the three readers) and SECT (N = 62) (OR, 2.01; 95% CI:0.89, 4.57; P = 0.093). Equivalent image noise to SECT DLIRmed (HU SD 10 ± 2) was obtained with DECT DLIRhigh (HU SD 10 ± 3) (P = 1). There was no significant difference in lesion detection between DECT and SECT (140/141 lesions) (99.3%; 95% CI:96.1%, 100%).The mean lesion confidence scores by each reader were 4.2 ± 1.3, 3.9 ± 1.0, and 4.8 ± 0.8 for SECT and 4.1 ± 1.4, 4.0 ± 1.0, and 4.7 ± 0.8 for DECT (odds ratio [OR], 0.83; 95% CI: 0.62, 1.11; P = 0.21). Small lesion (≤5mm) characterization accuracy on SECT and DECT was 89.1% (95% CI:76.4%, 96.4%; 41/46) and 84.8% (71.1%, 93.7%; 39/46), respectively (P = 0.41). Use of spectral HU lesion curves resulted in 34 correct changes in characterizations and no mischaracterizations. CONCLUSION: DECT required a higher strength of DLIR to obtain equivalent noise compared to SECT DLIR. At equivalent radiation doses and image noise, there was no significant difference in subjective image quality or observer lesion performance between DECT (70 keV) and SECT. However, DECT spectral HU curves of indeterminate lesions improved characterization.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction.

BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.

Thiol-Responsive Polypeptide Sulfur Dioxide Prodrug Nanoparticles for Effective Tumor Inhibition.

Sulfur dioxide (SO2) based gas therapy has emerged as a novel anticancer therapeutic strategy because of its high therapeutic efficacy and biosafety. To precisely adjust the SO2 content and control gas release, herein, a thiol-responsive polypeptide SO2 prodrug mPEG-block-poly(2-amino-6-(2,4-dinitrophenylsulfonamido)hexanoic acid) (PEG-b-PLys-DNs) was designed and facilely synthesized by polymerization of a novel N-carboxyanhydride SO2-NCA. The anticancer potential of the self-assembled nanoparticles (SO2-NPs) was investigated in detail. First, PEG-b-PLys-DNs were synthesized by ring-opening polymerization of SO2-NCA, which self-assembled into NPs sized 88.4 nm in aqueous. Subsequently, SO2-NPs were endocytosed into 4T1 cells and quickly released SO2 under a high concentration of glutathione in tumor cells. This process depleted cellular glutathione, generated reactive oxygen species, and dramatically increased oxidative stress, which led to cancer cell apoptosis. Finally, the in vivo anticancer efficacy of SO2-NPs was verified in 4T1-tumor-bearing mice. Our results indicated that this novel SO2 polymeric prodrug has great potential in eradicating tumors.

How Do Cancer-Specific Computed Tomography Protocols Compare With the American College of Radiology Dose Index Registry? An Analysis of Computed Tomography Dose at 2 Cancer Centers.

BACKGROUND: Little guidance exists on how to stratify radiation dose according to diagnostic task. Changing dose for different cancer types is currently not informed by the American College of Radiology Dose Index Registry dose survey. METHODS: A total of 9602 patient examinations were pulled from 2 National Cancer Institute designated cancer centers. Computed tomography dose (CTDI vol ) was extracted, and patient water equivalent diameter was calculated. N-way analysis of variance was used to compare the dose levels between 2 protocols used at site 1, and three protocols used at site 2. RESULTS: Sites 1 and 2 both independently stratified their doses according to cancer indications in similar ways. For example, both sites used lower doses ( P < 0.001) for follow-up of testicular cancer, leukemia, and lymphoma. Median dose at median patient size from lowest to highest dose level for site 1 were 17.9 (17.7-18.0) mGy (mean [95% confidence interval]) and 26.8 (26.2-27.4) mGy. For site 2, they were 12.1 (10.6-13.7) mGy, 25.5 (25.2-25.7) mGy, and 34.2 (33.8-34.5) mGy. Both sites had higher doses ( P < 0.001) between their routine and high-image-quality protocols, with an increase of 48% between these doses for site 1 and 25% for site 2. High-image-quality protocols were largely applied for detection of low-contrast liver lesions or subtle pelvic pathology. CONCLUSIONS: We demonstrated that 2 cancer centers independently choose to stratify their cancer doses in similar ways. Sites 1 and 2 dose data were higher than the American College of Radiology Dose Index Registry dose survey data. We thus propose including a cancer-specific subset for the dose registry.

Comparisons of different new-generation transcatheter aortic valve implantation devices for patients with severe aortic stenosis: a systematic review and network meta-analysis.

BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.

An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509. / 北部湾珊瑚来源构巢裸胞壳菌GXIMD 02509ä¸­å ·æœ‰ç»†èƒžæ¯’æ€§çš„ä¸€ä¸ªå¤šç¡«ä»£äºŒé ®å“Œå—ªç”Ÿç‰©ç¢±å’Œç»“æž„å¤šæ ·çš„èŠ³é¦™èšé ®ç±»åŒ–åˆç‰©.

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.

Oncology-specific radiation dose and image noise reference levels in adult abdominal-pelvic CT.

OBJECTIVES: To provide our oncology-specific adult abdominal-pelvic CT reference levels for image noise and radiation dose from a high-volume, oncologic, tertiary referral center. METHODS: The portal venous phase abdomen-pelvis acquisition was assessed for image noise and radiation dose in 13,320 contrast-enhanced CT examinations. Patient size (effective diameter) and radiation dose (CTDIvol) were recorded using a commercial software system, and image noise (Global Noise metric) was quantified using a custom processing system. The reference level and range for dose and noise were calculated for the full dataset, and for examinations grouped by CT scanner model. Dose and noise reference levels were also calculated for exams grouped by five different patient size categories. RESULTS: The noise reference level was 11.25 HU with a reference range of 10.25-12.25 HU. The dose reference level at a median effective diameter of 30.7 cm was 26.7 mGy with a reference range of 19.6-37.0 mGy. Dose increased with patient size; however, image noise remained approximately constant within the noise reference range. The doses were 2.1-2.5 times than the doses in the ACR DIR registry for corresponding patient sizes. The image noise was 0.63-0.75 times the previously published reference level in abdominal-pelvic CT examinations. CONCLUSIONS: Our oncology-specific abdominal-pelvic CT dose reference levels are higher than in the ACR dose index registry and our oncology-specific image noise reference levels are lower than previously proposed image noise reference levels. ADVANCES IN KNOWLEDGE: This study reports reference image noise and radiation dose levels appropriate for the indication of abdomen-pelvis CT examination for cancer diagnosis and staging. The difference in these reference levels from non-oncology-specific CT examinations highlight a need for indication-specific, dose index and image quality reference registries.

Elabela blunts doxorubicin-induced oxidative stress and ferroptosis in rat aortic adventitial fibroblasts by activating the KLF15/GPX4 signaling.

Doxorubicin (DOX) is a chemotherapeutic drug for a variety of malignancies, while its application is restricted by the cardiovascular toxic effects characterized by oxidative stress. Ferroptosis is a novel iron-dependent regulated cell death driven by lipid peroxidation. Our study aimed to investigate the role of Elabela (ELA) in DOX-induced oxidative stress and ferroptosis. In cultured rat aortic adventitial fibroblasts (AFs), stimulation with DOX dramatically induced cytotoxicity with reduced cell viability and migration ability, and enhanced lactate dehydrogenase (LDH) activity. Importantly, ELA and ferrostatin-1 (Fer-1) mitigated DOX-mediated augmentation of reactive oxygen species (ROS) in rat aortic AFs, accompanied by upregulated levels of Nrf2, SLC7A11, GPX4, and GSH. In addition, ELA reversed DOX-induced dysregulation of apoptosis- and inflammation-related factors including Bax, Bcl2, interleukin (IL)-1ß, IL6, IL-10, and CXCL1. Intriguingly, knockdown of Krüppel-like factor 15 (KLF15) by siRNA abolished ELA-mediated alleviation of ROS production and inflammatory responses. More importanly, KLF15 siRNA impeded the beneficial roles of ELA in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders.

Pathogenesis, clinical features, and treatment of plurihormonal pituitary adenoma.

Plurihormonal pituitary adenoma (PPA) is a type of pituitary tumor capable of producing two or more hormones and usually presents as an aggressive, large adenoma. As yet, its pathogenesis remains unclear. This is the first study to systematically summarize the underlying pathogenesis of PPA. The pathogenesis is related to plurihormonal primordial stem cells, co-transcription factors, hormone co-expression, differential gene expression, and cell transdifferentiation. We conducted a literature review of PPA and analyzed its clinical characteristics. We found that the average age of patients with PPA was approximately 40 years, and most showed only one clinical symptom. The most common manifestation was acromegaly. Currently, PPA is treated with surgical resection. However, recent studies suggest that immunotherapy may be a potentially effective treatment.

Treatment of Primary Pigmented Nodular Adrenocortical Disease.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS), which mainly occurs in children and young adults. Treatment options with proven clinical efficacy for PPNAD include adrenalectomy (bilateral or unilateral adrenalectomy) and drug treatment to control hypercortisolemia. Previously, the main treatment of PPNAD is bilateral adrenal resection and long-term hormone replacement after surgery. In recent years, cases reports suggest that unilateral or subtotal adrenal resection can also lead to long-term remission in some patients without the need for long-term hormone replacement therapy. Medications for hypercortisolemia, such as Ketoconazole, Metyrapone and Mitotane et.al, have been reported as a preoperative transition for in some patients with severe hypercortisolism. In addition, tryptophan hydroxylase inhibitor, COX2 inhibitor Celecoxib, somatostatin and other drugs targeting the possible pathogenic mechanisms of the disease are under study, which are expected to be applied to the clinical treatment of PPNAD in the future. In this review, we summarize the recent progress on treatment of PPNAD, in which options of surgical methods, research results of drugs acting on possible pathogenic mechanisms, and the management during gestation are described in order to provide new ideas for clinical treatment.

Combined intervention with N-acetylcysteine and desipramine alleviated silicosis development by regulating the Nrf2/HO-1 and ASMase/ceramide signaling pathways.

Silicosis is a systemic disease characterized by diffuse fibrosis of the lung tissue caused by long-term inhalation of large amounts of free silica (SiO2) dust. The pathogenesis of silicosis has not been fully elucidated, and there is a lack of effective treatment methods. N-acetylcysteine (NAC) can potentially treat pulmonary fibrosis by exerting antioxidant effects. Desipramine (DMI) can influence pulmonary fibrosis development by inhibiting acid sphingomyelinase (ASMase) activity and regulating ceramide concentrations. Both can interfere with pulmonary fibrosis through different mechanisms, but the intervention effects of NAC combined with DMI on silicosis fibrosis have not been reported. Therefore, this study established a rat silicosis model using a single tracheal drip of SiO2 dust suspension in Wistar rats to investigate the effect of NAC combined with DMI on SiO2 dust-induced silicosis and its related molecular mechanisms. The histopathological examination of the SiO2 dust-induced silicosis rats suggested that NAC and DMI alone or in combination could decrease the severity of pulmonary fibrosis in rats. The combined intervention had a better effect on reducing fibrosis than the individual interventions. NAC and DMI, alone or in combination, decreased the levels of markers related to pulmonary fibrosis in rats (smooth muscle α-actin (α-SMA), collagen (Col) I, Col III, hydroxyproline (HYP), inflammatory factors (transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α (TNF-α)), and lipid peroxidase malondialdehyde (MDA)). The nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme-oxygenase-1 (HO-1) and ASMase/ceramide pathways were inhibited to some extent by increasing the superoxide dismutase (SOD) levels of antioxidant enzymes and 8-iso-prostaglandin F2α (8-iso-PGF2α) levels of lipid peroxides. The combined intervention and NAC alone inhibited the SiO2 dust-induced elevation of matrix metalloproteinase 1 (MMP-1) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1), but the effect was not significant in the DMI-treated group. Combining DMI and NAC inhibited Col I deposition and reduced HO-1, TIMP-1, and ASMase levels in lung tissues compared to individual treatments. In summary, the SiO2 dust could induce oxidative stress and inflammation in rats, resulting in an imbalance in extracellular matrix (ECM) synthesis/catabolism and ASMase/ceramide signaling pathway activation, leading to silicosis development.The combined intervention of DMI and NAC may synergistically regulate the Nrf2/HO-1 pathway, maintain the anabolic balance of the ECM, inhibit ASMase/ceramide signaling pathway activation by suppressing the inflammatory response and effectively delay silicosis fibrosis progression.

Mechanism, diagnosis, and treatment of cyclic Cushing's syndrome: A review.

Cushing's syndrome (CS) is caused by hypercortisolemia, leading to the occurrence of characteristic clinical symptoms. A small number of patients with CS have periodic and intermittent increases in cortisol levels, resulting in recurrent episodes of clinical symptoms. Such patients are known as having cyclic CS (CCS). The cortisol secretion cycle of patients with CCS is unpredictable, and laboratory tests often show negative results during the normal cortisol secretion period; therefore, the diagnosis and treatment of the disease are currently difficult. Although the pathogenesis of CCS remains uncertain, recent studies have suggested that it may be closely related to hypothalamic factors, feedback mechanisms, and tumor infarction. Our review summarizes the current state of research on the potential mechanisms, diagnosis, and treatment of CS and provides an outlook for future studies.

A glutathione-responsive sulfur dioxide polymer prodrug selectively induces ferroptosis in gastric cancer therapy.

Nanoparticle-induced ferroptosis has been proven to be an appealing strategy in cancer treatment. Previously, we reported the synthesis of an amphiphilic polymer prodrug of SO2, mPEG-PLG(DNs), which could self-assemble to formulate nanoparticles (NP-DNs) and trigger cancer cell death by GSH consumption and SO2 release. In the current study, the potential mechanism of NP-DNs-induced cell death was further investigated. We demonstrated that NP-DNs exhibited efficient antitumor activity against gastric cancer via ferroptosis. NP-DNs could selectively accelerate lipid peroxidation through GSH depletion and SO2 generation in gastric cancer cells. In addition, the NP-DNs-induced GPX4 reduction played a collaborative role in ferroptosis. Concurrently, in vivo evaluations revealed that NP-DNs not only exhibited excellent antitumor efficiency via ferroptosis but also caused little systemic toxicity in mice. All the results showed that NP-DNs would be a promising prodrug in precision-targeted ferroptosis therapy.

Anti-Osteoclastogenic and Antibacterial Effects of Chlorinated Polyketides from the Beibu Gulf Coral-Derived Fungus Aspergillus unguis GXIMD 02505.

One new depsidone derivative, aspergillusidone H (3), along with seven known biosynthetically related chlorinated polyketides, were obtained from the Beibu Gulf coral-derived fungus Aspergillus unguis GXIMD 02505. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. Notably, the X-ray crystal structure of 2 and the previously unknown absolute configuration of 8, assigned by ECD calculations, are described here for the first time. Compounds 1-5, 7 and 8 exhibited inhibition of lipopolysaccharide (LPS)-induced NF-κB in RAW 264.7 macrophages at 20 µM. In addition, the two potent inhibitors (2 and 7) dose-dependently suppressed RANKL-induced osteoclast differentiation without any evidence of cytotoxicity in bone marrow macrophages cells (BMMs). This is the first report of osteoclastogenesis inhibitory activity for the metabolites of these kinds. Besides, compounds 1, 2, 4, and 6-8 showed inhibitory activity against marine biofilm-forming bacteria, methicillin-resistant Staphylococcus aureus, Microbulbifer variabilis, Marinobacterium jannaschii, and Vibrio pelagius, with their MIC values ranging from 2 to 64 µg/mL. These findings provide a basis for further development of chlorinated polyketides as potential inhibitors of osteoclast differentiation and/or for use as anti-fouling agents.

Knockdown of forkhead box protein P1 alleviates hypoxia reoxygenation injury in H9c2 cells through regulating Pik3ip1/Akt/eNOS and ROS/mPTP pathway.

Forkhead box protein P1 (Foxp1) exerts an extensive array of physiological and pathophysiological impacts on the cardiovascular system. However, the exact function of myocardial Foxp1 in myocardial ischemic reperfusion injury (MIRI) stays largely vague. The hypoxia reoxygenation model of H9c2 cells (the rat ventricular myoblasts) closely mimics myocardial ischemia-reperfusion injury. This report intends to research the effects and mechanisms underlying Foxp1 on H9c2 cells in response to hypoxia (12 h)/reoxygenation (4 h) (HR) stimulation. Expressions of Foxp1 and Phosphatidylinositol 3-kinase interacting protein 1 (Pik3ip1) were both upregulated in ischemia/reperfusion (IR)/HR-induced injury. Stimulation through HR led to marked increases in cellular apoptosis, mitochondrial dysfunction, and superoxide generation in H9c2 cells, which were rescued with knockdown of Foxp1 by siRNA. Silence of Foxp1 depressed expression of Pik3ip1 directly activated the PI3K/Akt/eNOS pathway and promoted nitric oxide (NO) release. Moreover, the knockdown of Foxp1 blunted HR-induced enhancement of reactive oxygen species (ROS) generation, thus alleviating excessive persistence of mitochondrial permeability transition pore (mPTP) opening and decreased mitochondrial apoptosis-associated protein expressions in H9c2 cells. Meanwhile, these cardioprotective effects can be abolished by LY294002, NG-nitro-L-arginine methyl ester (L-NAME), and Atractyloside (ATR), respectively. In summary, our findings indicated that knockdown of Foxp1 prevented HR-induced encouragement of apoptosis and oxidative stress via PI3K/Akt/eNOS signaling activation by targeting Pik3ip1 and improved mitochondrial function by inhibiting ROS-mediated mPTP opening. Inhibition of Foxp1 may be a promising therapeutic avenue for MIRI.

Use of bag-filter gas dust in anaerobic digestion of cattle manure for boosting the methane yield and digestate utilization.

Plenty of refractory and environmentally hazardous bag-filter gas dust (BGD) is produced in the iron-making process. The effects of untreated BGD on anaerobic digestion (AD) with cattle manure were investigated. The BGD had the potential to boost the methane yield and digestate utilization considerably. The digester with 2.0 wt% BGD gained the highest methane yield (256.3 mL/g VS) and chemical oxygen demand removal rate (56.8%), 51.3% and 20.1% higher than that (169.4 mL/g VS, 47.3%) of the control group, respectively. The digestates with BGD possessed a utilization potential with the stability of 49.5-57.9% and fertility of 4.65-4.86%. Electrochemical measurements demonstrated that 2.0 wt% BGD improved the electron transport capacity of the AD system and increased the limiting current and redox peak current by 40.3% and 12.9%, respectively. A strategy for understanding the BGD reinforcing methanogenesis was proposed. This work also provides a technical support for recycling the BGD.