Melatonin Alleviates Acute Respiratory Distress Syndrome by Inhibiting Alveolar Macrophage NLRP3 Inflammasomes Through the ROS/HIF-1α/GLUT1 Pathway.

Sepsis-induced acute respiratory distress syndrome (ARDS) is a devastating clinically severe respiratory disorder, and no effective therapy is available. Melatonin (MEL), an endogenous neurohormone, has shown great promise in alleviating sepsis-induced ARDS, but the underlying molecular mechanism remains unclear. Using a lipopolysaccharide (LPS)-treated mouse alveolar macrophage cell line (MH-S) model, we found that MEL significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation in LPS-treated macrophages, whereas this inhibitory effect of MEL was weakened in MH-S cells transfected with glucose transporter 1 (GLUT1) overexpressing lentivirus. Further experiments showed that MEL downregulated GLUT1 via inhibition of hypoxia-inducible factor 1 (HIF-1α). Notably, hydrogen peroxide (H2O2), a donor of reactive oxygen species (ROS), significantly increased the level of intracellular ROS and inhibited the regulatory effect of MEL on the HIF-1α/GLUT1 pathway. Interestingly, the protective effect of MEL was attenuated after the knockdown of melatonin receptor 1A (MT1) in MH-S cells. We also confirmed in vivo that MEL effectively downregulated the HIF-1α/GLUT1/NLRP3 pathway in the lung tissue of LPS-treated mice, as well as significantly ameliorated LPS-induced lung injury and improved survival in mice. Collectively, these findings revealed that MEL regulates the activation of the ROS/HIF-1α/GLUT1/NLRP3 pathway in alveolar macrophages via the MT1 receptor, further alleviating sepsis-induced ARDS.

Association between Body Composition and Peripheral Neurotoxicity in Cancer Patients from North China Taking Nab-Paclitaxel.

Determine the association of lean body mass (LBM) on the incidence and severity of peripheral neurotoxicity in cancer patients who received nab-paclitaxel alone or combined with cisplatin or carboplatin. This prospective clinical study examined 32 cancer patients classified into a sarcopenia or non-sarcopenia group according to the Asian L3 vertebra skeletal muscle index (L3-SMI) at Ordos Central Hospital (China) from December 2020-2021, to compare the incidence and severity of neurotoxicity and analizing the relationship between nab-paclitaxel dose per kg LBM and neurotoxicity. There were 18 patients (56.25%) in the sarcopenia group and 14 (43.75%) in the non-sarcopenia group. The incidences of peripheral and severe neurotoxicity were higher in the sarcopenia group (both P < 0.05). Patients in three different body surface area (BSA) groups received the same nab-paclitaxel dose (260 mg/m2 BSA). However, when patients were divided into three groups according to LBM, they received different doses (low-LBM: 15.18 mg/kg LBM, middle-LBM: 12.82 mg/kg LBM, and high-LBM: 11.14 mg/kg LBM). The incidence of grade-C or higher neurotoxicity of these three groups was 61.54% (8/13), 20.00% (1/5), and 11.11% (1/9). Sarcopenia and a higher dose of nab-paclitaxel per kg LBM were associated with peripheral and severe neurotoxicity. Chemotherapy dosing based on body composition may reduce neurotoxicity in patients receiving nab-paclitaxel.Registration number of Clinical Trial: ChiCTR2000040918.

Hsa_Circ_0104206 is An Oncogenic circRNA in Colon Cancer by Targeting Mir-188-3p/CCNA2 Axis.

The identification of specific biomarkers is essential to improve cancer therapy, and circular RNAs (circRNAs) have great potency to be biomarkers. We harbor the goal to unveil the role of circ_0104206 in colon cancer (CC). The relative expressions of circ_0104206, miR-188-3p and CCNA2 in different groups were studied using real-time quantitative PCR (qPCR) or western blotting. The proliferative and migratory capacity of cancer cells were monitored via CCK-8, colony formation and Transwell assays. The transplanted tumor models were generated to analyze circ_0104206's role in vivo. The putative relationship between miR-188-3p and circ_0104206 or CCNA2 by bioinformatics tools was testified through dual-luciferase or RIP assay. The abnormal elevation of circ_0104206 expression was observed in CC. Circ_0104206 silencing repressed CC cell proliferative and migratory behaviors, and also decelerated tumor development in animal models. MiR-188-3p was directly targeted by circ_0104206, and its inhibitor had the ability to reverse the anticancer effects of circ_0104206 silencing on CC cells. CCNA2 was a target downstream of circ_0104206/miR-188-3p network. Moreover, the repressive effects of CCNA2 absence on cell proliferation and migration were attenuated by miR-188-3p inhibitor. In conclusion, Circ_0104206 plays oncogenic roles in CC via the implication of miR-188-3p/CCNA2 network, which further discloses CC pathogenesis and supplies potential markers for CC.

Research trends in ferroptosis since the origin of the concept: A bibliometric analysis.

Ferroptosis is a newly characterized form of regulated cell death. This bibliometric analysis identified the scientific output, leading institutions and research teams, current research hotspots and trends in research on ferroptosis since the origin of the concept. We searched the Science Citation Index Expanded of Web of Science Core Collection for papers on ferroptosis up to 3 June 2022. The acquired data were analysed and visualized by Bibliometrix package and VOSviewer. The study ultimately included 3511 relevant papers, and annual production in this field has grown rapidly in recent years. Institutions and scholars from China contributed the most work, but the impact of their research was much less than that of the United States. Prof. Brent R. Stockwell's team from Columbia University in the United States has a very strong academic influence in the field. Front Cell Dev Biol published the most papers in the field of ferroptosis. As the keywords of the papers in this field changed from the most numerous 'oxidative stress', 'cell-death', 'iron', 'expression', and 'lipid-peroxidation', to 'prognosis', 'immunotherapy', 'progression', 'tumour microenvironment', and 'colorectal cancer', the hotspot of ferroptosis research is gradually shifting from basic research to clinical translational research. The mechanism of tumour formation and treatment will become the frontier in the field of ferroptosis research in the future.

Marine-Derived Natural Product HDYL-GQQ-495 Targets P62 to Inhibit Autophagy.

Autophagy is widely implicated in pathophysiological processes such as tumors and metabolic and neurodegenerative disorders, making it an attractive target for drug discovery. Several chemical screening approaches have been developed to uncover autophagy-modulating compounds. However, the modulation capacity of marine compounds with significant pharmacological activities is largely unknown. We constructed an EGFPKI-LC3B cell line using the CRISPR/Cas9 knock-in strategy in which green fluorescence indicated endogenous autophagy regulation. Using this cell line, we screened a compound library of approximately 500 marine natural products and analogues to investigate molecules that altered the EGFP fluorescence. We identified eight potential candidates that enhanced EGFP fluorescence, and HDYL-GQQ-495 was the leading one. Further validation with immunoblotting demonstrated that cleaved LC3 was increased in dose- and time-dependent manners, and the autophagy adaptor P62 showed oligomerization after HDYL-GQQ-495 treatment. We also demonstrated that HDYL-GQQ-495 treatment caused autophagy substrate aggregation, which indicated that HDYL-GQQ-495 serves as an autophagy inhibitor. Furthermore, HDYL-GQQ-495 induced Gasdermin E (GSDME) cleavage and promoted pyroptosis. Moreover, HDYL-GQQ-495 directly combined with P62 to induce P62 polymerization. In P62 knockout cells, the cleavage of LC3 or GSDME was blocked after HDYL-GQQ-495 treatment. The EGFPKI-LC3B cell line was an effective tool for autophagy modulator screening. Using this tool, we found a novel marine-derived compound, HDYL-GQQ-495, targeting P62 to inhibit autophagy and promote pyroptosis.

Olanzapine (5 mg) plus standard triple antiemetic therapy for the prevention of multiple-day cisplatin hemotherapy-induced nausea and vomiting: a prospective randomized controlled study.

OBJECTIVE: A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. METHODS: Patients who received a 3-day cisplatin-based chemotherapy (25 mg/m2/d) were given either 5 mg olanzapine plus triple therapy with aprepitant, tropisetron, and dexamethasone (quadruple group) or 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant (triplet group). The primary endpoint was the complete response (CR) in the overall phase (OP) (0-120 h) between quadruple group and triplet group. The secondary endpoints were the CR in the acute phase (AP) (0-24 h) and delayed phase (DP) (25-120 h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical. CONCLUSION: It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.

A Comparison of the Efficacy of 5 mg Olanzapine and Aprepitant in the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting.

Objective: The significance of this article is to talk about aprepitant and olanzapine 5 mg, compare them, and deeply explore the safety or effectiveness during the whole process of multiple-day cisplatin chemotherapy-induced vomiting and nausea. Methods: This trial was randomized and prospective. It is needed to receive cisplatin chemotherapy (25 mg/m2/d) for three days. Its patients would need to choose to use 5 mg olanzapine or aprepitant for this treatment, combined with 5-HT3 receptor antagonist plus dexamethasone. The primary endpoints were the total protection (TP) during the acute phase (AP) (0-24 hours), delayed phase (DP) (25-120 hours), and overall phase (OP) (0-120 h) between the two groups. The secondary endpoints were the complete response (CR) and total control (TC) during the three phases. The first time of the whole process is particularly important and needs to be observed vigorously. However, the time of the patient's first vomiting symptom is also compared accurately by using the Kaplan-Meier curve. The functional life index vomiting (FLIE) was used to calculate and carefully evaluate the serious impact of nausea and vomiting (CINV) induced by the whole chemotherapy process on the quality of life. About olanzapine, its related symptoms and other side effects and aprepitant were also recorded. Results: (1) The primary endpoint TP rates of the olanzapine and aprepitant groups were similar; for the AP, they were 94.23% (98/104) vs. 95.45% (98/106) P=0.61(P=0.61); for the DP, they were 54.81% (57/104) vs. 54.72% (58/106) (P=0.99), and for the OP, the values were 53.79% (58/105) and 55.31% (56/104), respectively (P=0.99). The secondary endpoints, the TC rates, and CR rates were also comparable in the three phases (P > 0.05). (2) After research and display, the results showed that there was no significant difference between the two groups when they were used for the first time of vomiting and the FLIE index (P > 0.05). (3) The main olanzapine-related adverse event was drowsiness, while that of aprepitant was constipation. Conclusion: The efficacy of 5 mg olanzapine was similar to that of aprepitant, and it also showed an advantageous economic potency ratio in preventing CINV induced by multiple-day cisplatin chemotherapy with increased sedation side effects.

Mitophagy in carcinogenesis, drug resistance and anticancer therapeutics.

The mitochondrion is an organelle that plays a vital role in energy production, cytoplasmic protein degradation and cell death. Mitophagy is an autophagic procedure that specifically clears damaged mitochondria and maintains its homeostasis. Emerging evidence indicates that mitophagy is involved in many physiological processes, including cellular homeostasis, cellular differentiation and nerve protection. In this review, we describe the regulatory mechanisms of mitophagy in mammals and yeasts and highlight the recent advances relevant to its function in carcinogenesis and drug resistance. Finally, a section has been dedicated to describing the role of mitophagy in anticancer therapeutics, which is a new frontier that offers a precise and promising strategy.

Gossypol, a novel modulator of VCP, induces autophagic degradation of mutant huntingtin by promoting the formation of VCP/p97-LC3-mHTT complex.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein (mHTT) in the brain. Decreasing mHTT is a potential strategy for therapeutic purpose of HD. Valosin-containing protein (VCP/p97) is a crucial regulator of proteostasis, which regulates the degradation of damaged protein through proteasome and autophagy pathway. Since VCP has been implicated in pathogenesis of HD as well as other neurodegenerative diseases, small molecules that specifically regulate the activity of VCP may be of therapeutic benefits for HD patients. In this study we established a high-throughput screening biochemical assay for VCP ATPase activity measurement and identified gossypol, a clinical approved drug in China, as a novel modulator of VCP. Gossypol acetate dose-dependently inhibited the enzymatic activity of VCP in vitro with IC50 of 6.53±0.6 µM. We further demonstrated that gossypol directly bound to the interface between the N and D1 domains of VCP. Gossypol acetate treatment not only lowered mHTT levels and rescued HD-relevant phenotypes in HD patient iPS-derived Q47 striatal neurons and HD knock-in mouse striatal cells, but also improved motor function deficits in both Drosophila and mouse HD models. Taken together, gossypol acetate acted through a gain-of-function way to induce the formation of VCP-LC3-mHTT ternary complex, triggering autophagic degradation of mHTT. This study reveals a new strategy for treatment of HD and raises the possibility that an existing drug can be repurposed as a new treatment of neurodegenerative diseases.

Inhibition of Autophagy by a Small Molecule through Covalent Modification of the LC3 Protein.

The autophagic ubiquitin-like protein LC3 functions through interactions with LC3-interaction regions (LIRs) of other autophagy proteins, including autophagy receptors, which stands out as a promising protein-protein interaction (PPI) target for the intervention of autophagy. Post-translational modifications like acetylation of Lys49 on the LIR-interacting surface could disrupt the interaction, offering an opportunity to design covalent small molecules interfering with the interface. Through screening covalent compounds, we discovered a small molecule modulator of LC3A/B that covalently modifies LC3A/B protein at Lys49. Activity-based protein profiling (ABPP) based evaluations reveal that a derivative molecule DC-LC3in-D5 exhibits a potent covalent reactivity and selectivity to LC3A/B in HeLa cells. DC-LC3in-D5 compromises LC3B lipidation in vitro and in HeLa cells, leading to deficiency in the formation of autophagic structures and autophagic substrate degradation. DC-LC3in-D5 could serve as a powerful tool for autophagy research as well as for therapeutic interventions.

Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin.

B-cell lymphomas are heterogeneous blood disorders with limited therapeutic options, largely because of their propensity to relapse and become refractory to treatments. Carabin, a key suppressor of B-cell receptor signaling and proliferation, is inactivated in B-cell lymphoma by unknown mechanisms. Here, we identify prolyl 4-hydroxylase 2 (P4HA2) as a specific proline hydroxylase of Carabin. Carabin hydroxylation leads to its proteasomal degradation, thereby activating the Ras/extracellular signal-regulated kinase pathway and increasing B-cell lymphoma proliferation. P4HA2 is undetectable in normal B cells but upregulated in the diffuse large B-cell lymphoma (DLBCL), driving Carabin inactivation and lymphoma proliferation. Our results indicate that P4HA2 is a potential prognosis marker for DLBCL and a promising pharmacological target for developing treatment of molecularly stratified B-cell lymphomas.

Acute progressive stroke with middle cerebral artery occlusion caused by idiopathic hypereosinophilic syndrome: a case report.

BACKGROUND: Idiopathic hypereosinophilic syndrome (IHES) is associated with various organ system dysfunctions. Neurologic abnormalities have been previously noted in this syndrome. Cerebral infarction secondary to occlusion of large cerebral artery is rarely reported. Here we described a patient with IHES presented progressive multiple cerebral infarctions caused by bilateral middle cerebral artery occlusion. CASE PRESENTATION: A 55-year-old Chinese woman presented to our hospital with acute onset of right limbs weakness and slurred speech. Laboratory tests showed a significant eosinophilia of 5.29 × 109/L (normal, < 0.5), 49.9% of leukocytes. Brain magnetic resonance imaging (MRI) revealed multiple acute cerebral ischemic lesions. Magnetic resonance angiography (MRA) demonstrated stenosis in horizontal segment of right middle cerebral artery. A pretibial skin biopsy revealed eosinophilic infiltration around the capillaries in deep dermis and adipose tissue. The patient was given oral dual anti platelet agents and intravenous methylprednisolone. However, one week later, the patient presented significant neurological deterioration with right-sided hemiparesis and totally motor aphasia. Brain MRI and computed tomography perfusion (CTP) demonstrated new acute cerebral ischemia in left hemisphere. Digital subtraction angiography (DSA) revealed left middle cerebral artery completely occluded. The patient received a high-dose of intravenous methylprednisolone 500 mg per day and the eosinophil count quickly fell to normal within 2 days. She was transferred to a rehabilitation center and her neurological symptoms improved with modified Ranking Scale from 4 to 2. CONCLUSIONS: IHES is one of the rare causes of acute ischemic stroke with large cerebral artery occlusion. An early high-dose of corticosteroids therapy should be considered in cases of IHES patients. Our case study is benefit to clinical diagnosis and treatment of cerebral infarction with IHES.

A multi-center survey on dietary knowledge and behavior among inpatients in oncology department.

OBJECTIVE: To investigate the current associated factors of dietary knowledge and behavior, the intake and nutritional status in malignancy Chinese inpatients, and the malnutrition causes involved in dietary nutrition knowledge level and behavior, providing recommendations to patients for nutrition education and intervention. METHOD: Five hundred and thirty-five participants from 18 hospitals were investigated by a questionnaire related to dietary knowledge and behavior. Physicians asked and recorded the level of dietary intake and appetite scoring of the participants. The nutritional risk screening with the Nutritional Risk Screening 2002 (NRS-2002) and the dietary survey by 24 h dietary recalls were completed by a dietitian. Besides, the target energy intake and the target protein intake were calculated by the "rule of thumb" recommended by ESPEN guideline, comparing the difference between the actual intake and target intake. RESULTS: According to the questionnaire, 95.2% of participants thought it was important to have a good dietetic habit, and nearly half of them have searched for guides on how to diet; 70% of the patients had no clear idea of what was a scientific diet; 82% of patients had contradictory dietary knowledge; 64.2% of patients would listen to the opinion of the attending physician when a contradiction happened. The main three ways of learning about healthy diet were attending physician, network, and TV, respectively, with the values 26.0, 18.5, and 16.1%. Importantly, 99.6% of patients have made mistakes about dietary knowledge, for example, crab, chicken, lamb, fish, and prawns should not be eaten in their concept. In addition, more than 90% of participants have taken Ganoderma lucidum spore powder, sea cucumber, ginseng, Cordyceps sinensis, and so on. Ninety-three percent of the patients never reached a qualified nutrition education. Besides, 15.6% of the participants had nutritional risk (NRS-2002 ≥ 3). The actual daily energy intake was 1169.20 ± 465.97 kcal, which was significantly less than target energy intake (P < 0.01), amounting to 65.3% of the target requirements. The actual daily protein intake was 46.55 ± 21.40 g, which was significantly less than target protein intake (P < 0.01), amounting to 74.44%. On the other hand, 69% of the participants were "Not too bad, Ok, Good, or Very good" according to the records of physicians, while 34% of them did not reach 60%of the target requirements through dietary survey. CONCLUSION: The survey indicated that cancer patients had poor understanding of the scientific dietary nutrition and were in low level of normative nutritional education among Chinese malignancy inpatients. Dietary intake of most cancer patients decreased, and the actual intake cannot be revealed by NRS-2002 score or the physicians' inquiry. It is necessary to enhance the cooperation between dietitians and physicians and develop nutrition education to improve the level of dietary knowledge.

Macromolecular Crowding Agents-Assisted Imprinted Polymers For Analysis Of Glycocholic Acid In Human Plasma And Urine.

Glycocholic acid (GCA) is a newly identified biomarker for hepatocellular carcinoma (HCC) patients. In this study, a method based on macromolecular crowding strategy has been applied for preparation of a molecularly imprinted polymer (MIP), which possesses high adsorption capacity for GCA. Polymethyl methacrylate was used as a macromolecular crowding agent, N-(3-aminopropyl)-methacrylamide hydrochloride as a functional monomer and ethylene dimethacrylate as a cross-linker. The morphology and binding characteristics of MIP were assessed by scanning electron microscopy and absorption experiments. The MIP was used as an adsorbent material to separate GCA, and the molecularly imprinted solid-phase extraction (MISPE) was carefully optimized. The MISPE combined with high-performance liquid chromatographic analysis was successfully used to determine the GCA in plasma and urine samples. When spiked levels ranged from 0.2 to 20 µmol L-1 , the recoveries were between 94.3 and 100.5%. As a proof of principle, this proposed method has been validated on a small subset of HCC patients (n = 10) and healthy volunteers (n = 10). The average GCA concentrations of HCC patients in plasma and urine were about 25 and 2.8 times than that of healthy volunteers. Copyright © 2016 John Wiley & Sons, Ltd.

Developing an Efficient and General Strategy for Immobilization of Small Molecules onto Microarrays Using Isocyanate Chemistry.

Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%.

Telocytes: novel interstitial cells present in the testis parenchyma of the Chinese soft-shelled turtle Pelodiscus sinensis.

Telocytes (TCs) are novel interstitial cells that have been found in various organs, but the existence of TCs in the testes has not yet been reported. The present ultrastructural and immunohistochemical study revealed the existence of TCs and differentiate these cells from the peritubular cells (Pc) in contact with the surrounding structures in the testes. Firstly, our results confirmed the existence of two cell types surrounding seminiferous tubules; these were Pc (smooth muscle like characteristics) and TCs (as an outer layer around Pc). Telocytes and their long thin prolongations called telopodes (Tps) were detected as alternations of thin segments (podomers) and thick bead-like portions (podoms), the latter of which accommodate the mitochondria and vesicles. The spindle and irregularly shaped cell bodies were observed with small amounts of cytoplasm around them. In contrast, the processes of Pc contained abundant actin filaments with focal densities, irregular spine-like outgrowths and nuclei that exhibited irregularities similar to those of smooth muscle cells. The TCs connected with each other via homocellular and heterocellular junctions with Pc, Leydig cells and blood vessels. The Tps of the vascular TCs had bands and shed more vesicles than the other TCs. Immunohistochemistry (CD34) revealed strong positive expression within the TC cell bodies and Tps. Our data confirmed the existence and the contact of TCs with their surroundings in the testes of the Chinese soft-shelled turtle Pelodiscus sinensis, which may offer new insights for understanding the function of the testes and preventing and treating testicular disorders.

[Research progress on pharmacology, pharmacokinetics and determination of ergosta-4,6,8 (14),22-tetraen-3-one].

Ergosta-4,6,8(14),22-tetraen-3-one (ergone) is one of main components in many medicinal fungi. Ergone has been reported to possess the activities of diuresis, cytotoxicity, antitumor, immunosuppression, as well as treatment of chronic kidney disease. According to reported literatures, an overview of spectroscopy characteristics, content determination, pharmacological activity and pharmacokinetics, etc. for ergone is presented in this review. Furthermore, the present review can provide a certain reference value for the further study and development of ergone.

A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.

Melatonin alleviates septic ARDS by inhibiting NCOA4-mediated ferritinophagy in alveolar macrophages.

Ferroptosis is a novel form of programmed cell death which can exacerbate lung injury in septic acute respiratory distress syndrome (ARDS). Alveolar macrophages, crucial innate immune cells, play a pivotal role in the pathogenesis of ARDS. Ferritinophagy is a process of ferritin degradation mediated by nuclear receptor coactivator 4 (NCOA4) which releases large amounts of iron ions thus promoting ferroptosis. Recent evidence revealed that inhibiting macrophage ferroptosis can effectively attenuate pulmonary inflammatory injury. Melatonin (MT), an endogenous neurohormone, has antioxidant and anti-inflammatory effects and can reduce septic ARDS. However, it is not clear whether MT's pulmonary protective effect is related to the inhibition of macrophage ferritinophagy. Our in vitro experiments demonstrated that MT decreased intracellular malondialdehyde (MDA), Fe2+, and lipid peroxidation levels, increased glutathione (GSH) levels and cell proliferation, and upregulated glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) protein levels in LPS-treated macrophages. Mechanistically, the antiferroptotic effect of MT on LPS-treated macrophages was significantly compromised by the overexpression of NCOA4. Our in vivo experiments revealed that MT alleviated the protein expression of NCOA4 and FTH1 in the alveolar macrophages of septic mice. Furthermore, MT improved lipid peroxidation and mitigated damage in alveolar macrophages and lung tissue, ultimately increasing the survival rates of septic mice. These findings indicate that MT can inhibit ferroptosis in an NCOA4-mediated ferritinophagy manner, thereby ameliorating septic ARDS.